- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04823611
A Study of AZD8233 in Participants With Dyslipidemia. (HAYATE)
A Phase 1 and 2 Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics and Pharmacodynamics of AZD8233 Following a Multiple Subcutaneous Dose Administration in Japanese Participants With Dyslipidemia
Study Overview
Status
Conditions
Detailed Description
Part A: This is designed as a randomized, single-blind (blinding of participants and sites), placebo-controlled, multiple dose, phase 1 study.
Approximately 11 Japanese participants will be randomized in an 8:3 ratio into 1 of the 2 single-blinded treatment arms; AZD8233 high dose or placebo. Participants will be dosed SC on Days 1, 8, 29, and 57.
Part B:This is designed as a randomized, double-blind, placebo-controlled, dose-ranging, phase 2 study. Approximately 60 Japanese participants will be randomized in a 1:1:1 ratio into 1 of the 4 double-blinded treatment arms; AZD8233 low dose, AZD8233 medium dose, or placebo. Participants will be dosed SC on Days 1, 29, and 57.
Part C:This is designed as a randomized, single-blind (blinding of participants and sites), placebo-controlled, multiple dose, phase 1 study.
Approximately 11 Japanese participants will be randomized in an 8:3 ratio into 1 of the 2 single-blinded treatment arms; AZD8233 medium dose or placebo. Participants will be dosed SC on Days 1, 29, and 57.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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Chiyoda-ku, Japan, 1010041
- Research Site
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Chuo-ku, Japan, 104-0031
- Research Site
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Chuo-ku, Japan, 103-0027
- Research Site
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Chuo-ku, Japan, 1040031
- Research Site
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Osaka-shi, Japan, 530-0001
- Research Site
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Shinjuku-ku, Japan, 160-0008
- Research Site
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Suita-shi, Japan, 565-0853
- Research Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Key Inclusion Criteria:
Part A
- Participants must be 20 to 60 years of age inclusive, at the time of signing the informed consent
- Participants who have a fasting LDL-C ≥ 70 mg/dL but < 140 mg/dL at screening
- Participants who have fasting triglycerides < 400 mg/dL at screening
- Participants who should be receiving statin therapy
- Participants who should be on stable medication for a certain time period prior to randomization
- Body mass index (BMI) between 19 and 40 kg/m2
- Females must not be pregnant and must have a negative pregnancy test at screening and randomisation, must not be lactating , and must be of nonchild-bearing potential
Part B
- Participants must be 20 to 75 years of age inclusive, at the time of signing the informed consent
- Have a fasting LDL-C ≥ 70 mg/dL but < 190 mg/dL at screening (Visit 2)
- Have fasting triglycerides < 400 mg/dL at screening (Visit 2)
- Should be receiving statin therapy
- LDL-lowering medications should be on stable dosing for ≥ 3 months prior to screening with no planned medication or dose change during study participation
- BMI between 19 and 40 kg/m2
- Female participants must not be pregnant and must have a negative pregnancy test at screening and randomisation, must not be lactating, and must not be of childbearing potential
Part C
- Participants must be 20 to 60 years of age inclusive, at the time of signing the informed consent
- Participants who have a fasting LDL-C ≥ 70 mg/dL but < 140 mg/dL at screening
- Participants who have fasting triglycerides < 400 mg/dL at screening
- Participants who should be receiving statin therapy
- Participants who should be on stable medication for a certain time period prior to randomization
- Body mass index (BMI) between 19 and 40 kg/m2
- Females must not be pregnant and must have a negative pregnancy test at screening and randomisation, must not be lactating , and must be of nonchild-bearing potential
Key Exclusion Criteria:
Part A
- eGFR < 60 mL/min/1.73m2 using the Japanese equation
- Blood dyscrasias with increased risk of bleeding including idiopathic thrombocytopenic purpura and thrombotic thrombocytopenic purpura or symptoms of increased risk of bleeding. Or participants receiving anti-coagulation therapy
- History of major bleed or high-risk of bleeding diathesis
- Subjects with a high 10-year risk of coronary heart disease as calculated using the Suita score
- Heart rate after 10 minutes of sitting rest < 50 or > 100 beats per minute
- Uncontrolled hypertension defined as sitting SBP > 140 mmHg or DBP > 90 mmHg
Part B
- eGFR < 40 mL/min/1.73m2 using the Japanese equation at Visit 1
- Poorly controlled type 2 diabetes mellitus (T2DM), defined as Haemoglobin A1c (HbA1c) > 10% at Visit 1
- Acute ischaemic cardiovascular event in the last 12 months prior to randomization
- Heart failure with New York Heart Association (NYHA) Class III-IV
- High-risk of bleeding diathesis as judged by the Investigator
- Uncontrolled hypertension defined as sitting SBP > 160 mmHg or DBP > 90 mmHg at Visit 1 or Visit 3
- Heart rate after 10 minutes sitting rest < 50 bpm or > 100 bpm at Visit 1 or Visit 3
Part C
- eGFR < 60 mL/min/1.73m2 using the Japanese equation
- Blood dyscrasias with increased risk of bleeding including idiopathic thrombocytopenic purpura and thrombotic thrombocytopenic purpura or symptoms of increased risk of bleeding. Or participants receiving anti-coagulation therapy
- History of major bleed or high-risk of bleeding diathesis
- Subjects with a high 10-year risk of coronary heart disease as calculated using the Suita score
- Heart rate after 10 minutes of sitting rest < 50 or > 100 beats per minute
- Uncontrolled hypertension defined as sitting SBP > 140 mmHg or DBP > 90 mmHg
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Placebo Comparator: Part A:Placebo
Placebo solution for subcutaneous injection.
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Placebo solution
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Experimental: Part A:AZD8233
AZD8233 for subcutaneous injection.
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PCSK9-targeted ASO for the reduction of circulating levels of LDL-C.
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Placebo Comparator: Part B:Placebo
Placebo solution for subcutaneous injection.
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Placebo solution
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Experimental: Part B:AZD8233 medium dose
AZD8233 medium dose for subcutaneous injection.
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PCSK9-targeted ASO for the reduction of circulating levels of LDL-C.
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Experimental: Part B:AZD8233 low dose
AZD8233 low dose for subcutaneous injection.
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PCSK9-targeted ASO for the reduction of circulating levels of LDL-C.
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Placebo Comparator: Part C: Placebo
Placebo solution for subcutaneous injection.
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Placebo solution
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Experimental: Part C: AZD8233 medium dose
AZD8233 medium dose for subcutaneous injection.
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PCSK9-targeted ASO for the reduction of circulating levels of LDL-C.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Part A: Number of subjects with adverse events (AEs) due to AZD8233 SC multiple dose treatment.
Time Frame: From randomization to final Follow-up Visit (Week 16 post last dose).
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To assess AEs as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
Serious AEs will be recorded from the time of informed consent.
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From randomization to final Follow-up Visit (Week 16 post last dose).
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Part A: Vital sign: Systolic blood pressure (SBP)
Time Frame: From Day1(pre-dose) to final Follow-up Visit (Week 16 post last dose).
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To assess SBP as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
BP will be collected after the subject has rested in the supine position for at least 5 minutes.
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From Day1(pre-dose) to final Follow-up Visit (Week 16 post last dose).
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Part A: Vital sign: Pulse rate
Time Frame: From Day1(pre-dose) to final Follow-up Visit (Week 16 post last dose)
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To assess supine position pulse as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
Pulse rate will be collected after the subject has rested in the supine position for at least 5 minutes.
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From Day1(pre-dose) to final Follow-up Visit (Week 16 post last dose)
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Part A: Vital sign: Body temperature
Time Frame: From Day 1(pre-dose) to final Follow-up Visit (Week 16 post last dose).
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To assess the oral body temperature as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
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From Day 1(pre-dose) to final Follow-up Visit (Week 16 post last dose).
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Part A: Number of patients with abnormal findings in resting 12-lead Electrocariogram (ECG) .
Time Frame: From Day1(pre-dose) to final Follow-up Visit (Week 16 post last dose).
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To assess the clinically significant abnormalities in the cardiovascular system functioning using a 12-lead ECG ( RR, PR, QRS, QT, QTcF, and heart rate )as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
ECG evaluations will be recorded after approximately 10 min resting in supine position.
During treatment period, ECG will be done on Days 1 and 57 (pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12 and 24, 36 and 48 hours post-dose), and Days 8 and 29 (pre-dose).
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From Day1(pre-dose) to final Follow-up Visit (Week 16 post last dose).
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Part A: Number of subject with abnormal findings in cardiac telemetry
Time Frame: At Day -1, Days 1 to 3 (pre-dose to 24 hours post-dose), and Day 57 (pre-dose to 24 hours post-dose).
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To assess cardiac telemetry as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
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At Day -1, Days 1 to 3 (pre-dose to 24 hours post-dose), and Day 57 (pre-dose to 24 hours post-dose).
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Part A: Laboratory assessments: Hematology - Blood cells count
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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To assess red blood cells (RBC) and white blood cells (WBC) as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
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Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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Part A: Laboratory assessments: Hematology - Hemoglobin (Hb)
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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To assess Hb as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
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Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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Part A: Laboratory assessments: Hematology - Hematocrit (HCT)
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose
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To assess HCT as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
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Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose
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Part A: Laboratory assessments: Hematology - Mean corpuscular volume (MCV)
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose
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To assess MCV as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
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Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose
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Part A: Laboratory assessments: Hematology - Mean corpuscular hemoglobin (MCH)
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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To assess MCH as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
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Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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Part A: Laboratory assessments: Hematology - Mean corpuscular hemoglobin concentration (MCHC)
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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To assess MCHC as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
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Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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Part A: Laboratory assessments: Hematology - Differential WBC count
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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To assess differential WBC count absolute count of neutrophils, lymphocytes, monocytes, eosinophils and basophils as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
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Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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Part A: Laboratory assessments: Hematology - Platelet count and platelet function assessment.
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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To assess platelet count in platelet rich plasma (PRP) using Light Transmission Aggregometry (LTA) as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
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Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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Part A: Laboratory assessments: Hematology - Reticulocytes absolute count
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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To assess Reticulocytes absolute count as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
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Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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Part A: Laboratory assessments: Serum clinical chemistry - Electrolytes
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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To assess serum level of sodium, potassium, calcium as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
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Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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Part A: Laboratory assessments: Serum clinical chemistry - Blood urea nitrogen (BUN)
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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To assess serum level of BUN as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
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Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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Part A: To assess serum level of BUN as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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To assess serum level of creatinine as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
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Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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Part A: Laboratory assessments: Serum clinical chemistry - Glucose (fasting)
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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To assess serum fasting glucose level as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
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Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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Part A: Laboratory assessments: Serum clinical chemistry - Creatine kinase
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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To assess the level of serum creatine kinase as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
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Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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Part A: Laboratory assessments: Serum clinical chemistry - Direct bilirubin
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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To assess the level of serum bilirubin (direct) as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
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Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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Part A: Laboratory assessments: Serum clinical chemistry - Hemoglobin A1c (HbA1c)
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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To assess the level of HbA1c as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
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Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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Part A: Laboratory assessments: Serum clinical chemistry - Liver enzymes
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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To assess the level of Alkaline phosphatase (ALP), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), and Gamma glutamyl transpeptidase (GGT) as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
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Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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Part A: Laboratory assessments: Serum clinical chemistry - Total bilirubin
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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To assess the level of serum bilirubin (total) as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
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Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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Part A: Laboratory assessments: Serum clinical chemistry - Cell enzymes
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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To assess the level of serum glutamate dehydrogenase (GLDH) and lactate dehydrogenase (LDH) as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
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Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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Part A: Laboratory assessments: Serum clinical chemistry - Bicarbonate
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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To assess the level of bicarbonate as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
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Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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Part A: Laboratory assessments: Serum clinical chemistry - Uric acid
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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To assess the level of uric acid as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
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Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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Part A: Laboratory assessments - Coagulation
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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To assess activated partial thrombin time (aPTT), prothrombin time (PT), and International normalized ratio (INR) as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
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Day-1, Day1 ( 24 hours post- dose), Day8 ( pre-dose), Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
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Part A: Renal safety biomarkers - Urine clusterin
Time Frame: Day 1 (pre-dose, 24 hours and 48 hours post-dose), Days 8 and 29 (pre-dose), and Day 57 (pre-dose).
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To assess renal biomarker by evaluation of urine clusterin level as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
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Day 1 (pre-dose, 24 hours and 48 hours post-dose), Days 8 and 29 (pre-dose), and Day 57 (pre-dose).
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Part A: Renal safety biomarkers - Urine cystatin-C
Time Frame: Day 1 (pre-dose, 24 hours and 48 hours post-dose), Days 8 and 29 (pre-dose), and Day 57 (pre-dose).
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To assess renal biomarker by evaluation of urine cystatin-C level as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
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Day 1 (pre-dose, 24 hours and 48 hours post-dose), Days 8 and 29 (pre-dose), and Day 57 (pre-dose).
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Part A: Renal safety biomarkers - Urine N-acetyl-beta-D-glucosaminidase (NAG)
Time Frame: Day 1 (pre-dose, 24 hours and 48 hours post-dose), Days 8 and 29 (pre-dose), and Day 57 (pre-dose).
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To assess renal biomarker by evaluation of urine NAG level as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
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Day 1 (pre-dose, 24 hours and 48 hours post-dose), Days 8 and 29 (pre-dose), and Day 57 (pre-dose).
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Part A: Renal safety biomarkers - Urine albumin
Time Frame: Day 1 (pre-dose, 24 hours and 48 hours post-dose), Days 8 and 29 (pre-dose), and Day 57 (pre-dose).
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To assess renal biomarker by evaluation of urine albumin level as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
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Day 1 (pre-dose, 24 hours and 48 hours post-dose), Days 8 and 29 (pre-dose), and Day 57 (pre-dose).
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Part A: Renal safety biomarkers - Urine creatinine
Time Frame: Day 1 (pre-dose, 24 hours and 48 hours post-dose), Days 8 and 29 (pre-dose), and Day 57 (pre-dose).
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To assess renal biomarker by evaluation of urine creatinine level as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
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Day 1 (pre-dose, 24 hours and 48 hours post-dose), Days 8 and 29 (pre-dose), and Day 57 (pre-dose).
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Part A: Renal safety biomarkers - Urine Kidney injury molecule1 (KIM-1)
Time Frame: Day 1 (pre-dose, 24 hours and 48 hours post-dose), Days 8 and 29 (pre-dose), and Day 57 (pre-dose).
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To assess renal biomarker by evaluation of urine KIM-1 level as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
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Day 1 (pre-dose, 24 hours and 48 hours post-dose), Days 8 and 29 (pre-dose), and Day 57 (pre-dose).
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Part A: Renal safety biomarkers - Urine Neutrophil gelatinase-associated lipocalin (NGAL)
Time Frame: Day 1 (pre-dose, 24 hours and 48 hours post-dose), Days 8 and 29 (pre-dose), and Day 57 (pre-dose).
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To assess renal biomarker by evaluation of urine NAG level as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
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Day 1 (pre-dose, 24 hours and 48 hours post-dose), Days 8 and 29 (pre-dose), and Day 57 (pre-dose).
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Part A: Renal safety biomarkers - Urine Osteopontin
Time Frame: Day 1 (pre-dose, 24 hours and 48 hours post-dose), Days 8 and 29 (pre-dose), and Day 57 (pre-dose).
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To assess renal biomarker by evaluation of urine osteopontin level as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
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Day 1 (pre-dose, 24 hours and 48 hours post-dose), Days 8 and 29 (pre-dose), and Day 57 (pre-dose).
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Part A: Renal safety biomarkers - Urine total protein
Time Frame: Day 1 (pre-dose, 24 hours and 48 hours post-dose), Days 8 and 29 (pre-dose), and Day 57 (pre-dose).
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To assess renal biomarker by evaluation of urine protein (total) level as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
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Day 1 (pre-dose, 24 hours and 48 hours post-dose), Days 8 and 29 (pre-dose), and Day 57 (pre-dose).
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Part A: Immune Activation Response - High-sensitivity C-reactive protein (hs-CRP)
Time Frame: From screening to final Follow-up Visit (Week 16 post last dose).
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To assess hs-CRP level as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
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From screening to final Follow-up Visit (Week 16 post last dose).
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Part A: Complement Activation panel
Time Frame: Days 1 and 57 (pre-dose, 1, 2, and 4 hours post-dose).
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To assess chemotactic factor (C3a, Bb, and C5a) levels as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
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Days 1 and 57 (pre-dose, 1, 2, and 4 hours post-dose).
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Part A: Laboratory assessments - Sampling for dipstick urinalysis for hematuria
Time Frame: Day1 to Day3 (pre-dose and then 24 and 48 h post -dose), Day8 (pre-dose), Day29 (pre-dose) and Day57 (pre-dose).
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To assess dipstick urinalysis for hematuria as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
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Day1 to Day3 (pre-dose and then 24 and 48 h post -dose), Day8 (pre-dose), Day29 (pre-dose) and Day57 (pre-dose).
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Part B:Absolute change from baseline in long-transformed LDL-C in serum at week12.
Time Frame: Measurement at week 12
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Absolute change from baseline in long-transformed LDL-C in serum.
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Measurement at week 12
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Part A: Vital sign: Diastolic blood pressure (DBP)
Time Frame: From Day1(pre-dose) to final Follow-up Visit (Week 16 post last dose).
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To assess DBP as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
BP will be collected after the subject has rested in the supine position for at least 5 minutes.
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From Day1(pre-dose) to final Follow-up Visit (Week 16 post last dose).
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Part C: Number of subjects with adverse events (AEs) due to AZD8233 SC multiple dose treatment.
Time Frame: From randomization to final Follow-up Visit (Week 16 post last dose).
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To assess AEs as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
Serious AEs will be recorded from the time of informed consent.
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From randomization to final Follow-up Visit (Week 16 post last dose).
|
Part C: Vital sign: Systolic blood pressure (SBP)
Time Frame: From Day1(pre-dose) to final Follow-up Visit (Week 16 post last dose).
|
To assess SBP as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
BP will be collected after the subject has rested in the supine position for at least 5 minutes.
|
From Day1(pre-dose) to final Follow-up Visit (Week 16 post last dose).
|
Part C: Vital sign: Pulse rate
Time Frame: From Day1(pre-dose) to final Follow-up Visit (Week 16 post last dose)
|
To assess supine position pulse as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
Pulse rate will be collected after the subject has rested in the supine position for at least 5 minutes.
|
From Day1(pre-dose) to final Follow-up Visit (Week 16 post last dose)
|
Part C: Vital sign: Body temperature
Time Frame: From Day 1(pre-dose) to final Follow-up Visit (Week 16 post last dose).
|
To assess the oral body temperature as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
|
From Day 1(pre-dose) to final Follow-up Visit (Week 16 post last dose).
|
Part C: Number of patients with abnormal findings in resting 12-lead Electrocariogram (ECG) .
Time Frame: From Day1(pre-dose) to final Follow-up Visit (Week 16 post last dose).
|
To assess the clinically significant abnormalities in the cardiovascular system functioning using a 12-lead ECG ( RR, PR, QRS, QT, QTcF, and heart rate )as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
ECG evaluations will be recorded after approximately 10 min resting in supine position.
During treatment period, ECG will be done on Days 1 and 57 (pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12 and 24, 36 and 48 hours post-dose), and Days 8 and 29 (pre-dose).
|
From Day1(pre-dose) to final Follow-up Visit (Week 16 post last dose).
|
Part C: Number of subject with abnormal findings in cardiac telemetry
Time Frame: At Day -1, Days 1 to 3 (pre-dose to 24 hours post-dose), and Day 57 (pre-dose to 24 hours post-dose).
|
To assess cardiac telemetry as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
|
At Day -1, Days 1 to 3 (pre-dose to 24 hours post-dose), and Day 57 (pre-dose to 24 hours post-dose).
|
Part C: Laboratory assessments: Hematology - Hemoglobin (Hb)
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8 , Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
To assess Hb as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
|
Day-1, Day1 ( 24 hours post- dose), Day8 , Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
Part C: Laboratory assessments: Hematology - Blood cells count
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8 , Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
To assess red blood cells (RBC) and white blood cells (WBC) as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
|
Day-1, Day1 ( 24 hours post- dose), Day8 , Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
Part C: Laboratory assessments: Hematology - Hematocrit (HCT)
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8, Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose
|
To assess HCT as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
|
Day-1, Day1 ( 24 hours post- dose), Day8, Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose
|
Part C: Laboratory assessments: Hematology - Mean corpuscular volume (MCV)
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8 , Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose
|
To assess MCV as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
|
Day-1, Day1 ( 24 hours post- dose), Day8 , Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose
|
Part C: Laboratory assessments: Hematology - Mean corpuscular hemoglobin (MCH)
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8, Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
To assess MCH as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
|
Day-1, Day1 ( 24 hours post- dose), Day8, Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
Part C: Laboratory assessments: Hematology - Mean corpuscular hemoglobin concentration (MCHC)
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8, Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
To assess MCHC as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
|
Day-1, Day1 ( 24 hours post- dose), Day8, Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
Part C: Laboratory assessments: Hematology - Differential WBC count
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8 , Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
To assess differential WBC count absolute count of neutrophils, lymphocytes, monocytes, eosinophils and basophils as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
|
Day-1, Day1 ( 24 hours post- dose), Day8 , Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
Part C: Laboratory assessments: Hematology - Platelet count and platelet function assessment.
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8, Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
To assess platelet count in platelet rich plasma (PRP) using Light Transmission Aggregometry (LTA) as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
|
Day-1, Day1 ( 24 hours post- dose), Day8, Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
Part C: Laboratory assessments: Hematology - Reticulocytes absolute count
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8 , Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
To assess Reticulocytes absolute count as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
|
Day-1, Day1 ( 24 hours post- dose), Day8 , Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
Part C: Laboratory assessments: Serum clinical chemistry - Electrolytes
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8, Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
To assess serum level of sodium, potassium, calcium as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
|
Day-1, Day1 ( 24 hours post- dose), Day8, Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
Part C: Laboratory assessments: Serum clinical chemistry - Blood urea nitrogen (BUN)
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8 , Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
To assess serum level of BUN as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
|
Day-1, Day1 ( 24 hours post- dose), Day8 , Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
Part C: To assess serum level of BUN as a variable of safety and tolerability of AZD8233 following SC administration of multiple ascending doses.
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8 , Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
To assess serum level of creatinine as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
|
Day-1, Day1 ( 24 hours post- dose), Day8 , Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
Part C: Vital sign: Diastolic blood pressure (DBP)
Time Frame: From Day1(pre-dose) to final Follow-up Visit (Week 16 post last dose).
|
To assess DBP as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
BP will be collected after the subject has rested in the supine position for at least 5 minutes.
|
From Day1(pre-dose) to final Follow-up Visit (Week 16 post last dose).
|
Part C: Laboratory assessments: Serum clinical chemistry - Glucose (fasting)
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8, Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
To assess serum fasting glucose level as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
|
Day-1, Day1 ( 24 hours post- dose), Day8, Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
Part C: Laboratory assessments: Serum clinical chemistry - Creatine kinase
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8, Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
To assess the level of serum creatine kinase as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
|
Day-1, Day1 ( 24 hours post- dose), Day8, Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
Part C: Laboratory assessments: Serum clinical chemistry - Direct bilirubin
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8, Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
To assess the level of serum bilirubin (direct) as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
|
Day-1, Day1 ( 24 hours post- dose), Day8, Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
Part C: Laboratory assessments: Serum clinical chemistry - Hemoglobin A1c (HbA1c)
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8, Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
To assess the level of HbA1c as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
|
Day-1, Day1 ( 24 hours post- dose), Day8, Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
Part C: Laboratory assessments: Serum clinical chemistry - Liver enzymes
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8, Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
To assess the level of Alkaline phosphatase (ALP), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), and Gamma glutamyl transpeptidase (GGT) as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
|
Day-1, Day1 ( 24 hours post- dose), Day8, Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
Part C: Laboratory assessments: Serum clinical chemistry - Total bilirubin
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8 , Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
To assess the level of serum bilirubin (total) as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
|
Day-1, Day1 ( 24 hours post- dose), Day8 , Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
Part C: Laboratory assessments: Serum clinical chemistry - Cell enzymes
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8, Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
To assess the level of serum glutamate dehydrogenase (GLDH) and lactate dehydrogenase (LDH) as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
|
Day-1, Day1 ( 24 hours post- dose), Day8, Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
Part C: Laboratory assessments: Serum clinical chemistry - Bicarbonate
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8, Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
To assess the level of bicarbonate as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
|
Day-1, Day1 ( 24 hours post- dose), Day8, Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
Part C: Laboratory assessments: Serum clinical chemistry - Uric acid
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8, Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
To assess the level of uric acid as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
|
Day-1, Day1 ( 24 hours post- dose), Day8, Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
Part C: Laboratory assessments - Coagulation
Time Frame: Day-1, Day1 ( 24 hours post- dose), Day8, Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
To assess activated partial thrombin time (aPTT), prothrombin time (PT), and International normalized ratio (INR) as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
|
Day-1, Day1 ( 24 hours post- dose), Day8, Day29 (pre-dose), Day57 (pre-dose), Week 2,4,8,12 and 16 post last dose.
|
Part C: Renal safety biomarkers - Urine clusterin
Time Frame: Day 1 (pre-dose, 24 hours and 48 hours post-dose), Day 8, Day 29 (pre-dose), and Day 57 (pre-dose).
|
To assess renal biomarker by evaluation of urine clusterin level as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
|
Day 1 (pre-dose, 24 hours and 48 hours post-dose), Day 8, Day 29 (pre-dose), and Day 57 (pre-dose).
|
Part C: Renal safety biomarkers - Urine cystatin-C
Time Frame: Day 1 (pre-dose, 24 hours and 48 hours post-dose), Day 8, Day 29 (pre-dose), and Day 57 (pre-dose).
|
To assess renal biomarker by evaluation of urine cystatin-C level as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
|
Day 1 (pre-dose, 24 hours and 48 hours post-dose), Day 8, Day 29 (pre-dose), and Day 57 (pre-dose).
|
Part C: Renal safety biomarkers - Urine N-acetyl-beta-D-glucosaminidase (NAG)
Time Frame: Day 1 (pre-dose, 24 hours and 48 hours post-dose), Day 8 , Day 29 (pre-dose), and Day 57 (pre-dose).
|
To assess renal biomarker by evaluation of urine NAG level as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
|
Day 1 (pre-dose, 24 hours and 48 hours post-dose), Day 8 , Day 29 (pre-dose), and Day 57 (pre-dose).
|
Part C: Renal safety biomarkers - Urine albumin
Time Frame: Day 1 (pre-dose, 24 hours and 48 hours post-dose), Day 8 , Day 29 (pre-dose), and Day 57 (pre-dose).
|
To assess renal biomarker by evaluation of urine albumin level as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
|
Day 1 (pre-dose, 24 hours and 48 hours post-dose), Day 8 , Day 29 (pre-dose), and Day 57 (pre-dose).
|
Part C: Renal safety biomarkers - Urine creatinine
Time Frame: Day 1 (pre-dose, 24 hours and 48 hours post-dose), Day 8, Day 29 (pre-dose), and Day 57 (pre-dose).
|
To assess renal biomarker by evaluation of urine creatinine level as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
|
Day 1 (pre-dose, 24 hours and 48 hours post-dose), Day 8, Day 29 (pre-dose), and Day 57 (pre-dose).
|
Part C: Renal safety biomarkers - Urine Neutrophil gelatinase-associated lipocalin (NGAL)
Time Frame: Day 1 (pre-dose, 24 hours and 48 hours post-dose), Day 8, Day 29 (pre-dose), and Day 57 (pre-dose).
|
To assess renal biomarker by evaluation of urine NAG level as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
|
Day 1 (pre-dose, 24 hours and 48 hours post-dose), Day 8, Day 29 (pre-dose), and Day 57 (pre-dose).
|
Part C: Renal safety biomarkers - Urine Osteopontin
Time Frame: Day 1 (pre-dose, 24 hours and 48 hours post-dose), Day 8 , Day 29 (pre-dose), and Day 57 (pre-dose).
|
To assess renal biomarker by evaluation of urine osteopontin level as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
|
Day 1 (pre-dose, 24 hours and 48 hours post-dose), Day 8 , Day 29 (pre-dose), and Day 57 (pre-dose).
|
Part C: Renal safety biomarkers - Urine total protein
Time Frame: Day 1 (pre-dose, 24 hours and 48 hours post-dose), Day 8 , Day 29 (pre-dose), and Day 57 (pre-dose).
|
To assess renal biomarker by evaluation of urine protein (total) level as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
|
Day 1 (pre-dose, 24 hours and 48 hours post-dose), Day 8 , Day 29 (pre-dose), and Day 57 (pre-dose).
|
Part C: Immune Activation Response - High-sensitivity C-reactive protein (hs-CRP)
Time Frame: From screening to final Follow-up Visit (Week 16 post last dose).
|
To assess hs-CRP level as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
|
From screening to final Follow-up Visit (Week 16 post last dose).
|
Part C: Complement Activation panel
Time Frame: Days 1 and 57 (pre-dose, 1, 2, and 4 hours post-dose).
|
To assess chemotactic factor (Bb, and C5a) levels as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
|
Days 1 and 57 (pre-dose, 1, 2, and 4 hours post-dose).
|
Part C: Laboratory assessments - Sampling for dipstick urinalysis for hematuria
Time Frame: Day1 to Day3 (pre-dose and then 24 and 48 h post -dose), Day8 , Day29 (pre-dose) and Day57 (pre-dose).
|
To assess dipstick urinalysis for hematuria as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
|
Day1 to Day3 (pre-dose and then 24 and 48 h post -dose), Day8 , Day29 (pre-dose) and Day57 (pre-dose).
|
Part C: Renal safety biomarkers - Urine Kidney injury molecule1 (KIM-1)
Time Frame: Day 1 (pre-dose, 24 hours and 48 hours post-dose), Day 8 , Day29 (pre-dose), and Day 57 (pre-dose).
|
To assess renal biomarker by evaluation of urine KIM-1 level as a variable of safety and tolerability of AZD8233 following SC administration of multiple doses.
|
Day 1 (pre-dose, 24 hours and 48 hours post-dose), Day 8 , Day29 (pre-dose), and Day 57 (pre-dose).
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Part A:Plasma PK analysis. Time delay between drug administration and the first observed concentration in plasma (tlag).
Time Frame: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
To characterize the PK of AZD8233 following SC administration of multiple doses.
|
Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
Part A:Plasma PK analysis: Time to reach peak or maximum observed concentration or response following drug administration (tmax).
Time Frame: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
To characterize the PK of AZD8233 following SC administration of multiple doses.
|
Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
Part A:Plasma PK analysis: Observed maximum plasma concentration (Cmax)
Time Frame: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
To characterize the PK of AZD8233 following SC administration of multiple doses.
|
Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
Part A:Area under the plasma concentration-curve from time zero to time last value above the limit of quantification (AUC[0-last]
Time Frame: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
To characterize the PK of AZD8233 following SC administration of multiple doses.
|
Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
Part A:Plasma PK analysis: Area under the concentration-time curve from time zero to 24 hours post-dose (AUC[0-24])
Time Frame: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24 hours post-dose).
|
To characterize the PK of AZD8233 following SC administration of multiple doses.
|
Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24 hours post-dose).
|
Part A:Plasma PK analysis: Area under the concentration-time curve from time zero to 48 hours post-dose (AUC[0-48])
Time Frame: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose).
|
To characterize the PK of AZD8233 following SC administration of multiple doses.
|
Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose).
|
Part A:Plasma PK analysis: Area under the concentration-time curve from time zero extrapolated to infinity (AUC).
Time Frame: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
To characterize the PK of AZD8233 following SC administration of multiple doses.
|
Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
Part A:Plasma PK analysis: Area under the plasma concentration-time curve from time during the dosing interval (AUCt).
Time Frame: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
To characterize the PK of AZD8233 following SC administration of multiple doses.
|
Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
Part A:Plasma PK analysis: Observed trough plasma drug concentration (Ctrough).
Time Frame: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
To characterize the PK of AZD8233 following SC administration of multiple doses.
|
Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
Part A:Plasma PK analysis: Apparent total body clearance of drug from plasma after extravascular administration (CL/F).
Time Frame: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
To characterize the PK of AZD8233 following SC administration of multiple doses.
|
Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
Part A:Plasma PK analysis: Apparent volume of distribution for parent drug at terminal phase (extravascular administration) (Vz/F).
Time Frame: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
To characterize the PK of AZD8233 following SC administration of multiple doses.
|
Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
Part A:Plasma PK analysis: Half-life associated with the terminal slope (λz) of a semi-logarithmic concentration-time curve (t1/2).
Time Frame: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
To characterize the PK of AZD8233 following SC administration of multiple doses.
|
Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
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Part A:Plasma PK analysis: Mean Residence Time (MRT).
Time Frame: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
To characterize the PK of AZD8233 following SC administration of multiple doses.
|
Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8 (pre-dose), Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
Part A:Urine PK analysis: Amount excreted in urine (Ae).
Time Frame: Treatment Days 1 to 3 (Pre-dose and intervals 0-6, 6-12 hours and 12-24 hours post-dose).
|
To characterize the PK of AZD8233 following SC administration of multiple doses.
|
Treatment Days 1 to 3 (Pre-dose and intervals 0-6, 6-12 hours and 12-24 hours post-dose).
|
Part A:Urine PK analysis: Fraction excreted unchanged in urine (Fe).
Time Frame: Treatment Days 1 to 3 (Pre-dose and intervals 0-6, 6-12 hours and 12-24 hours post-dose).
|
To characterize the PK of AZD8233 following SC administration of multiple doses.
|
Treatment Days 1 to 3 (Pre-dose and intervals 0-6, 6-12 hours and 12-24 hours post-dose).
|
Part A:Urine PK analysis: Renal clearance (CLR).
Time Frame: Treatment Days 1 to 3 (Pre-dose and intervals 0-6, 6-12 hours and 12-24 hours post-dose).
|
To characterize the PK of AZD8233 following SC administration of multiple doses.
|
Treatment Days 1 to 3 (Pre-dose and intervals 0-6, 6-12 hours and 12-24 hours post-dose).
|
Part A:Absolute change from baseline in log-transformed PCSK9 in plasma and Percent change from baseline in PCSK9 in plasma.
Time Frame: At screening, Day -1, Days 1 to 3 and Days 57 to 58 (pre-dose and 48 hours post-dose), Day 8 (pre-dose), Days 15, 22, Day 29 (pre-dose), Days 36, 44, Day 56, week 2 to 14 (at 2, 4, 6, 8, 10, 12, and 14 weeks) and week 16 post-dose.
|
To assess the effect of AZD8233 on levels of PCSK9 following SC administration of multiple doses.
|
At screening, Day -1, Days 1 to 3 and Days 57 to 58 (pre-dose and 48 hours post-dose), Day 8 (pre-dose), Days 15, 22, Day 29 (pre-dose), Days 36, 44, Day 56, week 2 to 14 (at 2, 4, 6, 8, 10, 12, and 14 weeks) and week 16 post-dose.
|
Part A:Percentage change from baseline in levels of LDL-C in serum.
Time Frame: At screening, Day -1, Days 1 to 3 and Days 57 to 58 (pre-dose and 48 hours post-dose), Day 8 (pre-dose), Days 15, 22, Day 29 (pre-dose), Days 36, 44, Day 56, week 2 to 14 (at 2, 4, 6, 8, 10, 12, and 14 weeks) and week 16 post-dose.
|
To assess the effect of AZD8233 on levels of LDL-C following SC administration of multiple doses.
|
At screening, Day -1, Days 1 to 3 and Days 57 to 58 (pre-dose and 48 hours post-dose), Day 8 (pre-dose), Days 15, 22, Day 29 (pre-dose), Days 36, 44, Day 56, week 2 to 14 (at 2, 4, 6, 8, 10, 12, and 14 weeks) and week 16 post-dose.
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Part B:Absolute change from baseline in log-transformed PCSK9 in plasma and Percent change from baseline in PCSK9 in plasma.
Time Frame: Measurement at screening, week 0, week 1, week 3, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 18, week 20, week 22, week 24.
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To assess the effect of different doses of AZD8233 on PCSK9 versus placebo.
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Measurement at screening, week 0, week 1, week 3, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 18, week 20, week 22, week 24.
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Part B:Percentage change from baseline in levels of LDL-C in serum.
Time Frame: Measurement at screening, week 0, week 1, week 3, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 18, week 20, week 22, week 24.
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To assess the effect of different doses of AZD8233 on LDL-C versus placebo.
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Measurement at screening, week 0, week 1, week 3, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 18, week 20, week 22, week 24.
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Part B:Levels of other lipid parameters of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a) , Triglycerides, Remnants cholesterol.
Time Frame: Measurement at screening, week 0, week 1, week 3, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 18, week 20, week 22, week 24.
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To assess the effect of AZD8233 on other lipid parameters versus placebo.
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Measurement at screening, week 0, week 1, week 3, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 18, week 20, week 22, week 24.
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Part B: Plasma concentration of AZD8233
Time Frame: Measurement at week 1, week 4, week 6, week 8, week 10, week 12, week 16, week 20, week 24.
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Measurement at week 1, week 4, week 6, week 8, week 10, week 12, week 16, week 20, week 24.
|
|
Part B:Anti-drug antibodies (ADAs) during the treatment period and follow-up period.
Time Frame: Measurement at week 0, week 1, week 4, week 8, week 12, week 16, week 20, week 24.
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To evaluate the immunogenicity of AZD8233.
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Measurement at week 0, week 1, week 4, week 8, week 12, week 16, week 20, week 24.
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Part A:Levels of other lipid parameters of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a) , Triglycerides.
Time Frame: Measurement at screening, Day -1, Days 1 to 3 and Days 57 to 58 (pre-dose and 48 hours post-dose), Day 8 (pre-dose), Days 15, 22, Day 29 (pre-dose), Days 36, 44, Day 56, week 2 to 14 (at 2, 4, 6, 8, 10, 12, and 14 weeks) and week 16 post-dose.
|
To assess the effect of AZD8233 on other lipid parameters versus placebo.
|
Measurement at screening, Day -1, Days 1 to 3 and Days 57 to 58 (pre-dose and 48 hours post-dose), Day 8 (pre-dose), Days 15, 22, Day 29 (pre-dose), Days 36, 44, Day 56, week 2 to 14 (at 2, 4, 6, 8, 10, 12, and 14 weeks) and week 16 post-dose.
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Part C:Plasma PK analysis. Time delay between drug administration and the first observed concentration in plasma (tlag).
Time Frame: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8, Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
To characterize the PK of AZD8233 following SC administration of multiple doses.
|
Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8, Days 15, 22, 29 (pre-dose), Days 36 and 44.
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Part C:Plasma PK analysis: Time to reach peak or maximum observed concentration or response following drug administration (tmax).
Time Frame: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8, Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
To characterize the PK of AZD8233 following SC administration of multiple doses.
|
Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8, Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
Part C:Plasma PK analysis: Observed maximum plasma concentration (Cmax)
Time Frame: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8, Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
To characterize the PK of AZD8233 following SC administration of multiple doses.
|
Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8, Days 15, 22, 29 (pre-dose), Days 36 and 44.
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Part C:Area under the plasma concentration-curve from time zero to time last value above the limit of quantification (AUC[0-last]
Time Frame: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8, Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
To characterize the PK of AZD8233 following SC administration of multiple doses.
|
Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8, Days 15, 22, 29 (pre-dose), Days 36 and 44.
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Part C:Plasma PK analysis: Area under the concentration-time curve from time zero to 24 hours post-dose (AUC[0-24])
Time Frame: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24 hours post-dose).
|
To characterize the PK of AZD8233 following SC administration of multiple doses.
|
Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24 hours post-dose).
|
Part C:Plasma PK analysis: Area under the concentration-time curve from time zero to 48 hours post-dose (AUC[0-48])
Time Frame: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose).
|
To characterize the PK of AZD8233 following SC administration of multiple doses.
|
Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose).
|
Part C:Plasma PK analysis: Area under the concentration-time curve from time zero extrapolated to infinity (AUC).
Time Frame: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8, Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
To characterize the PK of AZD8233 following SC administration of multiple doses.
|
Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8, Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
Part C:Plasma PK analysis: Area under the plasma concentration-time curve from time during the dosing interval (AUCt).
Time Frame: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8, Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
To characterize the PK of AZD8233 following SC administration of multiple doses.
|
Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8, Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
Part C:Plasma PK analysis: Observed trough plasma drug concentration (Ctrough).
Time Frame: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8, Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
To characterize the PK of AZD8233 following SC administration of multiple doses.
|
Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8, Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
Part C:Plasma PK analysis: Apparent total body clearance of drug from plasma after extravascular administration (CL/F).
Time Frame: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8, Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
To characterize the PK of AZD8233 following SC administration of multiple doses.
|
Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8, Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
Part C:Plasma PK analysis: Apparent volume of distribution for parent drug at terminal phase (extravascular administration) (Vz/F).
Time Frame: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8, Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
To characterize the PK of AZD8233 following SC administration of multiple doses.
|
Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8, Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
Part C:Plasma PK analysis: Half-life associated with the terminal slope (λz) of a semi-logarithmic concentration-time curve (t1/2).
Time Frame: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8, Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
To characterize the PK of AZD8233 following SC administration of multiple doses.
|
Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8, Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
Part C:Plasma PK analysis: Mean Residence Time (MRT).
Time Frame: Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8, Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
To characterize the PK of AZD8233 following SC administration of multiple doses.
|
Days 1 and 57 (Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 hours post-dose); Day 8, Days 15, 22, 29 (pre-dose), Days 36 and 44.
|
Part C:Urine PK analysis: Amount excreted in urine (Ae).
Time Frame: Treatment Days 1 to 3 (Pre-dose and intervals 0-6, 6-12 hours and 12-24 hours post-dose).
|
To characterize the PK of AZD8233 following SC administration of multiple doses.
|
Treatment Days 1 to 3 (Pre-dose and intervals 0-6, 6-12 hours and 12-24 hours post-dose).
|
Part C:Urine PK analysis: Fraction excreted unchanged in urine (Fe).
Time Frame: Treatment Days 1 to 3 (Pre-dose and intervals 0-6, 6-12 hours and 12-24 hours post-dose).
|
To characterize the PK of AZD8233 following SC administration of multiple doses.
|
Treatment Days 1 to 3 (Pre-dose and intervals 0-6, 6-12 hours and 12-24 hours post-dose).
|
Part C:Urine PK analysis: Renal clearance (CLR).
Time Frame: Treatment Days 1 to 3 (Pre-dose and intervals 0-6, 6-12 hours and 12-24 hours post-dose).
|
To characterize the PK of AZD8233 following SC administration of multiple doses.
|
Treatment Days 1 to 3 (Pre-dose and intervals 0-6, 6-12 hours and 12-24 hours post-dose).
|
Part C:Absolute change from baseline in log-transformed PCSK9 in plasma and Percent change from baseline in PCSK9 in plasma.
Time Frame: At screening, Day -1, Days 1 to 3 and Days 57 to 58 (pre-dose and 48 hours post-dose), Day 8, Days 15, 22, Day 29 (pre-dose), Days 36, 44, Day 56, week 2 to 14 (at 2, 4, 6, 8, 10, 12, and 14 weeks) and week 16 post-dose.
|
To assess the effect of AZD8233 on levels of PCSK9 following SC administration of multiple doses.
|
At screening, Day -1, Days 1 to 3 and Days 57 to 58 (pre-dose and 48 hours post-dose), Day 8, Days 15, 22, Day 29 (pre-dose), Days 36, 44, Day 56, week 2 to 14 (at 2, 4, 6, 8, 10, 12, and 14 weeks) and week 16 post-dose.
|
Part C:Percentage change from baseline in levels of LDL-C in serum.
Time Frame: At screening, Day -1, Days 1 to 3 and Days 57 to 58 (pre-dose and 48 hours post-dose), Day 8, Days 15, 22, Day 29 (pre-dose), Days 36, 44, Day 56, week 2 to 14 (at 2, 4, 6, 8, 10, 12, and 14 weeks) and week 16 post-dose.
|
To assess the effect of AZD8233 on levels of LDL-C following SC administration of multiple doses.
|
At screening, Day -1, Days 1 to 3 and Days 57 to 58 (pre-dose and 48 hours post-dose), Day 8, Days 15, 22, Day 29 (pre-dose), Days 36, 44, Day 56, week 2 to 14 (at 2, 4, 6, 8, 10, 12, and 14 weeks) and week 16 post-dose.
|
Part C:Levels of other lipid parameters of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a) , Triglycerides.
Time Frame: Measurement at screening, Day -1, Days 1 to 3 and Days 57 to 58 (pre-dose and 48 hours post-dose), Day 8, Days 15, 22, Day 29 (pre-dose), Days 36, 44, Day 56, week 2 to 14 (at 2, 4, 6, 8, 10, 12, and 14 weeks) and week 16 post-dose.
|
To assess the effect of AZD8233 on other lipid parameters versus placebo.
|
Measurement at screening, Day -1, Days 1 to 3 and Days 57 to 58 (pre-dose and 48 hours post-dose), Day 8, Days 15, 22, Day 29 (pre-dose), Days 36, 44, Day 56, week 2 to 14 (at 2, 4, 6, 8, 10, 12, and 14 weeks) and week 16 post-dose.
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- D7990C00006
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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