- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02512575
A Single Ascending Dose Study To Assess The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of AZD9567.
A Phase I, Randomized, Single-Blind, Placebo-Controlled Study To Assess The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Single Ascending Oral Doses Of AZD9567 In Healthy Subjects.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
-
Berlin, Germany, 14050
- Research Site
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Provision of signed and dated, written informed consent prior to any study specific procedures.
- Healthy male subjects aged 18 to 55 years with suitable veins for cannulation or repeated venipuncture.
- Have a body mass index (BMI) between 18 and 29.9 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.
- Normal OGTT at screening (<7.8 mmol/L).
- Serum cortisol levels within normal limits at screening (collected as part of the clinical chemistry panel).
- Able to understand, read and speak the German language.
Exclusion Criteria:
- History of any clinically important disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
- History or presence of gastrointestinal (GI), hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- History of or active or latent tuberculosis (TB), or at risk for having acquired TB (social workers or prison staff in countries with endemic rates of TB, having lived with patients with known TB).
- History suggesting abnormal immune function, as judged by the investigator.
- Any contraindications to be treated with prednisolone (allergy to any ingredient, systemic fungal infection, certain type of malaria, inflammation of the optic nerve, or herpes infection of the eye, scheduled to have a live or attenuated live vaccination or taking mifepristone).
- History of severe affective disorder including depressive or manic-depressive illness them self or first degree relatives.
- History of previous steroid psychosis
- Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
- Any latent or chronic infections (e.g., recurrent sinusitis, genital or ocular herpes, urinary tract infection) or at risk of infection (surgery, trauma, or significant infection), or history of skin abscesses within 90 days prior to the first administration of IMP.
- Any clinically important laboratory abnormalities (clinical chemistry, hematology, coagulation or urinalysis results), as judged by the investigator. In particular a subject with an abnormal value in alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), creatinine, thyroid-stimulating hormone (TSH), fasting glucose, International Normalised Ratio (INR), haemoglobin (Hb), white blood cell (WBC), absolute neutrophil or platelet count will be excluded.
- Any positive result on screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody and human immunodeficiency virus (HIV).
- Abnormal vital signs, after 10 minutes supine rest, defined as any of the following: Systolic BP (SBP) < 90mmHg or ≥ 140 mmHg, Diastolic BP (DBP) < 50mmHg or ≥ 90 mmHg, Pulse < 45 or > 85 beats per minute (bpm).
- Any clinically important abnormalities in rhythm, conduction or morphology of the resting ECG and any clinically important abnormalities in the 12-lead ECG, as considered by the investigator that may interfere with the interpretation of QTc interval changes, including abnormal ST-T-wave morphology, particularly in the protocol defined primary lead or left ventricular hypertrophy.
- Prolonged QTcF > 450 ms or family history of long QT syndrome.
- PR(PQ) interval shortening < 120 ms (PR > 110 ms but < 120 ms is acceptable if there is no evidence of ventricular pre-excitation).
- PR (PQ) interval prolongation (> 240 ms) intermittent second (Wenckebach block while asleep is not exclusive) or third degree AV block, or AV dissociation
Study Plan
How is the study designed?
Design Details
- Primary Purpose: BASIC_SCIENCE
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: SINGLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: AZD9567 oral suspension
In Part A: up to 8 cohorts with single ascending doses (starting at 2 mg up to 155 mg). In Part B: one cohort with a single dose |
AZD9567 oral suspension 0.5 to 10 mg/ml
|
Placebo Comparator: Placebo
Subjects randomized to placebo in the first 8 cohorts will receive the same dose volume of oral suspension as subjects on AZD9567 and subjects randomized to placebo in cohort 9(prednisolone cohort) will receive the same number of capsules as subjects on prednisolone.
|
Matching placebo
|
Experimental: Prednisolone capsules
Within each cohort 6 subjects will be randomized to receive prednisolone 60mg oral capsules and 2 subjects randomized to receive matching placebo in a fasted state. Sentinel dosing will not be employed for the prednisolone cohort. The SRC will not be required to evaluate the prednisolone cohort. This cohort can be performed at any time during clinical execution of the study provided the protocol amendment was approved. |
Prednisolone 60mg oral capsules (12 capsules of 5 mg each).
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety and Tolerability of AZD9567 by Assessing the Number of Participants With Adverse Events
Time Frame: At screening, Day -2, Day -1, Day 1 (at pre-dose; 3 & 12 hours post-dose), Day 2 (24 hours post-dose), Day 3 and follow-up (7 to 10 days post-dose)
|
Safety and tolerability variables included AEs, vital signs (blood pressure and pulse), ECGs (12-lead ECGs, safety ECGs and telemetry), clinical laboratory safety evaluations (haematology, clinical chemistry [including osteocalcin], coagulation, urinalysis [including 24 hour urine cortisol per day {tU-cortisol}]) and physical examinations. Note: No clinically relevant findings were noted in clinical laboratory results and vial signs assessments. Hence, none of the laboratory or vital signs findings were reported as AEs. |
At screening, Day -2, Day -1, Day 1 (at pre-dose; 3 & 12 hours post-dose), Day 2 (24 hours post-dose), Day 3 and follow-up (7 to 10 days post-dose)
|
Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Observed Maximum Plasma Concentration (Cmax)
Time Frame: On Day 1 (at pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours post-dose), Day 2 (24 hours post-dose) and Day 3 (48 hours post-dose)
|
To assess the Cmax of AZD9567 oral suspension following 8 single ascending doses (2, 10, 20, 40, 80, 100, 125 and 155 mg) in Cohorts 1 to 8 in the fasted state.
Cmax was taken directly from the individual concentration-time curve.
|
On Day 1 (at pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours post-dose), Day 2 (24 hours post-dose) and Day 3 (48 hours post-dose)
|
Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Time to Reach Maximum Plasma Concentration(Tmax)
Time Frame: On Day 1 (at pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours post-dose), Day 2 (24 hours post-dose) and Day 3 (48 hours post-dose)
|
To assess the tmax of AZD9567 oral suspension following 8 single ascending doses (2, 10, 20, 40, 80, 100, 125 and 155 mg) in Cohorts 1 to 8 in the fasted state.
tmax was taken directly from the individual concentration-time curve.
|
On Day 1 (at pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours post-dose), Day 2 (24 hours post-dose) and Day 3 (48 hours post-dose)
|
Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Terminal Half-life (t½λz)
Time Frame: On Day 1 (at pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours post-dose), Day 2 (24 hours post-dose) and Day 3 (48 hours post-dose)
|
To assess t½λz of AZD9567 oral suspension following 8 single ascending doses (2, 10, 20, 40, 80, 100, 125 and 155 mg) in Cohorts 1 to 8 in the fasted state.
t½λz was estimated as (ln2)/λz.
|
On Day 1 (at pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours post-dose), Day 2 (24 hours post-dose) and Day 3 (48 hours post-dose)
|
Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Area Under the Plasma Concentration-curve From Time Zero to the Time of Last Quantifiable Analyte Concentration (AUC(0-last))
Time Frame: On Day 1 (at pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours post-dose), Day 2 (24 hours post-dose) and Day 3 (48 hours post-dose)
|
To assess AUC(0-last) of AZD9567 oral suspension following 8 single ascending doses (2, 10, 20, 40, 80, 100, 125 and 155 mg) in Cohorts 1 to 8 in the fasted state.
|
On Day 1 (at pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours post-dose), Day 2 (24 hours post-dose) and Day 3 (48 hours post-dose)
|
Rate and Extent of Absorption of Single Ascending Doses of AZD9567 by Assessment of Area Under the Plasma Concentration-curve From Time Zero Extrapolated to Infinity (AUC)
Time Frame: On Day 1 (at pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours post-dose), Day 2 (24 hours post-dose) and Day 3 (48 hours post-dose)
|
To assess AUC of AZD9567 oral suspension following 8 single ascending doses (2, 10, 20, 40, 80, 100, 125 and 155 mg) in Cohorts 1 to 8 in the fasted state.
AUC was estimated by AUC(0-last) + Clast/λz.
Clast - the last observed quantifiable concentration.
|
On Day 1 (at pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours post-dose), Day 2 (24 hours post-dose) and Day 3 (48 hours post-dose)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Secondary Outcome: Relative Change From Baseline of AUC0-4h for Plasma Glucose to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT])
Time Frame: At Day -1 (baseline) and Day 1 (pre glucose intake and at 30, 60, 90, 120, 150, 180 and 240 minutes post glucose intake)
|
To assess the effect of AZD9567 and prednisolone on OGTT after administration of 75 g glucose solution, blood samples were collected pre glucose intake and at post glucose intake for the analyses of plasma glucose. AUC0-4h relative change between Day 1 and Day -1 was calculated for each subject in a specific treatment group. Note: Total AUC0-4h was calculated using the linear trapezoidal method. Statistical analysis for the change in OGTT plasma glucose total AUC0-4h values were assessed via an analysis of variance (ANCOVA), with treatment as fixed effect. |
At Day -1 (baseline) and Day 1 (pre glucose intake and at 30, 60, 90, 120, 150, 180 and 240 minutes post glucose intake)
|
Relative Change From Baseline of AUC0-4h for Serum Insulin to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT])
Time Frame: At Day -1 (baseline) and Day 1 (pre glucose intake and at 30, 60, 90, 120, 150, 180 and 240 minutes post glucose intake)
|
To assess the effect of AZD9567 and prednisolone on OGTT after administration of 75 g glucose solution, blood samples were collected pre glucose intake and at post glucose intake for the analyses of serum insulin. AUC0-4h relative change between Day 1 and Day -1 was calculated for each subject in a specific treatment group. Note: Total AUC0-4h was calculated using the linear trapezoidal method. Statistical analysis for the change in OGTT serum insulin total AUC0-4h values were assessed via an analysis of variance (ANCOVA), with treatment as fixed effect. |
At Day -1 (baseline) and Day 1 (pre glucose intake and at 30, 60, 90, 120, 150, 180 and 240 minutes post glucose intake)
|
Relative Change From Baseline of AUC0-4h for Serum C-peptide to Assess the Effects on Glucose Homeostasis (Oral Glucose Tolerance Test [OGTT])
Time Frame: At Day -1 (baseline) and Day 1 (pre glucose intake and at 30, 60, 90, 120, 150, 180 and 240 minutes post glucose intake)
|
To assess the effect of AZD9567 and prednisolone on OGTT after administration of 75 g glucose solution, blood samples were collected pre glucose intake and at post glucose intake for the analyses of serum C-peptide. AUC0-4h relative change between Day 1 and Day -1 was calculated for each subject in a specific treatment group. Note: Total AUC0-4h was calculated using the linear trapezoidal method. Statistical analysis for the change in OGTT serum C-peptide total AUC0-4h values were assessed via an analysis of variance (ANCOVA), with treatment as fixed effect. |
At Day -1 (baseline) and Day 1 (pre glucose intake and at 30, 60, 90, 120, 150, 180 and 240 minutes post glucose intake)
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Rainhard Fuhr, Dr. med., PAREXEL International GmbH, Berlin
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 (Estimate)
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
- Immune System Diseases
- Autoimmune Diseases
- Joint Diseases
- Musculoskeletal Diseases
- Rheumatic Diseases
- Connective Tissue Diseases
- Arthritis
- Arthritis, Rheumatoid
- Physiological Effects of Drugs
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Prednisolone
Other Study ID Numbers
- D6470C00001
- 2015-002002-37 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Rheumatoid Arthritis
-
Janssen Research & Development, LLCWithdrawnActive Rheumatoid Arthritis; Rheumatoid Arthritis
-
Centocor, Inc.CompletedRheumatoid Arthritis, Juvenile
-
AmgenTerminated
-
Children's Hospital Medical Center, CincinnatiNational Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)CompletedJuvenile Rheumatoid ArthritisUnited States
-
AmgenImmunex CorporationCompletedJuvenile Rheumatoid Arthritis
-
National Institute of Arthritis and Musculoskeletal...Children's Hospital Medical Center, CincinnatiCompleted
-
University of PittsburghNational Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)CompletedRheumatoid Arthritis | Juvenile Rheumatoid ArthritisUnited States
-
University of Missouri-ColumbiaCompletedJuvenile Rheumatoid ArthritisUnited States
-
Assistance Publique - Hôpitaux de ParisSociete Francaise de RhumatologieRecruiting
-
Amsterdam UMC, location VUmcEuropean CommissionCompletedRheumatoId ArthritisNetherlands, Germany, Portugal, Italy, Hungary, Romania, Slovakia
Clinical Trials on AZD9567 Monohydrat
-
AstraZenecaCompletedRheumatoid ArthritisGermany, United Kingdom
-
AstraZenecaCompletedRheumatoid ArthritisSweden, Netherlands
-
AstraZenecaParexelCompleted
-
Oslo University HospitalCompleted
-
Kirstine Nyvold Bojsen-MoellerUniversity of CopenhagenUnknownOverweight | Bariatric Surgery (Gastric Bypass)Denmark