Single and Multiple Ascending Doses of MEDI6570 in Subjects With Type 2 Diabetes Mellitus

A Phase 1 Randomized, Blinded, Placebo-controlled Study to Evaluate the Safety and Pharmacokinetics of Single and Multiple Ascending Doses of MEDI6570 in Subjects With Type 2 Diabetes Mellitus.

To evaluate the safety, tolerability, PK and immunogenicity of single and multiple ascending doses of MEDI6570 in subjects with Type 2 Diabetes Mellitus

Study Overview

• Status: Completed
• Conditions: Cardiovascular Disease; Atherosclerosis
• Intervention / Treatment: Biological: Placebo; Biological: MEDI6570; Biological: Part B Placebo

Detailed Description

A Phase 1 Randomized, Blinded, Placebo-controlled Study to Evaluate the Safety and Pharmacokinetics of Single and Multiple Ascending Doses of MEDI6570 in Subjects with Type 2 Diabetes Mellitus

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Research Site
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Research Site
    • Miami, Florida, United States, 33143
      • Research Site
    • Port Orange, Florida, United States, 32127
      • Research Site
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • Research Site
  • North Carolina
    • High Point, North Carolina, United States, 27265
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States, 45227
      • Research Site
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Research Site
  • Texas
    • San Antonio, Texas, United States, 78229
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

• In Part A, subjects aged 18 through 65 inclusive at screening. In Part B, male subjects aged 18 through 65 inclusive, and female subjects aged 40 to 65 inclusive, at screening.
• Body mass index of 18 to 45 kg/m2.
• Subjects with T2DM on stable medical therapy for at least 6 weeks prior to screening with no clinically significant dose change and/or new medications in the recent 6 weeks
• Capable of giving written informed consent and adhere to visit/protocol schedule
• Female subjects must be of non-childbearing potential, confirmed at screening by one of the following: (a) Postmenopausal, defined as amenorrhea for ≥ 12 months following cessation of all exogenous hormonal treatments, and luteinizing hormone and follicle stimulating hormone (FSH) levels in the postmenopausal range. (b) Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy. Tubal ligation is not considered as irreversible surgical sterilization.
• Non-sterilized male subjects who are sexually active with a female partner of childbearing potential must use a male condom plus spermicide, and in addition the female partner must use 1 highly effective method of contraception.
• In Part B, subjects must meet CTA criteria as follows: (Estimated glomular filtration rate (eGFR) ≥ 60 mL/min/1.73m2. No allergy to iodinated contrast, no history of contrast induced nephropathy or no contraindication to beta blockers or nitroglycerin. No recent pulmonary embolism and must able to hold breath for at least 6 seconds. No history of coronary bypass surgery and no active arrhythmia on day of CTA scan (atrial fibrillation, atrial flutter, frequent premature atrial, or ventricular contractions).
• For Part A Cohort 6, subjects must be Japanese (eg, natives of Japan or Japanese Americans), defined as having both parents and four grandparents who are Japanese. This includes second and third generation subjects of Japanese descent whose parents or grandparents are living in a country other than Japan.

Exclusion Criteria

• History of any clinically important disease or disorder (not including T2DM) 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 hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs.
• Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of investigational product, or planned surgical procedure before study completion.
• Female subjects who are pregnant and/or currently lactating.
• Any clinically important abnormalities in clinical chemistry, hematology, coagulation parameters, or urinalysis results -History of blood dyscrasia, hemostatic disorder, systemic bleeding, or prior trauma that places the subject at a higher risk of bleeding.
• History of vascular abnormalities including aneurysms, prior dissections; hx of severe hemorrhage, hematemesis, melena, haemoptysis, severe epistaxis, severe thrombocytopenia, intracranial hemorrhage, rectal bleeding, or major surgery/procedure within 3 months prior to Visit 1; a history suggestive of active peptic ulcer disease; or prior intracranial haemorrhage. -Dual-antiplatelet therapy, anticoagulation therapy or thrombolytic use, in the past month or planned use during the duration of the study. -Chronic aspirin therapy or chronic NSAID therapy.
• Clinically significant ECG that may interfere with the interpretation of serial ECG and QT interval changes screening. -Persistent or intermittent complete bundle branch block, incomplete bundle branch block, or intraventricular conduction delay with QRS > 110 ms. Subjects with QRS > 110 ms but < 115 ms are acceptable if there is no evidence of ventricular hypertrophy or pre excitation. -Abnormal vital signs
• Hemoglobin A1c>9.0% measured at screening. HbA1c can be retested once after approximately 4 weeks.
• Clinically significant late diabetic complications including symptoms consistent with angina, congestive heart failure, and peripheral arterial disease (claudication), or other complications such as proliferative retinopathy, maculopathy, or gastroparesis.
• Any positive result at screening for serum hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus (HIV).
• History of cancer in the last 5 years, with the exception of non-melanoma skin cancer. -History of alcohol substance abuse within the past 6 months. A positive drug screen including recreational marijuana will be exclusionary. However, subjects with a documented medical need or prescription may be included at the discretion of the principal investigator.
• History of hypersensitivity or ongoing severe allergy or history of hypersensitivity to drugs with a similar chemical structure or calss to MEDI6570.
• History of ongoing infection or febrile illness within 30 days prior to Day 1.
• Current or previous use of systemic corticosteroids within 28 days prior to screening.
• Receipt of any investigational product or use of any biologics within 6 months or 5 half lives prior to screening (whichever is longer), or planned participation in an additional study of an investigational product therapy or biologic prior to end of follow up period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

11

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A MEDI6570 Cohort 1; Part A MEDI6570 Cohort 1 dose level	Biological: MEDI6570; MEDI6570
Experimental: Part A MEDI6570 Cohort 2; Part A MEDI6570 Cohort 2 dose level	Biological: MEDI6570; MEDI6570
Experimental: Part A MEDI6570 Cohort 3; Part A MEDI6570 Cohort 3 dose level	Biological: MEDI6570; MEDI6570
Experimental: Part A MEDI6570 Cohort 4; Part A MEDI6570 Cohort 4 dose level	Biological: MEDI6570; MEDI6570
Placebo Comparator: Part A Placebo	Biological: Placebo; Placebo
Experimental: Part B MEDI6570 Cohort 1; Part B MEDI6570 Cohort 1 dose level	Biological: MEDI6570; MEDI6570
Experimental: Part B MEDI6570 Cohort 2; Part B MEDI6570 Cohort 2 dose level	Biological: MEDI6570; MEDI6570
Experimental: Part B MEDI6570 Cohort 3; Part B MEDI6570 Cohort 3 dose level	Biological: MEDI6570; MEDI6570
Placebo Comparator: Part B Placebo	Biological: Part B Placebo; Placebo
Experimental: Part A MEDI6570 Cohort 5; Part A MEDI6570 Cohort 5 Dose level	Biological: MEDI6570; MEDI6570
Experimental: Part A MEDI6570 Cohort 6; Part A MEDI6570 Cohort 6 dose level	Biological: MEDI6570; MEDI6570

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with adverse events and serious adverse events as a measure of safety and tolerability of MEDI6570	Measured by the incidence of treatment- emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs)	Day 1 - Day 190 (Part A); Day 1 - Day 250 (Part B)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics of MEDI6570 AUC	Non-compartmental analysis will be performed for MEDI6570 treated subjects. Descriptive statistics for PK parameters will be provided	Day 1 - Day 190 (Part A); Day 1 - Day 250 (Part B)
Pharmacokinetics of MEDI6570 Cmax	Non-compartmental analysis will be performed for MEDI6570 treated subjects. Descriptive statistics for PK parameters will be provided	Day 1 - Day 190 (Part A); Day 1 - Day 250 (Part B)
Pharmacokinetics of MEDI6570 Tmax	Non-compartmental analysis will be performed for MEDI6570 treated subjects. Descriptive statistics for PK parameters will be provided	Day 1 - Day 190 (Part A); Day 1 - Day 250 (Part B)
Pharmacokinetics of MEDI6570 Terminal Half life	Non-compartmental analysis will be performed for MEDI6570 treated subjects. Descriptive statistics for PK parameters will be provided	Day 1 - Day 190 (Part A); Day 1 - Day 250 (Part B)
Immunogenicity rate	ADA incidence rate and titer will be tabulated for each treatment group. Samples confirmed positive for ADA will be tested and analyzed for nAB titer and summarized similarly.	Day 1 - Day 190 (Part A); Day 1 - Day 250 (Part B)

Collaborators and Investigators

• Sponsor: MedImmune LLC
• Investigators: Study Director: Marvin Sinsakul, MedImmune LLC

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2018
• Primary Completion (Actual): July 21, 2020
• Study Completion (Actual): July 21, 2020

Study Registration Dates

• First Submitted: August 29, 2018
• First Submitted That Met QC Criteria: August 29, 2018
• First Posted (Actual): August 31, 2018

Study Record Updates

• Last Update Posted (Actual): August 24, 2020
• Last Update Submitted That Met QC Criteria: August 21, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Cardiovascular Disease; Atherosclerosis; CAD; Atherosclerotic Cardiovascular Disease
• Additional Relevant MeSH Terms: Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Endocrine System Diseases; Cardiovascular Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Atherosclerosis
• Other Study ID Numbers: D4920C00001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No