A Study to Evaluate the Efficacy and Safety of MEDI0382 in the Treatment of Overweight and Obese Subjects With Type 2 Diabetes

Phase 2

Completed

• Conditions: Diabetes Mellitus, Type 2
• Interventions: Drug: MEDI0382 high dose; Drug: Placebo; Drug: MEDI0382 low dose; Drug: MEDI0382 mid dose; Drug: Liraglutide

• Registration Number: NCT03235050
• Lead Sponsor: AstraZeneca

Brief Summary

This study is designed to evaluate the dose range for MEDI0382 with respect to blood glucose control and weight loss effects, as well as to further explore the safety profile of MEDI0382

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-07-21
• Study First Submitted QC: 2017-07-27
• Study First Posted: 2017-08-01
• Study Start: 2017-08-02
• Primary Completion: 2018-05-03
• Disposition First Submitted: 2019-03-07
• Study Completion: 2019-06-14
• Results First Submitted: 2020-06-03
• Status Verified: 2020-07
• Results First Submitted QC: 2020-07-03
• Disposition First Submitted QC: 2020-07-03
• Results First Posted: 2020-07-20
• Disposition First Posted: 2020-07-20
• Last Update Submitted: 2020-07-31
• Last Update Posted: 2020-08-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 834

Inclusion Criteria

• Provision of informed consent
• Male and female subjects aged ≥ 18 years at screening
• Body mass index ≥ 25 kg/m2 at screening
• HbA1c range of 7.0% to 10.5% (inclusive) at screening
• Diagnosed with type-2 diabetes mellitus (T2DM) and treated with metformin (stable dose of ≥1500 mg/day or maximal tolerated dose) for at least 2 months prior to screening. Use of another glucose-lowering medication for up to 2 weeks in the 2 months prior to screening is acceptable
• Women of childbearing potential (WOCBP), not breastfeeding and using appropriate birth control to avoid pregnancy throughout the study and for up to 4 weeks after the last dose of investigational product (IP), with a negative pregnancy test within 72 hours prior to the start of IP

Exclusion Criteria

• History of, or any existing condition that, in the opinion of the Investigator, would interfere with evaluation of the IP, put the subject at risk, influence the subject's ability to participate or affect the interpretation of the results of the study and/or any subject unable or unwilling to follow study procedures
• Any subject who has received another IP as part of a clinical study or a GLP-1 receptor agonist containing preparation within the last 30 days or 5 half lives of the drug (whichever is longer) at the time of screening
• Severe allergy/hypersensitivity to any of the proposed study treatments or excipients
• Symptoms of acutely decompensated blood glucose control, a history of type 1 diabetes mellitus or diabetic ketoacidosis, or if the subject has been treated with daily subcutaneous (SC) insulin for a period longer than 2 weeks within 90 days prior to screening
• Acute or chronic pancreatitis. Subjects with serum triglyceride concentrations above 1000 mg/dL (11 mmol/L) at screening
• Significant inflammatory bowel disease or other severe disease or surgery affecting the upper Gastrointestinal (GI) tract
• Significant hepatic disease
• Impaired renal function defined as estimated glomerular filtration rate (eGFR) ≤30 mL/minute/1.73m2 at screening
• Severely uncontrolled hypertension
• Unstable angina pectoris, myocardial infarction (MI), transient ischaemic attack (TIA), or stroke within 3 months prior to screening
• Severe congestive heart failure

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MEDI0382 high dose + Metformin	MEDI0382 high dose	Drug: MEDI0382 high dose Drug: Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
Placebo + Metformin	Placebo	Drug: Placebo Drug: Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
MEDI0382 low dose + Metformin	MEDI0382 low dose	Drug: MEDI0382 low dose Drug: Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
MEDI0382 mid dose + Metformin	MEDI0382 mid dose	Drug: MEDI0382 mid dose Drug: Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
Liraglutide + Metformin	Liraglutide	Drug: Liraglutide Drug: Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)

Primary Outcome Measures

Name	Time	Method
Change in HbA1c	From baseline to 14 weeks	To assess the effect of 100, 200, 300 μg of cotadutide on HbA1c versus placebo
Percent Change in Body Weight	From baseline to 14 weeks	To assess the effect of 100, 200, 300 μg of cotadutide on body weight versus placebo

Secondary Outcome Measures

Name	Time	Method
Change in HbA1c	from baseline to 26 weeks and 54 weeks	To assess the effect of 100, 200, 300 μg of cotadutide on HbA1c versus placebo
Percentage of Participants Achieving an HbA1c Target < 7.0%	after 14, 26, and 54 weeks	To assess the effect of 100, 200, and 300 μg of cotadutide on percentage of participants achieving an HbA1c target of \<7% versus placebo
Percent Change in Body Weight	from baseline to 26 weeks and 54 weeks	To assess the effect of 100, 200, and 300 μg of cotadutide on body weight versus placebo
Absolute Change in Body Weight	from baseline to 14 weeks, 26 weeks and 54 weeks	To assess the effect of 100, 200, 300 μg of cotadutide on body weight versus placebo
Percent Change in Body Weight Versus Active Comparator	from baseline to 14 weeks, 26 weeks and 54 weeks	To assess the effect of 100, 200, and 300 μg of cotadutide on body weight versus liraglutide 1.8 mg once daily
Pharmacokinetic (PK) Endpoint: Trough Plasma Concentration (Cmin)	Time points at which outcome measure were assessed for plasma concentration were Weeks 1,2,6,10,14,18,22,26, and 54	To characterise the PK profile of 100, 200, and 300 μg of cotadutide
Immunogenicity Endpoint: Overall Antidrug Antibody (ADA) Incidence (Number and Percentage of Positive Partipants)	Baseline through 54-week treatment period and 28-day follow-up	To characterise the immunogenicity of 100, 200, and 300 μg of cotadutide
Absolute Change in Body Weight Versus Active Comparator	from baseline to 14 weeks, 26 weeks and 54 weeks	To assess the effect of 100, 200, and 300 μg of cotadutide on body weight versus liraglutide 1.8 mg once daily
Percentage of Participants Rescued or Discontinued for Lack of Glycaemic Control	at 14 weeks, 26 weeks and 54 weeks	To assess the effect of 100, 200, and 300 μg of cotadutide on the requirement for additional blood glucose-lowering therapies versus placebo
Percentage of Participants Achieving Weight Loss of ≥5% and ≥10%	after 14 weeks, 26 weeks and 54 weeks	To assess the effect of 100, 200, and 300 μg of cotadutide on percentage of subjects achieving weight loss of ≥5% and ≥10% versus placebo
Immunogenicity Endpoint: Median Titer of the Anti-Drug Antibodies (ADA) to MEDI0382 in the Positive Participants	Baseline through 54-week treatment period and 28-day follow-up	To characterise the immunogenicity of 100, 200, and 300 μg of cotadutide

Trial Locations

Locations (1)

Research Site; 🇸🇰 Zilina, Slovakia