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

Study Overview
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Brief Summary
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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

Official Title
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A Phase IIb, Randomised, Parallel, Double-Blind Placebo-Controlled and Open-Label Active Comparator Study to Evaluate the Efficacy and Safety of MEDI0382 in the Treatment of Overweight and Obese Subjects With Type 2 Diabetes Mellitus

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: MEDI0382 low dose
* Drug: MEDI0382 mid dose
* Drug: MEDI0382 high dose
* Drug: Placebo
* Drug: Liraglutide


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomised, parallel, double-blind, placebo-controlled study with an open-label active comparator.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MEDI0382 low dose + Metformin<br>Drug: MEDI0382 low dose Drug: Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) | Drug: MEDI0382 low dose<br>* Pharmaceutical form: solution Route of administration: subcutaneous<br>|
| Experimental: MEDI0382 mid dose + Metformin<br>Drug: MEDI0382 mid dose Drug: Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) | Drug: MEDI0382 mid dose<br>* Pharmaceutical form: solution Route of administration: subcutaneous<br>|
| Experimental: MEDI0382 high dose + Metformin<br>Drug: MEDI0382 high dose Drug: Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) | Drug: MEDI0382 high dose<br>* Pharmaceutical form: solution Route of administration: subcutaneous<br>|
| Placebo Comparator: Placebo + Metformin<br>Drug: Placebo Drug: Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) | Drug: Placebo<br>* Pharmaceutical form: solution Route of administration: subcutaneous<br>|
| Active Comparator: Liraglutide + Metformin<br>Drug: Liraglutide Drug: Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) | Drug: Liraglutide<br>* Pharmaceutical form: solution Route of administration: subcutaneous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c | To assess the effect of 100, 200, 300 μg of cotadutide on HbA1c versus placebo | From baseline to 14 weeks | 
| Percent Change in Body Weight | To assess the effect of 100, 200, 300 μg of cotadutide on body weight versus placebo | From baseline to 14 weeks | 

Secondary Outcome Measures

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