A phase 2 study in two parts (A \& B) designed to evaluate the effect of MEDI0382 on Hepatic Glycogen Metabolism in subjects with Type 2 Diabetes Mellitus (T2DM). Approximately 20 subjects will be enrolled in Part A and approximately 30 subjects in Part B.
This is a 2-part exploratory Phase 2 study. Part A is a randomised, double-blind, placebo-controlled study to evaluate the effect of MEDI0382 (also known as Cotadutide) administered once daily subcutaneously (SC) for 28 days on hepatic glycogen metabolism in overweight and obese subjects with T2DM. Part A is planned to randomise up to 20 subjects. Subjects from Part A will not be re-enrolled in Part B. Part B is an exploratory Phase 2 randomised, double-blind, placebo-controlled and open-label active comparator study to evaluate the effect of MEDI0382 on hepatic glycogen metabolism in overweight and obese subjects with T2DM. Part B is planned to randomise approximately 30 subjects (not to exceed a maximum of 35 subjects). Subjects in Part B will be randomised to receive double-blind MEDI0382 or placebo, or open-label liraglutide once daily for 35 days.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
51
MEDI0382 administered subcutaneously
Placebo administered subcutaneously
Liraglutide administered subcutaneously
Research Site
Maastricht, Netherlands
Research Site
Uppsala, Sweden
Research Site
Nottingham, United Kingdom
Change in Hepatic Glycogen Concentration Adjusted for Liver Volume as Measured by MRS at T = 4 Hours Post Standardised Morning Meal From Baseline (Day -1) to the End of 28 Days of Treatment (Part A Only)
To assess the effect of MEDI0382 on hepatic glycogen levels postprandially versus placebo after 28 days of treatment
Time frame: Day -1 to Day 28
Percentage Change in Fasting Hepatic Glycogen Concentration Adjusted for Liver Volume as Measured by MRS at T = 24 Hours Post Standardised Morning Meal From Baseline (Day -1) to the End of 35 Days of Treatment (Day 36) (Part B)
To assess the effect of MEDI0382 on hepatic glycogen levels versus placebo after 35 days (Part B) of treatment
Time frame: Day -1 to Day 36
Percentage Change in Fasting Hepatic Glycogen Concentration Adjusted for Liver Volume as Measured by MRS at T = 24 Hours Post Standardised Morning Meal From Baseline (Day 1) to the End of 35 Days of Treatment (Day 36, Part B Only)
To assess the effect of MEDI0382 on hepatic glycogen levels versus liraglutide after 35 days of treatment (Part B only)
Time frame: Fom baseline (Day -1) to Day 35
Change of Hepatic Fat Fraction From Baseline as Measured by Magnetic Resonance Imaging (Day -1) to the End of 35 Days of Treatment (Part B Only)
Time frame: Day -1 to Day 36
Development of ADA
Time frame: Baseline to (Follow-up Period) 28 days post last dose + (3-month poststudy)
Measures of Safety and Tolerability of Daily SC Doses of MEDI0382 Titrated up to a Dose Level of 300μg (Parts A and B) by Assessment of Number of Participants withTreatment Emergent Adverse Events (TEAEs) as Assessed by CTCAE V4.0
Safety and tolerability of daily SC doses of MEDI0382 by assessment of the following using CTCAE V4.0: The number of Treatment Emergent Adverse events (TEAEs)
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Time frame: Post dosing (Day 1) to final follow-up (28 Days post last dose)
Measures of Safety and Tolerability of Daily SC Doses of MEDI0382 Titrated up to a Dose Level of 300μg (Parts A and B) by Assessment of Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs) as Assessed by CTCAE V4.0
Safety and tolerability of daily SC doses of MEDI0382 by assessment of the following using CTCAE V4.0: The number of Treatment-Emergent Serious Adverse Events (TESAEs)
Time frame: Post dosing (Day 1) to final follow-up (28 Days post last dose)
Measures of Safety and Tolerability of Daily SC Doses of MEDI0382 Titrated up to a Dose Level of 300μg (Parts A and B) by Assessment of Changes in Heart Rate and Blood Pressure
Number of subjects with clinically significant changes in heart rate (BPM) or systolic and diastolic blood pressure (mmHg)
Time frame: Post dosing (Day 1) to final follow-up (28 Days post last dose)
Measures of Safety and Tolerability of Daily SC Doses of MEDI0382 Titrated up to a Dose Level of 300μg (Parts A and B) by Assessment of Changes in ECG
Number of subjects with an ECG determined to be abnormal and clinically significant
Time frame: Post dosing (Day 1) to final follow-up (28 Days post last dose)
Measures of Safety and Tolerability of Daily SC Doses of MEDI0382 Titrated up to a Dose Level of 300μg (Parts A and B) by Assessment of Changes in Haematology and Clinical Chemistry Parameters
Number of subjects with clinically significant changes in in haematology and or clinical chemistry parameters
Time frame: Post dosing (Day 1) to final follow-up (28 Days post last dose)