A Study to Investigate Different Doses of 0382 in Overweight and Obese Subjects With Type 2 Diabetes Mellitus.

NCT03244800 | Completed Phase 2 Results

• 1 other identifier: D5670C00011
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 5

Brief Summary

A Phase 2 study with two cohorts of differing doses designed to evaluate the efficacy, safety and pharmacokinetics (PK) of MEDI0382 in patients with Type 2 Diabetes Mellitus (T2DM). Approximately 63 subjects will be enrolled across two cohorts.

Conditions

Type 2 Diabetes Mellitus

Keywords

0382, T2DM

Outcome Measures

Primary Outcomes (2)

• Cohort 1: Percent Change From Baseline in Plasma Glucose Area Under the Concentration-time Curve From Time 0 to 4 Hours (AUC0-4h) by Mixed-meal Tolerance Test (MMTT) to Day 49

  The MMTT test involved the consumption of a standardised liquid meal within 5 minutes and timed serial blood samples obtained for the measurement of glucose and parameters related to glucose metabolism through 240 minutes after consumption of the standardised meal (with no additional food intake during this time). The percent change in the MMTT plasma glucose AUC 0-4h from the baseline (Day -1) to Day 49 is reported.

  Zero minutes before and 15, 30, 45, 60, 90, 120, 180, and 240 minutes after consumption of the standardised liquid meal

• Cohort 1: Percent Change From Baseline in Body Weight to Day 50

  The percent change in body weight from baseline to Day 50 is reported.

  Day 1 through Day 50

Secondary Outcomes (23)

• Cohort 1: Change From Baseline in Glycated Haemoglobin (HbA1c) to Day 49

  Baseline (Day -1) through Day 49

• Cohort 1: Change From Baseline in Fasting Plasma Glucose to Day 49

  Baseline (Day -1) through Day 49

• Cohort 1: Change From Baseline in Body Weight to Day 50

  Day 1 through Day 50

• Cohort 1: Percentage of Participants Achieving Greater Than or Equal to 5% Body Weight Loss From Baseline to Day 50

  Day 1 through Day 50

• Cohort 1 and Cohort 2: Percent Change From Baseline in MMTT Plasma Glucose AUC 0-4h to Day 7

  Zero minutes before and 15, 30, 45, 60, 90, 120, 180, and 240 minutes after consumption of the standardised liquid meal

Study Arms (4)

Placebo Cohort 1

PLACEBO COMPARATOR

Participants will receive placebo matching with MEDI0382 subcutaneously once daily for 49 days.

Drug: Placebo

MEDI0382 Cohort 1

EXPERIMENTAL

Participants will receive subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 7 days, followed by Dose 2 for 7 days, Dose 3 for 7 days, and Dose 4 for 28 days

Drug: MEDI0382

PLacebo Cohort 2

PLACEBO COMPARATOR

Participants will receive placebo matching with MEDI0382 subcutaneously once daily for 49 days.

Drug: Placebo

MEDI0382 Cohort 2

EXPERIMENTAL

Participants will receive subcutaneous injection of MEDI0382 once daily for 49 days as Dose 1 for 14 days, followed by Dose 2 for 14 days, Dose 3 for 14 days, and Dose 4 for 7 days.

Drug: MEDI0382

Interventions

MEDI0382 DRUG

MEDI0382 will be administered subcutaneously once daily for 49 days.

MEDI0382 Cohort 1; MEDI0382 Cohort 2

Placebo DRUG

Placebo will be administered subcutaneously once daily for 49 days.

PLacebo Cohort 2; Placebo Cohort 1

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female subjects aged ≥ 18 years at screening
• Provision of signed and dated written informed consent
• BMI between 27 and 40 kg/m2
• HbA1c range of 6.5% to 8.5%
• Diagnosed with T2DM with glucose control managed with metformin monotherapy where no significant dose change (increase or decrease ≥ 500 mg/day) has occurred in the 3 months prior to screening
• Subjects prescribed oral dual therapy with a dipeptidyl peptidase-4 inhibitor, sulphonylurea, glitinide, or a sodium-glucose co-transporter 2 inhibitor in addition to metformin at screening may be eligible to enter the study following a 4-week washout period
• Female subjects of childbearing potential must have a negative pregnancy test at screening and randomisation, and must not be lactating
• Females of childbearing potential who are sexually active with a nonsterilised male partner must use at least one highly effective method of contraception from screening and must agree to continue using such precautions through to the end of the study. It is strongly recommended for the male partner of a female subject to also use male condom plus spermicide throughout this period. Cessation of contraception after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception.

You may not qualify if:

• History of, or any existing condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product, 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
• Concurrent participation in another study of any kind and repeat randomisation in this study is prohibited
• Severe allergy/hypersensitivity to any of the proposed study treatments
• Symptoms of acutely decompensated blood glucose control (eg, thirst, polyuria, weight loss), a history of type 1 diabetes mellitus or diabetic ketoacidosis, or if the subject has been treated with daily SC insulin within 90 days prior to screening
• Significant inflammatory bowel disease, gastroparesis, or other severe disease or surgery affecting the upper GI tract (including weight-reducing surgery and procedures) which may affect gastric emptying or could affect the interpretation of safety and tolerability data
• Significant hepatic disease (except for non-alcoholic steatohepatitis or non-alcoholic fatty liver disease without portal hypertension or cirrhosis) and/or subjects with any of the following results at screening:
• Aspartate transaminase (AST) ≥ 3 × upper limit of normal (ULN)
• Alanine transaminase (ALT) ≥ 3 × ULN
• Total bilirubin ≥ 2 × ULN
• Impaired renal function defined as estimated glomerular filtration rate (GFR) \< 60 mL/minute/1.73 m2 at screening (GFR estimated according to Modification of Diet in Renal Disease \[MDRD\] using the isotope dilution mass spectrometry \[IDMS\] traceable MDRD Study Equation \[SI units\])
• Poorly controlled hypertension defined as:
• Systolic BP \> 160 mm Hg
• Diastolic BP ≥ 95 mm Hg after 10 minutes of seated rest and confirmed by repeated measurement at screening.
• Unstable angina pectoris, myocardial infarction, transient ischemic attack or stroke within 3 months prior to screening, or subjects who have undergone percutaneous coronary intervention or a coronary artery bypass graft within the past 6 months or who are due to undergo these procedures at the time of screening
• Severe congestive heart failure (New York Heart Association Class III or IV)

Sponsors & Collaborators

• MedImmune LLC: lead

Study Sites (5)

Research Site

Berlin, 10117, Germany

Location

Research Site

Magdeburg, 39120, Germany

Location

Research Site

Mainz, 55116, Germany

Location

Research Site

Neu-Ulm, 89231, Germany

Location

Research Site

Neuss, 41460, Germany

Location

Related Publications (1)

• Parker VER, Robertson D, Wang T, Hornigold DC, Petrone M, Cooper AT, Posch MG, Heise T, Plum-Moerschel L, Schlichthaar H, Klaus B, Ambery PD, Meier JJ, Hirshberg B. Efficacy, Safety, and Mechanistic Insights of Cotadutide, a Dual Receptor Glucagon-Like Peptide-1 and Glucagon Agonist. J Clin Endocrinol Metab. 2020 Mar 1;105(3):dgz047. doi: 10.1210/clinem/dgz047.

  PMID: 31608926 DERIVED

Related Links

• D5670C00011\_protocol\_amendment\_2\_ct
• D5670C00011\_Statistical\_Analysis\_Plan

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

cotadutide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Victoria Parker
• Organization: MedImmune Limited

information.center@astrazeneca.com

+44 747 1357152

Study Officials

• Tim Heise, MD

  Profil Institut für Stoffwechselforschung GmbH

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2017
• First Posted: August 10, 2017
• Study Start: September 4, 2017
• Primary Completion: January 23, 2018
• Study Completion: January 23, 2018
• Last Updated: November 19, 2019
• Results First Posted: November 19, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (5)