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

NCT ID: NCT03244800

Last Updated: 2019-11-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 65 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-04
• Study Completion Date: 2018-01-23

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.

Detailed Description

This is a randomised, double-blind, placebo-controlled study designed to evaluate the efficacy, safety, tolerability, and pharmacokinetics of different doses of MEDI0382 administered as multiple SC doses to subjects with T2DM. Approximately 63 subjects will be enrolled across two cohorts.

For cohort 1, sufficient subjects will be invited to participate in the study such that a maximum of 39 subjects will complete dosing. Subjects in cohort 1 will be randomised using a ratio of 2:1 to one of 2 treatment arms to receive either MEDI0382 or placebo. A maximum of 26 will complete dosing in the active arm and 13 will complete dosing in the placebo arm.

For cohort 2, sufficient subjects will be invited to participate in the study such that a maximum of 24 subjects will complete dosing. Subjects in cohort 2 will be randomised using a ratio of 3:1 to receive either MEDI0382 or placebo. A maximum of 18 will complete dosing in the active arm and 6 will complete dosing in the placebo arm.

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo Cohort 1

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo will be administered subcutaneously once daily for 49 days.

MEDI0382 Cohort 1

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

Group Type: EXPERIMENTAL

MEDI0382

Intervention Type: DRUG

MEDI0382 will be administered subcutaneously once daily for 49 days.

PLacebo Cohort 2

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo will be administered subcutaneously once daily for 49 days.

MEDI0382 Cohort 2

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.

Group Type: EXPERIMENTAL

MEDI0382

Intervention Type: DRUG

MEDI0382 will be administered subcutaneously once daily for 49 days.

Interventions

MEDI0382

MEDI0382 will be administered subcutaneously once daily for 49 days.

Intervention Type: DRUG

Placebo

Placebo will be administered subcutaneously once daily for 49 days.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Male and female subjects aged ≥ 18 years at screening

2. Provision of signed and dated written informed consent

3. BMI between 27 and 40 kg/m2

4. HbA1c range of 6.5% to 8.5%

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

6. 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

7. Female subjects of childbearing potential must have a negative pregnancy test at screening and randomisation, and must not be lactating

8. 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.

Exclusion Criteria

1. 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

2. Concurrent participation in another study of any kind and repeat randomisation in this study is prohibited

3. Severe allergy/hypersensitivity to any of the proposed study treatments

4. 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

5. 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

6. 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

7. 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])

8. 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.

9. 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

10. Severe congestive heart failure (New York Heart Association Class III or IV)

11. Basal calcitonin level > 50 ng/L at screening or history/family history of medullary thyroid carcinoma or multiple endocrine neoplasia

12. Haemoglobinopathy, haemolytic anemia, or chronic anaemia (haemoglobin concentration < 11.5 g/dL [115 g/L] for males, < 10.5 g/dL [105 g/L] for females) at screening or any other condition known to interfere with interpretation of HbA1c measurement

13. History of neoplastic disease within 5 years prior to screening, except for adequately treated basal cell, squamous cell skin cancer, or in situ cervical cancer

14. Any positive results for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody, and human immunodeficiency virus (HIV) antibody

15. History of substance dependence, alcohol abuse, or excessive alcohol intake (defined as an average weekly intake of > 21 alcoholic drinks for men or > 10 alcoholic drinks for women) within 3 years prior to screening, and/or a positive screen for drugs of abuse or alcohol at screening or on admission to the study unit. Subjects who use tricyclic antidepressants or benzodiazepines for an established clinical indication may be permitted to enter the study based upon the judgement of the investigator.

16. Involvement of any AstraZeneca, MedImmune, contract research organization, or study site employee or their close relatives

17. History of acute or chronic pancreatitis or other diseases of the pancreas

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 130 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

MedImmune LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tim Heise, MD

Role: PRINCIPAL_INVESTIGATOR

Profil Institut für Stoffwechselforschung GmbH

Locations

Research Site

Berlin, , Germany

Research Site

Magdeburg, , Germany

Research Site

Mainz, , Germany

Research Site

Neu-Ulm, , Germany

Research Site

Neuss, , Germany

Countries

Germany

References

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.

Reference Type: DERIVED

PMID: 31608926 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=14682&filename=D5670C00011_protocol_amendment_2_ct.pdf

D5670C00011\_protocol\_amendment\_2\_ct

http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=14682&filename=D5670C00011_Statistical_Analysis_Plan.pdf

D5670C00011\_Statistical\_Analysis\_Plan

Other Identifiers

D5670C00011

Identifier Type: -

Identifier Source: org_study_id