Safety and Tolerability Study of MEDI0382 in Japanese Preobese or Obese Subjects With Type 2 Diabetes

AstraZeneca

Status and phase: Completed; Phase 2

Conditions: Type 2 Diabetes

Treatments: Drug: PlaceboA; Drug: MEDI0382 50 ug; Drug: PlaceboB; Drug: MEDI0382 300 μg; Drug: MEDI0382 100 μg; Drug: MEDI0382 200 μg

Study type: Interventional

Funder types: Industry

Identifiers

NCT03645421

D5674C00001

Details and patient eligibility

About

This is a Phase 2a study designed to assess the safety and tolerability of MEDI0382 titrated up to a dose level of 100, 200 or 300 µg from 50 µg vs Placebo across 48 days in Japanese subjects.

The study D5674C00001 can be conducted with a reasonable expectation of safety and tolerability in Japanese T2DM patients. The design of this study has taken into account the known benefits and risks of GLP-1 receptor agonists and glucagon receptor agonists as well as the translatable effects observed in nonclinical studies of MEDI0382.

Full description

This is a randomized, parallel-group, placebo-controlled, double-blind, multicenter Phase Ⅱa study to evaluate the safety, efficacy, and pharmacokinetics of MEDI0382 in Japanese preobese and obese subjects with type 2 diabetes who have inadequate glycemic control with diet and exercise. Subject fulfilling all of the inclusion criteria and none of the exclusion criteria will be randomised in a 1:1:1:1 ratio to four treatment arms. This is a Phase IIa study designed to evaluate the dose range for MEDI0382 to explore the safety profile, as well as blood glucose control and weight loss effects of MEDI0382 in Japanese patients with T2DM. The design of this study has taken into account the known benefits and risks of GLP-1 receptor agonists and glucagon receptor agonists as well as the translatable effects observed in nonclinical studies of MEDI0382, such that benefit-risk balance for the Japanese preobese and obese patients with T2DM in this study is considered favourable. A treatment period of 48 days is required to properly evaluate the dose range and safety and tolerability in three different doses. Inclusion of placebo in the study allows appropriate basis of AEs, glycaemic control, and weight loss. Benefits related to participation in this trial include close follow-up of a subject's diabetes and treatment with anti-diabetes agents. Although one of possible treatments is placebo, appropriate rescue therapy for worsening glycaemic control will be implemented if required.

Enrollment: 61 patients

Sex: All

Ages: 20 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Individuals whose HbA1c range of 7.0% to 10.5% (inclusive) at screening.
• Individuals who are diagnosed with T2DM
• Individuals whose current condition at enrolment (Visit 1) is drug naïve
• BMI within the range of 24 - 40 kg/m2 (inclusive) at screening

Exclusion criteria

• Subjects with any of the following results at screening:
• Aspartate transaminase (AST) ≥ 2.5 × upper limit of normal (ULN)
• Alanine transaminase (ALT) ≥ 2.5 × ULN
• Total bilirubin (TBL) ≥ 2 × ULN
• Impaired renal function defined as estimated glomerular filtration rate (eGFR) ≤ 60 mL/minute/1.73 m2 at screening
• Participation in another clinical study with an investigational product administered in the last 30 days or 5 half-lives of the drug (whichever is longer) at the time of screening

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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61 participants in 4 patient groups, including a placebo group

placebo

Placebo Comparator group

Description:

Placebo per day,SC injection on 48 days.

Treatment:

Drug: PlaceboB

Drug: PlaceboA

MEDI0382 100μg

Experimental group

Description:

50 μg/day,SC injection on the first 5 days and 100 μg/day,SC injection on 43 days

Treatment:

Drug: MEDI0382 100 μg

Drug: MEDI0382 50 ug

MEDI0382 200μg

Experimental group

Description:

50 μg/day,SC injection on the first 5 days, 100 μg/day,SC injection on 7 days and 200 μg/day,SC injection on 36 days.

Treatment:

Drug: MEDI0382 100 μg

Drug: MEDI0382 200 μg

Drug: MEDI0382 50 ug

MEDI0382 300μg

Experimental group

Description:

50 μg/day,SC injection on the first 5 days, 100 μg/day,SC injection on 7 days, 200 μg/day,SC injection on 7 days and 300 μg/day,SC injection on 29 days

Treatment:

Drug: MEDI0382 100 μg

Drug: MEDI0382 200 μg

Drug: MEDI0382 50 ug

Drug: MEDI0382 300 μg