A Multiple-ascending-dose Study to Evaluate the Efficacy, Safety, and Pharmacokinetics (PK) of MEDI0382 in Overweight and Obese Participants With Type 2 Diabetes Mellitus

MedImmune

Status and phase: Completed; Phase 2; Phase 1

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: Placebo; Drug: MEDI0382

Study type: Interventional

Funder types: Industry

Identifiers

NCT02548585

D5670C00002

Details and patient eligibility

About

A Phase 1/2, multiple dose study with 6 cohorts of ascending doses designed to evaluate the efficacy, safety and pharmacokinetics (PK) of MEDI0382 in participants with Type 2 Diabetes Mellitus (T2DM).

Full description

This is a randomized, double-blind, placebo controlled study designed to evaluate the efficacy, safety, and PK of MEDI0382 administered as multiple daily SC doses to participants with T2DM. Approximately one hundred and seven participants will be enrolled across 6 cohorts. In cohorts 1-3 the participants will be randomized to MEDI0382 or placebo (2:1). In Cohort 4, participants will be randomized to MEDI0382 or placebo (1:1). In cohort 5 and 6 participants will be randomized to MEDI0382 or placebo (3:1).

Enrollment: 113 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of T2DM
• Must provide written informed consent
• Body mass index greater than (>) 27 and less than (<) 40 kg/m^2, inclusive
• Venous access suitable for multiple cannulations
• Vital signs within normal specified ranges
• Females must be non-lactating and non-childbearing potential
• Males must practice 2 effective contraceptive measures if sexually active

Exclusion criteria

• Any concurrent condition that in the opinion of the investigator would interfere with the evaluation of the investigational product
• History or presence of gastrointestinal, renal, or hepatic disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs
• History of cancer within the last 10 years, with the exception of non-melanoma skin cancer
• Any clinically important illness (except for T2DM), medical/surgical procedure, or trauma within 4 weeks prior to dosing
• Fasting glucose greater than or equal to (>=) 200 mg/dL
• Positive Hepatitis B, Hepatitis C or human immunodeficiency virus test or use of antiretroviral medications at screening.
• Concurrent or previous use of a glucagon-like peptide 1 receptor agonist
• Current or previous use of systemic corticosteroids within the past 28 days prior to screening
• Use of any medicinal products or herbal preparations licensed for control of body weight or appetite is prohibited.
• Known or suspected history of alcohol or drug abuse within the past 3 years.
• Positive drug screen

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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113 participants in 7 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Participants will receive placebo (matched to either 100 micrograms \[mcg\], or 150 mcg or 200 mcg or 300 mcg of MEDI0382) subcutaneously (SC) once daily from Day 1 to Day 7 (Cohort 1); or Day 1 to Day 11 (Cohort 2); or Day 1 to Day 15 (Cohort 3); or Day 1 to Day 41 (Cohort 4); or Day 1 to Day 22 (Cohort 5); or Day 1 to Day 17 (Cohort 6).

Treatment:

Drug: Placebo

Cohort 1: MEDI0382 100 mcg

Experimental group

Description:

Participants will receive MEDI0382 100 mcg SC once daily from Day 1 to Day 7.

Treatment:

Drug: MEDI0382

Cohort 2: MEDI0382 150 mcg

Experimental group

Description:

Participants will receive MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).

Treatment:

Drug: MEDI0382

Cohort 3: MEDI0382 200 mcg

Experimental group

Description:

Participants will receive MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).

Treatment:

Drug: MEDI0382

Cohort 4: MEDI0382 200 mcg

Experimental group

Description:

Participants will receive MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).

Treatment:

Drug: MEDI0382

Cohort 5: MEDI0382 300 mcg

Experimental group

Description:

Participants will receive MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).

Treatment:

Drug: MEDI0382

Cohort 6: MEDI0382 300 mcg

Experimental group

Description:

Participants will receive MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).

Treatment:

Drug: MEDI0382