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

NCT03645421 | Completed Phase 2 Results

• 1 other identifier: D5674C00001
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Type 2 Diabetes

Keywords

Diabetes; MEDI0382; D5674C00001; T2DM; Type 2 Diabetes

Outcome Measures

Primary Outcomes (6)

• Mean Change From Baseline in 24-Hour Heart Rate at Days 20 and 48

  Twenty four-hour heart rate was determined using an ambulatory blood pressure monitoring (ABPM) device, and the mean change from baseline in the 24-hour heart rate is presented for Days 20 and 48.

  Baseline (Day -1) and Days 20 and 48.

• Mean Change From Baseline in 24-Hour Systolic and Diastolic Blood Pressure (BP) at Days 20 and 48

  Twenty four-hour BP was determined using an ABPM device, and the mean change from baseline in the 24-hour systolic BP and 24-hour diastolic BP are presented for Days 20 and 48.

  Baseline (Day -1) and Days 20 and 48.

• Mean Percentage Change From Baseline in Glucose Area Under the Plasma Concentration Curve (AUC[0-4h]) as Measured by a Standardised Mixed-Meal Test (MMT) at Day 48

  The MMT was conducted following a minimum 8-hour fast. Blood samples for glucose monitoring were taken 15 minutes before the patient consumed a standardised meal, and samples were taken at intervals after the meal, up to 4 hours. The MMT glucose AUC(0-4h) was calculated using a trapezoidal method, and the mean percentage change from baseline at Day 48 was analysed using an analysis of covariance (ANCOVA) model with treatment group as a factor and baseline as a covariate.

  Baseline (Day -1) and Day 48: 15 minutes before standardised meal, and then at 15, 30, 45, 60, 90, 120, 180 and 240 minutes (+/-5 minutes) after consumption of the standardised meal.

• Mean Percentage Change From Baseline in Body Weight at Day 48

  The mean percentage change from baseline in body weight at Day 48 was analysed using an ANCOVA model with treatment group as a factor and baseline as a covariate. For patients who prematurely discontinued IP, the last on-treatment measurement, regardless of rescue medication, was used (last observation carried forward \[LOCF\]).

  Baseline (Day -1) and Day 48.

• Mean Change From Baseline in Heart Rate Measured by Electrocardiogram (ECG) at Day 48.

  Digital ECGs were taken at baseline and predose and postdose on Days 1, 6, 13, 20 and 48. The mean change from baseline is presented.

  Baseline (Day -1) and Days 1, 6, 13, 20 and 48: predose and 6 hours (+/-15 minutes) postdose.

• Number of Patients Who Experienced Adverse Events (AEs)

  AEs were collected from Day 1 of treatment up to 14 days after the last dose of IP. Serious AEs (SAEs) were collected from signing of informed consent. The numbers of patients who experienced any AE, any SAE (including events with an outcome of death), and any AE leading to discontinuation of IP are presented.

  Day 1 up to 14 days after the last dose of IP (approximately 9 weeks).

Secondary Outcomes (9)

• Mean Change From Baseline in HbA1c at Day 48

  Baseline (Day -1) and Day 48 (predose).

• Mean Change From Baseline in Fasting Plasma Glucose at Day 48

  Baseline (Day -1) and Day 48 (predose).

• Mean Change From Baseline in Fructosamine at Day 48

  Baseline (Day -1) and Day 48 (predose).

• Mean Change From Baseline in the Percentage of Time in Hyperglycaemia Over 24 Hours at Days 5, 12, 19 and 47

  Baseline (Day -8 to -2) and Days 5, 12, 19 and 47.

• Mean Change From Baseline in the Percentage of Time in Hypoglycaemia Over 24 Hours at Days 5, 12, 19 and 47

  Baseline (Day -8 to -2) and Days 5, 12, 19 and 47.

Study Arms (4)

placebo

PLACEBO COMPARATOR

Placebo per day,SC injection on 48 days.

Drug: PlaceboA; Drug: PlaceboB

MEDI0382 100μg

EXPERIMENTAL

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

Drug: MEDI0382 100 μg; Drug: MEDI0382 50 ug

MEDI0382 200μg

EXPERIMENTAL

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.

Drug: MEDI0382 100 μg; Drug: MEDI0382 200 μg; Drug: MEDI0382 50 ug

MEDI0382 300μg

EXPERIMENTAL

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

Drug: MEDI0382 100 μg; Drug: MEDI0382 200 μg; Drug: MEDI0382 300 μg; Drug: MEDI0382 50 ug

Interventions

MEDI0382 100 μg DRUG

Solution for injection in 1.0 mL pre-filled syringe, 100 μg per dose, 1 dose

MEDI0382 100μg; MEDI0382 200μg; MEDI0382 300μg

MEDI0382 200 μg DRUG

Solution for injection in 1.0 mL pre filled syringe 200 μg per dose, 1 dose

MEDI0382 200μg; MEDI0382 300μg

MEDI0382 300 μg DRUG

Solution for injection in 1.0 mL pre filled syringe, 300 μg per dose, 1 dose

MEDI0382 300μg

PlaceboA DRUG

1.0 mL liquid formulation per Vial

placebo

MEDI0382 50 ug DRUG

Solution for injection, 1.0 mL per vial, 50 ug

MEDI0382 100μg; MEDI0382 200μg; MEDI0382 300μg

PlaceboB DRUG

Solution for injection in 1.0 mL pre-filled syringe.

placebo

Eligibility Criteria

• Age: 20 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (5)

Research Site

Chūōku, 103-0027, Japan

Location

Research Site

Chūōku, 104-0031, Japan

Location

Research Site

Shinjuku-ku, 160-0008, Japan

Location

Research Site

Shinjuku-ku, 162-0053, Japan

Location

Research Site

Suita-shi, 565-0853, Japan

Location

Related Links

• d5674c00001 CSP redacted
• Statistical Analysis Plan (SAP) redacted

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus

Interventions

cotadutide

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

ClinicalTrialTransparency@astrazeneca.com

+13028851180

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: June 25, 2018
• First Posted: August 24, 2018
• Study Start: August 10, 2018
• Primary Completion: January 17, 2019
• Study Completion: January 17, 2019
• Last Updated: December 23, 2019
• Results First Posted: December 23, 2019

Record last verified: 2019-12

Locations

JP (5)