Clinical trial NCT03645421: Safety and Tolerability Study of MEDI0382 in Japanese Preobese or Obese Subjects With Type 2 Diabetes
Official title: A Phase IIa, Randomised, Parallel, Double-Blind,Placebo-Controlled Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of MEDI0382 in Japanese Preobese or Obese Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control With Diet and Exercise
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 2 Diabetes
Keywords: Diabetes
MEDI0382
D5674C00001
T2DM
Type 2 Diabetes
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2018-08-24
Enrollment: 61
Sex: ALL
Minimum age (years): 20
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Mean Change From Baseline in 24-Hour Heart Rate at Days 20 and 48
timeFrame: Baseline (Day -1) and Days 20 and 48.
measure: Mean Change From Baseline in 24-Hour Systolic and Diastolic Blood Pressure (BP) at Days 20 and 48
timeFrame: Baseline (Day -1) and Days 20 and 48.
measure: 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
timeFrame: 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.
measure: Mean Percentage Change From Baseline in Body Weight at Day 48
timeFrame: Baseline (Day -1) and Day 48.
measure: Mean Change From Baseline in Heart Rate Measured by Electrocardiogram (ECG) at Day 48.
timeFrame: Baseline (Day -1) and Days 1, 6, 13, 20 and 48: predose and 6 hours (+/-15 minutes) postdose.
measure: Number of Patients Who Experienced Adverse Events (AEs)
timeFrame: Day 1 up to 14 days after the last dose of IP (approximately 9 weeks).
Secondary outcomes:
measure: Mean Change From Baseline in HbA1c at Day 48
timeFrame: Baseline (Day -1) and Day 48 (predose).
measure: Mean Change From Baseline in Fasting Plasma Glucose at Day 48
timeFrame: Baseline (Day -1) and Day 48 (predose).
measure: Mean Change From Baseline in Fructosamine at Day 48
timeFrame: Baseline (Day -1) and Day 48 (predose).
measure: Mean Change From Baseline in the Percentage of Time in Hyperglycaemia Over 24 Hours at Days 5, 12, 19 and 47
timeFrame: Baseline (Day -8 to -2) and Days 5, 12, 19 and 47.
measure: Mean Change From Baseline in the Percentage of Time in Hypoglycaemia Over 24 Hours at Days 5, 12, 19 and 47
timeFrame: Baseline (Day -8 to -2) and Days 5, 12, 19 and 47.
measure: Mean Change From Baseline in the Percentage of Time in Hyperglycaemia Over 5 Days for 50 mcg Dose Level and 7 Days for Other Dose Levels
timeFrame: Baseline (Day -8 to -2) and Days 1 to 5, 6 to 12, 13 to 19 and 41 to 47.
measure: Mean Change From Baseline in the Percentage of Time in Hypoglycaemia Over 5 Days for 50 mcg Dose Level and 7 Days for Other Dose Levels
timeFrame: Baseline (Day -8 to -2) and Days 1 to 5, 6 to 12, 13 to 19 and 41 to 47.
measure: Mean Trough Plasma Concentration (Ctrough) of MEDI0382 up to Day 48
timeFrame: Blood samples collected predose on Days 1 to 6, 13, 20, 34 and 48.
measure: Number of Patients With Antidrug Antibody (ADA) Response to MEDI0382
timeFrame: Samples were collected predose on days 1, 13, 20 and 48, and 7 to 14 days after administration of last dose of IP.
Other outcomes:
Locations:
city: Chuo-ku
country: Japan
facility: Research Site
city: Chuo-ku
country: Japan
facility: Research Site
city: Shinjuku-ku
country: Japan
facility: Research Site
city: Shinjuku-ku
country: Japan
facility: Research Site
city: Suita-shi
country: Japan
facility: Research Site
Study officials:
References: