A Phase 2a, Randomised, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of MEDI0382 in Subjects With Type 2 Diabetes Mellitus and Renal Impairment

MedImmune LLC1 site in 1 country41 target enrollmentJune 29, 2018

ConditionsType II Diabetes Mellitus Renal Insufficiency

InterventionsMEDI0382 Placebo

Overview

Phase: Phase 2
Intervention: MEDI0382
Conditions: Type II Diabetes Mellitus
Sponsor: MedImmune LLC
Enrollment: 41
Locations: 1
Primary Endpoint: Percent Change From Baseline in Plasma Glucose Area Under the Concentration Time-curve From Time 0 to 4 Hours (AUC0-4 Hrs) as Measured by Mixed-meal Tolerance Test (MMTT) to Day 32
Status: Completed
Last Updated: 6 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

A study to look at the effect MEDI0382 has on blood sugar in people with type 2 diabetes and kidney problems and also to check that MEDI0382 is well tolerated.

Registry

clinicaltrials.gov

Start Date

June 29, 2018

End Date

February 4, 2019

Last Updated

6 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

MedImmune LLC

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Age ≥ 18 and \< 85 years at screening.
•Signed and dated written informed consent (with the exception of consent for genetic and nongenetic research) prior to performing any protocol-related procedures, including screening evaluations.
•Diagnosed with type 2 diabetes mellitus (T2DM) with glucose control managed with any insulin and/or oral therapy combination where no significant dose changes of oral therapy of more than 50% have occurred in the 3 months prior to screening
•Body mass index (BMI) between 25 and 45 kg/m\^2 (inclusive) at screening
•Haemoglobin A1c (HbA1c) range of 6.5 % to 10.5% (inclusive) at screening
•Renal impairment with estimated glomerular filtration rate (eGFR) ≥ 30 and \< 60 mL/min/1.73 m\^2 at screening. Approximately 16 participants (40%) are required to have a screening eGFR ≥30 and \< 45 mL/min/1.73 m\^2 and at least 16 participants (40%) are required to have screening eGFR ≥45 and \< 60 mL/min/1.73 m\^
•Females of childbearing potential must have a negative pregnancy test at screening and randomisation, and must not be lactating. Women of childbearing potential who are sexually active with a non-sterilized male partner must be using at least one highly effective method of contraception from screening and up to 4 weeks after the last dose study drug.

Exclusion Criteria

•History or presence of significant medical or psychological conditions, including substance dependence/abuse, or significant abnormalities in laboratory parameters or vital signs including electrocardiogram (ECG), which in the opinion of the investigator, would compromise the participant's safety or successful participation in the study. As an example, severe anaemia (haemoglobin \< 7.0 g/dL) could be exclusionary due to blood sampling required by the protocol, at the discretion of investigator.
•Concurrent participation in another interventional study of any kind and repeat randomisation in this study is prohibited.
•Any participant who has received another study drug as part of a clinical study or a glucagon-like peptide-1 (GLP-1) analogue-containing preparation within the last 30 days or 5 half-lives of the drug (if known; whichever is longer) at the time of Visit
•Any participant who has received any of the following medications within the specified timeframe prior to the start of the study (Visit 2)
•Herbal preparations within 1 week prior to the start of dosing (Visit 4) or drugs licensed for control of body weight or appetite (eg, orlistat, bupropion-naltrexone, phentermine-topiramate, phentermine, lorcaserin) within 30 days (or 5 half-lives of the drug) prior to the start of dosing (Visit 4)
•Aspirin (acetylsalicylic acid) at a dose greater than 150 mg once daily and within the last 3 days prior to the start of the run-in period (Visit 2)
•Paracetamol (acetaminophen) or paracetamol-containing preparations at a total daily dose of greater than 3000 mg and within the last 3 days prior to the start of the run-in period (Visit 2)
•Ascorbic acid (vitamin C) supplements at a total daily dose of greater than 1000 mg and within the last 3 days prior to the start of the run-in period (Visit 2)
•Opiates, domperidone, metoclopramide, or other drugs known to alter gastric emptying and within 2 weeks prior to the start of dosing (Visit 4)
•Severe allergy/hypersensitivity to any of the proposed study treatments or excipients

Arms & Interventions

MEDI0382

Participants will receive subcutaneous (SC) dose of MEDI0382 titrated from 50 μg upto 300 μg (50 μg once daily for 4 days, followed by 100 μg daily for 7 days, 200 μg daily for 7 days, and 300 μg daily for 14 days) for 32 days.

Intervention: MEDI0382

Placebo

Participants will receive SC dose of placebo matched to MEDI0382 once daily for 32 days.

Intervention: Placebo

Outcomes

Primary Outcomes

Percent Change From Baseline in Plasma Glucose Area Under the Concentration Time-curve From Time 0 to 4 Hours (AUC0-4 Hrs) as Measured by Mixed-meal Tolerance Test (MMTT) to Day 32

Time Frame: Zero minutes before and 15, 30, 45, 60, 90, 120, 180, and 240 minutes after consumption of the standardised meal on Day -5 (Baseline) and Day 32

The MMTT involved the consumption of a standardised liquid meal (a nutritional supplement containing the components of fat, carbohydrate, and protein, which make up a standard MMTT) within 15 minutes, and timed serial blood samples obtained for measurement of glucose and parameters related to glucose metabolism through 240 minutes after consumption of the standardized meal (with no additional food intake during this time).

Secondary Outcomes

Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs(Day 1 through Day 60)
Number of Participants With Treatment-emergent Adverse Events of Special Interest (TEAESIs)(Day 1 through Day 60)
Change From Baseline in Mean 24-hrs Pulse Rate to the End of Each Dosing Level(Day -5 (Baseline) and on Days 5, 12, 19, and 32)
Change From Baseline in Mean 24-hrs Systolic and Diastolic Blood Pressure to the End of Each Dosing Level(Day -5 (Baseline) and on Days 5, 12, 19, and 32)
Change From Baseline in Haemoglobin A1c (HbA1c) to Day 32(Day 1 (Baseline) and Day 32)
Change From Baseline in Fasting Glucose to Day 32(Day 1 (Baseline) and Day 32)
Change From Baseline in Percentage of Time Spent Within a Target Glucose Range Over a 7-day Period to the Final Week of Treatment(Baseline (Days -8 to -2), Days 5 to 11, Days 12 to 18, Days 19 to 25, and Days 26 to 32 (final week of treatment))
Percent Change Frome Baseline in Body Weight to Day 33(Day 1 (Baseline) and Day 33)
Change From Baseline in Absolute Body Weight to Day 33(Day 1 (Baseline) and Day 33)
Area Under the Plasma Concentration Time Curve Over a Dosing Duration (AUCτ) of MEDI0382 at 300 μg(Predose and at 0.5, 1, 2, 4, 6, 8, and 24 hrs postdose on Day 32)
Maximum Observed Serum Concentration (Cmax) of MEDI0382 at 300 μg(Predose and at 0.5, 1, 2, 4, 6, 8, and 24 hrs postdose on Day 32)
Time to Observed Maximum Serum Concentration (Tmax) of MEDI0382 at 300 μg(Predose and at 0.5, 1, 2, 4, 6, 8, and 24 hrs postdose on Day 32)
Number of Participants With Abnormal Vital Signs Reported as TEAEs(Day 1 through Day 60)
Change From Baseline in Postural Blood Pressure(Baseline (Day 1) through Day 32)
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)(Day 1 through Day 60)
Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs(Day 1 through Day 60)
Trough Plasma Concentration (Ctrough) of MEDI0382(Days 1, 5, 12, and 19: Predose; and Day 32: Predose and at 0.5, 1, 2, 4, 6, 8, and 24 hrs postdose (Day 33))
Number of Participants With Positive Anti-drug Antibodies (ADA) Titre to MEDI0382(Pre-dose on Days 1, 12, and 32 and on Day 60)