Type 2 Diabetes Mellitus MedDRA version: 20.0 Level: PT Classification code 10067585 Term: Type 2 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Product Code: MEDI0382
Pharmaceutical Form: Solution for injection
INN or Proposed INN: -
CAS Number: 1686108-82-6
Current Sponsor code: MEDI0382
Concentration unit: mg/ml milligram(s)/millilitre
Conc
Sponsors
MedImmune Limited, a wholly owned subsidiary of AstraZeneca
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female subjects aged = 18 years at screening 2. Provision of signed and dated written informed consent (with the exception of consent for genetic and non-genetic research) prior to any study specific procedures 3. BMI between 27 and 40 kg/m2 (inclusive) at screening 4. HbA1c range of 6.5% to 8.5% (inclusive) at screening 5. Diagnosed with T2DM with glucose control managed with metformin monotherapy where no significant dose change (increase or decrease = 500 mg/day) has occurred in the 3 months prior to screening 6. Subjects prescribed oral dual therapy with a dipeptidyl peptidase-4 (DPPIV) inhibitor, sulphonylurea, glitinide, or a sodium-glucose co transporter 2 (SGLT-2) inhibitor in addition to metformin at screening may be eligible to enter the study following a 4-week washout period 7. Female subjects of childbearing potential must have a negative pregnancy test at screening and randomisation, and must not be lactating 8. Females of childbearing potential who are sexually active with a nonsterilised male partner must use at least one highly effective method of contraception (see Section 10.2 for definition of females of childbearing potential and for a description of highly effective methods of contraception) from screening and must agree to continue using such precautions through to the end of the study. It is strongly recommended for the male partner of a female subject to also use male condom plus spermicide throughout this period. Cessation of contraception after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 58 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: 1. History of, or any existing condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product, put the subject at risk, influence the subject’s ability to participate or affect the interpretation of the results of the study and/or any subject unable or unwilling to follow study procedures 2. Any subject who has received another investigational product as part of a clinical study or a GLP-1 analogue-containing preparation within the last 30 days or 5 half-lives of the drug (whichever is longer) at the time of screening 3. Any subject who has received any of the following medications within the specified time frame prior to the start of the study (Visit 2) (see Section 4.7.2 for further details): ? Herbal preparations or drugs licensed for control of body weight or appetite (eg, orlistat, bupropion naltrexone, phentermine-topiramate, phentermine, lorcaserin) ? Aspirin (acetylsalicylic acid) at a dose greater than 150 mg once daily ? Paracetamol (acetaminophen) or paracetamol containing preparations at a total daily dose of greater than 3g ? Ascorbic acid (vitamin C) supplements at a total daily dose of greater than 1000 mg ? Opiates, domperidone, metoclopramide, or other drugs known to alter gastric emptying 4. Concurrent participation in another study of any kind and repeat randomisation in this study is prohibited 5. Severe allergy/hypersensitivity to any of the proposed study treatments,excipients, or ingredients of standardised meals 6. Symptoms of acutely decompensated blood glucose control (eg, thirst, polyuria, weight loss), a history of type 1 diabetes mellitus (T1DM) or diabetic ketoacidosis, or if the subject has been treated with daily SC insulin within 90 days prior to screening 7. Significant inflammatory bowel disease, gastroparesis, or other severe disease or surgery affecting the upper GI tract (including weight-reducing surgery and procedures) which may affect gastric emptying or could affect the interpretation of safety and tolerability data 8. Significant hepatic disease (except for non-alcoholic steatohepatitis [NASH] or non alcoholic fatty liver disease [NAFLD]) without portal hypertension or cirrhosis) and/or subjects with any of the following results at screening: ? Aspartate transaminase (AST) = 3 × upper limit of normal (ULN) ? Alanine transaminase (ALT) = 3 × ULN ? Total bilirubin = 2 × ULN 9. Impaired renal function defined as estimated glomerular filtration rate (eGFR) 160 mm Hg ? Diastolic BP = 95 mm Hg after 10 minutes of seated rest and confirmed by repeated measurement at screening. Subjects who fail BP screening criteria may be considered for 24-hour ABPM at the discretion of the investigator. Subjects who maintain a mean 24-hour systolic BP = 160 or diastolic BP 15% will be considered eligible 11. Unstable angina pectoris, myocardial infarction, transient ischemic attack (TIA) or stroke within 3 months prior to screening, or subjects who have undergone percutaneous coronary intervention or a coronary artery bypass graft within the past 6 months or who are due to undergo these procedures at the time of screening 12. Severe congestive heart failure (New York Heart Associati
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effects of MEDI0382 titrated up to a dose level of 300 µg on glucose control and body weight versus placebo after 49 days of treatment (Cohort 1 only);Secondary Objective: • To assess the effects of MEDI0382 titrated up to a dose level of 300 µg on additional measures of glucose control and body weight versus placebo after 49 days of treatment (Cohort 1 only) • To characterise the safety profile and tolerability of MEDI0382 titrated up to a dose level of 300 µg during dosing and follow-up (Cohorts 1 and 2) • To characterise the PK profile and immunogenicity of 50 and 300µg of MEDI0382 (Cohorts 1 and 2) • To characterise the effect of 50 µg of MEDI0382 on glucose lowering versus placebo after 7 days (Cohorts 1 and 2);Primary end point(s): • Percentage change in glucose area under the curve (AUC) as measured by a standardised mixed-meal tolerance test (MMTT) from baseline (Day -1) to the end of 49 days of treatment • Percentage change in body weight from baseline (Day 1) to the end of 49 days of treatment;Timepoint(s) of evaluation of this end point: • Baseline (Day -1) to the end of 49 days of treatment • Baseline (Day 1) to the end of 49 days of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Change in glycated haemoglobin (HbA1c) from baseline (Day -1) to the end of 49 days of treatment • Change in fasting plasma glucose (Day -1) from baseline to the end of 49 days of treatment • Change in body weight (kg) from baseline (Day 1) to the end of 49 days of treatment • Proportion of subjects achieving > 5% body weight loss from baseline (Day 1) after 49 days of treatment • Measures of safety and tolerability (24 hour heart rate and blood pressure, other vital signs, ECG, laboratory test results, and adverse events [AEs]) • PK endpoints for 50 µg MEDI0382 after 1, 7, and 14 days of treatment and 300 µg MEDI0382 after 1 and 28 days of treatment; AUC over a dosing duration, maximum observed concentration, time to maximum observed concentration, terminal half-life, trough plasma concentration and accumulation ratio, Cmin [R0] • Development of anti-drug antibodies (ADA) and titre (if confirmed positive) • Percentage change in glucose AUC as measured by a standardised MMTT from baseline (Day -1) to the end of 7 days of treatment;Timepoint(s) of evaluation of this end point: • Baseline (Day -1) to the end of 49 days of treatment • Baseline to the end of 49 days of treatment • Baseline (Day 1) to the end of 49 days of treatment • Baseline (Day 1) after 49 days of treatment • Duration of study (refer to protocol schedule of events) • After 1, 7, 14 or 28 days of treatment (refer to protocol schedule of events) • Refer to protocol schedule of events • Baseline (Day -1) to the end of 7 days of treatment | — |
Countries
Germany
Contacts
Public ContactInformation Center
MedImmune LTD, a wholly owned subsidiary of AstraZeneca
Outcome results
None listed