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 Name: MEDI0382
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: -
CAS Number: 1686108-82-6
Current Sponsor code: MEDI0382
Concentration unit: mg/ml millig
Sponsors
MedImmune Limited, a wholly owned subsidiary of AstraZeneca
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1 Subjects aged = 30 and = 75 years at screening 2 Provision of signed and dated written informed consent (except for consent for genetic and non-genetic research and additional optional assessments) prior to any protocol-related procedures 3 Body Mass Index > 28 and = 40 kg/mˆ2 at screening 4 Glycated haemoglobin (HbA1c) = 8.0% at screening 5 Diagnosed with T2DM with glucose control managed with metformin, with or without a DPPIV inhibitor, SGLT2i, sulfonylurea, or glitinide, where no significant dose change (increase or decrease > 50%) has occurred in the 3 months prior to screening; if the subject is on dual therapy, a 4-week washout of the non-metformin therapy (DPPIV inhibitor, SGLT2i, sulfonylurea or glitinide) will be required prior to Visit 4 6 Female subjects of childbearing potential must have a negative pregnancy test at screening and randomisation, and must not be lactating 7 Female subjects of childbearing potential who are sexually active with a non-sterilised male partner must be using at least one highly effective method of contraception from screening and must agree to continue using such precautions up until 4 weeks after the last dose of investigational product 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 17 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 7
Exclusion criteria
Exclusion criteria: 1 History of, or any existing condition(s) 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 with a cardiac pacemaker or implanted/portable electronic device 3 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 (Visit 1) 4 Any subject who has received any of the following medications within the specified time frame prior to Visit 2: herbal preparations or drugs licensed for control of body weight or appetite (eg, orlistat, bupropion, naltrexone, phentermine-topiramate, phentermine, lorcaserin, opiates, domperidone, metoclopramide, or other drugs known to alter gastric emptying) 5 Concurrent participation in another study with an investigational product and prior randomisation in this study is prohibited 6 Severe allergy/hypersensitivity to any of the proposed study treatments, excipients, or standardised meals 7 Symptoms of acutely decompensated blood glucose control (eg, thirst, polyuria, weight loss), a history of type 1 diabetes mellitus or diabetic ketoacidosis, or if the subject has been treated with daily SC insulin within 90 days prior to screening 8 Abnormal thyroid stimulating hormone (TSH) level of 10 mIU/L confirmed on two consecutive tests 9 Regularly engage in high intensity exercise at least three times per week or have done so in the prior three months 10 Clinically 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 11 Acute or chronic pancreatitis with or without amylase > 1000 IU/L and/or lipase > 600 IU/L at screening 12 Significant hepatic disease (except for nonalcoholic steatohepatitis or nonalcoholic fatty liver disease without portal hypertension or cirrhosis) and/or subjects with any of the following results at screening: (a) Aspartate transaminase (AST) = 3 × upper limit of normal (ULN) (b) Alanine transaminase (ALT) = 3 × ULN (c) Total bilirubin = 2 × ULN 13 Impaired renal function defined as estimated glomerular filtration rate (eGFR) 180 mm Hg (b) Diastolic BP or > 100 mm Hg After 10 minutes of supine rest and confirmed by repeated measurement at screening. Subjects who fail BP screening criteria may be considered for 24-hour ambulatory blood pressure monitoring at the discretion of the investigator. Subjects who maintain a mean 24-hour BP = 180/100 mmHg with a preserved nocturnal dip of > 15% will be considered eligible 15 Unstable angina pectoris, myocardial infarction, transient ischemic attack or stroke within 3 months prior to screening, or subjects who have undergone percutaneous coronary intervention or a coro
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effect of MEDI0382 titrated up to a dose level of 300 µg on body weight versus placebo;Secondary Objective: • To assess the effect of MEDI0382 titrated up to a dose level of 300 µg versus placebo on energy intake during ad libitum lunchtime meals • To assess the effect of MEDI0382 titrated up to a dose level of 300 µg versus placebo on TEE, AEE, and REE • To assess the effect of a 16-day period of MEDI0382 titrated up to a dose level of 300 µg versus placebo on REE • To assess the effect of MEDI0382 titrated up to a dose level of 300 µg versus placebo on TEE • To assess the effect of MEDI0382 titrated up to a dose level of 300 µg on measures of body weight and composition versus placebo • To assess the effect of MEDI0382 titrated up to a dose level of 300 µg on glucose homeostasis versus placebo Please refer to the Protocol for full details of the Secondary objectives.;Primary end point(s): Percentage change in body weight in kg from Day 17 to 59;Timepoint(s) of evaluation of this end point: Day 17 to 59 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Percentage and absolute change in total energy intake in kJ from the ad libitum lunch from Day 16 to 32 and Day 16 to 59 2) Percentage and absolute change in TEE, AEE, and REE as measured by whole room indirect calorimetry in kJ per kg of fat body mass from Day 15 to 58 3) Percentage and absolute change in REE as measured by hood indirect calorimetry in kJ per kg of fat body mass in kJ from Day 16 to 32 4) Percentage and absolute change in total energy expenditure as measured by doubly labelled water in kJ per kg of fat body mass from baseline (Day 17) to the end of treatment (Day 58 or 59) 5) -Absolute change in body weight in kg from Day 17 to 59 -Change in absolute and percentage change in total body fat mass as measured by DXA in kg from Day -1 to 59 -Change in absolute and percentage change in total body fat mass: lean mass ratio as measured by DXA from Day -1 to 59 6) -Change in fasting glucose during a MMTT from Day -1 to 59 -Percentage change in glucose AUC during a MMTT from Day -1 to 59 7) During treatment and follow-up: • Vital signs • ECGs • Safety laboratory analysis • TEAEs and TESAEs 8) Development of ADA and titre (if confirmed ADA-positive) during treatment and follow up;Timepoint(s) of evaluation of this end point: 1) 2) 3) 4) 5) 6) Refer to schedule of study Procedures 7) 8) During treatment and follow-up | — |
Countries
United Kingdom
Contacts
Public ContactClinical Trial Enquires
MedImmune Limited, a wholly owned subsidiary of AstraZeneca
Outcome results
None listed