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 MEDI 0382 is well tolerated.
- Conditions
- Type 2 Diabetes MellitusMedDRA version: 20.0Level: PTClassification code 10067585Term: Type 2 diabetes mellitusSystem Organ Class: 10027433 - Metabolism and nutrition disordersTherapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2018-000019-26-GB
- Lead Sponsor
- MedImmune Limited, a wholly owned subsidiary of AstraZeneca
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 41
1. Age = 18 and < 85 years at screening.
2. 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.
3. Diagnosed with 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
4. Body mass index (BMI) between 25 and 45 kg/m2 (inclusive) at screening
5. HbA1c range of 6.5 % to 10.5% (inclusive) at screening
6. Renal impairment with eGFR = 30 and < 60 mL/min/1.73m2 at screening. At least 16 subjects (40%) are required to have a screening eGFR =30 and < 45 mL/min/1.73m2 and at least 16 subjects (40%) are required to have screening eGFR =45 and < 60 mL/min/1.73m2. eGFR will be determined by the chronic kidney disease-epidemiology collaboration (CKD-EPI) equation. In instances where the eGFR estimated during the screening period is outside the range expected from the subject’s medical history, the subject may be re-tested once.
7. 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 nonsterilized male partner must be using at least one highly effective method of contraception from screening and up to 4 weeks after the last dose of investigational product. 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 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30
1.History or presence of significant medical or psychological conditions, including substance dependence/abuse, or significant abnormalities in laboratory parameters or vital signs including ECG, which in the opinion of the investigator, would compromise the subject’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
2.Concurrent participation in another interventional study of any kind and repeat randomisation in this study is prohibited
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 (if known; whichever is longer) at the time of Visit 2
4.Any subject who has received any of the following medications within the specified timeframe prior to the start of the study (Visit 2)
o 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, bupropionnaltrexone, phentermine-topiramate, phentermine, lorcaserin) within 30 days (or 5 half-lives of the drug) prior to the start of dosing (Visit 4)
o 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)
o 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)
o 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)
o Opiates, domperidone, metoclopramide, or other drugs known to alter gastric emptying and within 2 weeks prior to the start of dosing (Visit 4)
5.Severe allergy/hypersensitivity to any of the proposed study treatments or excipients
6.Symptoms of acutely decompensated blood glucose control (eg, thirst, polyuria, weight loss), a history of type 1 diabetes mellitus or diabetic ketoacidosis
7.Subjects who have undergone a renal transplant
8.Subjects with suspicion of acute or subacute renal function deterioration (eg, subjects with large fluctuations of creatinine values documented within the 6 months prior to screening)
9.Significant inflammatory bowel disease, gastroparesis, or other severe disease or surgery affecting the upper gastrointestinal (GI) tract (including weight-reducing surgery and procedures) which may affect gastric emptying or could affect the interpretation of safety and tolerability data
10.History of acute or chronic pancreatitis
11.Significant hepatic disease (except for non-alcoholic steatohepatitis or nonalcoholic fatty liver disease without portal hypertension or cirrhosis) and/or subjects with any of the following results:
o Aspartate transaminase (AST) = 3 × upper limit of normal (ULN)
o Alanine transaminase (ALT) = 3 × ULN
o Total bilirubin = 2 × ULN
12.Poorly controlled hypertension defined as:
o Systolic BP > 180 mm Hg
o Diastolic BP = 100 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 = 180 or diastolic BP < 100 mm Hg with a preserv
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the effect of MEDI0382 titrated up to a dose level of 300 µg on glucose control versus placebo after 32 days of treatment;Secondary Objective: • To characterise the safety profile and tolerability of MEDI0382 titrated up to a dose level of 300 µg during dosing and follow-up in subjects with T2DM and renal impairment<br><br>• To assess the effects of MEDI0382 titrated up to a dose level of 300 µg on additional measures of glycaemic control versus placebo after 32 days of treatment<br><br>• To assess the effects of MEDI0382 titrated up to a dose level of 300 µg on weight versus placebo after 32 days of treatment<br><br>• To characterise the PK profile and immunogenicity of MEDI0382;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 -5) to the end of 32 days of treatment;Timepoint(s) of evaluation of this end point: Day 32
- Secondary Outcome Measures
Name Time Method