An Exploratory Phase 2, Randomised, Double-blind, Placebo-controlled, and Open-label Active Comparator Study to Evaluate the Effect of MEDI0382 on Hepatic Glycogen Metabolism in Overweight and Obese Subjects with Type 2 Diabetes Mellitus
- Conditions
- Type 2 Diabetes Melitus10018424
- Registration Number
- NL-OMON50158
- Lead Sponsor
- Astra Zeneca
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 16
1. Written Informed Consent and willing and able to adhere to all protocol
requirements
2. Male or female at least 18 years old
3. patient with body mass index of at least 27kg/m² and up to 40 kg/m²
4. patient with a diagnosis of T2DM on metformin monotherapy
5. patient with a glycated haemoglobin of maximum 8.0%
6. Female subjects must not be pregnant and lactating females will be excluded
7. Females of childbearing potential should be using appropriate contraception
For a complete list refer to page 32-33 of the protocol
1. History / 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 or a GLP-1
analogue-containing preparation within the last 30 days or 5half-lives of the
drug
3.Any subject who has received any of the following medications within the
specified time frame prior to the start of the study:
a. Herbal preparations or drugs licensed for control of body weight or
appetite
b. Opiates, domperidone, metoclopramide or other drugs known to alter gastric
emptying
c. Glucagon
d. Warfarin
4. concurrent participation in another study with investigational product and
repear randomistion in this study is prohibited
5. Severe allergy/hypersensitivity to any of the proposed study treatments,
excipients, C-13 labelled glucose, deuterated water (2H2O), or ingredients of
standardised meals
6 Any contraindication to magnetic resonance imaging/MRS scanning including
claustrophobia or dislike of confined spaces
7 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
8 Recurrent unexplained hypoglycaemic episodes (defined as glucose < 3.0 mmol/L
or < 54 mg/dL on more than 2 occasions in 6 months prior to screening)
9 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
10 Acute or chronic pancreatitis
11 Significant hepatic disease (except for NASH or nonalcoholic fatty liver
disease 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
12 Impaired renal function defined as estimated glomerular filtration rate
(eGFR) < 30 mL/minute/1.73m2 at screening (glomerular filtration rate estimated
according to Modification of Diet in Renal Disease (MDRD) using MDRD Study
Equation IDMS-traceable (International System of Units [SI] units)
13 Poorly controlled hypertension defined as:
* Systolic blood pressure (BP) > 180 mm Hg
* Diastolic BP > 105 mm Hg
14 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 * 180/105 mm Hg 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 coronary artery bypass graft within the
past 6 months or who ar
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>* Change in hepatic glycogen concentration adjusted for liver volume as<br /><br>measured by magnetic resonance spectroscopy (MRS) at Time (T) = 4 hours post<br /><br>standardised morning meal from baseline (Day 1) to the end of 28 days of<br /><br>treatment (Part A)<br /><br>* Percentage change in fasting hepatic glycogen concentration adjusted for<br /><br>liver volume as measured by magnetic resonance spectroscopy (MRS) at Time (T) =<br /><br>24 hours post standardised morning meal from baseline (Day 1) to the end of 35<br /><br>days of treatment (Day 36) (Part B)</p><br>
- Secondary Outcome Measures
Name Time Method <p>* Percentage change in fasting hepatic glycogen concentration adjusted for<br /><br>liver volume as measured by MRS at T = 24 hours post standardised morning meal<br /><br>from baseline (Day 1) to the end of 35 days of treatment (Day 36) (Part B only)<br /><br>* Change in hepatic fat fraction from baseline as measured by magnetic<br /><br>resonance imaging (Day 1) to the end of 35 days of treatment (Part B only)<br /><br>* Measures of safety and tolerability (vital signs, electrocardiograms [ECGs],<br /><br>laboratory test results, adverse events [AEs])<br /><br>* Development of anti drug antibodies (ADA) and titre (if confirmed positive)</p><br>