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A Study to Investigate the Effect of MEDI0382 on Hepatic Glycogen Metabolism in Overweight and Obese Subjects With Type 2 Diabetes Mellitus.

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ClinicalTrials.gov Identifier: NCT03555994
Recruitment Status : Recruiting
First Posted : June 14, 2018
Last Update Posted : September 10, 2018
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC

Brief Summary:
A phase 2 study in two parts (A & B) designed to evaluate the effect of MEDI0382 on Hepatic Glycogen Metabolism in subjects with Type 2 Diabetes Mellitus (T2DM). Approximately 16 subjects will be enrolled in Part A and approximately 24 subjects in Part B.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Drug: MEDI0382 Drug: Placebo Drug: Liraglutide Phase 2

Detailed Description:

This is a 2-part exploratory Phase 2 study.

Part A is a randomised, double-blind, placebo-controlled study to evaluate the effect of MEDI0382 administered once daily subcutaneously (SC) for 28 days on hepatic glycogen metabolism in overweight and obese subjects with T2DM. Part A is planned to randomise up to 16 subjects. Subjects will be consented, screened for suitability, and randomised within 60 days if eligible. Subjects from Part A will not be re-enrolled in Part B.

Part B is 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 T2DM. Part B is planned to randomise approximately 24 subjects (not to exceed a maximum of 30 subjects); however, the exact sample size will be determined by the results obtained on hepatic glycogen concentrations in Part A. Subjects in Part B will be randomised to receive double-blind MEDI0382 or placebo, or open-label liraglutide once daily for 28 days. Both Part A and Part B will use the same schedule of study procedures.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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.
Actual Study Start Date : May 31, 2018
Estimated Primary Completion Date : August 19, 2019
Estimated Study Completion Date : August 19, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Liraglutide

Arm Intervention/treatment
Experimental: MEDI0382 (Part A)
MEDI0382 administered subcutaneously (Part A)
Drug: MEDI0382
MEDI0382 administered subcutaneously

Placebo Comparator: Placebo (Part A)
Placebo comparator administered subcutaneously (Part A)
Drug: Placebo
Placebo administered subcutaneously

Active Comparator: Liraglutide (Part B)
Active comparator administered subcutaneously (Part B)
Drug: Liraglutide
Liraglutide administered subcutaneously

Experimental: MEDI0382 (Part B)
MEDI0382 administered subcutaneously (Part B)
Drug: MEDI0382
MEDI0382 administered subcutaneously

Placebo Comparator: Placebo (Part B)
Placebo comparator administered subcutaneously (Part B)
Drug: Placebo
Placebo administered subcutaneously




Primary Outcome Measures :
  1. Change in hepatic glycogen concentration postprandially, adjusted by liver volume (MEDI0382 vs Placebo) Parts A and B) [ Time Frame: 28 days post dosing ]
    Change in hepatic glycogen concentration adjusted for liver volume as measured by magnetic resonance spectroscopy (MRS) at Time (T) = 4 hours post standardised morning meal from baseline (Day -1) to the end of 28 days of treatment


Secondary Outcome Measures :
  1. Change in hepatic glycogen concentration postprandially, adjusted for liver volume (MEDI0382 vs Liraglutide; Part B only) [ Time Frame: 28 days post dosing ]
    Change in hepatic glycogen concentration adjusted for liver volume as measured by MRS at T = 4 hours post standardised morning meal from baseline (Day -1) to the end of 28 days of treatment (Part B only)

  2. Measures of safety and tolerability of daily SC doses of MEDI0382 titrated up to a dose level of 300μg (Parts A and B) by assessment of Treatment Emergent Adverse Events (TEAEs) as assessed by CTCAE V4.0 [ Time Frame: Post dosing (Day 1) to final follow-up (Day 29) ]

    Safety and tolerability of daily SC doses of MEDI0382 by assessment of the following using CTCAE V4.0:

    The number of Treatment Emergent Adverse events (TEAEs)


  3. Characterise the immunogenicity profile of MEDI0382 exposure titrated up to a dose level of 300 μg (Parts A and B) [ Time Frame: 28 days post dosing ]
    Development of anti-drug antibodies (ADA) and titre (if confirmed positive)

  4. Measures of safety and tolerability of daily SC doses of MEDI0382 titrated up to a dose level of 300μg (Parts A and B) by assessment of Treatment Emergent Serious Adverse Events (TESAEs) as assessed by CTCAE V4.0 [ Time Frame: Post dosing (Day 1) to final follow-up (Day 29) ]

    Safety and tolerability of daily SC doses of MEDI0382 by assessment of the following using CTCAE V4.0:

    The number of Treatment-Emergent Serious Adverse Events (TESAEs),


  5. Measures of safety and tolerability of daily SC doses of MEDI0382 titrated up to a dose level of 300μg (Parts A and B) by assessment of Treatment Emergent Adverse Events of Special Interest (AESIs) as assessed by CTCAE V4.0 [ Time Frame: Post dosing (Day 1) to final follow-up (Day 29) ]

    Safety and tolerability of daily SC doses of MEDI0382 by assessment of the following using CTCAE V4.0:

    The number of Treatment Emergent Adverse Events of Special Interest (AESIs)




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male and female subjects aged ≥ 18 years at screening
  2. Provision of signed and dated written informed consent (except for consent for genetic research and stool sample microbiome research) prior to any study-specific procedures
  3. Body mass index (BMI) ≥ 27 and ≤ 40 kg/m2 (inclusive) at screening
  4. Glycated haemoglobin (HbA1c) ≤ 8.0% 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. 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 up to 4 weeks after the last dose of investigational product.

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. Specific examples include: dislike/unable to eat any of the standardised meals that will be used during the study and poor venous access.
  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 prior to the start of the study:

    • 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
    • Glucagon
    • Warfarin
  4. Concurrent participation in another study with an investigational product and repeat randomisation in this study is prohibited; subjects randomised into Part A of the study may not be randomised into Part B of the study
  5. Severe allergy/hypersensitivity to any of the proposed study treatments
  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 weightreducing 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 After 10 minutes of supine rest and confirmed by repeated measurement at screening.
  14. 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 are due to undergo these procedures at the time of screening
  15. Severe congestive heart failure (New York Heart Association Class III or IV)
  16. Basal calcitonin level > 50 ng/L at screening or history/family history of medullary thyroid carcinoma or multiple endocrine neoplasia
  17. History of neoplastic disease within 5 years prior to screening, except for adequately treated basal cell, squamous cell skin cancer, or in situ cervical cancer
  18. Any positive results for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody and human immunodeficiency virus (HIV) antibody
  19. Substance dependence or history of alcohol abuse and/or excess alcohol intake (defined as > 21 units per week for a male subject, and >14 units per week for a female subject). Subjects must have a negative alcohol test result at screening and prior to randomisation.
  20. Involvement of any AstraZeneca, MedImmune, contract research organisation, or study site employee or their close relatives.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03555994


Contacts
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
Sweden
Research Site Recruiting
Uppsala, Sweden, 752 37
Sponsors and Collaborators
MedImmune LLC
Investigators
Principal Investigator: Folke Sjöberg, MD CTC Clinical Trial Consultants AB

Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT03555994     History of Changes
Other Study ID Numbers: D5670C00022
First Posted: June 14, 2018    Key Record Dates
Last Update Posted: September 10, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by MedImmune LLC:
0382, T2DM

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Overweight
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Body Weight
Signs and Symptoms
Liraglutide
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists