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

NCT03555994 | Completed Phase 2 Results

• 2 other identifiers: D5670C000222017-005081-22
• Study Type: interventional
• Target: 51
• Locations: 3 countries
• Sites: 3

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 20 subjects will be enrolled in Part A and approximately 30 subjects in Part B.

Conditions

Type 2 Diabetes Mellitus

Keywords

0382, T2DM, Cotadutide, Overweight, Obese, MEDI0382

Outcome Measures

Primary Outcomes (2)

• 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 A Only)

  To assess the effect of MEDI0382 on hepatic glycogen levels postprandially versus placebo after 28 days of treatment

  Day -1 to Day 28

• Percentage Change in Fasting Hepatic Glycogen Concentration Adjusted for Liver Volume as Measured by MRS at T = 24 Hours Post Standardised Morning Meal From Baseline (Day -1) to the End of 35 Days of Treatment (Day 36) (Part B)

  To assess the effect of MEDI0382 on hepatic glycogen levels versus placebo after 35 days (Part B) of treatment

  Day -1 to Day 36

Secondary Outcomes (8)

• Percentage Change in Fasting Hepatic Glycogen Concentration Adjusted for Liver Volume as Measured by MRS at T = 24 Hours Post Standardised Morning Meal From Baseline (Day 1) to the End of 35 Days of Treatment (Day 36, Part B Only)

  Fom baseline (Day -1) to Day 35

• Change of Hepatic Fat Fraction From Baseline as Measured by Magnetic Resonance Imaging (Day -1) to the End of 35 Days of Treatment (Part B Only)

  Day -1 to Day 36

• Development of ADA

  Baseline to (Follow-up Period) 28 days post last dose + (3-month poststudy)

• 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 Number of Participants withTreatment Emergent Adverse Events (TEAEs) as Assessed by CTCAE V4.0

  Post dosing (Day 1) to final follow-up (28 Days post last dose)

• 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 Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs) as Assessed by CTCAE V4.0

  Post dosing (Day 1) to final follow-up (28 Days post last dose)

Study Arms (5)

MEDI0382 (Part A)

EXPERIMENTAL

MEDI0382 administered subcutaneously (Part A)

Drug: MEDI0382

Placebo (Part A)

PLACEBO COMPARATOR

Placebo comparator administered subcutaneously (Part A)

Drug: Placebo

Liraglutide (Part B)

ACTIVE COMPARATOR

Active comparator administered subcutaneously (Part B)

Drug: Liraglutide

MEDI0382 (Part B)

EXPERIMENTAL

MEDI0382 administered subcutaneously (Part B)

Drug: MEDI0382

Placebo (Part B)

PLACEBO COMPARATOR

Placebo comparator administered subcutaneously (Part B)

Drug: Placebo

Interventions

MEDI0382 DRUG

MEDI0382 administered subcutaneously

MEDI0382 (Part A); MEDI0382 (Part B)

Placebo DRUG

Placebo administered subcutaneously

Placebo (Part A); Placebo (Part B)

Liraglutide DRUG

Liraglutide administered subcutaneously

Liraglutide (Part B)

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Body mass index (BMI) ≥ 27 and ≤ 40 kg/m2 (inclusive) at screening
• Glycated haemoglobin (HbA1c) ≤ 8.0% at screening
• 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

You may not qualify if:

• 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
• 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
• Any contraindication to magnetic resonance imaging/MRS scanning including claustrophobia or dislike of confined spaces
• 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
• 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)
• 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
• Acute or chronic pancreatitis
• 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

Sponsors & Collaborators

• MedImmune LLC: lead

Study Sites (3)

Research Site

Maastricht, 6229 ER, Netherlands

Location

Research Site

Uppsala, 752 37, Sweden

Location

Research Site

Nottingham, NG7 2UH, United Kingdom

Location

Related Publications (1)

• Parker VER, Robertson D, Erazo-Tapia E, Havekes B, Phielix E, de Ligt M, Roumans KHM, Mevenkamp J, Sjoberg F, Schrauwen-Hinderling VB, Johansson E, Chang YT, Esterline R, Smith K, Wilkinson DJ, Hansen L, Johansson L, Ambery P, Jermutus L, Schrauwen P. Cotadutide promotes glycogenolysis in people with overweight or obesity diagnosed with type 2 diabetes. Nat Metab. 2023 Dec;5(12):2086-2093. doi: 10.1038/s42255-023-00938-0. Epub 2023 Dec 8.

  PMID: 38066113 DERIVED

Related Links

• d5670C00022-amendment-6\_Redacted
• d5670c00022-sap-ed-3\_Redacted
• D5670C0022 Study Synopsis\_Redacted

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Overweight; Obesity

Interventions

cotadutide; Liraglutide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• Folke Sjöberg, MD

  CTC Clinical Trial Consultants AB

  PRINCIPAL INVESTIGATOR

• MacDonald

  Nottingham

  PRINCIPAL INVESTIGATOR

• Schrauwen

  Maastricht

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2018
• First Posted: June 14, 2018
• Study Start: May 31, 2018
• Primary Completion: April 14, 2021
• Study Completion: April 14, 2021
• Last Updated: November 12, 2024
• Results First Posted: November 12, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

GB (1); NL (1); SE (1)