Study of MEDI0382 in Combination With Dapagliflozin and Metformin in Overweight/Obese Participants With Type 2 Diabetes

NCT03444584 | Completed Phase 2 Results

• 2 other identifiers: D5670C000072017-002817-78
• Study Type: interventional
• Target: 49
• Locations: 3 countries
• Sites: 8

Brief Summary

A Phase 2 study Comparing the effects on glucose control of MEDI0382 in combination with Dapagliflozin and Metformin compared to placebo in combination with Dapagliflozin and Metformin in overweight/obese participants with Type 2 Diabetes Mellitus (T2DM).

Conditions

Type 2 Diabetes Mellitus

Keywords

0382; T2DM

Outcome Measures

Primary Outcomes (2)

• Change From Baseline to Day 28 in Plasma Glucose Area Under the Concentration Time-curve From Time 0 to 4 Hours (AUC0-4hrs) as Measured by Mixed-meal Tolerance Test (MMTT)

  The MMTT test involved the consumption of a standardised liquid meal (nutritional supplement of fat, carbohydrate, and protein) within 5 minutes. On Day -1 and on Day 28, following a minimum 10 hour fast, serial of blood samples were obtained prior and through 240 minutes after consumption of standardized meal for the measurement of glucose metabolism (with no additional food intake during this time).

  Zero minutes before and 15, 30, 45, 60, 90, 120, 180, and 240 minutes after consumption of the standardised meal on Day -1 (Baseline) and Day 28

• Percent Change From Baseline to Day 28 in Plasma Glucose AUC0-4hrs as Measured by MMTT

  The MMTT test involved the consumption of a standardised liquid meal (nutritional supplement of fat, carbohydrate, and protein)within 5 minutes. On Day -1 and on Day 28, following a minimum 10-hour fast, serial of blood samples were obtained prior and through 240 minutes after consumption of standardized meal for the measurement of glucose metabolism (with no additional food intake during this time).

  Zero minutes before and 15, 30, 45, 60, 90, 120, 180, and 240 minutes after consumption of the standardised meal on Day -1 (Baseline) and Day 28

Secondary Outcomes (27)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

  Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)

• Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Reported as TEAEs

  Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)

• Number of Participants With Abnormal Vital Signs Reported as TEAEs

  Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)

• Number of Participants With Abnormal Physical Examinations Reported as TEAEs

  Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)

• Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs

  Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)

Study Arms (2)

MEDI0382

EXPERIMENTAL

Participants will receive subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.

Drug: MEDI0382; Drug: Dapaglifozin; Drug: Metformin

Placebo

PLACEBO COMPARATOR

Participants will receive subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period

Drug: Placebo; Drug: Dapaglifozin; Drug: Metformin

Interventions

MEDI0382 DRUG

Subcutaneous dose of MEDI0382 (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days).

MEDI0382

Placebo DRUG

Subcutaneous dose of placebo matched to MEDI0382.

Placebo

Dapaglifozin DRUG

Oral dose of dapaglifozin 10 mg tablet.

MEDI0382; Placebo

Metformin DRUG

Oral dose of metformin tablet (maximum tolerated dose \[MTD\] \> 1 g).

MEDI0382; Placebo

Eligibility Criteria

• Age: 18 Years - 115 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female participants aged \>= 18 years at screening.
• Provision of signed and dated informed consent form (ICF) prior to any study specific procedures.
• Body mass index between 25 kg/m\^2 and 40 kg/m\^2 (inclusive) at screening.
• Hemoglobin A1c range between 7.0% and 10.0% (inclusive) at the time of screening.
• Diagnosed with T2DM and treated with of metformin monotherapy (MTD \> 1 g) at least 8 weeks prior to screening or treated with stable, oral doses of dapagliflozin 10 mg and metformin (MTD \> 1 g) for at least 3 months prior screening.
• Participants prescribed oral dual therapy with sulphonylurea, glitinide, or dipeptidyl peptidase-4 inhibitor (in addition to metformin) may be eligible to enter the study following a washout period of these medications totaling at least 28 days before initial screening evaluations have been completed.
• Participants treated with stable doses of metformin (MTD \> 1 g) with canagliflozin (maximum dose of 300 mg/day), or metformin (MTD \> 1 g) with empaglifozin (maximum dose of 25mg/day) for at least 3 months prior to screening may be eligible to enter the study after switching to dapagliflozin.
• Female participants of childbearing potential must have a negative pregnancy test at screening and randomization and must not be lactating.
• Females of childbearing potential who are sexually active with a nonsterilized male partner must use at least one highly effective method of contraception from screening and must agree to continue using such precautions through to the end of the study. It is strongly recommended for the male partner of a female participant 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.

You may not qualify if:

• History of, or any existing condition that in the opinion of the investigator would interfere with evaluation of the investigational product, put the participant at risk, influence the participant's ability to participate, or affect the interpretation of the results of the study and/or any participant unable or unwilling to follow study procedures.
• Any participant who has received another investigational product not included in the protocol as part of a clinical trial or a glucagon-like peptide-1 (GLP-1) analogue or sodium-glucose cotransporter-2 (SGLT2)-containing preparation (excluding dapagliflozin, canagliflozin, empagliflozin) within the last 30 days or 5 half-lives of the drug (whichever is longest) at the time of screening.
• Any participant who has received any of the following medications prior to the start of the screening period (Visit 1) or prior to the study start period (Visit 4):
• Concurrent use of any medicinal products, or herbal or over-the-counter (OTC) preparations licensed for control of body weight or appetite at the time of screening (Visit 1)
• Concurrent or previous use of drugs approved for weight loss (eg, orlistat, bupropion-naltrexone, phentermine-topiramate, phentermine, lorcaserin) within the last 30 days or 5 half-lives of the drug (whichever is longest) at the time of screening (Visit 1)
• Concurrent use of aspirin (acetylsalicylic acid) at a dose greater than 150 mg once daily and within the last 72 hours prior to the start of the study (Visit 4)
• Concurrent use of paracetamol (acetaminophen) or paracetamol-containing preparations at a total daily dose of greater than 3000 mg and within the last 72 hours prior to the start of the study (Visit 4)
• Concurrent use of ascorbic acid (vitamin C) supplements at a total daily dose greater than 1000 mg and within the last 72 hours prior to the start of the study (Visit 4)
• Concurrent use of opiates, domperidone, metoclopramide, or other drugs known to alter gastric emptying and within the last 72 hours prior to the start of the study (Visit 4)
• Concurrent participation in another study of any kind and repeat randomization in this study is prohibited.
• Severe allergy/hypersensitivity to any of the proposed study treatments or excipients.
• Diagnosis of type 1 diabetes mellitus, maturity-onset diabetes of the young, or latent autoimmune diabetes of adulthood or presence of anti-glutamic acid decarboxylase, anti-islet cell, or anti-insulin antibodies.
• Symptoms of acutely decompensate blood glucose control (eg, thirst, polyuria, weight loss) at screening or randomization, a history of diabetes ketoacidosis (DKA), or hyperosmolar nonketotic coma or treatment with daily subcutaneous insulin within 90 days prior to screening.
• Fasting hyperglycemia (\> 250 mg/dL/ \> 13.9 mmol/L) prior to randomization.
• C-peptide level \< lower limit of normal (LLN).

Sponsors & Collaborators

• MedImmune LLC: lead

Study Sites (8)

Research Site

Magdeburg, 39120, Germany

Location

Research Site

Mannheim, 68167, Germany

Location

Research Site

München, 81241, Germany

Location

Research Site

Balatonfüred, 8230, Hungary

Location

Research Site

Miskolc, 3529, Hungary

Location

Research Site

Szeged, 6720, Hungary

Location

Research Site

Manchester, M13 9NQ, United Kingdom

Location

Research Site

Rotherham, S65 1DA, United Kingdom

Location

Related Links

• D5670C00007-Clinical-Protocol draft Redacted
• D5670C00007 Statistical Analysis Plan Redacted

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

cotadutide; Metformin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Armando Flor
• Organization: MedImmune, LLC

information.center@astrazeneca.com

+1-301-398-1955

Study Officials

• Stephen Bain, MD

  Joint Clinical Research Facility

  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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Randomized, Placebo-controlled, Double-blind Study
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Efficacy and Safety of MEDI0382 versus Placebo in Overweight/Obese Participants with Type 2 Diabetes Mellitus Treated with Dapagliflozin and Metformin

Study Record Dates

• First Submitted: October 18, 2017
• First Posted: February 23, 2018
• Study Start: May 8, 2018
• Primary Completion: December 6, 2018
• Study Completion: December 6, 2018
• Last Updated: January 13, 2020
• Results First Posted: January 13, 2020

Record last verified: 2020-01

Locations

DE (3); GB (2); HU (3)