A Study to Evaluate the Safety and Tolerability of MEDI0382 in Overweight and Obese Participants With Type 2 Diabetes Mellitus

NCT03745937 | Completed Phase 2 Results

• 1 other identifier: D5670C00030
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 2a, randomized, blinded, placebo-controlled study in up to 20 overweight or obese participants with type 2 diabetes mellitus. The participants will participate in the study for approximately 18 weeks, including screening, run-in and treatment periods and a safety follow-up.

Conditions

Type 2 Diabetes Mellitus

Keywords

MEDI0382, diabetes, obesity, overweight, type 2 diabetes mellitus

Outcome Measures

Primary Outcomes (10)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) Through the End of the Up-titration Period

  An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.

  Baseline (Day -1) through Day 56 (end of Up-titration period)

• Number of Participants With TEAEs and TESAEs Through the End of the Follow-up Period

  An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.

  Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)

• Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs Through the End of the Up-titration Period

  Number of participants with abnormal ECGs reported as TEAEs are reported. Abnormal ECGs is defined as any abnormal findings in heart rate, RR interval, PR interval, QRS, QT intervals, and QTcF intervals from the primary lead of the digital 12-lead ECG.

  Baseline (Day -1) through Day 56 (end of Up-titration period)

• Number of Participants With Abnormal ECGs Reported as TEAEs Through the End of the Follow-up Period

  Number of participants with abnormal ECGs reported as TEAEs are reported. Abnormal ECGs is defined as any abnormal findings in heart rate, RR interval, PR interval, QRS, QT intervals, and QTcF intervals from the primary lead of the digital 12-lead ECG.

  Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)

• Number of Participants With Abnormal Vital Signs Reported as TEAEs Through the End of the Up-titration Period

  Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (blood pressure, heart rate, body temperature, and respiratory rate).

  Baseline (Day -1) through Day 56 (end of Up-titration period)

• Number of Participants With Abnormal Vital Signs Reported as TEAEs Through the End of the Follow-up Period

  Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (blood pressure, heart rate, body temperature, and respiratory rate).

  Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)

• Number of Participants With Abnormal Physical Examinations Reported as TEAEs Through the End of the Up-titration Period

  Number of participants with abnormal physical examinations reported as TEAEs are reported. Abnormal physical examinations findings are defined as any abnormal finding in the following body systems: immunologic/allergy; head, ears, eyes, nose, and throat; respiratory; cardiovascular; gastrointestinal; musculoskeletal; neurological psychiatric; dermatologic; hematologic/lymphatic; and, endocrine.

  Baseline (Day -1) through Day 56 (end of Up-titration period)

• Number of Participants With Abnormal Physical Examinations Reported as TEAEs Through the End of the Follow-up Period

  Number of participants with abnormal physical examinations reported as TEAEs are reported. Abnormal physical examination findings are defined as any abnormal finding in the following body systems: immunologic/allergy; head, ears, eyes, nose, and throat; respiratory; cardiovascular; gastrointestinal; musculoskeletal; neurological psychiatric; dermatologic; hematologic/lymphatic; and endocrine.

  Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)

• Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Through the End of the Up-titration Period

  Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of serum chemistry, hematology, and urine.

  Baseline (Day -1) through Day 56 (end of Up-titration period)

• Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Through the End of the Follow-up Period

  Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of serum chemistry, hematology, and urine.

  Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)

Secondary Outcomes (20)

• Area Under the Plasma Concentration Time Curve Over a Dosing Interval (AUCτ) of MEDI0382

  Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dose on Days 1, 7, 14, 35, 42, 49 and 56; pre-dose on Days 22, 29, 70, 84; additional 48 and 72 hours post-dose on Day 84

• Maximum Observed Serum Concentration (Cmax) of MEDI0382

  Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dose on Days 1, 7, 14, 35, 42, 49 and 56; pre-dose on Days 22, 29, 70, 84; additional 48 and 72 hours post-dose on Day 84

• Time to Observed Maximum Serum Concentration (Tmax) of MEDI0382

  Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dose on Days 1, 7, 14, 35, 42, 49 and 56; pre-dose on Days 22, 29, 70, 84; additional 48 and 72 hours post-dose on Day 84

• Trough Plasma Concentration (Ctrough) of MEDI0382

  Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dose on Days 1, 7, 14, 35, 42, 49 and 56; pre-dose on Days 22, 29, 70, 84; additional 48 and 72 hours post-dose on Day 84

• Observed Accumulation Ratio (Ro) of MEDI0382 Calculated Using AUC

  Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dose on Days 1, 7, 14, 35, 42, 49 and 56; pre-dose on Days 22, 29, 70, 84; additional 48 and 72 hours post-dose on Day 84

Study Arms (4)

MEDI0382 Cohort 1

EXPERIMENTAL

Participants will receive subcutaneous (SC) dose of MEDI0382 uptitrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week treatment extension period (TEP).

Drug: MEDI0382

Placebo Cohort 1

PLACEBO COMPARATOR

Participants will receive SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the uptitration period and thereafter once daily through 3 week TEP.

Drug: Placebo

MEDI0382 Cohort 2

EXPERIMENTAL

Participants will receive SC dose of MEDI0382 uptitrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP.

Drug: MEDI0382

Placebo Cohort 2

PLACEBO COMPARATOR

Participants will receive SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.

Drug: Placebo

Interventions

MEDI0382 DRUG

Subcutaneous dose of MEDI0382 will be up-titrated weekly once daily up to 8 weeks during the uptitration period and thereafter once daily in 3-week TEP.

MEDI0382 Cohort 1; MEDI0382 Cohort 2

Placebo DRUG

Subcutaneous dose of placebo matched to MEDI0382 will be administered once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP.

Placebo Cohort 1; Placebo Cohort 2

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants aged 18 to 74 years (inclusive) at screening.
• Provision of signed and dated written informed consent (with the exception of consent for genetic and non-genetic research) prior to any study specific procedures.
• Body mass index (BMI) between 27 and 35 kg/m\^2 (inclusive) at screening.
• Hemoglobin A1c (HbA1c) range of 6.5% to 8.5% (inclusive) at screening (Note: Participants may be re-tested for the HbA1c entry criterion only once.).
• Willing and able to self-inject study drug for the duration of the study.
• Diagnosed with type 2 diabetes mellitus with glucose control managed with metformin monotherapy where no significant dose change (increase or decrease \>= 500 mg/day) has occurred in the three months prior to screening.
• Female participants must have a negative pregnancy test at screening and randomization, and must not be lactating.
• Female participants of childbearing potential who are sexually active with a 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 study drug.

You may not qualify if:

• History of, or any existing condition that, in the opinion of the investigator, would interfere with evaluation of the study drug, 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 during the run-in period.
• Any participant who has received another study drug as part of a clinical study or a glucagon-like peptide-1 (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.
• Concurrent participation in another study of any kind and repeat randomization in this study is prohibited.
• Any participant 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
• Opiates, domperidone, metoclopramide, or other drugs known to alter gastric emptying
• Antimicrobials within the quinolone, macrolide or azole class
• Any change in antihypertensive medication
• Aspirin (acetylsalicylic acid)
• Paracetamol (acetaminophen) or paracetamol-containing preparations
• Ascorbic acid (vitamin C) supplements
• Severe allergy/hypersensitivity to any of the proposed study treatments, standardized meals, or excipients.
• Symptoms of acutely decompensated blood glucose control (eg, thirst, polyuria, weight loss), a history of type 1 diabetes mellitus or diabetic ketoacidosis, or if the participant has been treated with daily SC insulin within 90 days prior to screening.
• Acute pancreatitis, pancreatic amylase, and/or pancreatic lipase \> 3 × upper limit of normal range (ULN); history of chronic pancreatitis; or serum triglyceride levels \> 11 mmol/L (1000 mg/dL) at screening.
• Significant inflammatory bowel disease, gastroparesis or other severe disease or surgery affecting the upper gastrointestinal tract (including weight-reducing surgery and procedures), which may affect gastric emptying or could affect the interpretation of safety and tolerability data.

Sponsors & Collaborators

• MedImmune LLC: lead

Study Sites (1)

Research Site

Neuss, 41460, Germany

Location

Related Links

• CSP redacted protocol
• SAP redacted

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus; Obesity; Overweight

Interventions

cotadutide

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Lars Hansen
• Organization: MedImmune, LLC

information.center@astrazeneca.com

+1 301 398 4563

Study Officials

• Tim Heise, MD

  Profil Institut für Stoffwechselforschung GmbH

  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
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2018
• First Posted: November 19, 2018
• Study Start: January 7, 2019
• Primary Completion: May 28, 2019
• Study Completion: May 28, 2019
• Last Updated: June 5, 2020
• Results First Posted: June 5, 2020

Record last verified: 2020-05

Locations

DE (1)