A Study to Assess Safety, Tolerability, and Pharmacokinetics of MEDI0382 in Non-diabetic Obese Participants

NCT03625778 | Completed Phase 1 FDA Drug

• 1 other identifier: D5672C00001
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 2

Brief Summary

This is a Phase 1, randomized, blinded, placebo-controlled study in up to approximately 51 non-diabetic obese participants with a body mass index (BMI) ≥ 35 kg/m\^2. The participants will be observed among 3 separate cohorts and participate in the study for up to approximately 27 weeks, including a screening period (including a run-in), treatment period, and safety follow-up.

Conditions

Obesity

Keywords

Obesity; MEDI0382; Overweight

Outcome Measures

Primary Outcomes (8)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) for Cohorts 1, 2, and 3

  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.

  From Day 1 through 28 days after the last dose of study drug (approximately 13, 18, and 22 weeks for Cohorts 1, 2, and 3, respectively)

• Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs for Cohorts 1, 2, and 3

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

  From Day 1 through 28 days after the last dose of study drug (approximately 13, 18, and 22 weeks for Cohorts 1, 2, and 3, respectively)

• Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs for Cohorts 1, 2, and 3

  Number of participants with abnormal vital signs (body temperature, blood pressure, heart rate, and respiratory rate) and physical examinations reported as TEAEs are reported.

  From Day 1 through 28 days after the last dose of study drug (approximately 13, 18, and 22 weeks for Cohorts 1, 2, and 3, respectively)

• Number of Participants With Abnormal Electrocardiogram (ECG) Parameters Reported as TEAEs for Cohorts 1, 2, and 3

  Number of participants with abnormal ECG parameters reported as TEAEs are reported.

  From Day 1 through 28 days after the last dose of study drug (approximately 13, 18, and 22 weeks for Cohorts 1, 2, and 3, respectively)

• Change in Blood Pressure from Baseline to End of Dosing as Measured by Telemetry for Cohort 1

  Telemetry is the process of recording and transmitting the vital readings (temperature, blood pressure, pulse rate, and respiratory rate). It is used to continuously monitor vital reading as a real-time safety measure. Mean change in blood pressure from baseline to end of dosing measured by telemetry for Cohort 1 are reported.

  From Baseline (Day -1) through end of dosing (Day 63)

• Change in Respiratory Rate from Baseline to End of Dosing as Measured by Telemetry for Cohort 1

  Telemetry is the process of recording and transmitting the vital readings (temperature, blood pressure, pulse rate, and respiratory rate). It is used to continuously monitor vital reading as a real-time safety measure. Mean change in respiratory rate from baseline to end of dosing measured by telemetry for Cohort 1 are reported.

  From Baseline (Day -1) through end of dosing (Day 63)

• Change in Pulse Rate from Baseline to End of Dosing as Measured by Telemetry for Cohort 1

  Telemetry is the process of recording and transmitting the vital readings (temperature, blood pressure, pulse rate, and respiratory rate). It is used to continuously monitor vital reading as a real-time safety measure. Mean change in pulse rate from baseline to end of dosing measured by telemetry for Cohort 1 are reported.

  From Baseline (Day -1) through end of dosing (Day 63)

• Change in Temperature from Baseline to End of Dosing as Measured by Telemetry for Cohort 1

  Telemetry is the process of recording and transmitting the vital readings (temperature, blood pressure, pulse rate, and respiratory rate). It is used to continuously monitor vital reading as a real-time safety measure. Mean change in temperature from baseline to end of dosing measured by telemetry for Cohort 1 are reported.

  From Baseline (Day -1) through end of dosing ( Day 63)

Secondary Outcomes (9)

• Maximum Observed Plasma Concentration (Cmax) of MEDI0382 for Cohort 1

  Predose (-5 minutes) and 1, 2, 4, 6, 8, 12, and 24 hours postdose on Days 7, 14, 21, 28, 35, 42, and 49 for MEDI0382 Doses 1 to 7, respectively

• Cmax of MEDI0382 Dose 1 on Day 1 for Cohort 1

  Predose (-5 minutes) and 1, 2, 4, 6, 8, 12, and 24 hours postdose on Day 1

• Area Under the Concentration-time Curve at the end of the Dosing interval (AUCτ) of MEDI0382 for Cohort 1

  Predose (-5 minutes) and 1, 2, 4, 6, 8, 12, and 24 hours postdose on Days 7, 14, 21, 28, 35, 42, and 49 for MEDI0382 Doses 1 to 7, respectively

• AUCτ of MEDI0382 Dose 1 on Day 1 for Cohort 1

  Predose (-5 minutes) and 1, 2, 4, 6, 8, 12, and 24 hours postdose on Day 1

• Time to Maximum Observed Plasma Concentration (Tmax) of MEDI0382 for Cohort 1

  Predose (-5 minutes) and 1, 2, 4, 6, 8, 12, and 24 hours postdose on Days 7, 14, 21, 28, 35, 42, and 49 for MEDI0382 Doses 1 to 7, respectively

Study Arms (6)

Placebo Cohort 1

PLACEBO COMPARATOR

Participants will receive subcutaneous (SC) placebo matched to MEDI0382 Cohort 1 once daily for 9 weeks.

Drug: Placebo

MEDI0382 Cohort 1

EXPERIMENTAL

Participants will receive SC MEDI0382 titrated doses of Dose 1 to 7 once daily (7-step titration/ 1 week per dose) from Weeks 1 to 7 followed by additional treatment of SC MEDI0382 Dose 7 once daily from Weeks 7 to 9.

Drug: MEDI0382

Placebo Cohort 2

PLACEBO COMPARATOR

Participants will receive SC placebo matched to MEDI0382 Cohort 2 once daily for 14 weeks.

Drug: Placebo

MEDI0382 Cohort 2

EXPERIMENTAL

Participants will receive SC MEDI0382 titrated doses of Doses 1, 2, 3, 5, and 7 once daily (5-step titration/ 2 week per dose) from Weeks 1 to 10 followed by additional treatment of SC MEDI0382 Dose 7 once daily from Weeks 11 to 14.

Drug: MEDI0382

Placebo Cohort 3

PLACEBO COMPARATOR

Participants will receive SC placebo matched to MEDI0382 Cohort 3 once daily for 18 weeks.

Drug: Placebo

MEDI0382 Cohort 3

EXPERIMENTAL

Participants will receive SC MEDI0382 titrated doses of Doses 1, 8, 4, and 7 once daily (4-step titration/ 4 week per dose) from Weeks 1 to 16 followed by additional treatment of SC MEDI0382 Dose 7 once daily from Weeks 17 to 18.

Drug: MEDI0382

Interventions

MEDI0382 DRUG

MEDI0382 will be administered subcutaneously daily according to the MEDI0382 cohorts.

Also known as: Cotadutide

MEDI0382 Cohort 1; MEDI0382 Cohort 2; MEDI0382 Cohort 3

Placebo DRUG

Placebo will be administered subcutaneously daily according to the Placebo cohorts.

Placebo Cohort 1; Placebo Cohort 2; Placebo Cohort 3

Eligibility Criteria

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

You may qualify if:

• Provision of written informed consent
• Male and female participants age 18 through 65 years
• BMI ≥ 35 kg/m\^2
• Hemoglobin A1c level of \< 6.5%
• Female participants must have a negative pregnancy test and must not be lactating.
• Females of childbearing potential using appropriate birth control to avoid pregnancy during the study.
• Stable body weight
• Willing and able to adhere to the visit/protocol schedule, including following lifestyle advice with respect to diet and exercise for the duration of the study
• Willing and able to self-administer daily SC injections following an initial self-injection training

You may not qualify if:

• Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks prior to Study Day 1 dosing.
• Any condition that, in the opinion of the investigator, would interfere with the evaluation of the investigational product or interpretation of participants safety or study results.
• Active participation in any other investigation clinical study.
• Any prescription or non-prescription drugs for weight loss including herbal or other dietary supplements used within the past 3 months prior to screening.
• Previous glucagon-like peptide-1 (GLP-1) use within 3 months prior to screening.
• Any positive results for serum hepatitis B surface antigen, hepatitis C virus antibody and/or human immunodeficiency virus (HIV) antibody at screening.
• Laboratory tests results as specified in the protocol (laboratory tests may be repeated once for confirmation of out of range values at screening).
• Significant hepatic or renal impairment
• Poorly controlled hypertension
• Known or suspected history of drug or alcohol abuse within the past year or positive current test
• Previous surgical procedures for weight loss

Sponsors & Collaborators

• MedImmune LLC: lead

Study Sites (2)

Research Site

Daytona Beach, Florida, 32117, United States

Location

Research Site

Dallas, Texas, 75247, United States

Location

Related Links

• Results of this clinical trial are available on www.astrazenecaclinicaltrials.com

MeSH Terms

Conditions

Obesity; Overweight

Interventions

cotadutide

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: In Cohort 1 participants are blinded however site staff, investigator, and sponsor are unblinded. In Cohorts 2 and 3 participants, investigators, site staff, and clinical research organization staff are blinded and sponsor is unblinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2018
• First Posted: August 10, 2018
• Study Start: August 14, 2018
• Primary Completion: August 25, 2019
• Study Completion: August 25, 2019
• Last Updated: August 23, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will share
• 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 deidentified 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

US (2)