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

Primary Purpose

Obesity

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

MEDI0382

Placebo

About this trial

This is an interventional treatment trial for Obesity focused on measuring Obesity, MEDI0382, Overweight

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

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

Key Exclusion Criteria:

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

Sites / Locations

Research Site
Research Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Arm Label

Placebo Cohort 1

MEDI0382 Cohort 1

Placebo Cohort 2

MEDI0382 Cohort 2

Placebo Cohort 3

MEDI0382 Cohort 3

Arm Description

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

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.

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

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.

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

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.

Outcomes

Primary Outcome Measures

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.

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.

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.

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.

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.

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.

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.

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.

Secondary Outcome Measures

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

The Cmax of MEDI0382 (Cotadutide) for MEDI0382 Doses 1 to 7 for Cohort 1 are reported.

Cmax of MEDI0382 Dose 1 on Day 1 for Cohort 1

The Cmax of MEDI0382 Dose 1 for Cohort 1 is reported.

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

The AUCτ of MEDI0382 for MEDI0382 Doses 1 to 7 for Cohort 1 are reported.

AUCτ of MEDI0382 Dose 1 on Day 1 for Cohort 1

The AUCτ of MEDI0382 Dose 1 for Cohort 1 is reported.

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

The Tmax of MEDI0382 for MEDI0382 Doses 1 to 7 for Cohort 1 are reported.

Tmax of MEDI0382 Dose 1 on Day 1 for Cohort 1

The Tmax of MEDI0382 Dose 1 for Cohort 1 is reported.

Plasma Concentration of MEDI0382 for Cohorts 2 and 3

Plasma concentration of MEDI0382 for predose and 6 hours postdose for Cohorts 2 and 3 are reported.

Plasma Concentration of MEDI0382 Dose 7 on Day 71 for Cohort 2 and MEDI0382 Dose 7 on Day 113 for Cohort 3

Plasma concentration of MEDI0382 Dose 7 for predose and 6 hours postdose on Day 71 for Cohort 2 and on Day 113 for Cohort 3 are reported.

Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI0382 in all Cohorts

Number of participants with positive ADA to MEDI0382 are reported.

Full Information

NCT ID

NCT03625778

First Posted

July 27, 2018

Last Updated

August 16, 2021

Sponsor

MedImmune LLC

1. Study Identification

Unique Protocol Identification Number

NCT03625778

Brief Title

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

Official Title

A Randomized, Blinded, Placebo-controlled Study to Assess Pharmacokinetics, Safety, and Tolerability of Ascending Doses of MEDI0382 in Non-diabetic Obese Subjects

Study Type

Interventional

2. Study Status

Record Verification Date

August 2021

Overall Recruitment Status

Completed

Study Start Date

August 14, 2018 (Actual)

Primary Completion Date

August 25, 2019 (Actual)

Study Completion Date

August 25, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

MedImmune LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

Detailed Description

This is a Phase 1, randomized, blinded, placebo-controlled study in up to approximately 51 non-diabetic obese participants with a BMI ≥ 35 kg/m2. Participants will be blinded, but investigators/site staff and sponsor will be unblinded for Cohort 1. In Cohorts 2 and 3 participants, investigators, and contract research organization personnel are blinded to investigational product and sponsor is unblinded. The participants will participate in the study for up to approximately 27 weeks, including a screening period (including a run-in), treatment period, and safety follow-up. Participants will be randomized 4:1 to MEDI0382 (n=12) or placebo (n=3) for Cohort 1 and randomized 2:1 to MEDI0382 (n=12) or placebo (n=6) for Cohorts 2 and 3. In Cohort 1 participants randomized to MEDI0382 or placebo will be dosed daily with a weekly titration schedule until the highest clinically tolerated dose (CTD) is established. In Cohort 2 participants randomized to MEDI0382 or placebo will be dosed daily with a 2 week titration schedule up to the highest CTD is established in Cohort 1. In Cohort 3 participants randomized to MEDI0382 or placebo will be dosed daily with a 4 week participants schedule up to the highest CTD established in Cohort 1. Once the highest CTD is identified, participants will continue on the highest CTD for an additional 2 weeks of treatment for Cohort 1 and 3 and additional 4 weeks treatment for Cohort 2. All participants will return 28 days post last dose for a safety follow-up visit.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Obesity

Keywords

Obesity, MEDI0382, Overweight

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Masking Description

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.

Allocation

Randomized

Enrollment

51 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo Cohort 1

Arm Type

Placebo Comparator

Arm Description

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

Arm Title

MEDI0382 Cohort 1

Arm Type

Experimental

Arm Description

Arm Title

Placebo Cohort 2

Arm Type

Placebo Comparator

Arm Description

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

Arm Title

MEDI0382 Cohort 2

Arm Type

Experimental

Arm Description

Arm Title

Placebo Cohort 3

Arm Type

Placebo Comparator

Arm Description

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

Arm Title

MEDI0382 Cohort 3

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

MEDI0382

Other Intervention Name(s)

Cotadutide

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Description

Time Frame

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)

Title

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

Description

Time Frame

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)

Title

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

Description

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

Time Frame

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)

Title

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

Description

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

Time Frame

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)

Title

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

Description

Time Frame

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

Title

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

Description

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.

Time Frame

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

Title

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

Description

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.

Time Frame

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

Title

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

Description

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.

Time Frame

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

Secondary Outcome Measure Information:

Title

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

Description

The Cmax of MEDI0382 (Cotadutide) for MEDI0382 Doses 1 to 7 for Cohort 1 are reported.

Time Frame

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

Title

Cmax of MEDI0382 Dose 1 on Day 1 for Cohort 1

Description

The Cmax of MEDI0382 Dose 1 for Cohort 1 is reported.

Time Frame

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

Title

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

Description

The AUCτ of MEDI0382 for MEDI0382 Doses 1 to 7 for Cohort 1 are reported.

Time Frame

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

Title

AUCτ of MEDI0382 Dose 1 on Day 1 for Cohort 1

Description

The AUCτ of MEDI0382 Dose 1 for Cohort 1 is reported.

Time Frame

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

Title

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

Description

The Tmax of MEDI0382 for MEDI0382 Doses 1 to 7 for Cohort 1 are reported.

Time Frame

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

Title

Tmax of MEDI0382 Dose 1 on Day 1 for Cohort 1

Description

The Tmax of MEDI0382 Dose 1 for Cohort 1 is reported.

Time Frame

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

Title

Plasma Concentration of MEDI0382 for Cohorts 2 and 3

Description

Plasma concentration of MEDI0382 for predose and 6 hours postdose for Cohorts 2 and 3 are reported.

Time Frame

Cohort 2: predose and 6 hours postdose on Days 1, 15, 29, 43, and 57 for MEDI0382 Doses 1, 2, 3, 5, and 7, respectively; Cohort 3: predose and 6 hours postdose on Days 1, 29, 57, and 85 for MEDI0382 Doses 1, 8, 4, and 7, respectively

Title

Plasma Concentration of MEDI0382 Dose 7 on Day 71 for Cohort 2 and MEDI0382 Dose 7 on Day 113 for Cohort 3

Description

Plasma concentration of MEDI0382 Dose 7 for predose and 6 hours postdose on Day 71 for Cohort 2 and on Day 113 for Cohort 3 are reported.

Time Frame

Cohort 2: predose and 6 hours postdose on Day 71 for MEDI0382 Dose 7; Cohort 3: predose and 6 hours postdose on Day 113 for MEDI0382 Dose 7

Title

Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI0382 in all Cohorts

Description

Number of participants with positive ADA to MEDI0382 are reported.

Time Frame

Predose on Baseline (Day -1) and follow-up visit (28 days after the last dose) for each cohort; predose on Days 28 and 50 for Cohort 1, on Days 7, 28, 71, 98 for Cohort 2, and on Days 7, 28, 71, 126 for Cohort 3

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Key Inclusion Criteria: 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 Key Exclusion Criteria: 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

Facility Information:

Facility Name

Research Site

City

Daytona Beach

State/Province

Florida

ZIP/Postal Code

32117

Country

United States

Facility Name

Research Site

City

Dallas

State/Province

Texas

ZIP/Postal Code

75247

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

IPD Sharing 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.

IPD Sharing 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.

IPD Sharing URL

https://astrazenecagroup-dt.pharmacm.com/DT/Home

Links:

URL

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Search

Description

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

Learn more about this trial

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

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