search
Back to results

A Thorough QTC Study to Assess the Effect of Cotadutide on Cardiac Repolarization in Healthy Participants

Primary Purpose

Non-alcoholic Steatohepatitis

Status
Terminated
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Cotadutide
Cotadutide-placebo
Moxifloxacin
Moxifloxacin-placebo
Sponsored by
AstraZeneca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-alcoholic Steatohepatitis focused on measuring Non-alcoholic fatty liver disease, Glucagon-like peptide-1 (GLP-1) receptor

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Healthy male and female participants of age 18 to 55 years. Females must have a negative pregnancy test. Have a Body Mass Index (BMI) of ≥ 18 and ≤ 29.9 kg/m^2. Exclusion Criteria: History or presence of any clinically significant disease or disorder. History or presence of gastrointestinal, hepatic or renal disease, or any other condition (including gastrointestinal surgery) known to interfere with absorption, distribution, metabolism, or excretion of drugs. History of acute or chronic pancreatitis. Family history of sudden cardiac death before the age of 50 of a first-degree relative. History of additional risk factors for Torsade de Pointes (eg, heart failure, clinically important bradycardia and electrolyte disturbances eg, hypokalemia, hypocalcemia, hypomagnesemia or family history of long QT syndrome). History of neoplastic disease Any clinically significant abnormalities in clinical chemistry, hematology, urinalysis results or vital signs. Any clinically significant abnormalities in rhythm, conduction, or morphology of the 12-lead resting electrocardiogram (ECG). Any positive result on screening for serum hepatitis B surface antigen OR anti-HBc antibody, indicative of active hepatitis B (ie, participants with positive anti-HBc antibody result are acceptable if anti HBc IgM antibodies are negative), hepatitis C antibody, and Human immunodeficiency virus (HIV) antibody. Current smokers or those who have smoked or used nicotine products (including e-cigarettes). Known or suspected history of alcohol or drug abuse or excessive intake of alcohol. Use of drugs with enzyme-inducing properties such as St John's Wort. Participant has a positive test result for SARS-CoV-2 RT-PCR during screening period or at baseline. Participant has clinical signs and symptoms consistent with COVID-19 or a history of severe COVID-19 (hospitalization, extracorporeal membrane oxygenation, mechanically ventilated).

Sites / Locations

  • Research Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Arm 1

Arm 2A

Arm 2B

Arm Description

Participants will receive cotadutide and will receive a single dose of moxifloxacin-placebo on Day 1 and Day 93.

Participants will receive a single dose of moxifloxacin (Day 1) prior to initiating treatment with cotadutide-placebo for up to 13 weeks, followed by a single dose of moxifloxacin-placebo on Day 93.

Participants will receive a single dose of moxifloxacin-placebo (Day 1) prior to initiating treatment with cotadutide-placebo for up to 13 weeks, followed by a single dose of moxifloxacin on Day 93.

Outcomes

Primary Outcome Measures

Time-matched change-from-baseline Fridericia's correction of QT interval (QTcF)
Time-matched change-from-baseline QTcF after cotadutide administration compared with placebo will be assesed using a C-QTc interval analysis. The method that removes the HR dependence of the QT interval most efficiently will be chosen as the primary correction method and its corresponding change from baseline QTc will be the primary endpoint.

Secondary Outcome Measures

Change from baseline in QTcF
Change from baseline in QTcF after moxifloxacin administration compared with placebo will be assessed.
Change from baseline in Heart rate (HR)
The effect of cotadutide on HR will be assessed.
Change from baseline in PR interval
The effect of cotadutide on PR interval will be assessed.
Change from baseline in QRS interval
The effect of cotadutide on QRS will be assessed.
Number of participants with significant change in QTcF
The presence of categorical outliers for QTc after cotadutide administration will be assessed.
Number of participants with significant change in HR
The presence of categorical outliers for HR after cotadutide administration will be assessed.
Number of participants with significant change in PR interval
The presence of categorical outliers for PR after cotadutide administration will be assessed.
Number of participants with significant change in QRS interval
The presence of categorical outliers for QRS after cotadutide administration will be assessed.
Number of treatment-emergent changes in T-wave morphology
Morphological changes in the T-U complex after cotadutide administration will be investigated.
Number of treatment-emergent changes in U-waves presence
Morphological changes in the T-U complex after cotadutide administration will be investigated.
Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUClast) of cotadutide
AUClast as a variable of the pharmacokinetics (PK) of cotadutide will be assessed.
Area under concentration-time curve in the dose interval (AUCtau) of cotadutide
AUCtau as a variable of the PK of cotadutide will be assessed.
Maximum observed plasma concentration (Cmax) of cotadutide
Cmax as a variable of the PK of cotadutide will be assessed.
Time to reach maximum observed plasma concentration (tmax) of cotadutide
tmax as a variable of the PK of cotadutide will be assessed.
Change from baseline in mean systolic blood pressure (SBP)
The effect of cotadutide on blood pressure (BP) by Ambulatory blood pressure monitoring (ABPM) will be investigated.
Change from baseline in mean diastolic blood pressure (DBP)
The effect of cotadutide on BP by ABPM will be investigated.
Change from baseline in mean HR
The effect of cotadutide on HR by ABPM will be investigated.
Placebo-corrected mean change from baseline in SBP
The effect of cotadutide on BP by ABPM will be investigated.
Placebo-corrected mean change from baseline in DBP
The effect of cotadutide on BP by ABPM will be investigated.
Placebo-corrected mean change from baseline in HR
The effect of cotadutide on HR by ABPM will be investigated.
Number of participants with significant change in SBP
The effect of cotadutide on BP by ABPM will be investigated.
Number of participants with change in DBP
The effect of cotadutide on BP by ABPM will be investigated.
Number of participants with significant change in HR
The effect of cotadutide on HR by ABPM will be investigated.
Number of participants with Adverse Events (AEs)
The safety and tolerability of cotadutide will be assessed.
Number of participants with Antidrug Antibodies to cotadutide
The immunogenicity of cotadutide will be evaluated.

Full Information

First Posted
December 20, 2022
Last Updated
April 1, 2023
Sponsor
AstraZeneca
search

1. Study Identification

Unique Protocol Identification Number
NCT05668936
Brief Title
A Thorough QTC Study to Assess the Effect of Cotadutide on Cardiac Repolarization in Healthy Participants
Official Title
A Thorough QTc Evaluation of the Effect of Cotadutide on Cardiac Repolarization in Healthy Participants: A Randomized, Double-blind, Placebo-controlled, 3-arm Parallel Study With a Nested Crossover Design for Positive Control With Moxifloxacin Administration
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Terminated
Why Stopped
Discontinuing the development of cotadutide, a daily injectable GLP-1/glucagon co-agonist, is based on strategic pipeline considerations. The premature closure is not due to any newly observed safety signals or a change in the risk/benefit profile.
Study Start Date
January 3, 2023 (Actual)
Primary Completion Date
March 10, 2023 (Actual)
Study Completion Date
March 10, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
This study will investigate the effect of multiple doses of cotadutide on the cardiac activity (QTc interval) of healthy participants.
Detailed Description
This study will be a randomized, double-blind, placebo-controlled 3-arm parallel study with a nested crossover design for positive control with moxifloxacin administration in healthy male and female participants. Participants will be randomized to receive treatment with either cotadutide during the 13-week treatment period (Arm 1) or cotadutide-placebo (Arm 2). The cotadutide-placebo treatment arm will be further divided into 2 subgroups (Arms 2A and 2B), in a nested crossover design for only the placebo-treated participants. Participants will be randomized in a 2:1:1 ratio to Arm 1, Arm 2A, and Arm 2B. Approximately 80 participants will be randomized to have 64 evaluable participants in the study. Each participant will be involved in the study for approximately 22 weeks.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-alcoholic Steatohepatitis
Keywords
Non-alcoholic fatty liver disease, Glucagon-like peptide-1 (GLP-1) receptor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
31 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1
Arm Type
Experimental
Arm Description
Participants will receive cotadutide and will receive a single dose of moxifloxacin-placebo on Day 1 and Day 93.
Arm Title
Arm 2A
Arm Type
Experimental
Arm Description
Participants will receive a single dose of moxifloxacin (Day 1) prior to initiating treatment with cotadutide-placebo for up to 13 weeks, followed by a single dose of moxifloxacin-placebo on Day 93.
Arm Title
Arm 2B
Arm Type
Experimental
Arm Description
Participants will receive a single dose of moxifloxacin-placebo (Day 1) prior to initiating treatment with cotadutide-placebo for up to 13 weeks, followed by a single dose of moxifloxacin on Day 93.
Intervention Type
Drug
Intervention Name(s)
Cotadutide
Intervention Description
Participants will receive a subcutaneous injection of cotadutide.
Intervention Type
Drug
Intervention Name(s)
Cotadutide-placebo
Intervention Description
Participants will receive a subcutaneous injection of cotadutide-placebo.
Intervention Type
Drug
Intervention Name(s)
Moxifloxacin
Intervention Description
Participants will receive a single oral dose of Moxifloxacin film-coated tablet.
Intervention Type
Drug
Intervention Name(s)
Moxifloxacin-placebo
Intervention Description
Participants will receive a single oral dose of Moxifloxacin-placebo film-coated tablet.
Primary Outcome Measure Information:
Title
Time-matched change-from-baseline Fridericia's correction of QT interval (QTcF)
Description
Time-matched change-from-baseline QTcF after cotadutide administration compared with placebo will be assesed using a C-QTc interval analysis. The method that removes the HR dependence of the QT interval most efficiently will be chosen as the primary correction method and its corresponding change from baseline QTc will be the primary endpoint.
Time Frame
Up to Day 92
Secondary Outcome Measure Information:
Title
Change from baseline in QTcF
Description
Change from baseline in QTcF after moxifloxacin administration compared with placebo will be assessed.
Time Frame
Up to Day 94
Title
Change from baseline in Heart rate (HR)
Description
The effect of cotadutide on HR will be assessed.
Time Frame
From Day 2 up to Day 92 or early discontinuation
Title
Change from baseline in PR interval
Description
The effect of cotadutide on PR interval will be assessed.
Time Frame
From Day 2 up to Day 92 or early discontinuation
Title
Change from baseline in QRS interval
Description
The effect of cotadutide on QRS will be assessed.
Time Frame
From Day 2 up to Day 92 or early discontinuation
Title
Number of participants with significant change in QTcF
Description
The presence of categorical outliers for QTc after cotadutide administration will be assessed.
Time Frame
From Day 2 up to Day 92 or early discontinuation
Title
Number of participants with significant change in HR
Description
The presence of categorical outliers for HR after cotadutide administration will be assessed.
Time Frame
From Day 2 up to Day 92 or early discontinuation
Title
Number of participants with significant change in PR interval
Description
The presence of categorical outliers for PR after cotadutide administration will be assessed.
Time Frame
From Day 2 up to Day 92 or early discontinuation
Title
Number of participants with significant change in QRS interval
Description
The presence of categorical outliers for QRS after cotadutide administration will be assessed.
Time Frame
From Day 2 up to Day 92 or early discontinuation
Title
Number of treatment-emergent changes in T-wave morphology
Description
Morphological changes in the T-U complex after cotadutide administration will be investigated.
Time Frame
From Day 2 up to Day 92 or early discontinuation
Title
Number of treatment-emergent changes in U-waves presence
Description
Morphological changes in the T-U complex after cotadutide administration will be investigated.
Time Frame
From Day 2 up to Day 92 or early discontinuation
Title
Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUClast) of cotadutide
Description
AUClast as a variable of the pharmacokinetics (PK) of cotadutide will be assessed.
Time Frame
Day 57 and Day 91
Title
Area under concentration-time curve in the dose interval (AUCtau) of cotadutide
Description
AUCtau as a variable of the PK of cotadutide will be assessed.
Time Frame
Day 57 and Day 91
Title
Maximum observed plasma concentration (Cmax) of cotadutide
Description
Cmax as a variable of the PK of cotadutide will be assessed.
Time Frame
Day 57 and Day 91
Title
Time to reach maximum observed plasma concentration (tmax) of cotadutide
Description
tmax as a variable of the PK of cotadutide will be assessed.
Time Frame
Day 57 and Day 91
Title
Change from baseline in mean systolic blood pressure (SBP)
Description
The effect of cotadutide on blood pressure (BP) by Ambulatory blood pressure monitoring (ABPM) will be investigated.
Time Frame
Up to Day 92
Title
Change from baseline in mean diastolic blood pressure (DBP)
Description
The effect of cotadutide on BP by ABPM will be investigated.
Time Frame
Up to Day 92
Title
Change from baseline in mean HR
Description
The effect of cotadutide on HR by ABPM will be investigated.
Time Frame
Up to Day 92
Title
Placebo-corrected mean change from baseline in SBP
Description
The effect of cotadutide on BP by ABPM will be investigated.
Time Frame
Up to Day 92
Title
Placebo-corrected mean change from baseline in DBP
Description
The effect of cotadutide on BP by ABPM will be investigated.
Time Frame
Up to Day 92
Title
Placebo-corrected mean change from baseline in HR
Description
The effect of cotadutide on HR by ABPM will be investigated.
Time Frame
Up to Day 92
Title
Number of participants with significant change in SBP
Description
The effect of cotadutide on BP by ABPM will be investigated.
Time Frame
Up to Day 92
Title
Number of participants with change in DBP
Description
The effect of cotadutide on BP by ABPM will be investigated.
Time Frame
Up to Day 92
Title
Number of participants with significant change in HR
Description
The effect of cotadutide on HR by ABPM will be investigated.
Time Frame
Up to Day 92
Title
Number of participants with Adverse Events (AEs)
Description
The safety and tolerability of cotadutide will be assessed.
Time Frame
Up to follow-up visit 28 days post last dose (approximately Day 120)
Title
Number of participants with Antidrug Antibodies to cotadutide
Description
The immunogenicity of cotadutide will be evaluated.
Time Frame
Day 2, 30, 57, 91 and Day 120 (follow-up visit 28 days post last dose)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Healthy male and female participants of age 18 to 55 years. Females must have a negative pregnancy test. Have a Body Mass Index (BMI) of ≥ 18 and ≤ 29.9 kg/m^2. Exclusion Criteria: History or presence of any clinically significant disease or disorder. History or presence of gastrointestinal, hepatic or renal disease, or any other condition (including gastrointestinal surgery) known to interfere with absorption, distribution, metabolism, or excretion of drugs. History of acute or chronic pancreatitis. Family history of sudden cardiac death before the age of 50 of a first-degree relative. History of additional risk factors for Torsade de Pointes (eg, heart failure, clinically important bradycardia and electrolyte disturbances eg, hypokalemia, hypocalcemia, hypomagnesemia or family history of long QT syndrome). History of neoplastic disease Any clinically significant abnormalities in clinical chemistry, hematology, urinalysis results or vital signs. Any clinically significant abnormalities in rhythm, conduction, or morphology of the 12-lead resting electrocardiogram (ECG). Any positive result on screening for serum hepatitis B surface antigen OR anti-HBc antibody, indicative of active hepatitis B (ie, participants with positive anti-HBc antibody result are acceptable if anti HBc IgM antibodies are negative), hepatitis C antibody, and Human immunodeficiency virus (HIV) antibody. Current smokers or those who have smoked or used nicotine products (including e-cigarettes). Known or suspected history of alcohol or drug abuse or excessive intake of alcohol. Use of drugs with enzyme-inducing properties such as St John's Wort. Participant has a positive test result for SARS-CoV-2 RT-PCR during screening period or at baseline. Participant has clinical signs and symptoms consistent with COVID-19 or a history of severe COVID-19 (hospitalization, extracorporeal membrane oxygenation, mechanically ventilated).
Facility Information:
Facility Name
Research Site
City
Berlin
ZIP/Postal Code
14050
Country
Germany

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 requests 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 refer 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 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.
IPD Sharing URL
https://astrazenecagroup-dt.pharmacm.com/DT/Home

Learn more about this trial

A Thorough QTC Study to Assess the Effect of Cotadutide on Cardiac Repolarization in Healthy Participants

We'll reach out to this number within 24 hrs