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

NCT05668936 | Terminated Phase 1

• 2 other identifiers: D5671C000102022-002479-12
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

This study will investigate the effect of multiple doses of cotadutide on the cardiac activity (QTc interval) of healthy participants.

Conditions

Non-alcoholic Steatohepatitis

Keywords

Non-alcoholic fatty liver disease; Glucagon-like peptide-1 (GLP-1) receptor

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to Day 92

Secondary Outcomes (25)

• Change from baseline in QTcF

  Up to Day 94

• Change from baseline in Heart rate (HR)

  From Day 2 up to Day 92 or early discontinuation

• Change from baseline in PR interval

  From Day 2 up to Day 92 or early discontinuation

• Change from baseline in QRS interval

  From Day 2 up to Day 92 or early discontinuation

• Number of participants with significant change in QTcF

  From Day 2 up to Day 92 or early discontinuation

Study Arms (3)

Arm 1

EXPERIMENTAL

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

Drug: Cotadutide; Drug: Moxifloxacin-placebo

Arm 2A

EXPERIMENTAL

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.

Drug: Cotadutide-placebo; Drug: Moxifloxacin; Drug: Moxifloxacin-placebo

Arm 2B

EXPERIMENTAL

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.

Drug: Cotadutide-placebo; Drug: Moxifloxacin; Drug: Moxifloxacin-placebo

Interventions

Cotadutide DRUG

Participants will receive a subcutaneous injection of cotadutide.

Arm 1

Cotadutide-placebo DRUG

Participants will receive a subcutaneous injection of cotadutide-placebo.

Arm 2A; Arm 2B

Moxifloxacin DRUG

Participants will receive a single oral dose of Moxifloxacin film-coated tablet.

Arm 2A; Arm 2B

Moxifloxacin-placebo DRUG

Participants will receive a single oral dose of Moxifloxacin-placebo film-coated tablet.

Arm 1; Arm 2A; Arm 2B

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Berlin, 14050, Germany

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

cotadutide; Moxifloxacin

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2022
• First Posted: December 30, 2022
• Study Start: January 3, 2023
• Primary Completion: March 10, 2023
• Study Completion: March 10, 2023
• Last Updated: April 5, 2023

Record last verified: 2023-03

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 refer 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 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.

Locations

DE (1)