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

Phase 1TerminatedNCT05668936

AstraZeneca31 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Non-alcoholic Steatohepatitis

Interventions

CotadutideDRUG

Participants will receive a subcutaneous injection of cotadutide.

Cotadutide-placeboDRUG

Participants will receive a subcutaneous injection of cotadutide-placebo.

MoxifloxacinDRUG

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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).

Locations (1)

Research Site

Berlin, Germany

Outcomes

Primary Outcomes

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.

Time frame: Up to Day 92

Secondary Outcomes

Change from baseline in QTcF

Change from baseline in QTcF after moxifloxacin administration compared with placebo will be assessed.

Time frame: Up to Day 94

Change from baseline in Heart rate (HR)

The effect of cotadutide on HR will be assessed.

Time frame: From Day 2 up to Day 92 or early discontinuation

Change from baseline in PR interval

The effect of cotadutide on PR interval will be assessed.

Time frame: From Day 2 up to Day 92 or early discontinuation

Change from baseline in QRS interval

The effect of cotadutide on QRS will be assessed.

Time frame: From Day 2 up to Day 92 or early discontinuation

Number of participants with significant change in QTcF

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

Number of participants with significant change in HR

The presence of categorical outliers for HR after cotadutide administration will be assessed.

Data from ClinicalTrials.gov

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