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

AstraZeneca

Status and phase: Terminated; Phase 1

Conditions: Non-alcoholic Steatohepatitis

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT05668936

D5671C00010

2022-002479-12 (EudraCT Number)

Details and patient eligibility

About

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

Full 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.

Enrollment: 31 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts 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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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31 participants in 3 patient groups

Arm 1

Experimental group

Description:

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

Treatment:

Drug: Cotadutide

Drug: Moxifloxacin-placebo

Arm 2A

Experimental group

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.

Treatment:

Drug: Cotadutide-placebo

Drug: Moxifloxacin-placebo

Drug: Moxifloxacin

Arm 2B

Experimental group

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.

Treatment:

Drug: Cotadutide-placebo

Drug: Moxifloxacin-placebo

Drug: Moxifloxacin