Clinical trial NCT05668936: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Non-alcoholic Steatohepatitis
Keywords: Non-alcoholic fatty liver disease
Glucagon-like peptide-1 (GLP-1) receptor
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2022-12-30
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Time-matched change-from-baseline Fridericia's correction of QT interval (QTcF)
timeFrame: Up to Day 92
Secondary outcomes:
measure: Change from baseline in QTcF
timeFrame: Up to Day 94
measure: Change from baseline in Heart rate (HR)
timeFrame: From Day 2 up to Day 92 or early discontinuation
measure: Change from baseline in PR interval
timeFrame: From Day 2 up to Day 92 or early discontinuation
measure: Change from baseline in QRS interval
timeFrame: From Day 2 up to Day 92 or early discontinuation
measure: Number of participants with significant change in QTcF
timeFrame: From Day 2 up to Day 92 or early discontinuation
measure: Number of participants with significant change in HR
timeFrame: From Day 2 up to Day 92 or early discontinuation
measure: Number of participants with significant change in PR interval
timeFrame: From Day 2 up to Day 92 or early discontinuation
measure: Number of participants with significant change in QRS interval
timeFrame: From Day 2 up to Day 92 or early discontinuation
measure: Number of treatment-emergent changes in T-wave morphology
timeFrame: From Day 2 up to Day 92 or early discontinuation
measure: Number of treatment-emergent changes in U-waves presence
timeFrame: From Day 2 up to Day 92 or early discontinuation
measure: Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUClast) of cotadutide
timeFrame: Day 57 and Day 91
measure: Area under concentration-time curve in the dose interval (AUCtau) of cotadutide
timeFrame: Day 57 and Day 91
measure: Maximum observed plasma concentration (Cmax) of cotadutide
timeFrame: Day 57 and Day 91
measure: Time to reach maximum observed plasma concentration (tmax) of cotadutide
timeFrame: Day 57 and Day 91
measure: Change from baseline in mean systolic blood pressure (SBP)
timeFrame: Up to Day 92
measure: Change from baseline in mean diastolic blood pressure (DBP)
timeFrame: Up to Day 92
measure: Change from baseline in mean HR
timeFrame: Up to Day 92
measure: Placebo-corrected mean change from baseline in SBP
timeFrame: Up to Day 92
measure: Placebo-corrected mean change from baseline in DBP
timeFrame: Up to Day 92
measure: Placebo-corrected mean change from baseline in HR
timeFrame: Up to Day 92
measure: Number of participants with significant change in SBP
timeFrame: Up to Day 92
measure: Number of participants with change in DBP
timeFrame: Up to Day 92
measure: Number of participants with significant change in HR
timeFrame: Up to Day 92
measure: Number of participants with Adverse Events (AEs)
timeFrame: Up to follow-up visit 28 days post last dose (approximately Day 120)
measure: Number of participants with Antidrug Antibodies to cotadutide
timeFrame: Day 2, 30, 57, 91 and Day 120 (follow-up visit 28 days post last dose)
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Research Site
Study officials:
References: