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

Non-alcoholic Steatohepatitis Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05668936
• Other study ID #: D5671C00010
• Secondary ID: 2022-002479-12
• Status: Terminated
• Phase: Phase 1
• Start date: January 3, 2023
• Est. completion date: March 10, 2023

Study information

• Verified date: March 2023
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 31
• Est. completion date: March 10, 2023
• Est. primary completion date: March 10, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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).

Related Conditions & MeSH terms

• Fatty Liver
• Non-alcoholic Fatty Liver Disease
• Non-alcoholic Steatohepatitis

Intervention

Drug:
• Cotadutide
Participants will receive a subcutaneous injection of cotadutide.
• Cotadutide-placebo
Participants will receive a subcutaneous injection of cotadutide-placebo.
• Moxifloxacin
Participants will receive a single oral dose of Moxifloxacin film-coated tablet.
• Moxifloxacin-placebo
Participants will receive a single oral dose of Moxifloxacin-placebo film-coated tablet.

Locations

Country	Name	City	State
Germany	Research Site	Berlin

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change from baseline in QTcF	Change from baseline in QTcF after moxifloxacin administration compared with placebo will be assessed.	Up to Day 94
Secondary	Change from baseline in Heart rate (HR)	The effect of cotadutide on HR will be assessed.	From Day 2 up to Day 92 or early discontinuation
Secondary	Change from baseline in PR interval	The effect of cotadutide on PR interval will be assessed.	From Day 2 up to Day 92 or early discontinuation
Secondary	Change from baseline in QRS interval	The effect of cotadutide on QRS will be assessed.	From Day 2 up to Day 92 or early discontinuation
Secondary	Number of participants with significant change in QTcF	The presence of categorical outliers for QTc after cotadutide administration will be assessed.	From Day 2 up to Day 92 or early discontinuation
Secondary	Number of participants with significant change in HR	The presence of categorical outliers for HR after cotadutide administration will be assessed.	From Day 2 up to Day 92 or early discontinuation
Secondary	Number of participants with significant change in PR interval	The presence of categorical outliers for PR after cotadutide administration will be assessed.	From Day 2 up to Day 92 or early discontinuation
Secondary	Number of participants with significant change in QRS interval	The presence of categorical outliers for QRS after cotadutide administration will be assessed.	From Day 2 up to Day 92 or early discontinuation
Secondary	Number of treatment-emergent changes in T-wave morphology	Morphological changes in the T-U complex after cotadutide administration will be investigated.	From Day 2 up to Day 92 or early discontinuation
Secondary	Number of treatment-emergent changes in U-waves presence	Morphological changes in the T-U complex after cotadutide administration will be investigated.	From Day 2 up to Day 92 or early discontinuation
Secondary	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.	Day 57 and Day 91
Secondary	Area under concentration-time curve in the dose interval (AUCtau) of cotadutide	AUCtau as a variable of the PK of cotadutide will be assessed.	Day 57 and Day 91
Secondary	Maximum observed plasma concentration (Cmax) of cotadutide	Cmax as a variable of the PK of cotadutide will be assessed.	Day 57 and Day 91
Secondary	Time to reach maximum observed plasma concentration (tmax) of cotadutide	tmax as a variable of the PK of cotadutide will be assessed.	Day 57 and Day 91
Secondary	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.	Up to Day 92
Secondary	Change from baseline in mean diastolic blood pressure (DBP)	The effect of cotadutide on BP by ABPM will be investigated.	Up to Day 92
Secondary	Change from baseline in mean HR	The effect of cotadutide on HR by ABPM will be investigated.	Up to Day 92
Secondary	Placebo-corrected mean change from baseline in SBP	The effect of cotadutide on BP by ABPM will be investigated.	Up to Day 92
Secondary	Placebo-corrected mean change from baseline in DBP	The effect of cotadutide on BP by ABPM will be investigated.	Up to Day 92
Secondary	Placebo-corrected mean change from baseline in HR	The effect of cotadutide on HR by ABPM will be investigated.	Up to Day 92
Secondary	Number of participants with significant change in SBP	The effect of cotadutide on BP by ABPM will be investigated.	Up to Day 92
Secondary	Number of participants with change in DBP	The effect of cotadutide on BP by ABPM will be investigated.	Up to Day 92
Secondary	Number of participants with significant change in HR	The effect of cotadutide on HR by ABPM will be investigated.	Up to Day 92
Secondary	Number of participants with Adverse Events (AEs)	The safety and tolerability of cotadutide will be assessed.	Up to follow-up visit 28 days post last dose (approximately Day 120)
Secondary	Number of participants with Antidrug Antibodies to cotadutide	The immunogenicity of cotadutide will be evaluated.	Day 2, 30, 57, 91 and Day 120 (follow-up visit 28 days post last dose)