A Thorough QTC Study to Assess the Effect of Cotadutide on Cardiac Repolarization in Healthy Participants
- Conditions
- Non-alcoholic Steatohepatitis
- Interventions
- Registration Number
- NCT05668936
- Lead Sponsor
- AstraZeneca
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 31
- 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.
- 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).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 2A Cotadutide-placebo 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. Arm 2B Moxifloxacin-placebo 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. Arm 2A Moxifloxacin-placebo 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. Arm 1 Moxifloxacin-placebo Participants will receive cotadutide and will receive a single dose of moxifloxacin-placebo on Day 1 and Day 93. Arm 2B Cotadutide-placebo 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. Arm 1 Cotadutide Participants will receive cotadutide and will receive a single dose of moxifloxacin-placebo on Day 1 and Day 93. Arm 2A Moxifloxacin 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. Arm 2B Moxifloxacin 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.
- Primary Outcome Measures
Name Time Method Time-matched change-from-baseline Fridericia's correction of QT interval (QTcF) Up to Day 92 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.
- Secondary Outcome Measures
Name Time Method Placebo-corrected mean change from baseline in DBP Up to Day 92 The effect of cotadutide on BP by ABPM will be investigated.
Time to reach maximum observed plasma concentration (tmax) of cotadutide Day 57 and Day 91 tmax as a variable of the PK of cotadutide will be assessed.
Change from baseline in QRS interval From Day 2 up to Day 92 or early discontinuation The effect of cotadutide on QRS will be assessed.
Change from baseline in QTcF Up to Day 94 Change from baseline in QTcF after moxifloxacin administration compared with placebo will be assessed.
Change from baseline in Heart rate (HR) From Day 2 up to Day 92 or early discontinuation The effect of cotadutide on HR will be assessed.
Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUClast) of cotadutide Day 57 and Day 91 AUClast as a variable of the pharmacokinetics (PK) of cotadutide will be assessed.
Maximum observed plasma concentration (Cmax) of cotadutide Day 57 and Day 91 Cmax as a variable of the PK of cotadutide will be assessed.
Change from baseline in mean diastolic blood pressure (DBP) Up to Day 92 The effect of cotadutide on BP by ABPM will be investigated.
Change from baseline in mean HR Up to Day 92 The effect of cotadutide on HR by ABPM will be investigated.
Placebo-corrected mean change from baseline in HR Up to Day 92 The effect of cotadutide on HR by ABPM will be investigated.
Number of participants with Antidrug Antibodies to cotadutide Day 2, 30, 57, 91 and Day 120 (follow-up visit 28 days post last dose) The immunogenicity of cotadutide will be evaluated.
Change from baseline in PR interval From Day 2 up to Day 92 or early discontinuation The effect of cotadutide on PR interval will be assessed.
Number of participants with significant change in QRS interval From Day 2 up to Day 92 or early discontinuation The presence of categorical outliers for QRS after cotadutide administration will be assessed.
Number of treatment-emergent changes in U-waves presence From Day 2 up to Day 92 or early discontinuation Morphological changes in the T-U complex after cotadutide administration will be investigated.
Number of participants with significant change in PR interval From Day 2 up to Day 92 or early discontinuation The presence of categorical outliers for PR after cotadutide administration will be assessed.
Number of treatment-emergent changes in T-wave morphology From Day 2 up to Day 92 or early discontinuation Morphological changes in the T-U complex after cotadutide administration will be investigated.
Number of participants with significant change in SBP Up to Day 92 The effect of cotadutide on BP by ABPM will be investigated.
Number of participants with significant change in QTcF From Day 2 up to Day 92 or early discontinuation The presence of categorical outliers for QTc after cotadutide administration will be assessed.
Number of participants with significant change in HR Up to Day 92 The effect of cotadutide on HR by ABPM will be investigated.
Area under concentration-time curve in the dose interval (AUCtau) of cotadutide Day 57 and Day 91 AUCtau as a variable of the PK of cotadutide will be assessed.
Number of participants with change in DBP Up to Day 92 The effect of cotadutide on BP by ABPM will be investigated.
Placebo-corrected mean change from baseline in SBP Up to Day 92 The effect of cotadutide on BP by ABPM will be investigated.
Number of participants with Adverse Events (AEs) Up to follow-up visit 28 days post last dose (approximately Day 120) The safety and tolerability of cotadutide will be assessed.
Change from baseline in mean systolic blood pressure (SBP) Up to Day 92 The effect of cotadutide on blood pressure (BP) by Ambulatory blood pressure monitoring (ABPM) will be investigated.
Trial Locations
- Locations (1)
Research Site
🇩🇪Berlin, Germany