A Study in Healthy Subjects to Investigate Whether Administration of Clazosentan Can Affect Normal Heart Function

Study Overview
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Brief Summary
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The study will investigate whether administration of clazosentan can affect normal heart function in healthy subjects

Official Title
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Randomized, Double-blind (for Clazosentan), Placebo- and Moxifloxacincontrolled, 3-way Cross-over Phase 1 Study to Assess the Effect of Two Intravenous Doses of Clazosentan on the QTc Interval Duration in Healthy Subjects

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: Clazosentan
* Drug: Placebo
* Drug: Moxifloxacin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: General criteria Signed informed consent prior to any study-mandated procedure Body mass index of 18.0-30.0 kg/m2 (inclusive) at Screening Systolic blood pressure 100-145 mmHg, diastolic blood pressure 50-90 mmHg, and pulse rate 45-90 bpm (inclusive), measured on the same arm, after 5 min in the supine position at Screening and on Day -1 of the first Period 12-lead ECG: QT interval corrected using Fridericia's formula (QTcF) <450 ms for male subjects and < 470 ms for female subjects, QRS interval < 110 ms, PR interval ≤ 200 ms, and heart rate (HR) ≤ 90 bpm without clinically relevant abnormalities using a 12-lead ECG measured after 5 min in the supine position at Screening and on Day -1 of the first Period Study-specific criteria Women of non-childbearing potential Male subjects must accept to use a condom and not to procreate for the duration of the study and for 3 months thereafter Exclusion Criteria: General criteria Previous exposure to clazosentan or to moxifloxacin within 3 months prior to Screening Known hypersensitivity to any of clazosentan excipients or to moxifloxacin or any of its excipients Any contraindication to moxifloxacin treatment Acute, ongoing, recurrent, or chronic systemic disease able to interfere with the evaluation of the study Previous history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions if considered clinically significant by the investigator Veins unsuitable for i.v. puncture on either arm (e.g., veins that are difficult to locate, access, or puncture, veins with a tendency to rupture during or after puncture) Participation in a clinical study involving study treatment administration within 3 months prior to Screening or in more than 4 clinical studies within 1 year prior to Screening Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol Study-specific criteria • History or presence of rhythm disorders (e.g., sinoatrial heart block, sick-sinus syndrome, second- or third-degree atrioventricular block, long QT syndrome, symptomatic bradycardia, atrial flutter, or atrial fibrillation)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: 3-way cross-over Phase 1 study
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment sequence ABC<br>Period A: clazosentan Period B: placebo Period C: placebo + moxifloxacin | Drug: Clazosentan<br>* Continuous i.v. infusion of 20 mg/h or 60 mg/h of clazosentan for 3 h<br>Drug: Placebo<br>* Matching placebo infusion<br>Drug: Moxifloxacin<br>* Film-coated tablet containing 400 mg moxifloxacin<br>|
| Experimental: Treatment sequence ACB<br>Period A: clazosentan Period B: placebo Period C: placebo + moxifloxacinn | Drug: Clazosentan<br>* Continuous i.v. infusion of 20 mg/h or 60 mg/h of clazosentan for 3 h<br>Drug: Placebo<br>* Matching placebo infusion<br>Drug: Moxifloxacin<br>* Film-coated tablet containing 400 mg moxifloxacin<br>|
| Experimental: Treatment sequence BAC<br>Period A: clazosentan Period B: placebo Period C: placebo + moxifloxacin | Drug: Clazosentan<br>* Continuous i.v. infusion of 20 mg/h or 60 mg/h of clazosentan for 3 h<br>Drug: Placebo<br>* Matching placebo infusion<br>Drug: Moxifloxacin<br>* Film-coated tablet containing 400 mg moxifloxacin<br>|
| Experimental: Treatment sequence BCA<br>Period A: clazosentan Period B: placebo Period C: placebo + moxifloxacin | Drug: Clazosentan<br>* Continuous i.v. infusion of 20 mg/h or 60 mg/h of clazosentan for 3 h<br>Drug: Placebo<br>* Matching placebo infusion<br>Drug: Moxifloxacin<br>* Film-coated tablet containing 400 mg moxifloxacin<br>|
| Experimental: Treatment sequence CBA<br>Period A: clazosentan Period B: placebo Period C: placebo + moxifloxacin | Drug: Clazosentan<br>* Continuous i.v. infusion of 20 mg/h or 60 mg/h of clazosentan for 3 h<br>Drug: Placebo<br>* Matching placebo infusion<br>Drug: Moxifloxacin<br>* Film-coated tablet containing 400 mg moxifloxacin<br>|
| Experimental: Treatment sequence CAB<br>Period A: clazosentan Period B: placebo Period C: placebo + moxifloxacin | Drug: Clazosentan<br>* Continuous i.v. infusion of 20 mg/h or 60 mg/h of clazosentan for 3 h<br>Drug: Placebo<br>* Matching placebo infusion<br>Drug: Moxifloxacin<br>* Film-coated tablet containing 400 mg moxifloxacin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Placebo-corrected change-from-baseline QTcF (ΔΔQTcF) with its upper limit of the two-sided 95% confidence interval (CI) |  | From 1 hour pre-dose to 24 hour after the end of infusion |