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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: Clazosentan; Drug: Placebo; Drug: Moxifloxacin

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • QPS Netherlands B.V.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Idorsia Pharmaceuticals Ltd.

Publications and helpful links

General Publications

• Henrich A, Juif PE, Dingemanse J, Krause A. PK/PD modeling of a clazosentan thorough QT study with hysteresis in concentration-QT and RR-QT. J Pharmacokinet Pharmacodyn. 2021 Apr;48(2):213-224. doi: 10.1007/s10928-020-09728-7. Epub 2021 Jan 2.

Study record dates

Study Major Dates

• Study Start (Actual): September 18, 2018
• Primary Completion (Actual): October 26, 2018
• Study Completion (Actual): October 26, 2018

Study Registration Dates

• First Submitted: August 31, 2018
• First Submitted That Met QC Criteria: August 31, 2018
• First Posted (Actual): September 5, 2018

Study Record Updates

• Last Update Posted (Actual): November 20, 2018
• Last Update Submitted That Met QC Criteria: November 19, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Moxifloxacin
• Other Study ID Numbers: ID-054-107; 2018-002118-12 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No