Clinical trial NCT03657446: A Study in Healthy Subjects to Investigate Whether Administration of Clazosentan Can Affect Normal Heart Function
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Lead sponsor: Idorsia Pharmaceuticals Ltd.
Sponsor class: INDUSTRY
First posted: 2018-09-05
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 3-way cross-over Phase 1 study
Primary purpose: OTHER

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


Eligibility criteria: 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)

Primary outcomes:
measure: Placebo-corrected change-from-baseline QTcF (ΔΔQTcF) with its upper limit of the two-sided 95% confidence interval (CI)
timeFrame: From 1 hour pre-dose to 24 hour after the end of infusion
Secondary outcomes:
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: QPS Netherlands B.V.
Study officials:
affiliation: Idorsia Pharmaceuticals Ltd.
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.