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

NCT03657446 | Completed Phase 1

• 2 other identifiers: ID-054-1072018-002118-12
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy Subjects

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (6)

Treatment sequence ABC

EXPERIMENTAL

Period A: clazosentan Period B: placebo Period C: placebo + moxifloxacin

Drug: Clazosentan; Drug: Placebo; Drug: Moxifloxacin

Treatment sequence ACB

EXPERIMENTAL

Period A: clazosentan Period B: placebo Period C: placebo + moxifloxacinn

Drug: Clazosentan; Drug: Placebo; Drug: Moxifloxacin

Treatment sequence BAC

EXPERIMENTAL

Period A: clazosentan Period B: placebo Period C: placebo + moxifloxacin

Drug: Clazosentan; Drug: Placebo; Drug: Moxifloxacin

Treatment sequence BCA

EXPERIMENTAL

Period A: clazosentan Period B: placebo Period C: placebo + moxifloxacin

Drug: Clazosentan; Drug: Placebo; Drug: Moxifloxacin

Treatment sequence CBA

EXPERIMENTAL

Period A: clazosentan Period B: placebo Period C: placebo + moxifloxacin

Drug: Clazosentan; Drug: Placebo; Drug: Moxifloxacin

Treatment sequence CAB

EXPERIMENTAL

Period A: clazosentan Period B: placebo Period C: placebo + moxifloxacin

Drug: Clazosentan; Drug: Placebo; Drug: Moxifloxacin

Interventions

Clazosentan DRUG

Continuous i.v. infusion of 20 mg/h or 60 mg/h of clazosentan for 3 h

Treatment sequence ABC; Treatment sequence ACB; Treatment sequence BAC; Treatment sequence BCA; Treatment sequence CAB; Treatment sequence CBA

Placebo DRUG

Matching placebo infusion

Treatment sequence ABC; Treatment sequence ACB; Treatment sequence BAC; Treatment sequence BCA; Treatment sequence CAB; Treatment sequence CBA

Moxifloxacin DRUG

Film-coated tablet containing 400 mg moxifloxacin

Treatment sequence ABC; Treatment sequence ACB; Treatment sequence BAC; Treatment sequence BCA; Treatment sequence CAB; Treatment sequence CBA

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Idorsia Pharmaceuticals Ltd.: lead

Study Sites (1)

QPS Netherlands B.V.

Groningen, 9713 GZ, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 33389549 DERIVED

MeSH Terms

Interventions

clazosentan; Moxifloxacin

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Clinical Trials

  Idorsia Pharmaceuticals Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 3-way cross-over Phase 1 study

Study Record Dates

• First Submitted: August 31, 2018
• First Posted: September 5, 2018
• Study Start: September 18, 2018
• Primary Completion: October 26, 2018
• Study Completion: October 26, 2018
• Last Updated: November 20, 2018

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)