A Study to Assess the Effect of Single Doses of Daridorexant on Electrocardiogram Parameters in Healthy Subjects

NCT04250506 | Completed Phase 1

• 2 other identifiers: ID-078-1172019-003843-31
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

A study to assess the effect of single doses of daridorexant on electrocardiogram parameters in healthy subjects

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• Placebo-corrected change from baseline in the HR-corrected QTcF (ΔΔQTcF)

  Various time points (for up to 24 hours) on Day 1 and Day 2 of each period. The 4 periods will be separated by a wash-out period of 7-10 days. Total duration: up to 8 weeks.

Secondary Outcomes (4)

• Plasma PK parameters of daridorexant: - AUC from 0 to 24 hours (AUC0-24)

  Various time points (for up to 24 hours) on Day 1 and Day 2 of each period. The 4 periods will be separated by a wash-out period of 7-10 days. Total duration: up to 8 weeks.

• Plasma PK parameters of daridorexant: - Maximum plasma concentration (Cmax)

  Various time points (for up to 24 hours) on Day 1 and Day 2 of each period. The 4 periods will be separated by a wash-out period of 7-10 days. Total duration: up to 8 weeks.

• Plasma PK parameters of daridorexant: - Time to reach Cmax (tmax)

  Various time points (for up to 24 hours) on Day 1 and Day 2 of each period. The 4 periods will be separated by a wash-out period of 7-10 days. Total duration: up to 8 weeks.

• Plasma PK parameters of daridorexant: - T½

  Various time points (for up to 24 hours) on Day 1 and Day 2 of each period. The 4 periods will be separated by a wash-out period of 7-10 days. Total duration: up to 8 weeks.

Study Arms (4)

Treatment A: Daridorexant 50 mg

EXPERIMENTAL

Daridorexant (ACT-541468) administered as film-coated tablets for oral use.

Drug: Daridorexant

Treatment B: Daridorexant 200 mg

EXPERIMENTAL

Daridorexant (ACT-541468) administered as film-coated tablets (4 x 50 mg) for oral use.

Drug: Daridorexant

Treatment C: Placebo

PLACEBO COMPARATOR

Placebo administered as tablets (4 x 50 mg) for oral use.

Drug: Placebo

Treatment D: Moxifloxacin 400 mg

ACTIVE COMPARATOR

Moxifloxacin administered as film-coated tablets for oral use.

Drug: Moxifloxacin

Interventions

Daridorexant DRUG

Daridorexant (ACT-541468) administered as film-coated tablets for oral use.

Treatment A: Daridorexant 50 mg; Treatment B: Daridorexant 200 mg

Placebo DRUG

Placebo administered as tablets for oral use.

Treatment C: Placebo

Moxifloxacin DRUG

Moxifloxacin administered as film-coated tablets for oral use.

Treatment D: Moxifloxacin 400 mg

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Signed informed consent in the local language prior to any study-mandated procedure.
• Czech citizen with the ability to communicate well with the investigator, in a language understandable to the subject, and to understand and comply with the requirements of the study.
• Healthy male and female subjects aged 18 to 55 years (inclusive) at Screening.
• lead safety ECG: QTcF \< 450 ms for male subjects and \< 470 ms for female subjects, QRS \< 110 ms, and PR \< 220 ms, and resting HR \> 50 bpm and \< 90 bpm with no clinically relevant abnormalities on 12-lead ECG after 5 min in the supine position at Screening and on Day 1 pre-dose of Period 1.
• Healthy on the basis of medical history, physical examination, cardiovascular assessments, and clinical laboratory tests.
• Women of childbearing potential are eligible only if the following applies:
• Negative serum pregnancy test at Screening.
• Negative serum pregnancy test on Day 1 of the first period.
• Agreement to consistently and correctly use a highly effective method of contraception with a failure rate of \< 1% per year, be sexually inactive, or have a vasectomized partner from Screening up to at least 30 days after last study treatment administration in the last period with wash-out periods included. If a hormonal contraceptive is used, it must be initiated at least 1 month before first treatment administration.
• Women of non-childbearing potential must meet at least one of the following criteria:
• Previous bilateral salpingectomy, salpingo-oophorectomy, or hysterectomy.
• Premature ovarian failure confirmed by a specialist gynecologist.
• Post-menopausal, defined as 12 consecutive months with amenorrhea prior to Screening without alternative medical cause and confirmed with follicle-stimulating hormone (FSH) test.
• XY genotype.
• Turner syndrome.

You may not qualify if:

• Pregnant or lactating women.
• Previous exposure to daridorexant.
• Known hypersensitivity to moxifloxacin or any of the drug product excipients or to other fluoroquinolone antibiotics.
• Any contraindication to moxifloxacin treatment.
• History of major medical or surgical disorders which, in the opinion of the investigator, are likely to interfere with the absorption, distribution, metabolism, or excretion of the study treatments (appendectomy and herniotomy allowed, cholecystectomy not allowed).
• Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
• 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) or electrolyte disturbances, particularly hypokalemia.
• Any sleep-disorder including self-reported insomnia disorder, breathing-related sleep disorders, restless legs syndrome, nightmare disorder, non-rapid eye movement sleep arousal disorders (sleep terror disorder or sleepwalking disorder), rapid eye movement sleep behavior disorder, circadian rhythm sleep-wake disorders.

Sponsors & Collaborators

• Idorsia Pharmaceuticals Ltd.: lead

Study Sites (1)

CEPHA s.r.o.

Pilsen, 323 00, Czechia

Location

Related Publications (1)

• Schilling U, Henrich A, Muehlan C, Krause A, Dingemanse J, Ufer M. Impact of Daridorexant, a Dual Orexin Receptor Antagonist, on Cardiac Repolarization Following Bedtime Dosing: Results from a Thorough QT Study Using Concentration-QT Analysis. Clin Drug Investig. 2021 Aug;41(8):711-721. doi: 10.1007/s40261-021-01062-1. Epub 2021 Jul 31.

  PMID: 34331678 DERIVED

MeSH Terms

Interventions

daridorexant; 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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single-center, randomized, double-blind, placebo- and moxifloxacin-controlled, Phase 1 study

Study Record Dates

• First Submitted: January 30, 2020
• First Posted: January 31, 2020
• Study Start: February 28, 2020
• Primary Completion: July 22, 2020
• Study Completion: July 22, 2020
• Last Updated: September 16, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (1)