A Study to Investigate the Effects of ACT-541468 on Nighttime Respiratory Function in Patients With Mild to Moderate Obstructive Sleep Apnea

NCT03765294 | Completed Phase 1 FDA Drug

• 2 other identifiers: ID-078-1102018-002360-96
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

This study is conducted to investigate the effects of ACT-541468 on nighttime respiratory function in patients with mild to moderate obstructive sleep apnea

Conditions

Obstructive Sleep Apnea

Outcome Measures

Primary Outcomes (1)

• Apnea/hypopnea index (AHI) after multiple-dose administration of ACT-541468 as measured by polysomnography (PSG)

  AHI is defined by total number of apnea (pause in respiration ≥ 10 s) plus hypopnea (reduction in airflow or tidal volume from pre-event baseline by 30% for at least 10 s accompanied by a decrease of SaO2 ≥ 4%) events, divided by total sleep time (TST, in min), then multiplied by 60, during TST

  After multiple-dose administration (i.e., at Night 5) (duration: 8 hours PSG recording)

Other Outcomes (8)

• AHI during TST after single-dose administration

  After single-dose (i.e., Night 1) administration (duration: 8 hours PSG recording)

• Mean SaO2 during TST

  After single-dose (i.e., Night 1) administration (duration: 8 hours PSG recording)

• AHI during the awake, non-REM, and REM phases

  After single-dose (i.e., Night 1) administration (duration: 8 hours PSG recording)

Study Arms (2)

Treatment A: ACT-541468

EXPERIMENTAL

50 mg once daily from Day 1 to Day 5 of Period A

Drug: ACT-541468

Treatment B: Placebo

PLACEBO COMPARATOR

Matching placebo once daily from Day 1 to Day 5 of Period B

Drug: Placebo

Interventions

ACT-541468 DRUG

Film-coated tablet for oral use

Treatment A: ACT-541468

Placebo DRUG

Film-coated tablet for oral use

Treatment B: Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent in a language understandable to the subject prior to any study-mandated procedure.
• Male and female subjects aged ≥ 18 years at Screening.
• Women of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Screening Visit 2 and on Day 1 pre-dose of the first period. They must agree to consistently and correctly use a highly effective method of contraception with a failure rate of \< 1% per year.
• Women of non-childbearing potential, i.e., postmenopausal, with previous bilateral salpingectomy, bilateral salpingo-oophorectomy or hysterectomy, or with premature ovarian failure, XY genotype, Turner syndrome, and/or uterine agenesis.
• Diagnosis of OSA according to the International Classification of Sleep Disorders documented by medical history and confirmed in a sleep laboratory in the context of diagnosing OSA within the last 3 years.
• Patient with mild to moderate intensity of OSA determined during OSA diagnosis and confirmed on the screening night PSG and defined as apnea/hypopnea index (AHI) ranging from 5 to \< 30.

You may not qualify if:

• Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
• Pregnant or lactating women.
• Modified Swiss Narcolepsy Scale total score \< 0 at Screening, or history of narcolepsy or cataplexy.
• Subjects with clinically significant abnormality on the screening night PSG as per investigator judgment, including evidence of severe insomnia (i.e., sleep time \< 5 h) periodic limb movement disorder with arousal index ≥ 10/h, restless legs syndrome, circadian rhythm disorder, REM behavior disorder, parasomnia including nightmare disorder, sleep terror disorder, and/or sleepwalking disorder.
• Need for continuous positive airway pressure device or a dental appliance device within the preceding 7 days prior to Screening Visit 2 and during the course of the study, i.e., from Screening Visit 2 to EOS.
• Evidence of any other clinically significant active pulmonary disease such as chronic obstructive pulmonary disease (COPD) (as per Global Initiative for Obstructive Lung Disease), based on investigator's judgment.
• History of surgical intervention for obstructive sleep apnea, except nose surgery.
• SaO2 \< 90% during wakefulness or mean non-apneic SaO2 (i.e., outside events of apnea/hypopnea) \< 85% for \> 5 consecutive min during the screening night PSG.

Sponsors & Collaborators

• Idorsia Pharmaceuticals Ltd.: lead

Study Sites (1)

Advanced Sleep Research

Berlin, 10117, Germany

Location

Related Publications (2)

• Boof ML, Ufer M, Fietze I, Pepin JL, Guern AS, Lemoine V, Dingemanse J. Assessment of the effect of the dual orexin receptor antagonist daridorexant on various indices of disease severity in patients with mild to moderate obstructive sleep apnea. Sleep Med. 2022 Apr;92:4-11. doi: 10.1016/j.sleep.2021.11.015. Epub 2022 Feb 12.

  PMID: 35306405 DERIVED

• Boof ML, Dingemanse J, Lederer K, Fietze I, Ufer M. Effect of the new dual orexin receptor antagonist daridorexant on nighttime respiratory function and sleep in patients with mild and moderate obstructive sleep apnea. Sleep. 2021 Jun 11;44(6):zsaa275. doi: 10.1093/sleep/zsaa275.

  PMID: 33305817 DERIVED

MeSH Terms

Conditions

Sleep Apnea, Obstructive

Interventions

daridorexant

Condition Hierarchy (Ancestors)

Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

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: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 2-way cross-over

Study Record Dates

• First Submitted: December 4, 2018
• First Posted: December 5, 2018
• Study Start: March 14, 2019
• Primary Completion: November 5, 2019
• Study Completion: November 5, 2019
• Last Updated: December 19, 2019

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)