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

A Randomized, Double-blind, Placebo-controlled, 2-way Crossover Study to Investigate the Effects of ACT-541468 on Nighttime Respiratory Function in Patients With Mild to Moderate Obstructive Sleep Apnea

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

Study Overview

• Status: Completed
• Conditions: Obstructive Sleep Apnea
• Intervention / Treatment: Drug: Placebo; Drug: ACT-541468

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Advanced Sleep Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment A: ACT-541468; 50 mg once daily from Day 1 to Day 5 of Period A	Drug: ACT-541468; Film-coated tablet for oral use
PLACEBO_COMPARATOR: Treatment B: Placebo; Matching placebo once daily from Day 1 to Day 5 of Period B	Drug: Placebo; Film-coated tablet for oral use

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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)
Mean SaO2 during the awake, non-REM, and REM phases	After single-dose (i.e., Night 1) administration (duration: 8 hours PSG recording)
Percentage of TST during which SaO2 is < 90%, < 85%, and < 80%	After single-dose (i.e., Night 1) administration (duration: 8 hours PSG recording)
Change from baseline to EOP of both periods in subjective next-day performance (morning sleepiness, daytime alertness, and daytime ability to function) as assessed by VAS	After single-dose (i.e., Night 1) and multiple-dose (i.e., Night 5) administration (duration: 2 x 8 hours PSG recording)
Objective sleep parameters LPS, WASO, TST, and SEI following single- and multiple-dose administration, as measured by PSG	After single-dose (i.e., Night 1) and multiple-dose (i.e., Night 5) administration (duration: 2 x 8 hours PSG recording)
Safety profile including incidence of adverse events (AEs) and serious adverse events (SAEs)	From baseline to EOS (duration: for up to 10 weeks)

Collaborators and Investigators

• Sponsor: Idorsia Pharmaceuticals Ltd.

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 14, 2019
• Primary Completion (ACTUAL): November 5, 2019
• Study Completion (ACTUAL): November 5, 2019

Study Registration Dates

• First Submitted: December 4, 2018
• First Submitted That Met QC Criteria: December 4, 2018
• First Posted (ACTUAL): December 5, 2018

Study Record Updates

• Last Update Posted (ACTUAL): December 19, 2019
• Last Update Submitted That Met QC Criteria: December 18, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Apnea
• Other Study ID Numbers: ID-078-110; 2018-002360-96 (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: Yes
• Studies a U.S. FDA-regulated device product: No