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

• ClinicalTrials.gov Identifier: NCT03765294
• Recruitment Status: Completed
• First Posted: December 5, 2018
• Last Update Posted: December 19, 2019
• Sponsor: Idorsia Pharmaceuticals Ltd.
• Information provided by (Responsible Party): Idorsia Pharmaceuticals Ltd.

Study Description

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

Condition or disease	Intervention/treatment	Phase
Obstructive Sleep Apnea	Drug: ACT-541468; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: 2-way cross-over
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: March 14, 2019
• Actual Primary Completion Date: November 5, 2019
• Actual Study Completion Date: November 5, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Apnea/hypopnea index (AHI) after multiple-dose administration of ACT-541468 as measured by polysomnography (PSG) [ Time Frame: After multiple-dose administration (i.e., at Night 5) (duration: 8 hours PSG recording) ]
   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

Other Outcome Measures:

1. AHI during TST after single-dose administration [ Time Frame: After single-dose (i.e., Night 1) administration (duration: 8 hours PSG recording) ]
2. Mean SaO2 during TST [ Time Frame: After single-dose (i.e., Night 1) administration (duration: 8 hours PSG recording) ]
3. AHI during the awake, non-REM, and REM phases [ Time Frame: After single-dose (i.e., Night 1) administration (duration: 8 hours PSG recording) ]
4. Mean SaO2 during the awake, non-REM, and REM phases [ Time Frame: After single-dose (i.e., Night 1) administration (duration: 8 hours PSG recording) ]
5. Percentage of TST during which SaO2 is < 90%, < 85%, and < 80% [ Time Frame: After single-dose (i.e., Night 1) administration (duration: 8 hours PSG recording) ]
6. 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 [ Time Frame: After single-dose (i.e., Night 1) and multiple-dose (i.e., Night 5) administration (duration: 2 x 8 hours PSG recording) ]
7. Objective sleep parameters LPS, WASO, TST, and SEI following single- and multiple-dose administration, as measured by PSG [ Time Frame: After single-dose (i.e., Night 1) and multiple-dose (i.e., Night 5) administration (duration: 2 x 8 hours PSG recording) ]
8. Safety profile including incidence of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: From baseline to EOS (duration: for up to 10 weeks) ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

Germany

Advanced Sleep Research

Berlin, Germany, 10117

Sponsors and Collaborators

Idorsia Pharmaceuticals Ltd.

Investigators

• Study Director: Clinical Trials; Idorsia Pharmaceuticals Ltd.

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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). pii: zsaa275. doi: 10.1093/sleep/zsaa275.

• Responsible Party: Idorsia Pharmaceuticals Ltd.
• ClinicalTrials.gov Identifier: NCT03765294
• Other Study ID Numbers: ID-078-110; 2018-002360-96 ( EudraCT Number )
• First Posted: December 5, 2018
• Last Update Posted: December 19, 2019
• Last Verified: December 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Apnea; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases