Clinical trial NCT03765294: A Study to Investigate the Effects of ACT-541468 on Nighttime Respiratory Function in Patients With Mild to Moderate Obstructive Sleep Apnea
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Obstructive Sleep Apnea
Lead sponsor: Idorsia Pharmaceuticals Ltd.
Sponsor class: INDUSTRY
First posted: 2018-12-05
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 2-way cross-over
Primary purpose: TREATMENT

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


Eligibility 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.

Primary outcomes:
measure: Apnea/hypopnea index (AHI) after multiple-dose administration of ACT-541468 as measured by polysomnography (PSG)
timeFrame: After multiple-dose administration (i.e., at Night 5) (duration: 8 hours PSG recording)
Secondary outcomes:
Other outcomes:
measure: AHI during TST after single-dose administration
timeFrame: After single-dose (i.e., Night 1) administration (duration: 8 hours PSG recording)
measure: Mean SaO2 during TST
timeFrame: After single-dose (i.e., Night 1) administration (duration: 8 hours PSG recording)
measure: AHI during the awake, non-REM, and REM phases
timeFrame: After single-dose (i.e., Night 1) administration (duration: 8 hours PSG recording)
measure: Mean SaO2 during the awake, non-REM, and REM phases
timeFrame: After single-dose (i.e., Night 1) administration (duration: 8 hours PSG recording)
measure: Percentage of TST during which SaO2 is < 90%, < 85%, and < 80%
timeFrame: After single-dose (i.e., Night 1) administration (duration: 8 hours PSG recording)
measure: 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
timeFrame: After single-dose (i.e., Night 1) and multiple-dose (i.e., Night 5) administration (duration: 2 x 8 hours PSG recording)
measure: Objective sleep parameters LPS, WASO, TST, and SEI following single- and multiple-dose administration, as measured by PSG
timeFrame: After single-dose (i.e., Night 1) and multiple-dose (i.e., Night 5) administration (duration: 2 x 8 hours PSG recording)
measure: Safety profile including incidence of adverse events (AEs) and serious adverse events (SAEs)
timeFrame: From baseline to EOS (duration: for up to 10 weeks)
Locations:
city: Berlin
country: Germany
facility: Advanced Sleep Research
Study officials:
affiliation: Idorsia Pharmaceuticals Ltd.
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.