Obstructive Sleep Apnea
Conditions
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
Interventions
DRUGACT-541468
Film-coated tablet for oral use
DRUGPlacebo
Film-coated tablet for oral use
Sponsors
Idorsia Pharmaceuticals Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
2-way cross-over
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Apnea/hypopnea index (AHI) after multiple-dose administration of ACT-541468 as measured by polysomnography (PSG) | 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
| Measure | Time frame |
|---|---|
| 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) |
| AHI during TST after single-dose administration | 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) |
| Percentage of TST during which SaO2 is < 90%, < 85%, and < 80% | After single-dose (i.e., Night 1) administration (duration: 8 hours PSG recording) |
Countries
Germany
Outcome results
None listed