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

Obstructive Sleep Apnea Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03765294
• Other study ID #: ID-078-110
• Secondary ID: 2018-002360-96
• Status: Completed
• Phase: Phase 1
• Start date: March 14, 2019
• Est. completion date: November 5, 2019

Study information

• Verified date: December 2019
• Source: Idorsia Pharmaceuticals Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: November 5, 2019
• Est. primary completion date: November 5, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Apnea
• Obstructive Sleep Apnea
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive

Intervention

Drug:
• ACT-541468
Film-coated tablet for oral use
• Placebo
Film-coated tablet for oral use

Locations

Country	Name	City	State
Germany	Advanced Sleep Research	Berlin

Sponsors (1)

Lead Sponsor	Collaborator
Idorsia Pharmaceuticals Ltd.

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	AHI during TST after single-dose administration		After single-dose (i.e., Night 1) administration (duration: 8 hours PSG recording)
Other	Mean SaO2 during TST		After single-dose (i.e., Night 1) administration (duration: 8 hours PSG recording)
Other	AHI during the awake, non-REM, and REM phases		After single-dose (i.e., Night 1) administration (duration: 8 hours PSG recording)
Other	Mean SaO2 during the awake, non-REM, and REM phases		After single-dose (i.e., Night 1) administration (duration: 8 hours PSG recording)
Other	Percentage of TST during which SaO2 is < 90%, < 85%, and < 80%		After single-dose (i.e., Night 1) administration (duration: 8 hours PSG recording)
Other	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)
Other	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)
Other	Safety profile including incidence of adverse events (AEs) and serious adverse events (SAEs)		From baseline to EOS (duration: for up to 10 weeks)
Primary	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)