A Study to Evaluate the Effects of ACT-541468 on Respiration in Patients With Moderate Chronic Obstructive Pulmonary Disease

Study Overview
=================
Brief Summary
-----------------
A study to evaluate the effects of ACT-541468 on respiration in patients with moderate chronic obstructive pulmonary disease

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 Moderate Chronic Obstructive Pulmonary Disease

Conditions
-----------------
Chronic Obstructive Pulmonary Disease

Intervention / Treatment
-----------------
* Drug: ACT-541468
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed informed consent prior to any study-mandated procedure Male and female subjects aged ≥ 18 years Body mass index of 18.0 to 35.0 kg/m2 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 consistently and correctly use a reliable method of contraception with a failure rate of < 1% per year, be sexually inactive, or have a vasectomized partner. Women of non-childbearing potential, i.e., postmenopausal Diagnosis of moderate COPD documented by medical history (including risk factors and familial history) and confirmed by the assessment of dyspnea using the Modified British Medical Research Council (mMRC) questionnaire, the COPD assessment test (CATTM), and the post bronchodilator pulmonary function tests which should meet the modified Global Initiative for Obstructive Lung Disease (GOLD) criterion for moderate obstruction severity: Moderate COPD: Forced expiratory volume in 1 sec (FEV1) / Forced vital capacity (FVC) ratio ≤ 70% and 40% ≤ FEV1 < 80% of predicted Subjects with 0 to 1 (not leading to hospital admission) exacerbation in the last year (i.e., who belong to Group A and B of the GOLD classification) Exclusion Criteria: Pregnant or lactating women History of major medical or surgical disorders which, in the opinion of the investigator, are likely to interfere with the absorption, distribution, metabolism, or excretion of the study treatment Any known factor or disease that might interfere with treatment compliance, study conduct, or interpretation of the results such as history of non-compliance to medical regimen, psychiatric disease, neurological disorders which may impact sleep, motor performance, or cognition Need for continuous oxygen therapy or non invasive ventilation that would interfere with the study evaluation (e.g., required during the night), as per investigator judgement Subjects with clinically significant abnormality on the screening night PSG as per investigator judgement, including evidence of Periodic limb movement disorder with arousal index ≥ 15/h, restless legs syndrome, circadian rhythm disorder, rapid eye movement (REM) behavior disorder, parasomnia including nightmare disorder, sleep terror disorder, and/or sleepwalking disorder but excluding any COPD-related abnormalities Emergency treatment with antibiotics or systemic corticosteroids or any hospitalization due to COPD within 2 months prior to Screening SaO2 < 90% during wakefulness and/or SaO2 < 85% for > 5 consecutive min during the screening night PSG AHI > 10 within the last 3 months prior to Screening, or at the polygraphy (PG) assessed after Screening visit 1 and before Screening visit 2 (if no previous data available only) or on the screening night PSG (only for subjects having AHI<10 at Screening visit 1 or after PG)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: 2-way crossover study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A<br>ACT-541468 50 mg from Day 1 to Day 5 of Period A | Drug: ACT-541468<br>* ACT-541468 will be orally administered as a tablet (50 mg strength) at a once daily (o.d.) dose of 50 mg in the evening.<br>|
| Placebo Comparator: Treatment B<br>Placebo from Day 1 to Day 5 of Period B | Other: Placebo<br>* Placebo will be orally administered as a tablet matching ACT-541468, o.d. in the evening.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean SaO2 during total sleep time (TST) after multiple-dose administration (i.e., at Night 5) as measured by finger pulse oximetry and PSG |  | Duration: for up to 8 hours |