Clinical trial NCT03646864: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Obstructive Pulmonary Disease
Lead sponsor: Idorsia Pharmaceuticals Ltd.
Sponsor class: INDUSTRY
First posted: 2018-08-24
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 crossover study
Primary purpose: TREATMENT

Brief summary: A study to evaluate the effects of ACT-541468 on respiration in patients with moderate chronic obstructive pulmonary disease


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)

Primary outcomes:
measure: Mean SaO2 during total sleep time (TST) after multiple-dose administration (i.e., at Night 5) as measured by finger pulse oximetry and PSG
timeFrame: Duration: for up to 8 hours
Secondary outcomes:
Other outcomes:
measure: Mean SaO2 during TST after single-dose administration (i.e., at Night 1) as measured by finger pulse oximetry and PSG
timeFrame: Duration: for up to 8 hours
measure: Percentage of TST during which SaO2 is < 90%, < 85%, and < 80% following single- and multiple-dose administration as measured by finger pulse oximetry and PSG
timeFrame: Duration: for up to 8 hours
measure: Mean SaO2 during each sleep phase (awake, non REM, REM) following single- and multiple-dose administration as measured by finger pulse oximetry and PSG
timeFrame: Duration: for up to 8 hours
measure: Mean AHI following single- and multiple-dose administration, as measured by PSG.
timeFrame: Duration: for up to 8 hours
measure: Safety profile including incidence of adverse events (AEs) and serious adverse events (SAEs).
timeFrame: Duration: for up to 10 weeks
Locations:
city: Berlin
country: Germany
facility: Advanced Sleep Research
city: Dresden
country: Germany
facility: Klinische Forschungsgruppe Nord
city: Hannover
country: Germany
facility: Klinische Forschungsgruppe Nord
city: Rheinau
country: Germany
facility: framol-med GmbH, Lungenpraxis
city: Warendorf
country: Germany
facility: ZMS
Study officials:
affiliation: Idorsia Pharmaceuticals Ltd.
name: Clinical Trials
role: STUDY_DIRECTOR
References: