Clinical trial NCT01293006: Effects of Suvorexant in Patients With Chronic Obstructive Pulmonary Disease (MK-4305-032)
Official title: A Study to Evaluate the Effects of MK-4305 in Patients With Chronic Obstructive Pulmonary Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Insomnia
Keywords: Pulmonary Disease, Chronic Obstructive
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2011-02-10
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This study will evaluate the safety, tolerability, and effect of multiple doses of suvorexant (MK-4305) on respiratory function in participants with chronic obstructive pulmonary disease (COPD). This is a crossover study, so all participants will receive both suvorexant and placebo while on study. The primary hypothesis of this study is that multiple doses of suvorexant do not produce a clinically significant reduction of mean oxygen saturation (SaO2) during total sleep time in participants with COPD, as compared to placebo.


Eligibility criteria: Inclusion Criteria:

* Female participants of reproductive potential must demonstrate a serum beta-human chorionic gonadotropin (β-hCG) level consistent with the nongravid state at the prestudy (screening) visit and agree to use (and/or have their partner use) two (2) acceptable methods of birth control beginning at the prestudy visit throughout the study (including washout intervals between treatment periods/panels) and until 2 weeks after the last dose of study drug in the last treatment period. Females of non-childbearing potential (postmenopausal without menses for at least 1 year and follicle stimulating hormone \[FSH\] value in the postmenopausal range, or status post hysterectomy, oophorectomy or tubal ligation. Documented hysterectomy or oophorectomy)
* Body Mass Index (BMI) ≤40 kg/m2 at the prestudy (screening)
* COPD documented by medical history and pulmonary function tests with spirometry measurements at Visit 1 meet all of the following COPD study criteria according to the modified Global Initiative for Obstructive Lung Disease (GOLD) criteria (forced expiratory volume \[FEV1\]/ forced vital capacity \[FVC\] ratio ≤70% and FEV1 ≥40% predicted \[inclusive\])
* Stable physical health for at least 2 weeks prior to entering the study
* No clinically significant abnormality on electrocardiogram (ECG)
* No clinically significant abnormality on the screening polysomnography (PSG) including no evidence of obstructive sleep apnea, restless leg syndrome, periodic limb movement disorder, parasomnia including nightmare disorder, sleep terror disorder and sleepwalking disorder but participants with insomnia may be enrolled
* Nonsmoker or smokes ≤20 cigarettes or equivalent per day without the urge to wake up to smoke during the night
* Sleeps for 4 hours or more per night with a usual bedtime between 8:00 post meridian (PM) and 12:30 ante meridian (AM)
* Participant must complete a sleep diary for at least 5 consecutive days and up to 21 days prior to the screening PSG visit
* Participant is reliably able to perform the study assessments; demonstrates ability to understand task instructions, and is physically capable

Exclusion Criteria:

* Participant is mentally or legally incapacitated, has significant emotional problems at the time of prestudy or expected during conduct of the study, or has a history or evidence of a clinically significant psychiatric disorder that would interfere with participation in the study
* Abnormal pre-randomization laboratory values in alanine transaminase (ALT \>1.5 x the upper limit of normal \[ULN\]), aspartate transaminase (AST \>1.5 x ULN), total bilirubin \>1.5 x ULN, and serum creatinine of \>2 mg/dL
* Participant has any history of a neurological disorder, including but not limited to seizure disorder (other than single episodes of childhood febrile seizures), stroke, transient ischemic attack, multiple sclerosis, cognitive impairment, or significant head trauma with sustained loss of consciousness within the last 10 years
* History of bipolar disorder, a psychotic disorder, or posttraumatic stress disorder, or psychiatric condition requiring treatment with a prohibited medication, or psychiatric condition that, in the investigator's opinion, would interfere with the patient's ability to participate in the study
* Participant has other than COPD and evidence of another clinically significant, active pulmonary disorder, such as such as bronchiectasis or asthma documented by history, physical examination, or chest x-ray
* History within the past 6 months prior to the prestudy of acute coronary syndrome, unstable angina, congestive heart failure, cardiogenic syncope, cardiomyopathy, any symptomatic arrhythmia, orthostatic hypotension, or uncontrolled hypertension
* History of neoplastic disease except adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix, malignancies which have been successfully treated ≥10 years prior to the prestudy and follow-up has revealed no evidence of recurrence from the time of treatment through the time of the prestudy, or in the opinion of the Investigator, are highly unlikely to sustain a recurrence for the duration of the study
* History or diagnosis of narcolepsy, cataplexy (familial or idiopathic), circadian rhythm sleep disorder, parasomnia including nightmare disorder, sleep terror disorder, sleepwalking disorder, and REM behavior disorder, sleep-related Breathing Disorder (i.e., obstructive or central sleep apnea syndrome or central alveolar hypoventilation syndrome), periodic limb movement disorder, restless legs syndrome, or primary hypersomnia
* Normal PSG recording at screening
* Hematocrit \> 55%
* Participant has been treated in an emergency room or has been hospitalized for COPD within 2 months prior to the screening visit, necessitating antibiotics, systemic corticosteroids, oxygen therapy
* Positive screening urine alcohol test or drug test
* Nursing mother
* Condition, therapy, lab, or ECG abnormality or other circumstances that might confound the results of the study
* Taking, or plans to take, one or more of the prohibited concomitant medications
* Participant consumes excessive amounts of alcohol, defined as greater than 3 glasses of alcoholic beverages, or excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, or other caffeinated beverages per day
* Participant has had major surgery, donated or lost 1 unit of blood (approximately 500 mL) or participated in another investigational study within 4 weeks prior to the prestudy (screening) visit
* History of significant multiple and/or severe allergies (including latex allergy), or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food
* Currently a regular user (including "recreational use") of any illicit drugs or has a history of drug (including alcohol) abuse within approximately 2 years
* Need for more than 3 toilet visits during the night
* Participant has a history of shift work (defined as permanent night shift or rotating day/night shift work) within the past 2 weeks or anticipates the need to perform shift work during the study
* Travel across 3 or more time zones (transmeridian travel) within 1 week of study start
* Participant is at imminent risk of self-harm or harm to others in the investigator's opinion
* Concerns of the investigator regarding the safe participation of the participant in the study

Primary outcomes:
measure: Mean Arterial Oxygen Saturation (SaO2) During Total Sleep Time
timeFrame: Day 4 of each period
measure: Number of Participants With Adverse Events
timeFrame: Up to 14 days after last dose
measure: Number of Participants Discontinued From Study Drug Due to an AE
timeFrame: Up to 15 days
Secondary outcomes:
measure: Percentage of Total Sleep Time in Which SaO2 is Less Than 90%, 85% or 80%
timeFrame: Day 1 and Day 4 of each period
measure: Mean Apnea/Hypopnea Index (AHI)
timeFrame: Day 1 and Day 4 of each period
measure: Mean Arterial SaO2 for Different Sleep Stages
timeFrame: Day 1 and Day 4 of each period
measure: Mean Arterial SaO2 During Total Sleep Time
timeFrame: Day 1 of each period
Other outcomes:
Locations:
Study officials:
References:
citation: Sun H, Palcza J, Rosenberg R, Kryger M, Siringhaus T, Rowe J, Lines C, Wagner JA, Troyer MD. Effects of suvorexant, an orexin receptor antagonist, on breathing during sleep in patients with chronic obstructive pulmonary disease. Respir Med. 2015 Mar;109(3):416-26. doi: 10.1016/j.rmed.2014.12.010. Epub 2015 Jan 5.