Effects of Suvorexant in Patients With Chronic Obstructive Pulmonary Disease (MK-4305-032)
Condition: Insomnia
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Intervention: suvorexant; Placebo
Intervention description: one tablet (30 or 40 mg suvorexant depending on participant age: 40 mg for participants <65 years of age and 30 mg for participants ≥65 years of age), orally, once daily, for 4 consecutive days; one tablet matching suvorexant, orally, once daily, for 4 consecutive days
Intervention MeSH terms: Suvorexant
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: Pulmonary Disease, Chronic Obstructive

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