Safety and Tolerability of Gefapixant (MK-7264) in Participants With Obstructive Sleep Apnea (MK-7264-039)
Condition: Obstructive Sleep Apnea (OSA)
MeSH terms: Apnea; Sleep Apnea Syndromes; Sleep Apnea, Obstructive
Intervention: Gefapixant; Placebo
Intervention description: In Periods 1 and 2 (7 days each) participants receive 4 tablets (180 mg) of gefapixant (MK-7264) QHS.; In Periods 1 and 2 (7 days each) participants receive 4 tablets of placebo QHS.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The purpose of this study is to assess the safety and tolerability of multiple dose
      administration of gefapixant (MK-7264) in participants with moderate to severe obstructive
      sleep apnea (OSA). The primary hypothesis is that multiple dose administration of gefapixant
      (MK-7264) in participants with moderate to severe OSA reduces the Apnea Hypopnea Index (AHI)
      relative to placebo.
    

Eligibility criteria:

        Inclusion Criteria:

          -  International Classification of Sleep Disorders (ICSD-3) diagnosis of OSA, based on
             investigator's assessment of the obstructive sleep apnea (OSA) history and diagnostic
             interview which must include: Documented sleep study in the past that confirmed the
             OSA diagnosis without significant prior medical intervention.

          -  Apnea-Hypopnea Index (AHI) ≥ 20 events/hour at screening.

          -  No use of a positive airway pressure (PAP) device within the preceding 1 month or a
             dental appliance within the preceding 7 days prior to screening and is not allowed to
             use PAP or a dental appliance throughout the study (including washout intervals
             between treatment periods) and until the post-study visit.

          -  A baseline oxygen saturation via pulse oximetry (SpO2) ≥ 94% at screening to ensure
             that carotid body response to hyperoxia is not impaired.

          -  A body mass index (BMI) ≤ 35 kg/m^2 at the pre-study (Screening 1) visit.

          -  Judged to be in good health based on medical history, physical examination, vital sign
             measurements, and laboratory safety tests.

          -  No clinically significant abnormality on electrocardiogram (ECG)

          -  Contraceptive use by men and women should be consistent with local regulations
             regarding the methods of contraception for those participating in clinical studies.

          -  A female participant is eligible to participate if she is not pregnant or
             breastfeeding, and is not a woman of childbearing potential (WOCBP) OR is a WOCBP and
             using an acceptable contraceptive method.

          -  A WOCBP must have a negative highly sensitive pregnancy test (urine as required by
             local regulations) within 72 hours before the first dose of study intervention.

          -  If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum
             pregnancy test is required.

          -  The investigator is responsible for review of medical history, menstrual history, and
             recent sexual activity to decrease the risk for inclusion of a woman with an early
             undetected pregnancy.

          -  A consistent sleep-wake schedule that is not subject to any other unusual changes in
             sleeping routine (i.e., bedtimes and wake times do not vary more than 1-2 hours except
             on rare occasions).

          -  Able to maintain sleep for at least 4 consecutive hours based on self-report.

        Exclusion Criteria:

          -  Other than OSA, has evidence of another clinically significant, active pulmonary
             disorder such as bronchiectasis, emphysema, or asthma documented by history, physical
             examination, or chest x-ray.

          -  A history within the past 6 months prior to the pre-study visit or current evidence of
             an unstable or clinically significant cardiovascular disorder, including but not
             limited to: acute coronary syndrome, unstable angina, congestive heart failure,
             cardiogenic syncope, cardiomyopathy, any symptomatic arrhythmia, orthostatic
             hypotension, uncontrolled hypertension, chronic kidney disease, kidney transplant

          -  Abnormal pre-randomization laboratory values for alanine transaminase > 1.5 x the
             upper limit of normal (x ULN), aspartate transaminase > 1.5 x ULN, direct bilirubin >
             1.5 x ULN, serum creatinine of > 2 mg/dL

          -  A history or diagnosis of any of the following conditions, in the opinion of the
             investigator: narcolepsy (with or without cataplexy) or Idiopathic hypersomnia,
             circadian rhythm sleep disorder, parasomnia including nightmare disorder, sleep terror
             disorder, sleepwalking disorder, and rapid eye movement (REM) behavior disorder,
             periodic limb movement (PLM) disorder, restless legs syndrome, chronic insomnia

          -  A WOCBP who has a positive urine or serum pregnancy test within 24 hours before the
             baseline 1 of study intervention.

          -  A history of clinically significant or poorly-controlled endocrine, gastrointestinal,
             cardiovascular, hematological, hepatic, immunological, renal, respiratory,
             genitourinary, or major neurological (including stroke and chronic seizures)
             abnormalities or diseases.

          -  Mentally or legally incapacitated, or has significant emotional problems at the time
             of pre-study screening

          -  A history or current evidence of any condition, therapy, lab or ECG abnormality or
             other circumstances that might confound the results of the study, or interfere with
             the participant's participation for the full duration of the study.

          -  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.

          -  A history of significant multiple and/or severe allergies (e.g., food, drug, latex
             allergy), or has had an anaphylactic reaction or significant intolerability (i.e.,
             systemic allergic reaction) to prescription or non-prescription drugs or food.

          -  A history of anaphylaxis or cutaneous adverse drug reaction (with or without systemic
             symptoms) to sulfonamide antibiotics or other sulfonamide-containing drugs.

          -  Positive for hepatitis B surface antigen, hepatitis C antibodies or HIV.

          -  A history of cancer (malignancy) with some exceptions including adequately treated
             non-melanomatous skin carcinoma or carcinoma in situ of the cervix or; and other
             malignancies that have been successfully treated with appropriate follow up and
             therefore unlikely to recur for the duration of the study, in the opinion of the
             investigator and with agreement of the Sponsor (e.g., malignancies that have been
             successfully treated ≥ 10 years prior to the pre-study [screening] visit).

          -  An estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m^2 based on the
             Cockcroft-Gault (CG) Equation.