Effects of Suvorexant in Patients With Chronic Obstructive Pulmonary Disease (MK-4305-032)

NCT01293006 | Completed Phase 1 Results

• 1 other identifier: 4305-032
• Study Type: interventional
• Target: 25
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Insomnia

Keywords

Pulmonary Disease, Chronic Obstructive

Outcome Measures

Primary Outcomes (3)

• Mean Arterial Oxygen Saturation (SaO2) During Total Sleep Time

  Evaluation of the effect of multiple dose suvorexant (MK-4305) on SaO2 during total sleep time as measured by pulse oximetry. Lower SaO2 values are associated with sleep impairment. Total sleep time is the total of all rapid eye movement (REM) and non-REM sleep in a sleep episode.

  Day 4 of each period

• Number of Participants With Adverse Events

  An adverse event (AE) is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration whether or not considered related to the use of the product.

  Up to 14 days after last dose

• Number of Participants Discontinued From Study Drug Due to an AE

  An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration whether or not considered related to the use of the product.

  Up to 15 days

Secondary Outcomes (4)

• Percentage of Total Sleep Time in Which SaO2 is Less Than 90%, 85% or 80%

  Day 1 and Day 4 of each period

• Mean Apnea/Hypopnea Index (AHI)

  Day 1 and Day 4 of each period

• Mean Arterial SaO2 for Different Sleep Stages

  Day 1 and Day 4 of each period

• Mean Arterial SaO2 During Total Sleep Time

  Day 1 of each period

Study Arms (2)

Suvorexant first, then placebo

EXPERIMENTAL

During Period 1, participants \<65 years of age were administered a 40-mg oral dose of suvorexant once daily for 4 consecutive days in the evening and participants ≥65 years of age were administered a 30-mg oral dose of suvorexant once daily for 4 consecutive days in the evening. A washout period of at least 7 days followed Period 1. During Period 2, participants received one placebo tablet matching suvorexant, orally, once daily for 4 consecutive days in the evening.

Drug: suvorexant; Drug: Placebo

Placebo first, then suvorexant

EXPERIMENTAL

During Period 1, participants \<65 years of age received one placebo tablet matching suvorexant, orally, once daily for 4 consecutive days in the evening and participants ≥65 years of age received one placebo tablet matching suvorexant, orally, once daily for 4 consecutive days in the evening. A washout period of at least 7 days followed Period 1. During Period 2, participants were administered a 40-mg oral dose of suvorexant once daily for 4 consecutive days in the evening.

Drug: suvorexant; Drug: Placebo

Interventions

suvorexant DRUG

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

Also known as: MK-4305, SCH 900433

Placebo first, then suvorexant; Suvorexant first, then placebo

Placebo DRUG

one tablet matching suvorexant, orally, once daily, for 4 consecutive days

Placebo first, then suvorexant; Suvorexant first, then placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 25661282 RESULT

MeSH Terms

Conditions

Sleep Initiation and Maintenance Disorders; Pulmonary Disease, Chronic Obstructive

Interventions

suvorexant

Condition Hierarchy (Ancestors)

Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders; Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Vice President, Late Stage Development Group Leader
• Organization: Merck Sharp & Dohme Corp

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2011
• First Posted: February 10, 2011
• Study Start: March 25, 2011
• Primary Completion: January 20, 2012
• Study Completion: February 22, 2012
• Last Updated: September 21, 2018
• Results First Posted: September 10, 2014

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share