NCT01293006

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

Completed Phase 1 Results posted Last updated 21 September 2018

What this trial tests

Phase 1 trial testing suvorexant in Insomnia in 25 participants. Completed in 22 February 2012.

Timeline

25 March 2011

Primary endpoint
20 January 2012

22 February 2012

Quick facts

Lead sponsor	Merck Sharp & Dohme LLC
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	double
Primary purpose	treatment
Enrollment	25
Start date	25 March 2011
Primary completion	20 January 2012
Estimated completion	22 February 2012

Drugs / interventions tested

• suvorexant — full drug profile →
• Placebo

Conditions studied

• Insomnia — all drugs for Insomnia →

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

Adults 18 to 85, any sex, with Insomnia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Mean Arterial Oxygen Saturation (SaO2) During Total Sleep Time Primary · Day 4 of each period

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.

Group	Value	95% CI
Suvorexant (30 mg or 40 mg)	93.38	92.47 – 94.30
Placebo	92.99	92.06 – 93.92

Number of Participants With Adverse Events Primary · Up to 14 days after last dose

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.

Group	Value	95% CI
Suvorexant (40 mg)	6
Suvorexant (30 mg)	2
Placebo	5

Number of Participants Discontinued From Study Drug Due to an AE Primary · Up to 15 days

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.

Group	Value	95% CI
Suvorexant (40 mg)	0
Suvorexant (30 mg)	0
Placebo	0

Percentage of Total Sleep Time in Which SaO2 is Less Than 90%, 85% or 80% Secondary · Day 1 and Day 4 of each period

Evaluation of the percentage of the night in which SaO2 is less than 90%, less than 85% and less than 80% following multiple dose administration of suvorexant and placebo. Lower SaO2 values are associated with sleep impairment.

Day 1 (SaO2 is less than 90%) (n = 24, 24)

Group	Value	95% CI
Suvorexant (30 mg or 40 mg)	6.01	-1.48 – 13.49
Placebo	4.98	-2.51 – 12.46

Day 1 (SaO2 is less than 85%) (n = 24, 24)

Group	Value	95% CI
Suvorexant (30 mg or 40 mg)	0.32	-0.03 – 0.67
Placebo	0.11	-0.24 – 0.46

Day 1 (SaO2 is less than 80%) (n = 24, 24)

Group	Value	95% CI
Suvorexant (30 mg or 40 mg)	NA	NA – NA
Placebo	NA	NA – NA

Day 4 (SaO2 is less than 90%) (n = 24, 22)

Group	Value	95% CI
Suvorexant (30 mg or 40 mg)	7.45	0.01 – 14.89
Placebo	6.63	-1.05 – 14.31

Day 4 (SaO2 is less than 85%) (n = 24, 22)

Group	Value	95% CI
Suvorexant (30 mg or 40 mg)	0.32	0.06 – 0.58
Placebo	0.01	-0.26 – 0.28

Day 4 (SaO2 is less than 80%) (n = 24, 22)

Group	Value	95% CI
Suvorexant (30 mg or 40 mg)	NA	NA – NA
Placebo	NA	NA – NA

Mean Apnea/Hypopnea Index (AHI) Secondary · Day 1 and Day 4 of each period

Evaluation of the effect of multiple dose administration of suvorexant on AHI as measured by polysomnography. The AHI is an overall index of obstructive sleep apnea (OSA) severity. The AHI is calculated by dividing the number of apneas and hypopneas by the number of hours of sleep. AHI values are categorized as mild OSA = 5 to \<15/hr and moderate OSA = 15 to \<30/hr.

Day 1 (n = 24, 24)

Group	Value	95% CI
Suvorexant (30 mg or 40 mg)	6.64	4.63 – 8.66
Placebo	5.92	3.91 – 7.94

Day 4 (n = 24, 22)

Group	Value	95% CI
Suvorexant (30 mg or 40 mg)	8.27	5.71 – 10.84
Placebo	6.22	3.61 – 8.83

Mean Arterial SaO2 for Different Sleep Stages Secondary · Day 1 and Day 4 of each period

Comparison of the mean SaO2 during different sleep stages (REM, Non-REM, and awake) following multiple dose administration of suvorexant and placebo. Lower SaO2 values are associated with sleep impairment. Sleep stages were determined by polysomnography.

Day 1 - Mean SaO2 during REM (n = 24, 24)

Group	Value	95% CI
Suvorexant (30 mg or 40 mg)	93.06	92.12 – 94.00
Placebo	93.02	92.08 – 93.96

Day 1 - Mean SaO2 during Non-REM (n = 24, 24)

Group	Value	95% CI
Suvorexant (30 mg or 40 mg)	93.14	92.26 – 94.02
Placebo	93.27	92.39 – 94.15

Day 1 - Mean SaO2 during Wake (n = 24, 24)

Group	Value	95% CI
Suvorexant (30 mg or 40 mg)	94.15	93.42 – 94.89
Placebo	94.37	93.63 – 95.10

Day 4 - Mean SaO2 during REM (n = 24, 22)

Group	Value	95% CI
Suvorexant (30 mg or 40 mg)	93.21	92.23 – 94.19
Placebo	92.88	91.88 – 93.87

Day 4 - Mean SaO2 during Non-REM (n = 24, 22)

Group	Value	95% CI
Suvorexant (30 mg or 40 mg)	93.35	92.40 – 94.30
Placebo	93.09	92.13 – 94.05

Day 4 - Mean SaO2 during Wake (n = 24, 22)

Group	Value	95% CI
Suvorexant (30 mg or 40 mg)	94.31	93.54 – 95.08
Placebo	93.86	93.08 – 94.64

Mean Arterial SaO2 During Total Sleep Time Secondary · Day 1 of each period

Evaluation of the effect of multiple dose suvorexant on mean oxygen saturation (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.

Group	Value	95% CI
Suvorexant (40 mg or 30 mg)	93.14	92.28 – 94.00
Placebo	93.24	92.37 – 94.10

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 14 days after last dose. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Suvorexant (40 mg)

Serious: 0/20 (0%)

Deaths: —

Suvorexant (30 mg)

Serious: 0/5 (0%)

Deaths: —

Placebo

Serious: 0/25 (0%)

Deaths: —

Other adverse events (6 terms — click to expand)

Reaction	System	Suvorexant (40 mg)	Suvorexant (30 mg)	Placebo
Ventricular extrasystoles	Cardiac disorders	—	—	—
Headache	Nervous system disorders	—	—	—
Somnolence	Nervous system disorders	—	—	—
Atrioventricular block second degree	Cardiac disorders	—	—	—
Supraventricular tachycardia	Cardiac disorders	—	—	—
Muscle tightness	Musculoskeletal and connective tissue disorders	—	—	—

Data from ClinicalTrials.gov NCT01293006 adverse events section.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Effects of suvorexant, an orexin receptor antagonist, on breathing during sleep in patients with chronic obstructive pulmonary disease.
   Sun H, Palcza J, Rosenberg R, Kryger M, et al · · 2015 · cited 34× · PMID 25661282 · DOI 10.1016/j.rmed.2014.12.010