Trial Outcomes & Findings for Effects of Suvorexant in Participants With Obstructive Sleep Apnea (MK-4305-036) (NCT NCT01300455)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

26 participants

Primary outcome timeframe

Day 4

Results posted on

2018-09-21

Participant Flow

Participant milestones

Participant milestones
Measure	Suvorexant (40 mg) Then Placebo In Period 1, suvorexant (40 mg tablets) administered orally, once daily, for 4 consecutive days in the evening. Period 1 is followed by a washout period of a minimum of 5 days. Period 2 consists of placebo administered once daily for 4 consecutive days in the evening.	Placebo Then Suvorexant (40 mg) Period 1 consists of placebo administered once daily for 4 consecutive days in the evening. Period 1 is followed by a washout period of a minimum of 5 days. In Period 2, suvorexant (40 mg tablets) administered orally, once daily, for 4 consecutive days in the evening.
Period 1 STARTED	13	13
Period 1 COMPLETED	13	13
Period 1 NOT COMPLETED	0	0
Washout STARTED	13	13
Washout COMPLETED	12	13
Washout NOT COMPLETED	1	0
Period 2 STARTED	12	13
Period 2 COMPLETED	12	13
Period 2 NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Suvorexant (40 mg) Then Placebo In Period 1, suvorexant (40 mg tablets) administered orally, once daily, for 4 consecutive days in the evening. Period 1 is followed by a washout period of a minimum of 5 days. Period 2 consists of placebo administered once daily for 4 consecutive days in the evening.	Placebo Then Suvorexant (40 mg) Period 1 consists of placebo administered once daily for 4 consecutive days in the evening. Period 1 is followed by a washout period of a minimum of 5 days. In Period 2, suvorexant (40 mg tablets) administered orally, once daily, for 4 consecutive days in the evening.
Washout Withdrawal by Subject	1	0

Baseline Characteristics

Effects of Suvorexant in Participants With Obstructive Sleep Apnea (MK-4305-036)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Suvorexant (40 mg) Then Placebo n=13 Participants In Period 1, Suvorexant (40 mg tablets) administered orally, once daily, for 4 consecutive days in the evening. Period 1 is followed by a washout period of a minimum of 5 days. Period 2 consists of placebo administered once daily for 4 consecutive days in the evening.	Placebo Then Suvorexant (40 mg) n=13 Participants Period 1 consists of placebo administered once daily for 4 consecutive days in the evening. Period 1 is followed by a washout period of a minimum of 5 days. In Period 2, Suvorexant (40 mg tablets) administered orally, once daily, for 4 consecutive days in the evening.	Total n=26 Participants Total of all reporting groups
Age, Continuous	48 years n=5 Participants	50 years n=7 Participants	49 years n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	11 Participants n=7 Participants	19 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 4

Population: Twenty-five of 26 participants had Day 4 data; one participant did not receive placebo.

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.

Outcome measures

Outcome measures
Measure	Suvorexant (40 mg) n=26 Participants Participants administered a 40-mg dose of suvorexant.	Placebo n=25 Participants Participants administered placebo.
Mean Apnea-Hypopnea Index (AHI)	17.07 Events per hour Interval 13.3 to 20.84	14.41 Events per hour Interval 10.61 to 18.22

PRIMARY outcome

Timeframe: Up to 14 days after last dose

Population: All participants were included in the Safety Population.

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.

Outcome measures

Outcome measures
Measure	Suvorexant (40 mg) n=26 Participants Participants administered a 40-mg dose of suvorexant.	Placebo n=26 Participants Participants administered placebo.
Number of Participants With an Adverse Event	8 participants	4 participants

PRIMARY outcome

Timeframe: Up to 13 days

Population: All participants were included in the Safety Population.

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.

Outcome measures

Outcome measures
Measure	Suvorexant (40 mg) n=26 Participants Participants administered a 40-mg dose of suvorexant.	Placebo n=26 Participants Participants administered placebo.
Number of Participants Who Discontinued Study Drug Due to an AE	0 participants	0 participants

SECONDARY outcome

Timeframe: Day 1 and Day 4

Population: Twenty-four of 26 participants were included in the primary evaluation of Day 1 AHI/SaO2 data; 2 participants had no data due to either not receiving placebo or an equipment malfunction. Twenty-five of 26 participants had Day 4 data; one participant did not receive placebo.

Evaluation of the effect of multidose dose suvorexant on mean SaO2 during total sleep time as measured by pulse oximetry. Total sleep time is the total of all rapid eye movement (REM) and non-REM sleep in a sleep episode.

Outcome measures

Outcome measures
Measure	Suvorexant (40 mg) n=26 Participants Participants administered a 40-mg dose of suvorexant.	Placebo n=25 Participants Participants administered placebo.
Mean Arterial Oxygen Saturation (SaO2) During Total Sleep Time Day 1 (n = 26, 24)	94.12 Percentage of Oxygen Saturation Interval 93.48 to 94.75	94.15 Percentage of Oxygen Saturation Interval 93.5 to 94.8
Mean Arterial Oxygen Saturation (SaO2) During Total Sleep Time Day 4 (n = 26, 25)	94.15 Percentage of Oxygen Saturation Interval 93.53 to 94.78	94.21 Percentage of Oxygen Saturation Interval 93.59 to 94.84

SECONDARY outcome

Timeframe: Day 1 and Day 4

Population: Twenty-four of 26 participants were included in the primary evaluation of Day 1 AHI/SaO2 data; 2 participants had no data due to either not receiving placebo or an equipment malfunction. Twenty-five of 26 participants had Day 4 data; one participant did not receive placebo.

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. Total sleep time is the total of all REM and non-REM sleep in a sleep episode.

Outcome measures

Outcome measures
Measure	Suvorexant (40 mg) n=26 Participants Participants administered a 40-mg dose of suvorexant.	Placebo n=25 Participants Participants administered placebo.
Percentage of Total Sleep Time That Arterial SaO2 is Less Than 90%, 85%, and 80% Day 4 (SaO2 is less than 90%) (n = 26, 25)	2.16 Percentage of Total Sleep Time Interval 0.88 to 3.45	1.95 Percentage of Total Sleep Time Interval 0.66 to 3.25
Percentage of Total Sleep Time That Arterial SaO2 is Less Than 90%, 85%, and 80% Day 4 (SaO2 is less than 85%) (n = 26, 25)	0.69 Percentage of Total Sleep Time Interval 0.16 to 1.23	0.41 Percentage of Total Sleep Time Interval -0.13 to 0.95
Percentage of Total Sleep Time That Arterial SaO2 is Less Than 90%, 85%, and 80% Day 4 (SaO2 is less than 80%) (n = 26, 25)	NA Percentage of Total Sleep Time Due to the small number of participants experiencing SaO2 less than 80%, a formal statistical analysis was not conducted.	NA Percentage of Total Sleep Time Due to the small number of participants experiencing SaO2 less than 80%, a formal statistical analysis was not conducted.
Percentage of Total Sleep Time That Arterial SaO2 is Less Than 90%, 85%, and 80% Day 1 (SaO2 is less than 90%) (n = 26, 24)	3.31 Percentage of Total Sleep Time Interval 1.03 to 5.58	2.57 Percentage of Total Sleep Time Interval 0.22 to 4.92
Percentage of Total Sleep Time That Arterial SaO2 is Less Than 90%, 85%, and 80% Day 1 (SaO2 is less than 85%) (n = 26, 24)	0.48 Percentage of Total Sleep Time Interval 0.12 to 0.85	0.24 Percentage of Total Sleep Time Interval -0.14 to 0.61
Percentage of Total Sleep Time That Arterial SaO2 is Less Than 90%, 85%, and 80% Day 1 (SaO2 is less than 80%) (n = 26, 24)	NA Percentage of Total Sleep Time Due to the small number of participants experiencing SaO2 less than 80%, a formal statistical analysis was not conducted.	NA Percentage of Total Sleep Time Due to the small number of participants experiencing SaO2 less than 80%, a formal statistical analysis was not conducted.

SECONDARY outcome

Timeframe: Day 1 and Day 4

Population: Twenty-four of 26 participants were included in the primary evaluation of Day 1 AHI/SaO2 data; 2 participants had no data due to either not receiving placebo or an equipment malfunction. Twenty-five of 26 participants had Day 4 data; one participant did not receive placebo.

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

Outcome measures

Outcome measures
Measure	Suvorexant (40 mg) n=26 Participants Participants administered a 40-mg dose of suvorexant.	Placebo n=25 Participants Participants administered placebo.
Mean Arterial SaO2 for Different Sleep Stages Day 1 - Mean SaO2 During REM (n = 26, 24)	94.08 Percentage of Oxygen Saturation Interval 93.34 to 94.82	94.14 Percentage of Oxygen Saturation Interval 93.38 to 94.9
Mean Arterial SaO2 for Different Sleep Stages Day 1 - Mean SaO2 during Non-REM (n = 26, 24)	94.12 Percentage of Oxygen Saturation Interval 93.47 to 94.76	94.07 Percentage of Oxygen Saturation Interval 93.41 to 94.73
Mean Arterial SaO2 for Different Sleep Stages Day 1 - Mean SaO2 during Wake (n = 26, 24)	94.42 Percentage of Oxygen Saturation Interval 93.74 to 95.11	94.94 Percentage of Oxygen Saturation Interval 94.23 to 95.65
Mean Arterial SaO2 for Different Sleep Stages Day 4 - Mean SaO2 During REM (n = 26, 25)	93.96 Percentage of Oxygen Saturation Interval 93.17 to 94.76	93.83 Percentage of Oxygen Saturation Interval 93.03 to 94.63
Mean Arterial SaO2 for Different Sleep Stages Day 4 - Mean SaO2 during Non-REM (n = 26, 25)	94.27 Percentage of Oxygen Saturation Interval 93.64 to 94.9	94.25 Percentage of Oxygen Saturation Interval 93.62 to 94.89
Mean Arterial SaO2 for Different Sleep Stages Day 4 - Mean SaO2 during Wake (n = 26, 25)	94.73 Percentage of Oxygen Saturation Interval 94.11 to 95.36	94.91 Percentage of Oxygen Saturation Interval 94.28 to 95.54

SECONDARY outcome

Timeframe: Day 1

Population: Twenty-four of 26 participants were included in the primary evaluation of Day 1 AHI/SaO2 data; 2 participants had no data due to either not receiving placebo or an equipment malfunction.

Evaluation of the effect of multiple dose administration of suvorexant on AHI as measured by polysomnography. The AHI is an overall index of 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.

Outcome measures

Outcome measures
Measure	Suvorexant (40 mg) n=26 Participants Participants administered a 40-mg dose of suvorexant.	Placebo n=24 Participants Participants administered placebo.
Mean AHI	16.25 Events per hour Interval 12.65 to 19.86	16.72 Events per hour Interval 13.02 to 20.42

Adverse Events

Suvorexant (40 mg)

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Suvorexant (40 mg) n=26 participants at risk Participants administered a 40-mg dose of suvorexant.	Placebo n=26 participants at risk Participants administered placebo.
Gastrointestinal disorders Nausea	0.00% 0/26 • Up to 14 days after last dose	7.7% 2/26 • Up to 14 days after last dose
Nervous system disorders Somnolence	19.2% 5/26 • Up to 14 days after last dose	0.00% 0/26 • Up to 14 days after last dose

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the sponsor as confidential must be deleted prior to submission.
Publication restrictions are in place

Restriction type: OTHER