Trial Outcomes & Findings for Effects of Suvorexant in Patients With Chronic Obstructive Pulmonary Disease (MK-4305-032) (NCT NCT01293006)

NCT ID: NCT01293006

Last Updated: 2018-09-21

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 25 participants
• Primary outcome timeframe: Day 4 of each period
• Results posted on: 2018-09-21

Participant Flow

Participant milestones

Measure	Suvorexant (40 mg) Then Placebo 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. 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.	Suvorexant (30 mg) Then Placebo During Period 1, 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.	Placebo Then Suvorexant (40 mg) During Period 1, 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.	Placebo Then Suvorexant (30 mg) During Period 1, 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 30-mg oral dose of suvorexant once daily for 4 consecutive days in the evening.
Period 1 STARTED	11	2	9	3
Period 1 COMPLETED	11	2	9	3
Period 1 NOT COMPLETED	0	0	0	0
Washout STARTED	11	2	9	3
Washout COMPLETED	11	2	9	3
Washout NOT COMPLETED	0	0	0	0
Period 2 STARTED	11	2	9	3
Period 2 COMPLETED	10	2	9	3
Period 2 NOT COMPLETED	1	0	0	0

Reasons for withdrawal

Measure	Suvorexant (40 mg) Then Placebo 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. 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.	Suvorexant (30 mg) Then Placebo During Period 1, 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.	Placebo Then Suvorexant (40 mg) During Period 1, 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.	Placebo Then Suvorexant (30 mg) During Period 1, 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 30-mg oral dose of suvorexant once daily for 4 consecutive days in the evening.
Period 2 Lost to Follow-up	1	0	0	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Suvorexant (40 mg) Then Placebo n=11 Participants 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. 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.	Suvorexant (30 mg) Then Placebo n=2 Participants During Period 1, participants ≥65 years of age were administered a 30-mg oral dose of MK-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.	Placebo Then Suvorexant (40 mg) n=9 Participants During Period 1, 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.	Placebo Then Suvorexant (30 mg) n=3 Participants During Period 1, 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 30-mg oral dose of suvorexant once daily for 4 consecutive days in the evening.	Total n=25 Participants Total of all reporting groups
Age, Continuous	54.9 years n=5 Participants	67.0 years n=7 Participants	56.7 years n=5 Participants	70.3 years n=4 Participants	58.2 years n=21 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	1 Participants n=4 Participants	16 Participants n=21 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants	2 Participants n=4 Participants	9 Participants n=21 Participants

PRIMARY outcome

Timeframe: Day 4 of each period

Population: Twenty-four of the 25 participants were included in the primary evaluation of SaO2 and AHI data; one participant was excluded due to a protocol violation. During the Placebo periods, there were 22 evaluable participants at Day 4; 2 participants had either no data or missing data.

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.

Outcome measures

Measure	Suvorexant (30 mg or 40 mg) n=24 Participants Participants administered either a 40-mg or a 30-mg oral dose of suvorexant.	Placebo n=22 Participants Participants administered placebo.	Placebo Participants administered placebo.
Mean Arterial Oxygen Saturation (SaO2) During Total Sleep Time	93.38 Percentage of Oxygen Saturation Interval 92.47 to 94.3	92.99 Percentage of Oxygen Saturation Interval 92.06 to 93.92	—

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

Measure	Suvorexant (30 mg or 40 mg) n=20 Participants Participants administered either a 40-mg or a 30-mg oral dose of suvorexant.	Placebo n=5 Participants Participants administered placebo.	Placebo n=25 Participants Participants administered placebo.
Number of Participants With Adverse Events	6 participants	2 participants	5 participants

PRIMARY outcome

Timeframe: Up to 15 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

Measure	Suvorexant (30 mg or 40 mg) n=20 Participants Participants administered either a 40-mg or a 30-mg oral dose of suvorexant.	Placebo n=5 Participants Participants administered placebo.	Placebo n=25 Participants Participants administered placebo.
Number of Participants Discontinued From Study Drug Due to an AE	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Day 1 and Day 4 of each period

Population: Twenty-four of the 25 participants were included in the primary evaluation of SaO2 and AHI data; one participant was excluded due to a protocol violation. During the Placebo periods, there were 22 evaluable participants at Day 4; 2 participants had either no data or missing data.

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.

Outcome measures

Measure	Suvorexant (30 mg or 40 mg) n=24 Participants Participants administered either a 40-mg or a 30-mg oral dose of suvorexant.	Placebo n=24 Participants Participants administered placebo.	Placebo Participants administered placebo.
Percentage of Total Sleep Time in Which SaO2 is Less Than 90%, 85% or 80% Day 1 (SaO2 is less than 90%) (n = 24, 24)	6.01 Percentage of Total Sleep Time Interval -1.48 to 13.49	4.98 Percentage of Total Sleep Time Interval -2.51 to 12.46	—
Percentage of Total Sleep Time in Which SaO2 is Less Than 90%, 85% or 80% Day 1 (SaO2 is less than 85%) (n = 24, 24)	0.32 Percentage of Total Sleep Time Interval -0.03 to 0.67	0.11 Percentage of Total Sleep Time Interval -0.24 to 0.46	—
Percentage of Total Sleep Time in Which SaO2 is Less Than 90%, 85% or 80% Day 1 (SaO2 is less than 80%) (n = 24, 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.	—
Percentage of Total Sleep Time in Which SaO2 is Less Than 90%, 85% or 80% Day 4 (SaO2 is less than 90%) (n = 24, 22)	7.45 Percentage of Total Sleep Time Interval 0.01 to 14.89	6.63 Percentage of Total Sleep Time Interval -1.05 to 14.31	—
Percentage of Total Sleep Time in Which SaO2 is Less Than 90%, 85% or 80% Day 4 (SaO2 is less than 85%) (n = 24, 22)	0.32 Percentage of Total Sleep Time Interval 0.06 to 0.58	0.01 Percentage of Total Sleep Time Interval -0.26 to 0.28	—
Percentage of Total Sleep Time in Which SaO2 is Less Than 90%, 85% or 80% Day 4 (SaO2 is less than 80%) (n = 24, 22)	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 of each period

Population: Twenty-four of the 25 participants were included in the primary evaluation of SaO2 and AHI data; one participant was excluded due to a protocol violation. During the Placebo periods, there were 22 evaluable participants at Day 4; 2 participants had either no data or missing data.

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

Measure	Suvorexant (30 mg or 40 mg) n=24 Participants Participants administered either a 40-mg or a 30-mg oral dose of suvorexant.	Placebo n=24 Participants Participants administered placebo.	Placebo Participants administered placebo.
Mean Apnea/Hypopnea Index (AHI) Day 1 (n = 24, 24)	6.64 Events per hour Interval 4.63 to 8.66	5.92 Events per hour Interval 3.91 to 7.94	—
Mean Apnea/Hypopnea Index (AHI) Day 4 (n = 24, 22)	8.27 Events per hour Interval 5.71 to 10.84	6.22 Events per hour Interval 3.61 to 8.83	—

SECONDARY outcome

Timeframe: Day 1 and Day 4 of each period

Population: Twenty-four of the 25 participants were included in the primary evaluation of SaO2 and AHI data; one participant was excluded due to a protocol violation. During the Placebo periods, there were 22 evaluable participants at Day 4; 2 participants had either no data or missing data.

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.

Outcome measures

Measure	Suvorexant (30 mg or 40 mg) n=24 Participants Participants administered either a 40-mg or a 30-mg oral dose of suvorexant.	Placebo n=24 Participants Participants administered placebo.	Placebo Participants administered placebo.
Mean Arterial SaO2 for Different Sleep Stages Day 1 - Mean SaO2 during REM (n = 24, 24)	93.06 Percentage of Oxygen Saturation Interval 92.12 to 94.0	93.02 Percentage of Oxygen Saturation Interval 92.08 to 93.96	—
Mean Arterial SaO2 for Different Sleep Stages Day 1 - Mean SaO2 during Non-REM (n = 24, 24)	93.14 Percentage of Oxygen Saturation Interval 92.26 to 94.02	93.27 Percentage of Oxygen Saturation Interval 92.39 to 94.15	—
Mean Arterial SaO2 for Different Sleep Stages Day 1 - Mean SaO2 during Wake (n = 24, 24)	94.15 Percentage of Oxygen Saturation Interval 93.42 to 94.89	94.37 Percentage of Oxygen Saturation Interval 93.63 to 95.1	—
Mean Arterial SaO2 for Different Sleep Stages Day 4 - Mean SaO2 during REM (n = 24, 22)	93.21 Percentage of Oxygen Saturation Interval 92.23 to 94.19	92.88 Percentage of Oxygen Saturation Interval 91.88 to 93.87	—
Mean Arterial SaO2 for Different Sleep Stages Day 4 - Mean SaO2 during Non-REM (n = 24, 22)	93.35 Percentage of Oxygen Saturation Interval 92.4 to 94.3	93.09 Percentage of Oxygen Saturation Interval 92.13 to 94.05	—
Mean Arterial SaO2 for Different Sleep Stages Day 4 - Mean SaO2 during Wake (n = 24, 22)	94.31 Percentage of Oxygen Saturation Interval 93.54 to 95.08	93.86 Percentage of Oxygen Saturation Interval 93.08 to 94.64	—

SECONDARY outcome

Timeframe: Day 1 of each period

Population: Twenty-four of the 25 participants were included in the primary evaluation of SaO2 and AHI data; one participant was excluded due to a protocol violation.

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.

Outcome measures

Measure	Suvorexant (30 mg or 40 mg) n=24 Participants Participants administered either a 40-mg or a 30-mg oral dose of suvorexant.	Placebo n=24 Participants Participants administered placebo.	Placebo Participants administered placebo.
Mean Arterial SaO2 During Total Sleep Time	93.14 Percentage of Oxygen Saturation Interval 92.28 to 94.0	93.24 Percentage of Oxygen Saturation Interval 92.37 to 94.1	—

Adverse Events

Suvorexant (40 mg)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Suvorexant (30 mg)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Suvorexant (40 mg) n=20 participants at risk Participants administered a 40-mg dose of suvorexant.	Suvorexant (30 mg) n=5 participants at risk Participants administered a 30-mg oral dose of suvorexant.	Placebo n=25 participants at risk Participants administered placebo.
Cardiac disorders Atrioventricular block second degree	0.00% 0/20 • Up to 14 days after last dose	20.0% 1/5 • Number of events 1 • Up to 14 days after last dose	0.00% 0/25 • Up to 14 days after last dose
Cardiac disorders Supraventricular tachycardia	0.00% 0/20 • Up to 14 days after last dose	20.0% 1/5 • Number of events 1 • Up to 14 days after last dose	0.00% 0/25 • Up to 14 days after last dose
Cardiac disorders Ventricular extrasystoles	0.00% 0/20 • Up to 14 days after last dose	0.00% 0/5 • Up to 14 days after last dose	8.0% 2/25 • Number of events 2 • Up to 14 days after last dose
Musculoskeletal and connective tissue disorders Muscle tightness	0.00% 0/20 • Up to 14 days after last dose	20.0% 1/5 • Number of events 1 • Up to 14 days after last dose	0.00% 0/25 • Up to 14 days after last dose
Nervous system disorders Headache	5.0% 1/20 • Number of events 1 • Up to 14 days after last dose	0.00% 0/5 • Up to 14 days after last dose	8.0% 2/25 • Number of events 2 • Up to 14 days after last dose
Nervous system disorders Somnolence	10.0% 2/20 • Number of events 2 • Up to 14 days after last dose	20.0% 1/5 • Number of events 2 • Up to 14 days after last dose	0.00% 0/25 • Up to 14 days after last dose

Additional Information

Vice President, Late Stage Development Group Leader

Merck Sharp & Dohme Corp

Phone: 1-800-672-6372

Email: ClinicalTrialsDisclosure@merck.com

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