Trial Outcomes & Findings for A Study to Evaluate the Effects of Single Doses of MK-1064 and MK-6096 on Polysomnography (PSG) (MK-1064-003) (NCT NCT02549027)

NCT ID: NCT02549027

Last Updated: 2018-10-23

Results Overview

LPS is measured during overnight sleep laboratory (polysomnography \[PSG\]) assessment and is defined as the duration of time from the beginning of PSG assessment to the first interval of 10 consecutive minutes of sleep.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

20 participants

Primary outcome timeframe

1 to 9 hours post dose, within each treatment period

Results posted on

2018-10-23

Participant Flow

Participants were randomized to 1 of 4 treatment sequences of single doses of MK-1064 or placebo, administered over 4 study periods in a crossover design; then in Period 5 participants received, according to separate randomization, either a single dose of 20 mg MK-6096 or placebo, in an 18:2 ratio for overall study population.

Participant milestones

Participant milestones
Measure
MK-1064: 50 mg→250 mg→Placebo→120 mg (Period 1-4)
Period 1 - single dose of 50 mg MK-1064, Period 2 - single dose of 250 mg MK-1064, Period 3 - single dose of placebo, Period 4 - single dose of 120 mg MK-1064.
MK-1064: Placebo→50 mg→120 mg→250 mg (Period 1-4)
Period 1 - single dose of placebo, Period 2 - single dose of 50 mg MK-1064, Period 3 - single dose of 120 mg MK-1064, Period 4 - single dose of 250 mg MK-1064.
MK-1064: 120 mg→Placebo→250 mg→50 mg (Period 1-4)
Period 1 - single dose of 120 mg MK-1064, Period 2 - single dose of placebo, Period 3 - single dose of 250 mg MK-1064, Period 4 - single dose of 50 mg MK-1064.
MK-1064: 250 mg→120 mg→50 mg→Placebo (Period 1-4)
Period 1 - single dose of 250 mg MK-1064, Period 2 - single dose of 120 mg MK-1064, Period 3 - single dose of 50 mg MK-1064, Period 4 - single dose of placebo.
MK-6096 20 mg (Period 5)
Participants in this arm had completed the first 4 study periods, and were randomized to receive a single dose of 20 mg of MK-6096 in Period 5.
Placebo (Period 5)
Participants in this arm had completed the first 4 study periods, and were randomized to receive a single dose of placebo in Period 5.
Period 1 - MK-1064 or Placebo
STARTED
5
5
5
5
0
0
Period 1 - MK-1064 or Placebo
COMPLETED
5
5
5
5
0
0
Period 1 - MK-1064 or Placebo
NOT COMPLETED
0
0
0
0
0
0
Washout After Period 1
STARTED
5
5
5
5
0
0
Washout After Period 1
COMPLETED
5
5
5
5
0
0
Washout After Period 1
NOT COMPLETED
0
0
0
0
0
0
Period 2 - MK-1064 or Placebo
STARTED
5
5
5
5
0
0
Period 2 - MK-1064 or Placebo
COMPLETED
5
5
5
5
0
0
Period 2 - MK-1064 or Placebo
NOT COMPLETED
0
0
0
0
0
0
Washout After Period 2
STARTED
5
5
5
5
0
0
Washout After Period 2
COMPLETED
5
5
5
5
0
0
Washout After Period 2
NOT COMPLETED
0
0
0
0
0
0
Period 3 - MK-1064 or Placebo
STARTED
5
5
5
5
0
0
Period 3 - MK-1064 or Placebo
COMPLETED
5
5
5
5
0
0
Period 3 - MK-1064 or Placebo
NOT COMPLETED
0
0
0
0
0
0
Washout After Period 3
STARTED
5
5
5
5
0
0
Washout After Period 3
COMPLETED
5
5
5
5
0
0
Washout After Period 3
NOT COMPLETED
0
0
0
0
0
0
Period 4 - MK-1064 or Placebo
STARTED
5
5
5
5
0
0
Period 4 - MK-1064 or Placebo
COMPLETED
5
5
5
5
0
0
Period 4 - MK-1064 or Placebo
NOT COMPLETED
0
0
0
0
0
0
Washout After Period 4
STARTED
5
5
5
5
0
0
Washout After Period 4
COMPLETED
5
4
4
4
0
0
Washout After Period 4
NOT COMPLETED
0
1
1
1
0
0
Period 5 - MK-6096 or Placebo
STARTED
0
0
0
0
16
1
Period 5 - MK-6096 or Placebo
COMPLETED
0
0
0
0
14
1
Period 5 - MK-6096 or Placebo
NOT COMPLETED
0
0
0
0
2
0

Reasons for withdrawal

Reasons for withdrawal
Measure
MK-1064: 50 mg→250 mg→Placebo→120 mg (Period 1-4)
Period 1 - single dose of 50 mg MK-1064, Period 2 - single dose of 250 mg MK-1064, Period 3 - single dose of placebo, Period 4 - single dose of 120 mg MK-1064.
MK-1064: Placebo→50 mg→120 mg→250 mg (Period 1-4)
Period 1 - single dose of placebo, Period 2 - single dose of 50 mg MK-1064, Period 3 - single dose of 120 mg MK-1064, Period 4 - single dose of 250 mg MK-1064.
MK-1064: 120 mg→Placebo→250 mg→50 mg (Period 1-4)
Period 1 - single dose of 120 mg MK-1064, Period 2 - single dose of placebo, Period 3 - single dose of 250 mg MK-1064, Period 4 - single dose of 50 mg MK-1064.
MK-1064: 250 mg→120 mg→50 mg→Placebo (Period 1-4)
Period 1 - single dose of 250 mg MK-1064, Period 2 - single dose of 120 mg MK-1064, Period 3 - single dose of 50 mg MK-1064, Period 4 - single dose of placebo.
MK-6096 20 mg (Period 5)
Participants in this arm had completed the first 4 study periods, and were randomized to receive a single dose of 20 mg of MK-6096 in Period 5.
Placebo (Period 5)
Participants in this arm had completed the first 4 study periods, and were randomized to receive a single dose of placebo in Period 5.
Washout After Period 4
Withdrawal by Subject
0
1
1
1
0
0
Period 5 - MK-6096 or Placebo
Protocol Violation
0
0
0
0
2
0

Baseline Characteristics

A Study to Evaluate the Effects of Single Doses of MK-1064 and MK-6096 on Polysomnography (PSG) (MK-1064-003)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
All Study Participants
n=20 Participants
Age, Continuous
29.2 years
STANDARD_DEVIATION 4.60 • n=5 Participants
Sex: Female, Male
Female
0 Participants
n=5 Participants
Sex: Female, Male
Male
20 Participants
n=5 Participants

PRIMARY outcome

Timeframe: 1 to 9 hours post dose, within each treatment period

Population: Per-Protocol. Note: Data included are those obtained from subjects during administration of MK-1064 doses in Period 1-4 and during administration of placebo in Period 1-4

LPS is measured during overnight sleep laboratory (polysomnography \[PSG\]) assessment and is defined as the duration of time from the beginning of PSG assessment to the first interval of 10 consecutive minutes of sleep.

Outcome measures

Outcome measures
Measure
MK-1064 50 mg
n=20 Participants
Single dose of 50 mg MK-1064
MK-1064 120 mg
n=20 Participants
Single dose of 120 mg MK-1064
MK-1064 250 mg
n=20 Participants
Single dose of 250 mg MK-1064
Placebo
n=20 Participants
Single dose of placebo
Placebo
Single dose of placebo
Latency to Persistent Sleep (LPS) Following Single Doses of MK-1064 and Placebo
4.27 minutes
Interval 2.34 to 7.78
3.68 minutes
Interval 2.01 to 6.71
2.67 minutes
Interval 1.46 to 4.88
17.93 minutes
Interval 9.82 to 32.73

PRIMARY outcome

Timeframe: 1 to 9 hours post dose, within each treatment period

Population: Per-Protocol. Note: Data included are those obtained from subjects during MK-6096 dose in Period 5 and during administration of placebo in any period. 1 subject took placebo within Periods 1-4 and also in Period 5. Data for both administrations of placebo are included (i.e., for placebo, analysis includes 21 observations from 20 subjects)

LPS is measured during overnight sleep laboratory (PSG) assessment and is defined as the duration of time from the beginning of PSG assessment to the first interval of 10 consecutive minutes of sleep.

Outcome measures

Outcome measures
Measure
MK-1064 50 mg
n=14 Participants
Single dose of 50 mg MK-1064
MK-1064 120 mg
n=20 Participants
Single dose of 120 mg MK-1064
MK-1064 250 mg
Single dose of 250 mg MK-1064
Placebo
Single dose of placebo
Placebo
Single dose of placebo
LPS Following Single Doses of MK-6096 and Placebo
0.87 minutes
Interval 0.39 to 1.93
17.79 minutes
Interval 9.21 to 34.35

PRIMARY outcome

Timeframe: Up to 14 days after the last dose of study drug (Up to approximately 42 days)

Population: All Participants as Treated - all participants who received at least one dose of study drug.

An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the study drug, is also an AE.

Outcome measures

Outcome measures
Measure
MK-1064 50 mg
n=20 Participants
Single dose of 50 mg MK-1064
MK-1064 120 mg
n=20 Participants
Single dose of 120 mg MK-1064
MK-1064 250 mg
n=20 Participants
Single dose of 250 mg MK-1064
Placebo
n=14 Participants
Single dose of placebo
Placebo
n=20 Participants
Single dose of placebo
Number of Participants With Adverse Events (AEs)
4 participants
4 participants
7 participants
3 participants
3 participants

PRIMARY outcome

Timeframe: Up to 14 days after the last dose of study drug (Up to approximately 42 days)

Population: All Participants as Treated - all participants who received at least one dose of study drug.

An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the study drug, is also an AE.

Outcome measures

Outcome measures
Measure
MK-1064 50 mg
n=20 Participants
Single dose of 50 mg MK-1064
MK-1064 120 mg
n=20 Participants
Single dose of 120 mg MK-1064
MK-1064 250 mg
n=20 Participants
Single dose of 250 mg MK-1064
Placebo
n=14 Participants
Single dose of placebo
Placebo
n=20 Participants
Single dose of placebo
Number of Participants Who Discontinued Study Due to an AE
0 participants
0 participants
0 participants
0 participants
0 participants

SECONDARY outcome

Timeframe: 1 to 9 hours post dose, within each treatment period

Population: Per-Protocol. Note: Data included are those obtained from subjects during administration of MK-1064 doses in Period 1-4 and during administration of placebo in Period 1-4

WASO is measured during overnight sleep laboratory (PSG) assessment and is defined as the duration of wakefulness from the onset of persistent sleep (i.e., 10 consecutive minutes of sleep) to the end of PSG assessment the following morning.

Outcome measures

Outcome measures
Measure
MK-1064 50 mg
n=20 Participants
Single dose of 50 mg MK-1064
MK-1064 120 mg
n=20 Participants
Single dose of 120 mg MK-1064
MK-1064 250 mg
n=20 Participants
Single dose of 250 mg MK-1064
Placebo
n=20 Participants
Single dose of placebo
Placebo
Single dose of placebo
Wake Time After Sleep Onset (WASO) Following Single Doses of MK-1064 and Placebo
22.41 minutes
Interval 17.69 to 28.4
18.01 minutes
Interval 14.21 to 22.82
19.90 minutes
Interval 15.7 to 25.21
26.41 minutes
Interval 20.84 to 33.46

SECONDARY outcome

Timeframe: 1 to 9 hours post dose, within each treatment period

Population: Per-Protocol. Note: Data included are those obtained from subjects during MK-6096 dose in Period 5 and during administration of placebo in any period. 1 subject took placebo within Periods 1-4 and also in Period 5. Data for both administrations of placebo are included (i.e., for placebo, analysis includes 21 observations from 20 subjects)

WASO is measured during overnight sleep laboratory (PSG) assessment and is defined as the duration of wakefulness from the onset of persistent sleep (i.e., 10 consecutive minutes of sleep) to the end of PSG assessment the following morning.

Outcome measures

Outcome measures
Measure
MK-1064 50 mg
n=14 Participants
Single dose of 50 mg MK-1064
MK-1064 120 mg
n=20 Participants
Single dose of 120 mg MK-1064
MK-1064 250 mg
Single dose of 250 mg MK-1064
Placebo
Single dose of placebo
Placebo
Single dose of placebo
WASO Following Single Doses of MK-6096 and Placebo
16.65 minutes
Interval 12.91 to 21.48
26.41 minutes
Interval 21.17 to 32.95

SECONDARY outcome

Timeframe: Pre-dose and 10 hours post dose, within each treatment period

Population: Per-Protocol. Note: Data included are those obtained from subjects during administration of MK-1064 doses in Period 1-4 and during administration of placebo in Period 1-4

CRT assessment used in this study is a two-choice, computer-controlled test in which the participant responds to stimulus words presented on the screen of a laptop computer. During the test either the word "NO" or the word "YES" is presented on the screen and the participant is instructed to press the corresponding button as quickly as possible. There are 50 trials for which each stimulus word is chosen randomly with equal probability and there is a varying inter-stimulus interval. The mean reaction time of accurate responses is determined. The assessment is performed pre-dose and at 10 hours post dose. The outcome measure is change from baseline to post dose in reaction time.

Outcome measures

Outcome measures
Measure
MK-1064 50 mg
n=20 Participants
Single dose of 50 mg MK-1064
MK-1064 120 mg
n=20 Participants
Single dose of 120 mg MK-1064
MK-1064 250 mg
n=20 Participants
Single dose of 250 mg MK-1064
Placebo
n=20 Participants
Single dose of placebo
Placebo
Single dose of placebo
Change From Baseline in Choice Reaction Time (CRT) Following Single Doses of MK-1064 and Placebo
Baseline (Pre-dose)
408.79 milliseconds
Interval 390.94 to 426.64
423.39 milliseconds
Interval 400.05 to 446.72
418.83 milliseconds
Interval 399.44 to 438.22
414.85 milliseconds
Interval 392.9 to 436.79
Change From Baseline in Choice Reaction Time (CRT) Following Single Doses of MK-1064 and Placebo
Change at 10 hours post dose
17.25 milliseconds
Interval 4.41 to 30.1
19.94 milliseconds
Interval 7.1 to 32.78
21.04 milliseconds
Interval 8.2 to 33.88
14.66 milliseconds
Interval 1.82 to 27.5

SECONDARY outcome

Timeframe: Pre-dose and 10 hours post dose, within each treatment period

Population: Per-Protocol. Note: Data included are those obtained from subjects during MK-6096 dose in Period 5 and during administration of placebo in any period. 1 subject took placebo within Periods 1-4 and also in Period 5. Data for both administrations of placebo are included (i.e., for placebo, analysis includes 21 observations from 20 subjects)

CRT assessment used in this study is a two-choice, computer-controlled test in which the participant responds to stimulus words presented on the screen of a laptop computer. During the test either the word "NO" or the word "YES" is presented on the screen and the participant is instructed to press the corresponding button as quickly as possible. There are 50 trials for which each stimulus word is chosen randomly with equal probability and there is a varying inter-stimulus interval. The mean reaction time of accurate responses is determined. The assessment is performed pre-dose and at 10 hours post dose. The outcome measure is change from baseline to post dose in reaction time.

Outcome measures

Outcome measures
Measure
MK-1064 50 mg
n=14 Participants
Single dose of 50 mg MK-1064
MK-1064 120 mg
n=20 Participants
Single dose of 120 mg MK-1064
MK-1064 250 mg
Single dose of 250 mg MK-1064
Placebo
Single dose of placebo
Placebo
Single dose of placebo
Change From Baseline in CRT Following Single Doses of MK-6096 and Placebo
Baseline (Pre-dose)
425.94 milliseconds
Interval 391.76 to 460.12
417.81 milliseconds
Interval 396.11 to 439.51
Change From Baseline in CRT Following Single Doses of MK-6096 and Placebo
Change at 10 hours post dose
24.04 milliseconds
Interval 8.04 to 40.04
14.74 milliseconds
Interval 1.49 to 27.99

Adverse Events

MK-1064 50 mg

Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths

MK-1064 120 mg

Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths

MK-1064 250 mg

Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths

MK-6096 20 mg

Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths

Placebo

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
MK-1064 50 mg
n=20 participants at risk
Single dose of 50 mg MK-1064
MK-1064 120 mg
n=20 participants at risk
Single dose of 120 mg MK-1064
MK-1064 250 mg
n=20 participants at risk
Single dose of 250 mg MK-1064
MK-6096 20 mg
n=14 participants at risk
Single dose of 20 mg MK-6096
Placebo
n=20 participants at risk
Single dose of placebo
Infections and infestations
Viral upper respiratory tract infection
0.00%
0/20 • Up to 14 days after the last dose of study drug (Up to approximately 42 days)
Analysis population is All Participants as Treated, defined as all participants who received at least one dose of study drug
0.00%
0/20 • Up to 14 days after the last dose of study drug (Up to approximately 42 days)
Analysis population is All Participants as Treated, defined as all participants who received at least one dose of study drug
5.0%
1/20 • Number of events 1 • Up to 14 days after the last dose of study drug (Up to approximately 42 days)
Analysis population is All Participants as Treated, defined as all participants who received at least one dose of study drug
7.1%
1/14 • Number of events 1 • Up to 14 days after the last dose of study drug (Up to approximately 42 days)
Analysis population is All Participants as Treated, defined as all participants who received at least one dose of study drug
0.00%
0/20 • Up to 14 days after the last dose of study drug (Up to approximately 42 days)
Analysis population is All Participants as Treated, defined as all participants who received at least one dose of study drug
Nervous system disorders
Dizziness
5.0%
1/20 • Number of events 1 • Up to 14 days after the last dose of study drug (Up to approximately 42 days)
Analysis population is All Participants as Treated, defined as all participants who received at least one dose of study drug
0.00%
0/20 • Up to 14 days after the last dose of study drug (Up to approximately 42 days)
Analysis population is All Participants as Treated, defined as all participants who received at least one dose of study drug
5.0%
1/20 • Number of events 1 • Up to 14 days after the last dose of study drug (Up to approximately 42 days)
Analysis population is All Participants as Treated, defined as all participants who received at least one dose of study drug
7.1%
1/14 • Number of events 1 • Up to 14 days after the last dose of study drug (Up to approximately 42 days)
Analysis population is All Participants as Treated, defined as all participants who received at least one dose of study drug
0.00%
0/20 • Up to 14 days after the last dose of study drug (Up to approximately 42 days)
Analysis population is All Participants as Treated, defined as all participants who received at least one dose of study drug
Nervous system disorders
Headache
5.0%
1/20 • Number of events 1 • Up to 14 days after the last dose of study drug (Up to approximately 42 days)
Analysis population is All Participants as Treated, defined as all participants who received at least one dose of study drug
0.00%
0/20 • Up to 14 days after the last dose of study drug (Up to approximately 42 days)
Analysis population is All Participants as Treated, defined as all participants who received at least one dose of study drug
10.0%
2/20 • Number of events 2 • Up to 14 days after the last dose of study drug (Up to approximately 42 days)
Analysis population is All Participants as Treated, defined as all participants who received at least one dose of study drug
0.00%
0/14 • Up to 14 days after the last dose of study drug (Up to approximately 42 days)
Analysis population is All Participants as Treated, defined as all participants who received at least one dose of study drug
0.00%
0/20 • Up to 14 days after the last dose of study drug (Up to approximately 42 days)
Analysis population is All Participants as Treated, defined as all participants who received at least one dose of study drug
Psychiatric disorders
Confusional state
0.00%
0/20 • Up to 14 days after the last dose of study drug (Up to approximately 42 days)
Analysis population is All Participants as Treated, defined as all participants who received at least one dose of study drug
0.00%
0/20 • Up to 14 days after the last dose of study drug (Up to approximately 42 days)
Analysis population is All Participants as Treated, defined as all participants who received at least one dose of study drug
0.00%
0/20 • Up to 14 days after the last dose of study drug (Up to approximately 42 days)
Analysis population is All Participants as Treated, defined as all participants who received at least one dose of study drug
7.1%
1/14 • Number of events 1 • Up to 14 days after the last dose of study drug (Up to approximately 42 days)
Analysis population is All Participants as Treated, defined as all participants who received at least one dose of study drug
0.00%
0/20 • Up to 14 days after the last dose of study drug (Up to approximately 42 days)
Analysis population is All Participants as Treated, defined as all participants who received at least one dose of study drug
Psychiatric disorders
Nightmare
5.0%
1/20 • Number of events 1 • Up to 14 days after the last dose of study drug (Up to approximately 42 days)
Analysis population is All Participants as Treated, defined as all participants who received at least one dose of study drug
10.0%
2/20 • Number of events 2 • Up to 14 days after the last dose of study drug (Up to approximately 42 days)
Analysis population is All Participants as Treated, defined as all participants who received at least one dose of study drug
5.0%
1/20 • Number of events 1 • Up to 14 days after the last dose of study drug (Up to approximately 42 days)
Analysis population is All Participants as Treated, defined as all participants who received at least one dose of study drug
0.00%
0/14 • Up to 14 days after the last dose of study drug (Up to approximately 42 days)
Analysis population is All Participants as Treated, defined as all participants who received at least one dose of study drug
0.00%
0/20 • Up to 14 days after the last dose of study drug (Up to approximately 42 days)
Analysis population is All Participants as Treated, defined as all participants who received at least one dose of study drug

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

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. Sponsor review can be expedited to meet publication timelines.
  • Publication restrictions are in place

Restriction type: OTHER