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The purpose of this randomized, double-blind, placebo-controlled, 5-period crossover study is to assess the effect of single oral doses of MK-1064 on latency to persistent sleep (LPS) as measured by polysomnography (PSG) in healthy young male participants, and to evaluate the safety and tolerability of single oral doses of MK-1064 and MK-6096 in healthy young male participants. The primary efficacy hypothesis is that at least one dose of MK-1064 is superior to placebo in decreasing LPS in healthy male participants as assessed by PSG.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sequence (MK-1064): 50 mg→250 mg→Placebo→120 mg | Experimental | For overall study population, 5 participants each were to be allocated to one of 4 sequences. In this sequence, participants received the following: 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. Participants completing the first 4 periods also were to receive the following: Period 5 - single dose of 20 mg MK-6096 or placebo, in an 18:2 ratio for overall study population, according to separate allocation. There was a minimum 7-day washout between doses. |
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| Sequence (MK-1064): Placebo→50 mg→120 mg→250 mg | Experimental | For overall study population, 5 participants each were to be allocated to one of 4 sequences. In this sequence, participants received the following: 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. Participants completing the first 4 periods also were to receive the following: Period 5 - single dose of 20 mg MK-6096 or placebo, in an 18:2 ratio for overall study population, according to separate allocation. There was a minimum 7-day washout between doses. |
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| Sequence (MK-1064): 120 mg→Placebo→250 mg→50 mg | Experimental | For overall study population, 5 participants each were to be allocated to one of 4 sequences. In this sequence, participants received the following: 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. Participants completing the first 4 periods also were to receive the following: Period 5 - single dose of 20 mg MK-6096 or placebo, in an 18:2 ratio for overall study population, according to separate allocation. There was a minimum 7-day washout between doses. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MK-1064 | Drug | Oral MK-1064 tablets (10 and 50 mg strengths) |
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| Measure | Description | Time Frame |
|---|---|---|
| Latency to Persistent Sleep (LPS) Following Single Doses of MK-1064 and Placebo | 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. | 1 to 9 hours post dose, within each treatment period |
| LPS Following Single Doses of MK-6096 and Placebo | 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. | 1 to 9 hours post dose, within each treatment period |
| Number of Participants With Adverse Events (AEs) | 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. | Up to 14 days after the last dose of study drug (Up to approximately 42 days) |
| Number of Participants Who Discontinued Study Due to an AE | 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. | Up to 14 days after the last dose of study drug (Up to approximately 42 days) |
| Measure | Description | Time Frame |
|---|---|---|
| Wake Time After Sleep Onset (WASO) Following Single Doses of MK-1064 and Placebo | 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. | 1 to 9 hours post dose, within each treatment period |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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| ID | Type | URL | Comment |
|---|---|---|---|
| CSR Synopsis | View IPD |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| FG002 | 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. |
| FG003 | 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. |
| FG004 | 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. |
| FG005 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 - MK-1064 or Placebo |
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| Washout After Period 1 |
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| Period 2 - MK-1064 or Placebo |
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| Washout After Period 2 |
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| Period 3 - MK-1064 or Placebo |
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| Washout After Period 3 |
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| Period 4 - MK-1064 or Placebo |
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| Washout After Period 4 |
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| Period 5 - MK-6096 or Placebo |
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| ID | Title | Description |
|---|---|---|
| BG000 | All Study Participants |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Latency to Persistent Sleep (LPS) Following Single Doses of MK-1064 and Placebo | 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. | 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 | Posted | Geometric Mean | 95% Confidence Interval | minutes | 1 to 9 hours post dose, within each treatment period |
|
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
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | MK-1064 50 mg | Single dose of 50 mg MK-1064 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Viral upper respiratory tract infection | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
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| ID | Term |
|---|---|
| C573816 | MK-6096 |
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| Sequence (MK-1064): 250 mg→120 mg→50 mg→Placebo | Experimental | For overall study population, 5 participants each were to be allocated to one of 4 sequences. In this sequence, participants received the following: 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. Participants completing the first 4 periods also were to receive the following: Period 5 - single dose of 20 mg MK-6096 or placebo, in an 18:2 ratio for overall study population, according to separate allocation. There was a minimum 7-day washout between doses. |
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| MK-6096 | Drug | Oral MK-6096 tablets (5 mg strength) |
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| Placebo | Drug | Oral placebo tablets (matching active MK-1064 tablets, matching active MK-6096 tablets) |
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| WASO Following Single Doses of MK-6096 and Placebo | 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. | 1 to 9 hours post dose, within each treatment period |
| Change From Baseline in Choice Reaction Time (CRT) Following Single Doses of MK-1064 and Placebo | 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. | Pre-dose and 10 hours post dose, within each treatment period |
| Change From Baseline in CRT Following Single Doses of MK-6096 and Placebo | 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. | Pre-dose and 10 hours post dose, within each treatment period |
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| Sex: Female, Male | Count of Participants | Participants |
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Single dose of 120 mg MK-1064
| OG002 | MK-1064 250 mg | Single dose of 250 mg MK-1064 |
| OG003 | Placebo | Single dose of placebo |
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| Primary | LPS Following Single Doses of MK-6096 and Placebo | 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. | 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) | Posted | Geometric Mean | 95% Confidence Interval | minutes | 1 to 9 hours post dose, within each treatment period |
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| Primary | Number of Participants With Adverse Events (AEs) | 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. | All Participants as Treated - all participants who received at least one dose of study drug. | Posted | Number | participants | Up to 14 days after the last dose of study drug (Up to approximately 42 days) |
|
|
|
| Primary | Number of Participants Who Discontinued Study Due to an AE | 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. | All Participants as Treated - all participants who received at least one dose of study drug. | Posted | Number | participants | Up to 14 days after the last dose of study drug (Up to approximately 42 days) |
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| Secondary | Wake Time After Sleep Onset (WASO) Following Single Doses of MK-1064 and Placebo | 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. | 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 | Posted | Geometric Mean | 95% Confidence Interval | minutes | 1 to 9 hours post dose, within each treatment period |
|
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| Secondary | WASO Following Single Doses of MK-6096 and Placebo | 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. | 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) | Posted | Geometric Mean | 95% Confidence Interval | minutes | 1 to 9 hours post dose, within each treatment period |
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| Secondary | Change From Baseline in Choice Reaction Time (CRT) Following Single Doses of MK-1064 and Placebo | 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. | 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 | Posted | Mean | 95% Confidence Interval | milliseconds | Pre-dose and 10 hours post dose, within each treatment period |
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| Secondary | Change From Baseline in CRT Following Single Doses of MK-6096 and Placebo | 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. | 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) | Posted | Mean | 95% Confidence Interval | milliseconds | Pre-dose and 10 hours post dose, within each treatment period |
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| 0 |
| 20 |
| 3 |
| 20 |
| EG001 | MK-1064 120 mg | Single dose of 120 mg MK-1064 | 0 | 20 | 2 | 20 |
| EG002 | MK-1064 250 mg | Single dose of 250 mg MK-1064 | 0 | 20 | 5 | 20 |
| EG003 | MK-6096 20 mg | Single dose of 20 mg MK-6096 | 0 | 14 | 3 | 14 |
| EG004 | Placebo | Single dose of placebo | 0 | 20 | 0 | 20 |
| Dizziness | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
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| Confusional state | Psychiatric disorders | MedDRA 13.0 | Systematic Assessment |
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| Nightmare | Psychiatric disorders | MedDRA 13.0 | Systematic Assessment |
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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.
| Analysis used a step-down approach. Mean log treatment difference of the highest MK-1064 dose versus placebo (MK-1064 - placebo) and 90% CI were computed and back-transformed to obtain the 90% CI interval for WASO treatment ratio. If the CI lies completely below 1, testing continued to next lower MK-1064 dose. The hypothesis that MK-1064 is superior to placebo in decreasing WASO was supported if the CI lies below 1 for at least one dose. | Geometric Mean Ratio | 0.68 | 2-Sided | 90 | 0.54 | 0.86 | Ratio is MK-1064/placebo | Superiority or Other |
| Analysis used a step-down approach. Mean log treatment difference of the highest MK-1064 dose versus placebo (MK-1064 - placebo) and 90% CI were computed and back-transformed to obtain the 90% CI interval for WASO treatment ratio. If the CI lies completely below 1, testing continued to next lower MK-1064 dose. The hypothesis that MK-1064 is superior to placebo in decreasing WASO was supported if the CI lies below 1 for at least one dose. | Geometric Mean Ratio | 0.75 | 2-Sided | 90 | 0.60 | 0.95 | Ratio is MK-1064/placebo | Superiority or Other |
| Change at 10 hours post dose |
|
| Analysis used a step-up approach. Mean treatment difference in change from baseline of the lowest MK-1064 dose versus placebo (MK-1064 - placebo) and 90% CI were computed. If the CI lies completely below 25 milliseconds, testing continued to the next higher MK-1064 dose. The hypothesis that at least one dose of MK-1064 does not produce psychomotor impairment versus placebo as assessed by CRT will be supported if the CI lies below 25 milliseconds for at least one dose. | Mean Difference (Final Values) | 5.28 | 2-Sided | 90 | -9.33 | 19.88 | Difference is MK-1064 - placebo | Superiority or Other |
| Analysis used a step-up approach. Mean treatment difference in change from baseline of the lowest MK-1064 dose versus placebo (MK-1064 - placebo) and 90% CI were computed. If the CI lies completely below 25 milliseconds, testing continued to the next higher MK-1064 dose. The hypothesis that at least one dose of MK-1064 does not produce psychomotor impairment versus placebo as assessed by CRT will be supported if the CI lies below 25 milliseconds for at least one dose. | Mean Difference (Final Values) | 6.38 | 2-Sided | 90 | -8.23 | 20.98 | Difference is MK-1064 - placebo | Superiority or Other |