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The purpose of this study is to investigate the effectiveness, safety and tolerability of a combination drug product (SM-1) containing diphenhydramine, zolpidem and lorazepam, in adult participants who sometimes have difficulty in falling asleep or staying asleep, but who do not have chronic insomnia. Participants will receive SM-1, or a combination of diphenhydramine and zolpidem, or a combination of diphenhydramine and lorazepam, or placebo during 4 one-night stays at a sleep center.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sequence 1 | Experimental | SM-1 (Treatment Period 1), D+Z (Treatment Period 2), D+L (Treatment Period 3), Placebo (Treatment Period 4). |
|
| Sequence 2 | Experimental | D+Z (Treatment Period 1), D+L (Treatment Period 2), Placebo (Treatment Period 3), SM-1 (Treatment Period 4). |
|
| Sequence 3 | Experimental | D+L (Treatment Period 1), Placebo (Treatment Period 2), SM-1 (Treatment Period 3), D+Z (Treatment Period 4). |
|
| Sequence 4 | Experimental | Placebo (Treatment Period 1), SM-1 (Treatment Period 2), D+Z (Treatment Period 3), D+L (Treatment Period 4). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SM-1 | Drug | 3-drug combination product containing 50-mg diphenhydramine, 5-mg delayed-release zolpidem and 0.5-mg delayed-release lorazepam. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Total Sleep Time (TST) | TST efficacy of SM-1 versus placebo, combination product diphenhydramine plus zolpidem and combination product diphenhydramine plus lorazepam measured by polysomnography (PSG)-defined total sleep time (TST) | 8 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Latency to Persistent Sleep (LPS) | Efficacy of SM-1 versus placebo, combination product diphenhydramine plus zolpidem and combination product diphenhydramine plus lorazepam measured by polysomnography (PSG)-measured sleep induction, the amount of time it takes the subject to fall asleep. | 8 hours |
| Number of Awakenings (NAW) |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Minutes of Sleep in Stages N1, N2, N3, Rapid Eye Movement (REM) and Latency to REM Onset. | Effect of SM-1 and the two 2-drug combination products (diphenhydramine plus zolpidem and diphenhydramine plus lorazepam) on sleep stage distribution. | 8 hours |
Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| NeuroTrials Research, Inc. | Atlanta | Georgia | 30342 | United States | ||
| Clinilabs, Inc. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Sequence 1 | SM-1 (Treatment Period 1), D+Z (Treatment Period 2), D+L (Treatment Period 3), Placebo (Treatment Period 4). SM-1: 3-drug combination product containing 50-mg diphenhydramine, 5-mg delayed-release zolpidem and 0.5-mg delayed-release lorazepam. D+Z: 2-drug combination comparator product containing 50-mg diphenhydramine and 5-mg delayed-release zolpidem. D+L: 2-drug combination comparator product containing 50-mg diphenhydramine and 0.5-mg delayed-release lorazepam. Placebo: Identical in appearance to SM-1, D+Z and D+L and has the same excipients, but no diphenhydramine, zolpidem, lorazepam or delayed-release coating materials. |
| FG001 | Sequence 2 | D+Z (Treatment Period 1), D+L (Treatment Period 2), Placebo (Treatment Period 3), SM-1 (Treatment Period 4). SM-1: 3-drug combination product containing 50-mg diphenhydramine, 5-mg delayed-release zolpidem and 0.5-mg delayed-release lorazepam. D+Z: 2-drug combination comparator product containing 50-mg diphenhydramine and 5-mg delayed-release zolpidem. D+L: 2-drug combination comparator product containing 50-mg diphenhydramine and 0.5-mg delayed-release lorazepam. Placebo: Identical in appearance to SM-1, D+Z and D+L and has the same excipients, but no diphenhydramine, zolpidem, lorazepam or delayed-release coating materials. |
| FG002 | Sequence 3 | D+L (Treatment Period 1), Placebo (Treatment Period 2), SM-1 (Treatment Period 3), D+Z (Treatment Period 4). SM-1: 3-drug combination product containing 50-mg diphenhydramine, 5-mg delayed-release zolpidem and 0.5-mg delayed-release lorazepam. D+Z: 2-drug combination comparator product containing 50-mg diphenhydramine and 5-mg delayed-release zolpidem. D+L: 2-drug combination comparator product containing 50-mg diphenhydramine and 0.5-mg delayed-release lorazepam. Placebo: Identical in appearance to SM-1, D+Z and D+L and has the same excipients, but no diphenhydramine, zolpidem, lorazepam or delayed-release coating materials. |
| FG003 | Sequence 4 | Placebo (Treatment Period 1), SM-1 (Treatment Period 2), D+Z (Treatment Period 3), D+L (Treatment Period 4). SM-1: 3-drug combination product containing 50-mg diphenhydramine, 5-mg delayed-release zolpidem and 0.5-mg delayed-release lorazepam. D+Z: 2-drug combination comparator product containing 50-mg diphenhydramine and 5-mg delayed-release zolpidem. D+L: 2-drug combination comparator product containing 50-mg diphenhydramine and 0.5-mg delayed-release lorazepam. Placebo: Identical in appearance to SM-1, D+Z and D+L and has the same excipients, but no diphenhydramine, zolpidem, lorazepam or delayed-release coating materials. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Subjects were randomized to one of four possible planned order of treatments (Sequences) given in the protocol.
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| ID | Title | Description |
|---|---|---|
| BG000 | Sequence 1 | SM-1 (Treatment Period 1), D+Z (Treatment Period 2), D+L (Treatment Period 3), Placebo (Treatment Period 4). SM-1: 3-drug combination product containing 50-mg diphenhydramine, 5-mg delayed-release zolpidem and 0.5-mg delayed-release lorazepam. D+Z: 2-drug combination comparator product containing 50-mg diphenhydramine and 5-mg delayed-release zolpidem. D+L: 2-drug combination comparator product containing 50-mg diphenhydramine and 0.5-mg delayed-release lorazepam. Placebo: Identical in appearance to SM-1, D+Z and D+L and has the same excipients, but no diphenhydramine, zolpidem, lorazepam or delayed-release coating materials. |
| Units | Counts |
|---|---|
| Participants |
|
| 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 | Total Sleep Time (TST) | TST efficacy of SM-1 versus placebo, combination product diphenhydramine plus zolpidem and combination product diphenhydramine plus lorazepam measured by polysomnography (PSG)-defined total sleep time (TST) | Full analysis set consisted of all subjects who were randomized to a treatment sequence, and had taken any study drug. | Posted | Mean | Standard Deviation | minutes | 8 hours |
|
From Day 1 until 7 days after the last 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 | SM-1 | Triple drug combination | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| nightmare | Nervous system disorders | nightmare | Systematic Assessment | Nightmare |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Thomas Dahl | Sequential Medicine Ltd | 617-818-2735 | tadahl@outlook.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 9, 2018 | Apr 16, 2019 | SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | Dec 12, 2017 | Apr 16, 2019 | Prot_001.pdf |
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| ID | Term |
|---|---|
| D007319 | Sleep Initiation and Maintenance Disorders |
| ID | Term |
|---|---|
| D020919 | Sleep Disorders, Intrinsic |
| D020920 | Dyssomnias |
| D012893 | Sleep Wake Disorders |
| D009422 | Nervous System Diseases |
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| D+Z | Drug | 2-drug combination comparator product containing 50-mg diphenhydramine and 5-mg delayed-release zolpidem. |
|
| D+L | Drug | 2-drug combination comparator product containing 50-mg diphenhydramine and 0.5-mg delayed-release lorazepam. |
|
| Placebo | Drug | Identical in appearance to SM-1, D+Z and D+L and has the same excipients, but no diphenhydramine, zolpidem, lorazepam or delayed-release coating materials. |
|
NAW efficacy of SM-1 versus placebo, combination product diphenhydramine plus zolpidem and combination product diphenhydramine plus lorazepam measured by polysomnography (PSG)-measured sleep maintenance. |
| 8 hours |
| Wakefulness After Sleep Onset (WASO) | WASO efficacy of SM-1 versus placebo, combination product diphenhydramine plus zolpidem and combination product diphenhydramine plus lorazepam measured by polysomnography (PSG)-measured sleep maintenance as the amount of time spent awake after falling asleep. | 8 hours |
| Karolinska Sleepiness Scale (KSS) of Morning Alertness. | Morning alertness measured by Karolinska Sleepiness Scale (KSS). KSS ranges from 1-9, with higher numbers indicating sleepier and lower numbers more alert. | Up to Visit 5 |
| Number Correct on Digit Symbol Substitution Test (DSST) | Morning alertness measured by DSST. The digit symbol substitution test assesses attention, psychomotor speed, complex scanning, visual tracking, and immediate memory. This test consists of 4 rows each with 25 small blank squares; above each square is a number between 1 and 9. At the top is a 'key,' which pairs each number (1 through 9) with an unfamiliar symbol. The participant has 90 seconds to work as quickly as possible (left to right across the rows) to fill in each blank square with the appropriate symbol based on the number above the square. Results are presented as total number correct; therefore, lower numbers indicate greater impairment. Scores on the DSST range from 0-93 | Up to Visit 5 |
| Subjective Total Sleep Time (sTST) | Subject reported TST from Post-Sleep Questionnaire (PSQ). | Up to 22 days. |
| Subjective Sleep Onset Latency (sSOL) | Subject reported SOL, the amount of time the subject felt it took to fall asleep, from Post-Sleep Questionnaire (PSQ). | Up to 22 days. |
| Subjective Number of Awakenings (sNAW) | Subject reported NAW from Post-Sleep Questionnaire (PSQ). | Up to 22 days. |
| Number of Participants According to Sleep Quality | Subject reported sleep quality, how well the subject felt he or she slept, from Post-Sleep Questionnaire (PSQ). | Up to 22 days. |
| New York |
| New York |
| 10019 |
| United States |
| Physician Decision |
|
| Lost to Follow-up |
|
| BG001 | Sequence 2 | D+Z (Treatment Period 1), D+L (Treatment Period 2), Placebo (Treatment Period 3), SM-1 (Treatment Period 4). SM-1: 3-drug combination product containing 50-mg diphenhydramine, 5-mg delayed-release zolpidem and 0.5-mg delayed-release lorazepam. D+Z: 2-drug combination comparator product containing 50-mg diphenhydramine and 5-mg delayed-release zolpidem. D+L: 2-drug combination comparator product containing 50-mg diphenhydramine and 0.5-mg delayed-release lorazepam. Placebo: Identical in appearance to SM-1, D+Z and D+L and has the same excipients, but no diphenhydramine, zolpidem, lorazepam or delayed-release coating materials. |
| BG002 | Sequence 3 | D+L (Treatment Period 1), Placebo (Treatment Period 2), SM-1 (Treatment Period 3), D+Z (Treatment Period 4). SM-1: 3-drug combination product containing 50-mg diphenhydramine, 5-mg delayed-release zolpidem and 0.5-mg delayed-release lorazepam. D+Z: 2-drug combination comparator product containing 50-mg diphenhydramine and 5-mg delayed-release zolpidem. D+L: 2-drug combination comparator product containing 50-mg diphenhydramine and 0.5-mg delayed-release lorazepam. Placebo: Identical in appearance to SM-1, D+Z and D+L and has the same excipients, but no diphenhydramine, zolpidem, lorazepam or delayed-release coating materials. |
| BG003 | Sequence 4 | Placebo (Treatment Period 1), SM-1 (Treatment Period 2), D+Z (Treatment Period 3), D+L (Treatment Period 4). SM-1: 3-drug combination product containing 50-mg diphenhydramine, 5-mg delayed-release zolpidem and 0.5-mg delayed-release lorazepam. D+Z: 2-drug combination comparator product containing 50-mg diphenhydramine and 5-mg delayed-release zolpidem. D+L: 2-drug combination comparator product containing 50-mg diphenhydramine and 0.5-mg delayed-release lorazepam. Placebo: Identical in appearance to SM-1, D+Z and D+L and has the same excipients, but no diphenhydramine, zolpidem, lorazepam or delayed-release coating materials. |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG002 | Diphenhydramine Plus Lorazepam | Subjects received a single dose of the 2-drug product containing Diphenhydramine plus Lorazepam; i.e., SM-1 without Zolpidem |
| OG003 | Placebo | Subjects received a single dose of a Placebo matching the appearance of the active treatments but containing no active drug components |
|
|
| Secondary | Latency to Persistent Sleep (LPS) | Efficacy of SM-1 versus placebo, combination product diphenhydramine plus zolpidem and combination product diphenhydramine plus lorazepam measured by polysomnography (PSG)-measured sleep induction, the amount of time it takes the subject to fall asleep. | Full analysis set consisted of all subjects who were randomized to a treatment sequence, and had taken any study drug. | Posted | Mean | Standard Deviation | minutes | 8 hours |
|
|
|
| Secondary | Number of Awakenings (NAW) | NAW efficacy of SM-1 versus placebo, combination product diphenhydramine plus zolpidem and combination product diphenhydramine plus lorazepam measured by polysomnography (PSG)-measured sleep maintenance. | Full analysis set consisted of all subjects who were randomized to a treatment sequence, and had taken any study drug. | Posted | Mean | Standard Deviation | awakenings | 8 hours |
|
|
|
| Secondary | Wakefulness After Sleep Onset (WASO) | WASO efficacy of SM-1 versus placebo, combination product diphenhydramine plus zolpidem and combination product diphenhydramine plus lorazepam measured by polysomnography (PSG)-measured sleep maintenance as the amount of time spent awake after falling asleep. | Full analysis set consisted of all subjects who were randomized to a treatment sequence, and had taken any study drug. | Posted | Mean | Standard Deviation | minutes | 8 hours |
|
|
|
| Secondary | Karolinska Sleepiness Scale (KSS) of Morning Alertness. | Morning alertness measured by Karolinska Sleepiness Scale (KSS). KSS ranges from 1-9, with higher numbers indicating sleepier and lower numbers more alert. | The Safety Population included all subjects that received any study drug, and were grouped by actual treatment. | Posted | Mean | Standard Deviation | units on a scale | Up to Visit 5 |
|
|
|
| Secondary | Number Correct on Digit Symbol Substitution Test (DSST) | Morning alertness measured by DSST. The digit symbol substitution test assesses attention, psychomotor speed, complex scanning, visual tracking, and immediate memory. This test consists of 4 rows each with 25 small blank squares; above each square is a number between 1 and 9. At the top is a 'key,' which pairs each number (1 through 9) with an unfamiliar symbol. The participant has 90 seconds to work as quickly as possible (left to right across the rows) to fill in each blank square with the appropriate symbol based on the number above the square. Results are presented as total number correct; therefore, lower numbers indicate greater impairment. Scores on the DSST range from 0-93 | Safety Population included all subjects that received any study drug, and were grouped by actual treatment. | Posted | Mean | Standard Deviation | number correct | Up to Visit 5 |
|
|
|
| Secondary | Subjective Total Sleep Time (sTST) | Subject reported TST from Post-Sleep Questionnaire (PSQ). | All subjects who were randomized to a treatment sequence, and had taken any study drug. | Posted | Mean | Standard Deviation | minutes | Up to 22 days. |
|
|
|
| Secondary | Subjective Sleep Onset Latency (sSOL) | Subject reported SOL, the amount of time the subject felt it took to fall asleep, from Post-Sleep Questionnaire (PSQ). | All subjects who were randomized to a treatment sequence, and had taken any study drug. | Posted | Mean | Standard Error | minutes | Up to 22 days. |
|
|
|
| Secondary | Subjective Number of Awakenings (sNAW) | Subject reported NAW from Post-Sleep Questionnaire (PSQ). | All subjects who were randomized to a treatment sequence, and had taken any study drug. | Posted | Mean | Standard Deviation | awakenings | Up to 22 days. |
|
|
|
| Secondary | Number of Participants According to Sleep Quality | Subject reported sleep quality, how well the subject felt he or she slept, from Post-Sleep Questionnaire (PSQ). | All subjects who were randomized to a treatment sequence, and had taken any study drug. | Posted | Count of Participants | Participants | Up to 22 days. |
|
|
|
| Other Pre-specified | Number of Minutes of Sleep in Stages N1, N2, N3, Rapid Eye Movement (REM) and Latency to REM Onset. | Effect of SM-1 and the two 2-drug combination products (diphenhydramine plus zolpidem and diphenhydramine plus lorazepam) on sleep stage distribution. | Not Posted | 8 hours | Participants |
| 84 |
| 0 |
| 84 |
| 3 |
| 84 |
| EG001 | Diphenhydramine Plus Zolpidem | Diphenhydramine plus Zolpidem | 0 | 83 | 0 | 83 | 2 | 83 |
| EG002 | Diphenhydramine Plus Lorazepam | Diphenhydramine plus Lorazepam | 0 | 83 | 0 | 83 | 1 | 83 |
| EG003 | Placebo | Placebo | 0 | 83 | 0 | 83 | 1 | 83 |
| somnolence | Nervous system disorders | somnolence | Systematic Assessment | somnolence |
|
| abdominal pain | Gastrointestinal disorders | abdominal pain | Systematic Assessment | upper abdominal pain |
|
| asthenia | General disorders | asthenia | Systematic Assessment | asthenia |
|
| fatigue | General disorders | fatigue | Systematic Assessment | fatigue |
|
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| D001523 |
| Mental Disorders |
| 2 = fair |
|
| 3 = good |
|
| 4 = excellent |
|