Transient InsomniaPhase 3NCT03331042
SM-1 vs 2 Comparators and Placebo in Participants With a History of Transient Insomnia.
A Phase 3 study testing SM-1, D+Z and D+L in people with Transient Insomnia, run by Sequential Medicine Ltd at 2 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Transient Insomnia
- What is being tested?
- SM-1, D+Z and D+L
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 85 participants
- Where
- 2 sitesUnited States
- Study dates
- 9 Oct 2017to 22 Mar 2018
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed written consent form.
- Experienced at least 1 prior episode of transient insomnia meeting all of the following criteria: difficulty falling asleep or staying asleep; next day impairment or distress associated with the disturbed sleep; frequency of 1 to 7 nights per week; duration of less than 1 month or more than 1 month of intermittent episodes.
- Routinely spends 6.5 - 9.5 hours in bed each night, with bed time varying no more than 2 hours over a week. Potential participants will be required to complete a paper diary for a minimum of 7 days during the screening period, with at least 5 entries completed over the 7 days.
- Body Mass Index (BMI) between 19 and 32 kg/m2.
- Good general health, as determined by a thorough medical, sleep and psychiatric history review, brief physical examination including vital sign measurements, and an assessment of screening laboratory test results.
- Female subjects of childbearing potential must be using an acceptable method of contraception during the study and for the 30 days following the last dose of study drug, and must have a negative urine pregnancy test at every study visit. Female subjects of non-childbearing potential are not required to use contraception if they have been surgically sterilized or are post-menopausal as defined by the cessation of menses for a period of at least 2 years before screening.
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- Male subjects must use an acceptable method of contraception during the study and for the 30 days following the last dose of study drug.
- Willing and able to be confined to the study center for 1 night in each of 4 treatment periods, as required by the protocol.
- Refrains from the use of alcohol within 24 hours of check-in for each of 4 treatment periods involving an overnight stay at the study center.
- Refrains from napping (any sleep episode occurring outside subject's main sleep episode) on days of check-in for each of 4 treatment periods involving an overnight stay at the study center.
Who cannot join
- Females who are pregnant, breast-feeding, or planning a pregnancy during the study period.
- Clinically significant medical disorder or currently unstable medical condition that, in the opinion of the investigator, would confound the results of the study.
- Abnormal laboratory value at screening, judged clinically significant by the investigator.
- History or current evidence of severe hepatic (liver) impairment.
- Clinically significant psychiatric illness, or the history or presence of a major psychiatric illness in the past year.
- Clinically significant abnormal finding on physical examination, as determined by the investigator.
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- Lifetime history of seizure disorder (other than childhood febrile seizures) or serious head injury.
- History of chronic insomnia or other sleep disorders, such as sleep apnea, narcolepsy, parasomnia, restless leg syndrome, or circadian rhythm disorder.
- Air travel across more than 2 time zones, an expected change in sleep schedule, or involvement in night work or shift work within 1 month before screening or during the study period.
- Reports a recent history of napping of more than once per week.
- History of alcohol or substance use disorder within the year before screening, or current evidence of alcohol or substance use disorder.
- Self-report of a usual consumption of more than 14 units of alcohol per week. One unit of alcohol is equivalent to 12 ounces of beer, 4 ounces of wine, or 1 ounce of liquor.
- Regular consumption of more than 500 mg of caffeine per day.
- History of routinely smoking during sleep period.
- Discontinuation of smoking or participation in a smoking cessation program within 30 days of screening or plans to discontinue smoking during the study.
- Positive urine drug screen at screening.
- Positive alcohol breathalyzer test at any visit.
- History of allergy or known sensitivity, hypersensitivity, or adverse reaction to diphenhydramine, zolpidem, or lorazepam or other drugs of the same pharmaceutical classes.
- Use of any medication which affects sleep-wake function within 5 half-lives or 2 weeks, whichever is longer, before screening until study completion. This includes prescription, over-the-counter (OTC), and herbal (e.g. valerian root, melatonin) medications.
- Use of any investigational drug within 30 days or 5 half-lives, whichever is longer, before screening.
- Planned surgery (inpatient or outpatient) during the study period.
- Employee or family member of the investigator or study center personnel.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
NeuroTrials Research, Inc.
Atlanta, Georgia, 30342
Clinilabs, Inc.
New York, New York, 10019
About this study
Official title: A Randomized, Double-Blind, Single-Dose, 4-Way Crossover Study to Assess the Efficacy and Safety of SM-1 (50-mg Diphenhydramine, 5-mg Delayed-Release Zolpidem, and 0.5-mg Delayed-Release Lorazepam) Versus 2 Comparators (50-mg Diphenhydramine and 5-mg Delayed-Release Zolpidem; 50-mg Diphenhydramine and 0.5-mg Delayed-Release Lorazepam) and Placebo in a 5-Hour Phase Advance Model of Transient Insomnia.
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.
- Conditions
- Transient Insomnia
- Being tested
- SM-1, D+Z, D+L, Placebo
- Keywords
- Insomnia, Transient Insomnia, Sleep initiation and maintenance disorder
- Medical subject headings
- Sleep Initiation and Maintenance Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SM-1Drug
3-drug combination product containing 50-mg diphenhydramine, 5-mg delayed-release zolpidem and 0.5-mg delayed-release lorazepam.
D+ZDrug
2-drug combination comparator product containing 50-mg diphenhydramine and 5-mg delayed-release zolpidem.
D+LDrug
2-drug combination comparator product containing 50-mg diphenhydramine and 0.5-mg delayed-release lorazepam.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Sequence 1 | Experimental | SM-1 (Treatment Period 1), D+Z (Treatment Period 2), D+L (Treatment Period 3), Placebo (Treatment Period 4). Receives: Drug: SM-1; Drug: D+Z; Drug: D+L; Drug: Placebo |
| Sequence 2 | Experimental | D+Z (Treatment Period 1), D+L (Treatment Period 2), Placebo (Treatment Period 3), SM-1 (Treatment Period 4). Receives: Drug: SM-1; Drug: D+Z; Drug: D+L; Drug: Placebo |
| Sequence 3 | Experimental | D+L (Treatment Period 1), Placebo (Treatment Period 2), SM-1 (Treatment Period 3), D+Z (Treatment Period 4). Receives: Drug: SM-1; Drug: D+Z; Drug: D+L; Drug: Placebo |
| Sequence 4 | Experimental | Placebo (Treatment Period 1), SM-1 (Treatment Period 2), D+Z (Treatment Period 3), D+L (Treatment Period 4). Receives: Drug: SM-1; Drug: D+Z; Drug: D+L; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 8 hours
Secondary outcomes (9)
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.
Measured: 8 hours
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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: Up to Visit 5
Subjective Total Sleep Time (sTST)
Subject reported TST from Post-Sleep Questionnaire (PSQ).
Measured: 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).
Measured: Up to 22 days.
Subjective Number of Awakenings (sNAW)
Subject reported NAW from Post-Sleep Questionnaire (PSQ).
Measured: 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).
Measured: Up to 22 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2017
- Study start9 Oct 2017
- Primary completion20 Mar 2018
- Study completion22 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Transient InsomniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 85 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sequential Medicine Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03331042
- Sponsor's protocol ID
- SM-A-05
- Status last verified
- May 2019
- First submitted
- 29 Oct 2017
- Last updated
- 5 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Single-Dose, 4-Way Crossover Study to Assess the Efficacy and Safety of SM-1 (50-mg Diphenhydramine, 5-mg Delayed-Release Zolpidem, and 0.5-mg Delayed-Release Lorazepam) Versus 2 Comparators (50-mg Diphenhydramine and 5-mg Delayed-Release Zolpidem; 50-mg Diphenhydramine and 0.5-mg Delayed-Release Lorazepam) and Placebo in a 5-Hour Phase Advance Model of Transient Insomnia.
- ClinicalTrials.gov ID
- NCT03331042
- Acronym / sponsor ID
- SM-A-05
- Conditions
- Transient Insomnia
- Keywords
- Insomnia, Transient Insomnia, Sleep initiation and maintenance disorder
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 85 participants (actual)
- Lead sponsor
- Sequential Medicine LtdIndustry (pharma, biotech, devices)
- Study start
- 9 Oct 2017 (actual)
- Primary completion
- 20 Mar 2018 (actual)
- Study completion
- 22 Mar 2018 (actual)
- First posted
- 6 Nov 2017 (actual)
- Results
- Posted 5 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Sequence 1 | Experimental | Drug: SM-1, Drug: D+Z, Drug: D+L, Drug: PlaceboSM-1 (Treatment Period 1), D+Z (Treatment Period 2), D+L (Treatment Period 3), Placebo (Treatment Period 4). |
| Sequence 2 | Experimental | Drug: SM-1, Drug: D+Z, Drug: D+L, Drug: PlaceboD+Z (Treatment Period 1), D+L (Treatment Period 2), Placebo (Treatment Period 3), SM-1 (Treatment Period 4). |
| Sequence 3 | Experimental | Drug: SM-1, Drug: D+Z, Drug: D+L, Drug: PlaceboD+L (Treatment Period 1), Placebo (Treatment Period 2), SM-1 (Treatment Period 3), D+Z (Treatment Period 4). |
| Sequence 4 | Experimental | Drug: SM-1, Drug: D+Z, Drug: D+L, Drug: PlaceboPlacebo (Treatment Period 1), SM-1 (Treatment Period 2), D+Z (Treatment Period 3), D+L (Treatment Period 4). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Signed written consent form.
- Experienced at least 1 prior episode of transient insomnia meeting all of the following criteria: difficulty falling asleep or staying asleep; next day impairment or distress associated with the disturbed sleep; frequency of 1 to 7 nights per week; duration of less than 1 month or more than 1 month of intermittent episodes.
- Routinely spends 6.5 - 9.5 hours in bed each night, with bed time varying no more than 2 hours over a week. Potential participants will be required to complete a paper diary for a minimum of 7 days during the screening period, with at least 5 entries completed over the 7 days.
- Body Mass Index (BMI) between 19 and 32 kg/m2.
- Good general health, as determined by a thorough medical, sleep and psychiatric history review, brief physical examination including vital sign measurements, and an assessment of screening laboratory test results.
Key exclusion criteria (22 listed)
- Females who are pregnant, breast-feeding, or planning a pregnancy during the study period.
- Clinically significant medical disorder or currently unstable medical condition that, in the opinion of the investigator, would confound the results of the study.
- Abnormal laboratory value at screening, judged clinically significant by the investigator.
- History or current evidence of severe hepatic (liver) impairment.
- Clinically significant psychiatric illness, or the history or presence of a major psychiatric illness in the past year.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SM-13-drug combination product containing 50-mg diphenhydramine, 5-mg delayed-release zolpidem and 0.5-mg delayed-release lorazepam. | Drug | Sequence 1, Sequence 2, Sequence 3, Sequence 4 |
| D+Z2-drug combination comparator product containing 50-mg diphenhydramine and 5-mg delayed-release zolpidem. | Drug | Sequence 1, Sequence 2, Sequence 3, Sequence 4 |
| D+L2-drug combination comparator product containing 50-mg diphenhydramine and 0.5-mg delayed-release lorazepam. | Drug | Sequence 1, Sequence 2, Sequence 3, Sequence 4 |
| PlaceboIdentical 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. | Drug | Sequence 1, Sequence 2, Sequence 3, Sequence 4 |
Primary outcome
Total Sleep Time (TST)
Time frame: 8 hours
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)
9 secondary outcomes
Latency to Persistent Sleep (LPS)
Time frame: 8 hours
Number of Awakenings (NAW)
Time frame: 8 hours
Wakefulness After Sleep Onset (WASO)
Time frame: 8 hours
Karolinska Sleepiness Scale (KSS) of Morning Alertness.
Time frame: Up to Visit 5
Number Correct on Digit Symbol Substitution Test (DSST)
Time frame: Up to Visit 5
Subjective Total Sleep Time (sTST)
Time frame: Up to 22 days.
Subjective Sleep Onset Latency (sSOL)
Time frame: Up to 22 days.
Subjective Number of Awakenings (sNAW)
Time frame: Up to 22 days.
Number of Participants According to Sleep Quality
Time frame: Up to 22 days.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Transient Insomnia
Active, not recruiting
Sleep Restriction Therapy for Insomnia in Primary Health Care
Insomnia
Not yet recruitingPhase 2
SM-1 vs. an Active Comparator in A Model of Transient Insomnia
Transient Insomnia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing SM-1, D+Z and D+L in people with Transient Insomnia, run by Sequential Medicine Ltd at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total Sleep Time (TST) (time frame: 8 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2019.