Short-term InsomniaPhase 2NCT02671760
Pilot Study of a Combination Drug Product for Treatment of Short-term Insomnia
A Phase 2 study testing SM-1 and Comparator in people with Short-term Insomnia, run by Sequential Medicine Ltd.
Trial summary
The purpose of this study is to evaluate the effect of a combination drug product containing diphenhydramine, zolpidem and lorazepam on total sleep time. Participants will be adults who sometimes have difficulty falling asleep or staying asleep, but who do not have chronic insomnia. Read more about this study
- Who is it for?
- Ages 25 to 64 years
- Conditions the study is for
- Short-term Insomnia
- What is being tested?
- SM-1 and Comparator
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 39 participants
- Where
- No sites listed yet
- Study dates
- Feb 2016to Jun 2016
- Phase
- Phase 2
- 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 25 to 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Body mass index (BMI) between 19 and 32 kg/m2, inclusive;
- Report occasional difficulty falling asleep or staying asleep;
- Report a regular, habitual bedtime between 21:00 and 24:00, routinely spend at least 7.5 and no more than 9.0 hours in bed each night and observe a bedtime that does not vary by more than 2 hours over the course of the week. Subjects will be required to complete at least 5 days of sleep information in a diary provided at the screening visit and returned to study personnel no later than 24 hours prior to check-in for the first overnight visit.
- Be in good general health as determined by a thorough medical history and physical examination including vital signs and clinical laboratory tests;
- Females of childbearing potential must be using an acceptable method of contraception, have a negative serum pregnancy test at screening and have a negative urine pregnancy test before randomization and prior to each Treatment Period. Acceptable methods of contraception include oral, intrauterine and injectable contraceptives or double barrier methods. After screening, subjects using oral contraceptives must agree to add a double barrier method until 30 days following the last dose of study medication. Female subjects relying on oral contraceptives must have been using them for at least one month prior to screening;
- Female subjects who have been surgically sterilized are eligible if they have a negative serum pregnancy test at screening and negative urine pregnancy test at check-in for Visits 2 and 3, or are post-menopausal as defined by the cessation of menses for a period of at least 2 years prior to screening or have had a complete hysterectomy;
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- Male subjects must use an acceptable method of contraception during the course of the study and for the 30 days following the last dose of study medication. Acceptable methods of contraception include:
- Abstinence
- A condom and one of the following:
- Vasectomy for more than 6 months. ii. Female partner who meets one of the following conditions:
- Uses a spermicidal gel or foam; or
- Has had a tubal ligation, hysterectomy or bilateral oophorectomy; or
- Is post-menopausal (menopause is defined as over the age of 60 years, or between 45 and 60 years being amenorrheic for at least 2 years with plasma follicle stimulating hormone (FSH) level > 30 UI/L); or
- Be able to read, understand, and provide written/dated informed consent before enrolling in the study and must be willing to comply with all study procedures;
- Be willing and able to be confined to the clinical research site for one night in each of 3 treatment periods as required by the protocol.
- Refrain from alcohol on PSG days;
- On the days of check-in for each of the study's two treatment periods, refrain from the use of alcohol and from napping, defined as any sleep episode occurring outside of the subject's main sleep episode of the day;
- Report a recent history of napping of no more than once per week.
- An Epworth Sleepiness Scale score ≤8 at screening.
Who cannot join
- Clinically significant, acute illness within 14 days prior to screening (Visit 1).
- Clinically significant, unstable medical illness;
- Evidence or history of clinically significant allergic (except for untreated, asymptomatic, seasonal allergies at time of dosing), hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic or neurological disease;
- History of cancer or diabetes;
- A supine blood pressure > 140/90 millimeters mercury (mm/Hg) at screening;
- Heart rate > 100 beats per minute (BPM) at screening;
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- Clinically significant psychiatric illness, including chronic psychiatric illness or the history or presence of any Axis I condition;
- History or presence of chronic pain;
- Lifetime history of seizure disorder or serious head injury;
- Clinically significant sleep disorder, including insomnia, sleep apnea, narcolepsy, parasomnia, restless leg syndrome or circadian rhythm disorder;
- Any condition that may affect drug absorption;
- Travel across more than three time zones, an expected change in sleep schedule or involvement in night shift work within one month prior to screening or during the study period;
- Any clinically significant abnormal finding on physical examination, vital signs or clinical laboratory tests, as determined by the Investigator;
- History of allergies, or known sensitivity, hypersensitivity, or adverse reaction to any drug similar to diphenhydramine, zolpidem or lorazepam;
- Pregnant or lactating females;
- Positive serum pregnancy test at Visit 1 or positive urine pregnancy test at check-in for Visit 2 or 3;
- Positive urine drug screen at the Visit 1;
- Recent history (≤ one year) of alcohol or drug abuse, or current evidence of substance dependence or abuse as defined by DSM-V criteria;
- Regular consumption of "large amounts" of xanthine-containing substances (i.e., more than 500 mg of caffeine per day or equivalent amounts of xanthine-containing substances);
- 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;
- Use of more than 10 products containing nicotine per day or routinely smokes during sleep period
- Discontinuation of smoking or participation in a smoking cessation program within 90 days of screening;
- Any use with the six months prior to screening of restricted concomitant medications including prescription hypnotics, antidepressants, anxiolytics, anticonvulsants or narcotics;
- Use of any prescription drug, OTC medication, grapefruit juice, herbal preparation or food supplement, excluding vitamins, acetaminophen or hormonal contraceptives within two weeks of randomization;
- Use of any investigational drug within 30 days prior to screening or any prior exposure to the study drugs diphenhydramine, zolpidem or lorazepam or other drugs of the same pharmaceutical classes;
- Positive alcohol breathalyzer test at the time of screening or prior to dosing at Visit 2, 3 or 4.
About this study
Official title: A Randomized, Double-Blind, Single-Dose Study to Assess the Pharmacodynamic Effects of SM-1 Versus Comparator and Placebo in a 5 Hour Phase Advance Model of Insomnia in Adults Who Suffer From Short-Term Insomnia
The purpose of this study is to evaluate the effect of a combination drug product containing diphenhydramine, zolpidem and lorazepam on total sleep time. Participants will be adults who sometimes have difficulty falling asleep or staying asleep, but who do not have chronic insomnia. The study involves 3 one-night stays in a sleep center in New York City.
Read the detailed description
The purpose of this study is to evaluate the effect of a combination drug product containing 50 mg diphenhydramine, 5 mg zolpidem and 0.5 mg lorazepam on total sleep time, and to determine the contribution of diphenhydramine to the combination, using a 5-hour Phase Advance model of sleep challenge. This is a 3-arm cross-over study; each participant will receive 3 single-dose treatments on consecutive visits. The 3 arms are: investigational combination product, placebo, and a 2-drug comparator containing the zolpidem and lorazepam components but not diphenhydramine. Participants will be adults who sometimes have difficulty falling asleep or staying asleep, but who are generally healthy and do not have chronic insomnia or sleep apnea.
A total of 39 subjects are being recruited. Subjects who qualify for participation will be asked to keep a sleep diary to document their sleep times leading up to and during the study, and will be asked to spend 7-8 hours in bed at a regular bedtime during the study. Qualifying participants also will not anticipate significant disruptions in their sleep schedules, for example by traveling across timezones or changing shifts at work, during the study. The study requires 3 one-night stays in a sleep center in New York City, for administration of the study treatments and EEG measurements. Qualifying subjects will anticipate being able to return to the sleep center, located in Manhattan, for a total of 4 visits, including initial screening and 3 treatment times.
During each sleep center visit, subjects will be given their study treatment and be put to bed 5 hours before their usual bedtime, and sleep time will be monitored for 8 hours. Each subject will receive all 3 treatments, although the sequence of the 3 treatments will be randomized. Both subjects and study personnel monitoring the subjects will be blinded to the identity of the treatment administered at each visit.
- Conditions
- Short-term Insomnia
- Being tested
- SM-1, Comparator, Placebo
- Keywords
- Short-term insomnia, difficulty sleeping, sedative, hypnotic
- Medical subject headings
- Parasomnias
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 zolpidem and 0.5 mg lorazepam
ComparatorDrug
2-drug combination comprised of 5 mg zolpidem and 0.5 mg lorazepam
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | SM-1 Receives: Drug: SM-1 |
| Comparator | Active comparator | 2-drug combination Receives: Drug: Comparator |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total Sleep Time
Measured: 8 hours
Secondary outcomes (6)
Latency to Persistent Sleep
Time it takes to fall asleep
Measured: 8 hours
Awakenings
Measured: 8 hours
Latency to REM Sleep Onset
Time required to achieve REM sleep
Measured: 8 hours
Adverse Events
Safety and tolerability assessed in terms of the incidence of AEs
Measured: 8 hours
Safety and Tolerability in Terms of Residual Sleepiness
Karolinska Sleepiness Scale. This is a 9-point scale with values ranging from 1 (extremely alert) to 9 (extremely sleepy). Lower scores indicate less residual sleepiness.
Measured: 8 hours
Safety and Tolerability in Terms of Residual Sleepiness
Digit Symbol Substitution Test. The test score is number of correct answers in 90 seconds. Higher scores indicate favorable response (i.e., less residual sleepiness). The duration of the challenge is the 90 second time limit; there is no theoretical maximum score to attain.
Measured: 8 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2016 (estimated)
- Study startFeb 2016
- Primary completionJun 2016
- Study completionJun 2016
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Short-term 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sequential Medicine Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Clinilabs, Inc.
- Responsible party
- Sponsor
- Investigators
- Thomas Dahl, PhD, Study director, Sequential Medicine LtdMaha Ahamad, MD, Principal investigator, Clinilabs, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02671760
- Sponsor's protocol ID
- SM-A-02
- Status last verified
- Jan 2018
- First submitted
- 20 Jan 2016
- Last updated
- 6 Mar 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Dahl T, Chen LB, Zammit G, Ahmad M, Roth T. Efficacy of SM-1 in a transient insomnia model. Hum Psychopharmacol. 2019 Nov;34(6):e2713. doi: 10.1002/hup.2713.
PubMed 31837050
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Single-Dose Study to Assess the Pharmacodynamic Effects of SM-1 Versus Comparator and Placebo in a 5 Hour Phase Advance Model of Insomnia in Adults Who Suffer From Short-Term Insomnia
- ClinicalTrials.gov ID
- NCT02671760
- Acronym / sponsor ID
- SM-A-02
- Conditions
- Short-term Insomnia
- Keywords
- Short-term insomnia, difficulty sleeping, sedative, hypnotic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- Sequential Medicine LtdIndustry (pharma, biotech, devices)
- Collaborators
- Clinilabs, Inc.
- Study start
- Feb 2016
- Primary completion
- Jun 2016 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 2 Feb 2016 (estimated)
- Results
- Posted 6 Mar 2018
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 evaluate the effect of a combination drug product containing diphenhydramine, zolpidem and lorazepam on total sleep time. Participants will be adults who sometimes have difficulty falling asleep or staying asleep, but who do not have chronic insomnia. The study involves 3 one-night stays in a sleep center in New York City.
Detailed description
The purpose of this study is to evaluate the effect of a combination drug product containing 50 mg diphenhydramine, 5 mg zolpidem and 0.5 mg lorazepam on total sleep time, and to determine the contribution of diphenhydramine to the combination, using a 5-hour Phase Advance model of sleep challenge. This is a 3-arm cross-over study; each participant will receive 3 single-dose treatments on consecutive visits. The 3 arms are: investigational combination product, placebo, and a 2-drug comparator containing the zolpidem and lorazepam components but not diphenhydramine. Participants will be adults who sometimes have difficulty falling asleep or staying asleep, but who are generally healthy and do not have chronic insomnia or sleep apnea.
A total of 39 subjects are being recruited. Subjects who qualify for participation will be asked to keep a sleep diary to document their sleep times leading up to and during the study, and will be asked to spend 7-8 hours in bed at a regular bedtime during the study. Qualifying participants also will not anticipate significant disruptions in their sleep schedules, for example by traveling across timezones or changing shifts at work, during the study. The study requires 3 one-night stays in a sleep center in New York City, for administration of the study treatments and EEG measurements. Qualifying subjects will anticipate being able to return to the sleep center, located in Manhattan, for a total of 4 visits, including initial screening and 3 treatment times.
During each sleep center visit, subjects will be given their study treatment and be put to bed 5 hours before their usual bedtime, and sleep time will be monitored for 8 hours. Each subject will receive all 3 treatments, although the sequence of the 3 treatments will be randomized. Both subjects and study personnel monitoring the subjects will be blinded to the identity of the treatment administered at each visit.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: SM-1SM-1 |
| Comparator | Active comparator | Drug: Comparator2-drug combination |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 25 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (19 listed)
- Body mass index (BMI) between 19 and 32 kg/m2, inclusive;
- Report occasional difficulty falling asleep or staying asleep;
- Report a regular, habitual bedtime between 21:00 and 24:00, routinely spend at least 7.5 and no more than 9.0 hours in bed each night and observe a bedtime that does not vary by more than 2 hours over the course of the week. Subjects will be required to complete at least 5 days of sleep information in a diary provided at the screening visit and returned to study personnel no later than 24 hours prior to check-in for the first overnight visit.
- Be in good general health as determined by a thorough medical history and physical examination including vital signs and clinical laboratory tests;
- Females of childbearing potential must be using an acceptable method of contraception, have a negative serum pregnancy test at screening and have a negative urine pregnancy test before randomization and prior to each Treatment Period. Acceptable methods of contraception include oral, intrauterine and injectable contraceptives or double barrier methods. After screening, subjects using oral contraceptives must agree to add a double barrier method until 30 days following the last dose of study medication. Female subjects relying on oral contraceptives must have been using them for at least one month prior to screening;
Key exclusion criteria (26 listed)
- Clinically significant, acute illness within 14 days prior to screening (Visit 1).
- Clinically significant, unstable medical illness;
- Evidence or history of clinically significant allergic (except for untreated, asymptomatic, seasonal allergies at time of dosing), hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic or neurological disease;
- History of cancer or diabetes;
- A supine blood pressure > 140/90 millimeters mercury (mm/Hg) at screening;
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 zolpidem and 0.5 mg lorazepam | Drug | Treatment |
| Comparator2-drug combination comprised of 5 mg zolpidem and 0.5 mg lorazepam | Drug | Comparator |
| PlaceboPlacebo | Drug | Placebo |
Primary outcome
Total Sleep Time
Time frame: 8 hours
6 secondary outcomes
Latency to Persistent Sleep
Time frame: 8 hours
Awakenings
Time frame: 8 hours
Latency to REM Sleep Onset
Time frame: 8 hours
Adverse Events
Time frame: 8 hours
Safety and Tolerability in Terms of Residual Sleepiness
Time frame: 8 hours
Safety and Tolerability in Terms of Residual Sleepiness
Time frame: 8 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31837050Dahl T, Chen LB, Zammit G, Ahmad M, Roth T. Efficacy of SM-1 in a transient insomnia model. Hum Psychopharmacol. 2019 Nov;34(6):e2713. doi: 10.1002/hup.2713.
- Individual participant dataSharing planned: No
Related trials for Short-term Insomnia
Not yet recruitingPhase 3
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Insomnia Disorder
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.
Thomas Dahl, PhD study director
Sequential Medicine Ltd
Maha Ahamad, MD principal investigator
Clinilabs, Inc.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing SM-1 and Comparator in people with Short-term Insomnia, run by Sequential Medicine Ltd.
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 19 inclusion and 26 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 6 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 6 Mar 2018). 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 (time frame: 8 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02671760, which also lists 1 linked publication.
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 6 Mar 2018.