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HealthyPhase 4NCT02353299

Assess the Effect of Zolpidem, Silenor & Placebo on Arousability, Ataxia/Balance & Cognition in Healthy Volunteers

A Phase 4 study testing Silenor 6 mg and zolpidem 10 mg in people with Healthy, run by Currax Pharmaceuticals at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a Phase IV, randomized, double-blind, placebo-controlled, four-arm crossover study. The study will assess the effects of a single dose of Silenor 6 mg compared with matching placebo and a single dose of zolpidem 10 mg compared to its matching placebo at the respective T-max in normal healthy adult male… Read more about this study

Who is it for?
Ages 21 to 50 years, men onlyHealthy volunteers can take part
Conditions the study is for
Healthy
What is being tested?
Silenor 6 mg and zolpidem 10 mg
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
52 participants
Where
1 siteUnited States
Study dates
Jan 2015to Mar 2016
Phase
Phase 4
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 21 to 50 years
  • Men only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Be in good general health as determined by the investigator;
  • Have a 3-month history of a normal nightly sleep pattern based on the subject's self report ;
  • A usual time in bed
  • A regular bedtime between 2200 and 2400 hours
  • No habitual daytime napping;
  • Epworth Sleepiness Scale score ≤ 10;
  • Be able to read, understand, and provide written/dated informed consent before enrolling in the study, and must be willing and able to comply with all study procedures;
  • Be able to follow verbal and written instructions provided in English

Who cannot join

  • Have a body mass index (BMI) >35 kg/m2
  • Have symptoms consistent with the diagnosis of any sleep disorder (e.g., insomnia, sleep apnea, narcolepsy, periodic leg movements, or restless leg syndrome);
  • On screening PSG AHI > 10 or PLMAI >10;
  • Have a known or suspected diagnosis of Acquired Immune Deficiency Syndrome (AIDS), or have tested seropositive for human immunodeficiency virus (HIV) antibody or antigen previously;
  • Have any clinically significant abnormal finding in physical examination, neurological assessment, vital signs, elevated body temperature, or clinical laboratory tests, as determined by the Investigator;
  • Have a known exaggerated pharmacological sensitivity, hypersensitivity, or history of a clinically significant adverse reaction to zolpidem;
Show all 18Show fewer
  • Have a known or exaggerated pharmacological sensitivity, hypersensitivity, or intolerance to doxepin HCl, any tricyclic antidepressant, or antihistamine;
  • Currently taking cimetidine or a monoamine oxidase inhibitor (MAOI);
  • Current diagnosis of severe urinary retention;
  • Current diagnosis of untreated glaucoma;
  • Intends to use any medication including over-the-counter (OTC) medications that would interfere with normal sleep architecture (such as systemic steroids, beta-adrenergic blockers, amphetamines, modafinil, etc.);
  • Self-reports use of products containing nicotine of greater than 15 cigarettes daily, or cannot avoid products containing nicotine during the normal sleep periods;
  • Self report consumption of more than five alcoholic beverages on any one day or greater than 14 alcoholic beverages weekly over the past week;
  • Have a history of epilepsy or serious head injury;
  • Used CYP450 2D6 inducers or inhibitors within 7 days before screening;
  • Have used prescribed or OTC medications within 30 days of screening (Day 0) or intend to use any prescription or OTC medication during the study that may interfere with the evaluation of the study drug.
  • Have used an investigational drug within 30 days or five half lives (whichever is longer) before screening, or plans to use an investigational drug during the study or have used doxepin or zolpidem previously.
  • Score of < 40 on the BBS at screening

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Henry Ford Hospital Sleep Disorders & Research Center

    Novi, Michigan, 48377

Other trials in United States

About this study

Official title: Phase IV 4 Way Crossover Study to Assess and Compare the Effect of a Single Nighttime Administration of Zolpidem, Silenor and Placebo on Arousability, Ataxia/Balance and Cognitive Performance in Healthy Volunteers.

This is a Phase IV, randomized, double-blind, placebo-controlled, four-arm crossover study. The study will assess the effects of a single dose of Silenor 6 mg compared with matching placebo and a single dose of zolpidem 10 mg compared to its matching placebo at the respective T-max in normal healthy adult male volunteers. The study will be conducted in approximately 52 male subjects

Read the detailed description

Subjects will be screened and asked to complete sleep disorders questionnaires and a sleep diary to establish normal sleep patterns and to rule out any sleep disorder.

Eligible subjects will be scheduled for a Screening PSG to rule out PLMS, sleep apnea and other sleep disorders.

Subjects who meet the screening PSG criteria will be randomly assigned to a treatment sequence order that involves both the study drug and the time subjects are awakened in the middle-of-the-night using a crossover study design. These four sequences include Silenor 6 mg with a middle-of-the-night awakening at 4 hours (DXP-4H), zolpidem 10 mg with a middle-of-the-night awakening at 1.5 hours (ZOL-1.5H), placebo with a middle-of-the-night awakening at 4 hours (PBO-4H), and placebo with a middle-of-the-night awakening at 1.5 hours (PBO-1.5H). Study drug will be administered under fasted conditions (at least 4 hours) as a single dose at bedtime (approximately 2300 hours), and each subject will receive one dose of each active drug (Silenor 6 mg and zolpidem 10 mg), and two doses of placebo during the treatment period.

Safety assessments will be performed throughout the study.

During the night of assessment, subjects will be awoken at the estimated T-max of the active drugs, with a matching placebo group awakened at each of these time points with the same arousability protocol. Arousability will be assessed using the Auditory Awakening Threshold test (AAT) .

Once the Auditory Awakening Threshold has been determined, subjects will perform a Tandem Walk assessment followed by the Berg Balance Scale (BBS) and finally by Free Recall Memory testing.

Subjects will be discharged from the sleep center once all assessments have been completed. A final study visit will be performed for subjects either after they have completed all four Treatment Periods or they have prematurely discontinued the study.

Conditions
Healthy
Being tested
Silenor 6 mg, zolpidem 10 mg, Placebo
Keywords
Cognition, Balance

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Silenor 6 mgDrug

    Also called doxepin

    Silenor 6 mg single nighttime dose.

  • zolpidem 10 mgDrug

    Also called zolpidem

    Zolpidem 10 mg single nighttime dose

  • PlaceboDrug

    placebo single nighttime dose-1.5 hours

  • PlaceboDrug

    placebo single nighttime dose-4 hours

Study groups in NCT02353299
Study groupRoleWhat they receive
Silenor 6 mg (DXP-4H)Active comparatorSilenor 6 mg single nightime dose- 4 hour post dose arousability and cognitive assessments
Receives: Drug: Silenor 6 mg; Drug: zolpidem 10 mg; Drug: Placebo
Placebo (PBO-4H)Placebo comparatorplacebo single nightime dose -4 hour post dose arousability and cognitive assessments
Receives: Drug: Silenor 6 mg; Drug: zolpidem 10 mg; Drug: Placebo
Zolpidem 10 mg (ZOL-1.5H)Active comparatorzolpidem 10 mg single nightime dose - 1.5 hour arousability and cognitive assessments
Receives: Drug: Silenor 6 mg; Drug: zolpidem 10 mg; Drug: Placebo
Placebo (PBO-1.5H)Placebo comparatorplacebo single nightime dose -1.5 hour arousability and cognitive assessments
Receives: Drug: Silenor 6 mg; Drug: zolpidem 10 mg; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Auditory Arousal Threshold (AAT) at T-max

    AAT will performed at T-max for Silenor and matching placebo at 4 hours post dose. Assessments performed at t max for zolpidem and placebo at 1.5 hours post dose.

    An acoustic stimulus (1000 Hz tone) was presented through audiometric earphones (E-A-RTone 3A Insert Earphones). Tones began at 30 dB and increased by 5 dB until the participant woke up or the maximum dB-level (110 dB) was reached.

    Measured: at either 1.5 or 4 hours post dose

Secondary outcomes (6)
  1. Tandem Walk Step-Offs

    Tandem walk will be performed at T-max for Silenor and matching placebo at 4 hours post dose and at 1.5 hours post dose for zolpidem 10 mg and matching placebo.

    Fall risk as impacted by balance was measured using the Tandem Walk Test (TWT), which assesses balance via a method of walking in which the toes of the back foot must touch the heel of the front foot at each step; this elicits postural control by reducing the base of support compared to normal walking. Endpoints were the number of step-offs from the beam.

    Measured: at either 1.5 or 4 hours post dose

  2. Tandem Walk Duration Over Five Trials

    Tandem walk will be performed at T-max for Silenor and matching placebo at 4 hours post dose and at 1.5 hours post dose for zolpidem 10 mg and matching placebo.

    Fall risk as impacted by balance was measured using the Tandem Walk Test (TWT), which assesses balance via a method of walking in which the toes of the back foot must touch the heel of the front foot at each step; this elicits postural control by reducing the base of support compared to normal walking. Endpoint: mean completion duration over five trials.

    Measured: at either 1.5 or 4 hours post dose

  3. Berg Balance Test

    Berg Balance will be performed at T-max for silenor and matching placebo at 4 hours post dose and at 1.5 hours post dose for zolpidem 10 mg and matching placebo.

    Fall risk as impacted by gait was measured using the Berg Balance Scale (BBS). The BBS is a widely used clinical test of static and dynamic balance abilities. Comprising of 14 simple balance-related tasks, ranging from standing up from a sitting position to standing on one foot, the BBS takes 15-20 minutes to complete. Each component task is scored on a Likert scale: 0 (unable to perform) to 4 (performed independently). The sum of component scores yields the final BBS score (0-20: high fall risk; 21-40: medium fall risk; 41-56: low fall risk).

    Measured: at either 1.5 or 4 hours post dose

  4. Immediate Free Recall Task

    Immediate Free Recall will be performed at T-max for silenor and matching placebo at 4 hours post dose and at 1.5 hours post dose for zolpidem 10 mg and matching placebo.

    Free Recall is a basic paradigm in the psychological study of memory. In this paradigm, participants were presented with a total of 16 words serially. They were informed prior to the task that memory for the presented words would be tested later in the session.

    Measured: directly after the encoding task

  5. Delayed Free Recall Task

    Delayed Free Recall Task was performed 15 minutes after final awakening the morning

    Free Recall is a basic paradigm in the psychological study of memory. In this paradigm, participants were presented with a total of 16 words serially. They were informed prior to the task that memory for the presented words would be tested later in the session. Participants were asked to recall as many words as they can 15 minutes after final awakening in the morning

    Measured: 15 minutes after final awakening the morning

  6. Number of Participants With Adverse Events

    Adverse events were defined by any negative event experienced by a participant during the study (assessed in the morning prior to participants leaving the lab) and included the washout period following each treatment.

    Measured: throughout the study until the final study visit, up to 6 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Feb 2015 (estimated)
  2. Study startJan 2015
  3. Primary completionJan 2016
  4. Study completionMar 2016

Resources

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 4
Primary purpose
Diagnosis
Allocation
Randomised
Intervention model
Crossover
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
52 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02353299
Sponsor's protocol ID
PT-D1402
Status last verified
Dec 2017
First submitted
23 Jan 2015
Last updated
2 Jan 2018
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Davis KL, Charey D, Cuyle JT, Nemeroff C. Neuropsychopharmacology, The Fifth Generation of Progress. 2002; Section 13: 1938-1939

  • Silenor [prescribing information]. Pernix Pharmaceuticals, Inc., San Diego, CA; March 2010.

  • Sanofi-Synthelabo. Ambien (zolpidem tartrate) complete prescribing information. 2002.

  • Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991 Dec;14(6):540-5. doi: 10.1093/sleep/14.6.540.

    PubMed 1798888
  • Rechtschaffen A, Kales A, eds. A Manual of Standardized Terminology, Techniques and Scoring System for Sleep Stages of Human Subjects. Los Angeles, Calif; Brain Information Service/Brain Research Institute, UCLA; 1968

  • Berg Balance Scale (BBS)

  • Mintzer MZ, Griffiths RR. Selective effects of zolpidem on human memory functions. J Psychopharmacol. 1999;13(1):18-31. doi: 10.1177/026988119901300103.

    PubMed 10221356
  • Gottlieb DJ, Yenokyan G, Newman AB, O'Connor GT, Punjabi NM, Quan SF, Redline S, Resnick HE, Tong EK, Diener-West M, Shahar E. Prospective study of obstructive sleep apnea and incident coronary heart disease and heart failure: the sleep heart health study. Circulation. 2010 Jul 27;122(4):352-60. doi: 10.1161/CIRCULATIONAHA.109.901801. Epub 2010 Jul 12.

    PubMed 20625114
  • Chung F, Yegneswaran B, Liao P, Chung SA, Vairavanathan S, Islam S, Khajehdehi A, Shapiro CM. STOP questionnaire: a tool to screen patients for obstructive sleep apnea. Anesthesiology. 2008 May;108(5):812-21. doi: 10.1097/ALN.0b013e31816d83e4.

    PubMed 18431116
  • Drake CL, Durrence H, Cheng P, Roth T, Pillai V, Peterson EL, Singh M, Tran KM. Arousability and Fall Risk During Forced Awakenings From Nocturnal Sleep Among Healthy Males Following Administration of Zolpidem 10 mg and Doxepin 6 mg: A Randomized, Placebo-Controlled, Four-Way Crossover Trial. Sleep. 2017 Jul 1;40(7). doi: 10.1093/sleep/zsx086.

    PubMed 28575467

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Silenor 6 mg and zolpidem 10 mg in people with Healthy, run by Currax Pharmaceuticals at 1 site 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 8 inclusion and 18 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 2 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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 7 Dec 2017). 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?

Auditory Arousal Threshold (AAT) at T-max (time frame: at either 1.5 or 4 hours post dose). 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 NCT02353299, which also lists 10 linked publications.

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 2 Jan 2018.

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