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

NCT02353299 | Completed Phase 4 Results FDA Drug

• 1 other identifier: PT-D1402
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief 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 volunteers. The study will be conducted in approximately 52 male subjects

Conditions

Healthy

Keywords

Cognition; Balance

Outcome Measures

Primary Outcomes (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.

  at either 1.5 or 4 hours post dose

Secondary Outcomes (6)

• Tandem Walk Step-Offs

  at either 1.5 or 4 hours post dose

• Tandem Walk Duration Over Five Trials

  at either 1.5 or 4 hours post dose

• Berg Balance Test

  at either 1.5 or 4 hours post dose

• Immediate Free Recall Task

  directly after the encoding task

• Delayed Free Recall Task

  15 minutes after final awakening the morning

Study Arms (4)

Silenor 6 mg (DXP-4H)

ACTIVE COMPARATOR

Silenor 6 mg single nightime dose- 4 hour post dose arousability and cognitive assessments

Drug: Silenor 6 mg; Drug: zolpidem 10 mg; Drug: Placebo

Placebo (PBO-4H)

PLACEBO COMPARATOR

placebo single nightime dose -4 hour post dose arousability and cognitive assessments

Drug: Silenor 6 mg; Drug: zolpidem 10 mg; Drug: Placebo

Zolpidem 10 mg (ZOL-1.5H)

ACTIVE COMPARATOR

zolpidem 10 mg single nightime dose - 1.5 hour arousability and cognitive assessments

Drug: Silenor 6 mg; Drug: zolpidem 10 mg; Drug: Placebo

Placebo (PBO-1.5H)

PLACEBO COMPARATOR

placebo single nightime dose -1.5 hour arousability and cognitive assessments

Drug: Silenor 6 mg; Drug: zolpidem 10 mg; Drug: Placebo

Interventions

Silenor 6 mg DRUG

Silenor 6 mg single nighttime dose.

Also known as: doxepin

Placebo (PBO-1.5H); Placebo (PBO-4H); Silenor 6 mg (DXP-4H); Zolpidem 10 mg (ZOL-1.5H)

zolpidem 10 mg DRUG

Zolpidem 10 mg single nighttime dose

Also known as: zolpidem

Placebo (PBO-1.5H); Placebo (PBO-4H); Silenor 6 mg (DXP-4H); Zolpidem 10 mg (ZOL-1.5H)

Placebo DRUG

placebo single nighttime dose-1.5 hours

Placebo (PBO-1.5H); Placebo (PBO-4H); Silenor 6 mg (DXP-4H); Zolpidem 10 mg (ZOL-1.5H)

Eligibility Criteria

• Age: 21 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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;
• 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;

Sponsors & Collaborators

• Currax Pharmaceuticals: lead
• Henry Ford Hospital: collaborator

Study Sites (1)

Henry Ford Hospital Sleep Disorders & Research Center

Novi, Michigan, 48377, United States

Location

Related Publications (10)

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

  BACKGROUND

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

  BACKGROUND

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

  BACKGROUND

• 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.

  PMID: 1798888 BACKGROUND

• 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

  RESULT

• Berg Balance Scale (BBS)

  RESULT

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

  PMID: 10221356 RESULT

• 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.

  PMID: 20625114 RESULT

• 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.

  PMID: 18431116 RESULT

• 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.

  PMID: 28575467 DERIVED

MeSH Terms

Interventions

Doxepin; Zolpidem

Intervention Hierarchy (Ancestors)

Oxepins; Ethers, Cyclic; Ethers; Organic Chemicals; Dibenzoxepins; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Christopher L Drake
• Organization: Sleep Disorders and Research Center Henry Ford Hospital

cdrake1@hfhs.org

248-344-6672

Study Officials

• Chris Drake, PhD

  Henry Ford Hospital Sleep Disorder Research Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2015
• First Posted: February 2, 2015
• Study Start: January 1, 2015
• Primary Completion: January 1, 2016
• Study Completion: March 1, 2016
• Last Updated: January 2, 2018
• Results First Posted: December 7, 2017

Record last verified: 2017-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)