Trial Outcomes & Findings for Assess the Effect of Zolpidem, Silenor & Placebo on Arousability, Ataxia/Balance & Cognition in Healthy Volunteers (NCT NCT02353299)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

52 participants

Primary outcome timeframe

at either 1.5 or 4 hours post dose

Results posted on

2018-01-02

Participant Flow

Participant milestones

Participant milestones
Measure	PBO-4H Then PBO-1.5H Then DXP-4H Then ZOL-1.5H Period 1: Doxepin-matching placebo-single nighttime dose Period 2: Zolpidem-matching placebo-single nighttime dose Period 3: Doxepin 6mg-single nighttime dose Period 4: Zolpidem 10 mg-single nighttime dose	PBO-1.5H Then ZOL-1.5H Then PBO-4H Then DXP-4H Period 1: Zolpidem-matching placebo-single nighttime dose Period 2: Zolpidem 10 mg-single nighttime dose Period 3: Doxepin-matching placebo-single nighttime dose Period 4: Doxepin 6mg-single nighttime dose	ZOL-1.5H Then DXP-4H Then PBO-1.5H Then PBO-4H Period 1: Zolpidem 10mg-single nighttime dose Period 2: Doxepin 6mg-single nighttime dose Period 3: Zolpidem-matching placebo-single nighttime dose Period 4: Doxepin-matching placebo-single nighttime dose	DXP-4H Then PBO-4H Then ZOL-1.5H Then PBO-1.5H Period 1: Doxepin 6mg-single nighttime dose Period 2: Doxepin-matching placebo-single nighttime dose Period 3: Zolpidem 10mg-single nighttime dose Period 4: Zolpidem-matching placebo-single nighttime dose
First Intervention (1 Night) STARTED	13	13	13	13
First Intervention (1 Night) COMPLETED	13	13	13	13
First Intervention (1 Night) NOT COMPLETED	0	0	0	0
Second Intervention (1 Night) STARTED	13	13	13	13
Second Intervention (1 Night) COMPLETED	13	13	13	13
Second Intervention (1 Night) NOT COMPLETED	0	0	0	0
Third Intervention (1 Night) STARTED	13	13	13	13
Third Intervention (1 Night) COMPLETED	13	13	13	13
Third Intervention (1 Night) NOT COMPLETED	0	0	0	0
Fourth Intervention (1 Night) STARTED	13	12	13	13
Fourth Intervention (1 Night) COMPLETED	13	12	13	13
Fourth Intervention (1 Night) NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Study Participants n=52 Participants A single group of subjects were recruited and assigned all study treatments in random order
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	52 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex/Gender, Customized male	52 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants
Race (NIH/OMB) White	30 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	14 Participants n=5 Participants
Region of Enrollment United States	52 participants n=5 Participants

PRIMARY outcome

Timeframe: at either 1.5 or 4 hours post dose

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.

Outcome measures

Outcome measures
Measure	Placebo (PBO-4H) n=52 Participants placebo single nightime dose -4 hour post dose arousability and cognitive assessments Silenor 6 mg: Silenor 6 mg single nighttime dose.	Zolpidem 10 mg (ZOL-1.5H) n=52 Participants zolpidem 10 mg single nightime dose - 1.5 hour arousability and cognitive assessments zolpidem 10 mg: Zolpidem 10 mg single nighttime dose	Placebo (PBO-1.5H) n=52 Participants placebo single nightime dose -1.5 hour arousability and cognitive assessments zolpidem 10 mg: Zolpidem 10 mg single nighttime dose	Silenor 6 mg (DXP-4H) n=51 Participants Silenor 6 mg single nightime dose- 4 hour post dose arousability and cognitive assessments Silenor 6 mg: Silenor 6 mg single nighttime dose. zolpidem 10 mg: Zolpidem 10 mg single nighttime dose Placebo: placebo single nighttime dose-1.5 hours Placebo: placebo single nighttime dose-4 hours
Auditory Arousal Threshold (AAT) at T-max	78.0 Decibels (dB) Standard Deviation 18.6	103.2 Decibels (dB) Standard Deviation 11.8	84.7 Decibels (dB) Standard Deviation 17.1	85.2 Decibels (dB) Standard Deviation 11.8

SECONDARY outcome

Timeframe: at either 1.5 or 4 hours post dose

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.

Outcome measures

Outcome measures
Measure	Placebo (PBO-4H) n=51 Participants placebo single nightime dose -4 hour post dose arousability and cognitive assessments Silenor 6 mg: Silenor 6 mg single nighttime dose.	Zolpidem 10 mg (ZOL-1.5H) n=52 Participants zolpidem 10 mg single nightime dose - 1.5 hour arousability and cognitive assessments zolpidem 10 mg: Zolpidem 10 mg single nighttime dose	Placebo (PBO-1.5H) n=52 Participants placebo single nightime dose -1.5 hour arousability and cognitive assessments zolpidem 10 mg: Zolpidem 10 mg single nighttime dose	Silenor 6 mg (DXP-4H) n=52 Participants Silenor 6 mg single nightime dose- 4 hour post dose arousability and cognitive assessments Silenor 6 mg: Silenor 6 mg single nighttime dose. zolpidem 10 mg: Zolpidem 10 mg single nighttime dose Placebo: placebo single nighttime dose-1.5 hours Placebo: placebo single nighttime dose-4 hours
Tandem Walk Step-Offs	1.5 number of step offs Standard Deviation 2.4	8.1 number of step offs Standard Deviation 8.0	1.0 number of step offs Standard Deviation 1.3	0.9 number of step offs Standard Deviation 1.4

SECONDARY outcome

Timeframe: at either 1.5 or 4 hours post dose

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.

Outcome measures

Outcome measures
Measure	Placebo (PBO-4H) n=51 Participants placebo single nightime dose -4 hour post dose arousability and cognitive assessments Silenor 6 mg: Silenor 6 mg single nighttime dose.	Zolpidem 10 mg (ZOL-1.5H) n=52 Participants zolpidem 10 mg single nightime dose - 1.5 hour arousability and cognitive assessments zolpidem 10 mg: Zolpidem 10 mg single nighttime dose	Placebo (PBO-1.5H) n=52 Participants placebo single nightime dose -1.5 hour arousability and cognitive assessments zolpidem 10 mg: Zolpidem 10 mg single nighttime dose	Silenor 6 mg (DXP-4H) n=52 Participants Silenor 6 mg single nightime dose- 4 hour post dose arousability and cognitive assessments Silenor 6 mg: Silenor 6 mg single nighttime dose. zolpidem 10 mg: Zolpidem 10 mg single nighttime dose Placebo: placebo single nighttime dose-1.5 hours Placebo: placebo single nighttime dose-4 hours
Tandem Walk Duration Over Five Trials	4.97 Seconds Standard Deviation 1.57	6.69 Seconds Standard Deviation 2.60	4.83 Seconds Standard Deviation 1.60	4.82 Seconds Standard Deviation 1.68

SECONDARY outcome

Timeframe: at either 1.5 or 4 hours post dose

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).

Outcome measures

Outcome measures
Measure	Placebo (PBO-4H) n=52 Participants placebo single nightime dose -4 hour post dose arousability and cognitive assessments Silenor 6 mg: Silenor 6 mg single nighttime dose.	Zolpidem 10 mg (ZOL-1.5H) n=52 Participants zolpidem 10 mg single nightime dose - 1.5 hour arousability and cognitive assessments zolpidem 10 mg: Zolpidem 10 mg single nighttime dose	Placebo (PBO-1.5H) n=52 Participants placebo single nightime dose -1.5 hour arousability and cognitive assessments zolpidem 10 mg: Zolpidem 10 mg single nighttime dose	Silenor 6 mg (DXP-4H) n=51 Participants Silenor 6 mg single nightime dose- 4 hour post dose arousability and cognitive assessments Silenor 6 mg: Silenor 6 mg single nighttime dose. zolpidem 10 mg: Zolpidem 10 mg single nighttime dose Placebo: placebo single nighttime dose-1.5 hours Placebo: placebo single nighttime dose-4 hours
Berg Balance Test	55.1 sum of component scores Standard Deviation 1.4	51.4 sum of component scores Standard Deviation 4.3	55.1 sum of component scores Standard Deviation 1.4	54.5 sum of component scores Standard Deviation 1.9

SECONDARY outcome

Timeframe: directly after the encoding 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.

Outcome measures

Outcome measures
Measure	Placebo (PBO-4H) n=52 Participants placebo single nightime dose -4 hour post dose arousability and cognitive assessments Silenor 6 mg: Silenor 6 mg single nighttime dose.	Zolpidem 10 mg (ZOL-1.5H) n=52 Participants zolpidem 10 mg single nightime dose - 1.5 hour arousability and cognitive assessments zolpidem 10 mg: Zolpidem 10 mg single nighttime dose	Placebo (PBO-1.5H) n=52 Participants placebo single nightime dose -1.5 hour arousability and cognitive assessments zolpidem 10 mg: Zolpidem 10 mg single nighttime dose	Silenor 6 mg (DXP-4H) n=51 Participants Silenor 6 mg single nightime dose- 4 hour post dose arousability and cognitive assessments Silenor 6 mg: Silenor 6 mg single nighttime dose. zolpidem 10 mg: Zolpidem 10 mg single nighttime dose Placebo: placebo single nighttime dose-1.5 hours Placebo: placebo single nighttime dose-4 hours
Immediate Free Recall Task	8.14 Number of words Standard Deviation 2.99	4.78 Number of words Standard Deviation 3.42	7.71 Number of words Standard Deviation 3.12	7.86 Number of words Standard Deviation 3.20

SECONDARY outcome

Timeframe: 15 minutes after final awakening the morning

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

Outcome measures

Outcome measures
Measure	Placebo (PBO-4H) n=52 Participants placebo single nightime dose -4 hour post dose arousability and cognitive assessments Silenor 6 mg: Silenor 6 mg single nighttime dose.	Zolpidem 10 mg (ZOL-1.5H) n=52 Participants zolpidem 10 mg single nightime dose - 1.5 hour arousability and cognitive assessments zolpidem 10 mg: Zolpidem 10 mg single nighttime dose	Placebo (PBO-1.5H) n=52 Participants placebo single nightime dose -1.5 hour arousability and cognitive assessments zolpidem 10 mg: Zolpidem 10 mg single nighttime dose	Silenor 6 mg (DXP-4H) n=51 Participants Silenor 6 mg single nightime dose- 4 hour post dose arousability and cognitive assessments Silenor 6 mg: Silenor 6 mg single nighttime dose. zolpidem 10 mg: Zolpidem 10 mg single nighttime dose Placebo: placebo single nighttime dose-1.5 hours Placebo: placebo single nighttime dose-4 hours
Delayed Free Recall Task	7.02 Number of words Standard Deviation 3.59	2.24 Number of words Standard Deviation 2.77	6.51 Number of words Standard Deviation 3.48	6.78 Number of words Standard Deviation 3.68

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Placebo (PBO-4H) n=52 Participants placebo single nightime dose -4 hour post dose arousability and cognitive assessments Silenor 6 mg: Silenor 6 mg single nighttime dose.	Zolpidem 10 mg (ZOL-1.5H) n=52 Participants zolpidem 10 mg single nightime dose - 1.5 hour arousability and cognitive assessments zolpidem 10 mg: Zolpidem 10 mg single nighttime dose	Placebo (PBO-1.5H) n=52 Participants placebo single nightime dose -1.5 hour arousability and cognitive assessments zolpidem 10 mg: Zolpidem 10 mg single nighttime dose	Silenor 6 mg (DXP-4H) n=51 Participants Silenor 6 mg single nightime dose- 4 hour post dose arousability and cognitive assessments Silenor 6 mg: Silenor 6 mg single nighttime dose. zolpidem 10 mg: Zolpidem 10 mg single nighttime dose Placebo: placebo single nighttime dose-1.5 hours Placebo: placebo single nighttime dose-4 hours
Number of Participants With Adverse Events	11 Participants	12 Participants	10 Participants	13 Participants

Adverse Events

Silenor 6 mg (DXP-4H)

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Placebo (PBO-4H)

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Zolpidem 10 mg (ZOL-1.5H)

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Placebo (PBO-1.5H)

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Silenor 6 mg (DXP-4H) n=51 participants at risk Silenor 6 mg single nightime dose- 4 hour post dose arousability and cognitive assessments Silenor 6 mg: Silenor 6 mg single nighttime dose.	Placebo (PBO-4H) n=52 participants at risk placebo single nightime dose -4 hour post dose arousability and cognitive assessments Silenor 6 mg: Silenor 6 mg single nighttime dose.	Zolpidem 10 mg (ZOL-1.5H) n=52 participants at risk zolpidem 10 mg single nightime dose - 1.5 hour arousability and cognitive assessments zolpidem 10 mg: Zolpidem 10 mg single nighttime dose	Placebo (PBO-1.5H) n=52 participants at risk placebo single nightime dose -1.5 hour arousability and cognitive assessments zolpidem 10 mg: Zolpidem 10 mg single nighttime dose
Nervous system disorders Memory Impairment	0.00% 0/51 • Throughout the study period until the final study visit, up to 6 weeks.	1.9% 1/52 • Number of events 1 • Throughout the study period until the final study visit, up to 6 weeks.	5.8% 3/52 • Number of events 3 • Throughout the study period until the final study visit, up to 6 weeks.	0.00% 0/52 • Throughout the study period until the final study visit, up to 6 weeks.
Nervous system disorders Somnolence	7.8% 4/51 • Number of events 4 • Throughout the study period until the final study visit, up to 6 weeks.	7.7% 4/52 • Number of events 4 • Throughout the study period until the final study visit, up to 6 weeks.	7.7% 4/52 • Number of events 4 • Throughout the study period until the final study visit, up to 6 weeks.	0.00% 0/52 • Throughout the study period until the final study visit, up to 6 weeks.
Nervous system disorders Insomnia	5.9% 3/51 • Number of events 3 • Throughout the study period until the final study visit, up to 6 weeks.	5.8% 3/52 • Number of events 3 • Throughout the study period until the final study visit, up to 6 weeks.	3.8% 2/52 • Number of events 2 • Throughout the study period until the final study visit, up to 6 weeks.	3.8% 2/52 • Number of events 2 • Throughout the study period until the final study visit, up to 6 weeks.
Nervous system disorders Syncope	2.0% 1/51 • Number of events 1 • Throughout the study period until the final study visit, up to 6 weeks.	0.00% 0/52 • Throughout the study period until the final study visit, up to 6 weeks.	0.00% 0/52 • Throughout the study period until the final study visit, up to 6 weeks.	0.00% 0/52 • Throughout the study period until the final study visit, up to 6 weeks.
Nervous system disorders Presyncope	2.0% 1/51 • Number of events 1 • Throughout the study period until the final study visit, up to 6 weeks.	0.00% 0/52 • Throughout the study period until the final study visit, up to 6 weeks.	1.9% 1/52 • Number of events 1 • Throughout the study period until the final study visit, up to 6 weeks.	0.00% 0/52 • Throughout the study period until the final study visit, up to 6 weeks.
General disorders Fatigue/lethargy	3.9% 2/51 • Number of events 2 • Throughout the study period until the final study visit, up to 6 weeks.	3.8% 2/52 • Number of events 2 • Throughout the study period until the final study visit, up to 6 weeks.	0.00% 0/52 • Throughout the study period until the final study visit, up to 6 weeks.	0.00% 0/52 • Throughout the study period until the final study visit, up to 6 weeks.
Gastrointestinal disorders Xerostomia	0.00% 0/51 • Throughout the study period until the final study visit, up to 6 weeks.	0.00% 0/52 • Throughout the study period until the final study visit, up to 6 weeks.	1.9% 1/52 • Number of events 1 • Throughout the study period until the final study visit, up to 6 weeks.	0.00% 0/52 • Throughout the study period until the final study visit, up to 6 weeks.
Nervous system disorders Rigors	0.00% 0/51 • Throughout the study period until the final study visit, up to 6 weeks.	0.00% 0/52 • Throughout the study period until the final study visit, up to 6 weeks.	0.00% 0/52 • Throughout the study period until the final study visit, up to 6 weeks.	1.9% 1/52 • Number of events 1 • Throughout the study period until the final study visit, up to 6 weeks.
General disorders Other	3.9% 2/51 • Number of events 2 • Throughout the study period until the final study visit, up to 6 weeks.	1.9% 1/52 • Number of events 1 • Throughout the study period until the final study visit, up to 6 weeks.	1.9% 1/52 • Number of events 1 • Throughout the study period until the final study visit, up to 6 weeks.	13.5% 7/52 • Number of events 7 • Throughout the study period until the final study visit, up to 6 weeks.

Additional Information

Christopher L Drake

Sleep Disorders and Research Center Henry Ford Hospital

Phone: 248-344-6672

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place