A Study of Zolpidem Tartrate Sublingual Tablet in Adult Patients With Insomnia

• Sponsor: Transcept Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00466193
• Collaborator: (none)
• Enrollment: 295
• Location: 1
• Arms: 2
• Duration (Months): 6
• Patients Per Site Per Month: 48.8

Study Details

Study Description

Brief Summary

The purpose of the study is to evaluate sleep onset following administration of zolpidem tartrate sublingual tablet (Intermezzo) versus placebo in adult insomnia patients.

Condition or Disease	Intervention/Treatment	Phase
Insomnia	Drug: zolpidem tartrate sublingual tablet; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 295 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled, Parallel Group Study of the Efficacy and Safety of the Zolpidem Tartrate Sublingual Tablet in Adult Subjects With Insomnia Characterized by Difficulty Returning to Sleep After Awakening in the Middle-of-the-Night (MOTN)
• Study Start Date: May 1, 2007
• Actual Primary Completion Date: Nov 1, 2007
• Actual Study Completion Date: Nov 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Zolpidem 3.5mg	Drug: zolpidem tartrate sublingual tablet; 3.5 milligram zolpidem tartrate sublingual tablet taken as needed following a middle-of-the-night awakening over the 28-night study period. Participants placed the study drug under the tongue and allowed it to dissolve there for about 2 minutes, then swallowed after dissolved.; Other Names: Intermezzo®
Placebo Comparator: Placebo	Drug: Placebo; Placebo sublingual tablet taken as needed following a middle-of-the-night awakening over the 28-night study period. Participants placed the study drug under the tongue and allowed it to dissolve there for about 2 minutes, then swallowed after dissolved.

Outcome Measures

Primary Outcome Measures

1. Latency to Sleep Onset After Middle-of-the-Night Awakening at Baseline [Weeks -1 to 0]

   Time was recorded by study participants using a telephone interactive voice response system (IVRS) to answer the question: How long did it take you to fall asleep after taking your study medication?

2. Latency to Sleep Onset After Middle-of-the-Night Awakening During Double-blind Treatment [Weeks 1 to 4]

   Time was recorded by study participants using a telephone interactive voice response system (IVRS) to answer the question: How long did it take you to fall asleep after taking your study medication?

Secondary Outcome Measures

1. Subjective Total Sleep Time Following Middle-of-the-Night Awakening at Baseline [Weeks -1 to 0]

   Total sleep time in minutes after waking in the middle of the night. The values were recorded by participants using a telephone interactive voice response system (IVRS) to answer the question: After you fell back to sleep, how long did you sleep until you woke up this morning?

2. Subjective Total Sleep Time Following Middle-of-the-Night Awakening During Double-blind Treatment [Weeks 1 to 4]

   Total sleep time in minutes after waking in the middle of the night. The values were recorded by participants using a telephone interactive voice response system (IVRS) to answer the question: After you fell back to sleep, how long did you sleep until you woke up this morning?

3. Subjective Number of Awakenings Following Middle-of-the-Night Awakening at Baseline. [Weeks -1 to 0]

   Number of awakenings following middle-of-the-night awakening were recorded by study participants using a telephone interactive voice response system (IVRS) to answer the question: After you fell back to sleep, how many times did you wake up again before waking up in the morning?

4. Subjective Number of Awakenings Following Middle-of-the-Night Awakening During Double-blind Treatment [Weeks 1 to 4]

   Number of awakenings following middle-of-the-night awakening were recorded by study participants using a telephone interactive voice response system (IVRS) to answer the question: After you fell back to sleep, how many times did you wake up again before waking up in the morning?

5. Subjective Wake Time After Sleep Onset Following Middle-of-the-Night Awakening at Baseline [Weeks -1 to 0]

   The number of minutes subjects reported being awake after onset of sleep following middle-of-the-night awakening during the baseline period. Values were recorded using a telephone interactive voice response system (IVRS) to answer the question: Considering all of these awakenings (after taking study medication and returning to sleep), how long were you awake from the time you went back to sleep after dosing until you got out of bed this morning?

6. Subjective Wake Time After Sleep Onset Following Middle-of-the-Night Awakening During Double-blind Treatment [Weeks 1 to 4]

   The number of minutes subjects reported being awake after onset of sleep following middle-of-the-night awakening during double-blind treatment. Values were recorded using a telephone interactive voice response system (IVRS) to answer the question: Considering all of these awakenings (after taking study medication and returning to sleep), how long were you awake from the time you went back to sleep after dosing until you got out of bed this morning?

7. Morning Sleepiness Rating Following Dosing Post Middle-of-the-Night Awakening at Baseline [Weeks -1 to 0]

   Morning sleepiness was assessed using a 9-point sleepiness scale (1=very sleepy to 9=wide awake and alert). During the baseline period, all participants received placebo.

8. Morning Sleepiness Rating Following Dosing Post Middle-of-the-Night Awakening During Double-blind Treatment [Weeks 1 to 4]

   Morning sleepiness was assessed using a 9-point sleepiness scale (1=very sleepy to 9=wide awake and alert). Values are from dosing nights during double-blind treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 64 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adults with history of sleeplessness

Exclusion Criteria:

• Allergic to investigational drug

• Any conditions and medications that may interfere with study drug evaluation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Transcept Investigational Site	Durham	North Carolina	United States	27710

Sponsors and Collaborators

• Transcept Pharmaceuticals

Investigators

• Principal Investigator: Andrew Krystal, MD, Clinical Neurophysiology Training Program, Duke University
• Principal Investigator: Thomas Roth, PhD, Sleep Disorders and Research Center, Henry Ford Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Transcept Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00466193
• Other Study ID Numbers: ZI-12
• First Posted: Apr 27, 2007
• Last Update Posted: Feb 14, 2012
• Last Verified: Feb 1, 2012

• Keywords provided by Transcept Pharmaceuticals: Insomnia
• Additional relevant MeSH terms: Sleep Initiation and Maintenance Disorders; Zolpidem

Study Results

Participant Flow

Pre-assignment Detail	Seven hundred and three (703) subjects were screened. Three hundred (300) subjects were randomized, but 5 subjects never took drug.

Arm/Group Title	Zolpidem 3.5 mg	Placebo
Arm/Group Description	Zolpidem tartrate sublingual tablet, 3.5 milligram, taken following a middle-of-the-night awakening.	Placebo sublingual tablet taken following a middle-of-the-night awakening.
Period Title: Overall Study
STARTED	150	145
COMPLETED	138	137
NOT COMPLETED	12	8

Baseline Characteristics

Arm/Group Title	Zolpidem 3.5 mg	Placebo	Total
Arm/Group Description	Zolpidem tartrate sublingual tablet, 3.5 milligram, taken following a middle-of-the-night awakening.	Placebo sublingual tablet taken following a middle-of-the-night awakening.	Total of all reporting groups
Overall Participants	150	145	295
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	150 100%	145 100%	295 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.3 (11.38)	43.4 (11.30)	42.8 (11.33)
Sex: Female, Male (Count of Participants)
Female	107 71.3%	94 64.8%	201 68.1%
Male	43 28.7%	51 35.2%	94 31.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.7%	2 1.4%	3 1%
Asian	3 2%	2 1.4%	5 1.7%
Native Hawaiian or Other Pacific Islander	1 0.7%	0 0%	1 0.3%
Black or African American	47 31.3%	45 31%	92 31.2%
White	96 64%	94 64.8%	190 64.4%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	2 1.3%	2 1.4%	4 1.4%
Region of Enrollment (participants) [Number]
United States	150 100%	145 100%	295 100%
Body Mass Index (kilogram per square meter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram per square meter]	26.17 (3.860)	26.55 (3.754)	26.35 (3.807)
Weight (kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms]	74.27 (15.050)	75.73 (13.434)	74.99 (14.273)

Outcome Measures

1. Primary Outcome

Title	Latency to Sleep Onset After Middle-of-the-Night Awakening at Baseline
Description	Time was recorded by study participants using a telephone interactive voice response system (IVRS) to answer the question: How long did it take you to fall asleep after taking your study medication?
Time Frame	Weeks -1 to 0

Outcome Measure Data

Analysis Population Description

Efficacy population: randomized participants who took at least one dose of study medication and had at least one latency to sleep onset following a middle-of-the-night awakening value.

Arm/Group Title	Zolpidem 3.5 mg	Placebo
Arm/Group Description	Zolpidem tartrate sublingual tablet, 3.5 milligram, taken following a middle-of-the-night awakening.	Placebo sublingual tablet taken following a middle-of-the-night awakening.
Measure Participants	150	144
Least Squares Mean (95% Confidence Interval) [minutes]	68.13	69.42

2. Secondary Outcome

Title	Subjective Total Sleep Time Following Middle-of-the-Night Awakening at Baseline
Description	Total sleep time in minutes after waking in the middle of the night. The values were recorded by participants using a telephone interactive voice response system (IVRS) to answer the question: After you fell back to sleep, how long did you sleep until you woke up this morning?
Time Frame	Weeks -1 to 0

Outcome Measure Data

Analysis Population Description

Efficacy population: randomized participants who took at least one dose of study medication and had at least one latency to sleep onset following a middle-of-the-night awakening value.

Arm/Group Title	Zolpidem 3.5 mg	Placebo
Arm/Group Description	Zolpidem tartrate sublingual tablet, 3.5 milligram, taken following a middle-of-the-night awakening.	Placebo sublingual tablet taken following a middle-of-the-night awakening.
Measure Participants	150	144
Least Squares Mean (95% Confidence Interval) [minutes]	241.2	222.9

3. Secondary Outcome

Title	Subjective Total Sleep Time Following Middle-of-the-Night Awakening During Double-blind Treatment
Description	Total sleep time in minutes after waking in the middle of the night. The values were recorded by participants using a telephone interactive voice response system (IVRS) to answer the question: After you fell back to sleep, how long did you sleep until you woke up this morning?
Time Frame	Weeks 1 to 4

Outcome Measure Data

Analysis Population Description

Efficacy population: randomized participants who took at least one dose of study medication and had at least one latency to sleep onset following a middle-of-the-night awakening value.

Arm/Group Title	Zolpidem 3.5 mg	Placebo
Arm/Group Description	Zolpidem tartrate sublingual tablet, 3.5 milligram, taken following a middle-of-the-night awakening.	Placebo sublingual tablet taken following a middle-of-the-night awakening.
Measure Participants	150	144
Least Squares Mean (95% Confidence Interval) [minutes]	264.1	255.0

4. Secondary Outcome

Title	Subjective Number of Awakenings Following Middle-of-the-Night Awakening at Baseline.
Description	Number of awakenings following middle-of-the-night awakening were recorded by study participants using a telephone interactive voice response system (IVRS) to answer the question: After you fell back to sleep, how many times did you wake up again before waking up in the morning?
Time Frame	Weeks -1 to 0

Outcome Measure Data

Analysis Population Description

Efficacy population: randomized participants who took at least one dose of study medication and had at least one latency to sleep onset following a middle-of-the-night awakening value.

Arm/Group Title	Zolpidem 3.5 mg	Placebo
Arm/Group Description	Zolpidem tartrate sublingual tablet, 3.5 milligram, taken following a middle-of-the-night awakening.	Placebo sublingual tablet taken following a middle-of-the-night awakening.
Measure Participants	150	144
0 awakenings	16.7 11.1%	11.8 8.1%
>0 and <=1 awakenings	46.0 30.7%	45.1 31.1%
>1 and <=2 awakenings	26.0 17.3%	27.1 18.7%
>2 awakenings	11.3 7.5%	16.0 11%

5. Secondary Outcome

Title	Subjective Number of Awakenings Following Middle-of-the-Night Awakening During Double-blind Treatment
Description	Number of awakenings following middle-of-the-night awakening were recorded by study participants using a telephone interactive voice response system (IVRS) to answer the question: After you fell back to sleep, how many times did you wake up again before waking up in the morning?
Time Frame	Weeks 1 to 4

Outcome Measure Data

Analysis Population Description

Efficacy population: randomized participants who took at least one dose of study medication and had at least one latency to sleep onset following a middle-of-the-night awakening value.

Arm/Group Title	Zolpidem 3.5 mg	Placebo
Arm/Group Description	Zolpidem tartrate sublingual tablet, 3.5 milligram, taken following a middle-of-the-night awakening.	Placebo sublingual tablet taken following a middle-of-the-night awakening.
Measure Participants	150	144
0 awakenings	30.0 20%	16.7 11.5%
>0 and <=1 awakenings	46.0 30.7%	43.1 29.7%
>1 and <=2 awakenings	17.3 11.5%	25.0 17.2%
>2 awakenings	6.7 4.5%	15.3 10.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Zolpidem 3.5 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	p-value is for treatment
	Method	ANCOVA
	Comments

6. Secondary Outcome

Title	Subjective Wake Time After Sleep Onset Following Middle-of-the-Night Awakening at Baseline
Description	The number of minutes subjects reported being awake after onset of sleep following middle-of-the-night awakening during the baseline period. Values were recorded using a telephone interactive voice response system (IVRS) to answer the question: Considering all of these awakenings (after taking study medication and returning to sleep), how long were you awake from the time you went back to sleep after dosing until you got out of bed this morning?
Time Frame	Weeks -1 to 0

Outcome Measure Data

Analysis Population Description

Efficacy population: randomized participants who took at least one dose of study medication and had at least one latency to sleep onset following a middle-of-the-night awakening value.

Arm/Group Title	Zolpidem 3.5 mg	Placebo
Arm/Group Description	Zolpidem tartrate sublingual tablet, 3.5 milligram, taken following a middle-of-the-night awakening.	Placebo sublingual tablet taken following a middle-of-the-night awakening.
Measure Participants	150	144
No wake time	16.7 11.1%	11.8 8.1%
>0 to 20 minutes	18.7 12.5%	14.6 10.1%
21 to 60 minutes	25.3 16.9%	32.6 22.5%
>60 minutes	39.3 26.2%	41.0 28.3%

7. Secondary Outcome

Title	Subjective Wake Time After Sleep Onset Following Middle-of-the-Night Awakening During Double-blind Treatment
Description	The number of minutes subjects reported being awake after onset of sleep following middle-of-the-night awakening during double-blind treatment. Values were recorded using a telephone interactive voice response system (IVRS) to answer the question: Considering all of these awakenings (after taking study medication and returning to sleep), how long were you awake from the time you went back to sleep after dosing until you got out of bed this morning?
Time Frame	Weeks 1 to 4

Outcome Measure Data

Analysis Population Description

Efficacy population: randomized participants who took at least one dose of study medication and had at least one latency to sleep onset following a middle-of-the-night awakening value.

Arm/Group Title	Zolpidem 3.5 mg	Placebo
Arm/Group Description	Zolpidem tartrate sublingual tablet, 3.5 milligram, taken following a middle-of-the-night awakening.	Placebo sublingual tablet taken following a middle-of-the-night awakening.
Measure Participants	150	144
No wake time	30.0 20%	16.7 11.5%
>0 to 20 minutes	27.3 18.2%	26.4 18.2%
21 to 60 minutes	26.0 17.3%	31.9 22%
> 60 minutes	16.7 11.1%	25.0 17.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Zolpidem 3.5 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.006
	Comments	p-value is for treatment
	Method	ANCOVA
	Comments

8. Secondary Outcome

Title	Morning Sleepiness Rating Following Dosing Post Middle-of-the-Night Awakening at Baseline
Description	Morning sleepiness was assessed using a 9-point sleepiness scale (1=very sleepy to 9=wide awake and alert). During the baseline period, all participants received placebo.
Time Frame	Weeks -1 to 0

Outcome Measure Data

Analysis Population Description

Safety population: participants who took at least one dose of study medication post-randomization.

Arm/Group Title	Zolpidem 3.5 mg	Placebo
Arm/Group Description	Zolpidem tartrate sublingual tablet, 3.5 milligram, taken following a middle-of-the-night awakening.	Placebo sublingual tablet taken following a middle-of-the-night awakening.
Measure Participants	150	145
Least Squares Mean (95% Confidence Interval) [units on a scale]	4.87	4.71

9. Primary Outcome

Title	Latency to Sleep Onset After Middle-of-the-Night Awakening During Double-blind Treatment
Description	Time was recorded by study participants using a telephone interactive voice response system (IVRS) to answer the question: How long did it take you to fall asleep after taking your study medication?
Time Frame	Weeks 1 to 4

Outcome Measure Data

Analysis Population Description

Efficacy population: randomized participants who took at least one dose of study medication and had at least one latency to sleep onset following a middle-of-the-night awakening value.

Arm/Group Title	Zolpidem 3.5 mg	Placebo
Arm/Group Description	Zolpidem tartrate sublingual tablet, 3.5 milligram, taken following a middle-of-the-night awakening.	Placebo sublingual tablet taken following a middle-of-the-night awakening.
Measure Participants	150	144
Least Squares Mean (95% Confidence Interval) [minutes]	38.22	56.37

10. Secondary Outcome

Title	Morning Sleepiness Rating Following Dosing Post Middle-of-the-Night Awakening During Double-blind Treatment
Description	Morning sleepiness was assessed using a 9-point sleepiness scale (1=very sleepy to 9=wide awake and alert). Values are from dosing nights during double-blind treatment.
Time Frame	Weeks 1 to 4

Outcome Measure Data

Analysis Population Description

Safety population: participants who took at least one dose of study medication post-randomization.

Arm/Group Title	Zolpidem 3.5 mg	Placebo
Arm/Group Description	Zolpidem tartrate sublingual tablet, 3.5 milligram, taken following a middle-of-the-night awakening.	Placebo sublingual tablet taken following a middle-of-the-night awakening.
Measure Participants	150	145
Least Squares Mean (95% Confidence Interval) [units on a scale]	5.59	5.24

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Zolpidem 3.5 mg, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0041
	Comments	P-value is for treatment
	Method	ANCOVA
	Comments

Adverse Events

Time Frame	Weeks 1-4
Arm/Group Title	Zolpidem 3.5 mg		Placebo
Arm/Group Description	Zolpidem tartrate sublingual tablet, 3.5 milligram, taken following a middle-of-the-night awakening.		Placebo sublingual tablet taken following a middle-of-the-night awakening.
All Cause Mortality
	Zolpidem 3.5 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Zolpidem 3.5 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/150 (0%)		0/145 (0%)
Other (Not Including Serious) Adverse Events
	Zolpidem 3.5 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/150 (0%)		0/145 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Sponsor agrees to review manuscripts within sixty (60) days prior to submission for publication. If sponsor determines the publication includes patentable subject matter, sponsor may take an additional sixty (60) days to permit the filing of any patent applications.