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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Transcept Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00380081
First received: September 21, 2006
Last updated: February 10, 2012
Last verified: February 2012
Results First Received: December 15, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Crossover Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Insomnia
Interventions: Drug: zolpidem tartrate sublingual tablet 3.5mg
Drug: zolpidem tartrate sublingual tablet 1.75mg
Drug: Placebo

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 83 patient volunteers were enrolled and of these, 82 patients were randomized, received at least 1 dose of study drug during the double-blind treatment period and were included in safety and efficacy analyses.

Reporting Groups
  Description
Placebo/Zolpidem 3.5/Zolpidem 1.75 Cross-over interventions administered in the order listed.
Placebo/Zolpidem 1.75/Zolpidem 3.5 Cross-over interventions administered in the order listed.
Zolpidem 3.5/Placebo/Zolpidem 1.75 Cross-over interventions administered in the order listed.
Zolpidem 3.5/Zolpidem 1.75/Placebo Cross-over interventions administered in the order listed.
Zolpidem 1.75/Placebo/Zolpidem 3.5 Cross-over interventions administered in the order listed.
Zolpidem 1.75/Zolpidem 3.5/Placebo Cross-over interventions administered in the order listed.

Participant Flow:   Overall Study
    Placebo/Zolpidem 3.5/Zolpidem 1.75     Placebo/Zolpidem 1.75/Zolpidem 3.5     Zolpidem 3.5/Placebo/Zolpidem 1.75     Zolpidem 3.5/Zolpidem 1.75/Placebo     Zolpidem 1.75/Placebo/Zolpidem 3.5     Zolpidem 1.75/Zolpidem 3.5/Placebo  
STARTED     14     13     13     15     13     14  
COMPLETED     14     13     13     15     12     13  
NOT COMPLETED     0     0     0     0     1     1  
Withdrawal by Subject                 0                 0                 0                 0                 1                 0  
Family Emergency                 0                 0                 0                 0                 0                 1  



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Placebo/Zolpidem 3.5/Zolpidem 1.75 Cross-over interventions administered in the order listed.
Placebo/Zolpidem 1.75/Zolpidem 3.5 Cross-over interventions administered in the order listed.
Zolpidem 3.5/Placebo/Zolpidem 1.75 Cross-over interventions administered in the order listed.
Zolpidem 3.5/Zolpidem 1.75/Placebo Cross-over interventions administered in the order listed.
Zolpidem 1.75/Placebo/Zolpidem 3.5 Cross-over interventions administered in the order listed.
Zolpidem 1.75/Zolpidem 3.5/Placebo Cross-over interventions administered in the order listed.
Total Total of all reporting groups

Baseline Measures
    Placebo/Zolpidem 3.5/Zolpidem 1.75     Placebo/Zolpidem 1.75/Zolpidem 3.5     Zolpidem 3.5/Placebo/Zolpidem 1.75     Zolpidem 3.5/Zolpidem 1.75/Placebo     Zolpidem 1.75/Placebo/Zolpidem 3.5     Zolpidem 1.75/Zolpidem 3.5/Placebo     Total  
Number of Participants  
[units: participants]
  14     13     13     15     13     14     82  
Age  
[units: participants]
             
<=18 years     0     0     0     0     0     0     0  
Between 18 and 65 years     14     13     13     15     13     14     82  
>=65 years     0     0     0     0     0     0     0  
Age  
[units: years]
Mean ± Standard Deviation
  48.2  ± 10.21     47.2  ± 14.90     49.6  ± 10.74     45.0  ± 9.64     41.8  ± 13.33     43.5  ± 12.99     45.9  ± 11.97  
Gender  
[units: participants]
             
Female     8     10     10     11     10     9     58  
Male     6     3     3     4     3     5     24  
Race/Ethnicity, Customized  
[units: participants]
             
Caucasian     8     8     7     6     7     6     42  
Hispanic     1     0     1     0     0     0     2  
Black     5     5     4     9     6     7     36  
Asian/Pacific     0     0     1     0     0     1     2  
Region of Enrollment  
[units: participants]
             
United States     14     13     13     15     13     14     82  
Body Mass Index [1]
[units: kilograms/square meters]
Mean ± Standard Deviation
  27.72  ± 3.494     27.10  ± 4.164     27.27  ± 4.164     27.43  ± 3.717     25.92  ± 4.393     26.84  ± 2.681     27.06  ± 3.718  
Height  
[units: centimeters]
Mean ± Standard Deviation
  174.6  ± 9.353     166.4  ± 7.574     172.4  ± 10.740     167.2  ± 10.246     167.4  ± 8.775     169.8  ± 9.955     169.6  ± 9.700  
Number of Nights with Middle of the Night Awakening [2]
[units: number of nights]
Mean ± Standard Deviation
  9.3  ± 0.99     9.4  ± 1.19     8.9  ± 1.38     9.3  ± 0.98     9.3  ± 1.11     8.6  ± 1.50     9.1  ± 1.20  
Weight  
[units: kilograms]
Mean ± Standard Deviation
  84.41  ± 11.409     75.10  ± 12.665     81.83  ± 17.816     77.46  ± 16.739     72.91  ± 14.421     77.50  ± 10.331     78.25  ± 14.249  
[1] Body mass index is an estimate of body fat based on body weight divided by height squared.
[2] Number of nights with Middle of the Night (MOTN) Awakenings is based upon self-reports on more than or equal to 3 nights and completion of at least 7 days of the 10-day Screening Morning Sleep Diary.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Latency to Persistent Sleep After Middle-of-the-Night Awakening as Measured by Polysomnography   [ Time Frame: Days 1 and 2 for each treatment ]

2.  Secondary:   Number of Treatment Responders Based on Polysomnography Latency to Persistent Sleep After Middle-of-the-Night Awakening   [ Time Frame: Days 1 and 2 for each treatment ]

3.  Secondary:   Total Sleep Time After Scheduled Middle-of-the-Night Awakening Measured by Polysomnography   [ Time Frame: Days 1 and 2 for each treatment ]

4.  Secondary:   Average Subjective Total Sleep Time After Scheduled Middle-of-the-Night Awakening   [ Time Frame: Days 1 and 2 for each treatment ]

5.  Secondary:   Subjective Sleep Quality Rating   [ Time Frame: Days 1 and 2 for each treatment ]
  Hide Outcome Measure 5

Measure Type Secondary
Measure Title Subjective Sleep Quality Rating
Measure Description Sleep quality was rated by participants for each day of every two-day treatment period using the Treatment Morning Sleep Questionnaire. The percentage of participants within each rating category is reported. The rating scale was poor, fair, good and excellent.
Time Frame Days 1 and 2 for each treatment  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent to treat population

Reporting Groups
  Description
Zolpidem 3.5 mg Zolpidem tartrate sublingual tablet 3.5 milligram administered between 2:15 and 3:15 a.m. on Night 1 and 2 of each treatment period. Participants placed the study drug under the tongue until it dissolved.
Zolpidem 1.75 mg Zolpidem tartrate sublingual tablet 1.75 milligram administered between 2:15 and 3:15 a.m. on Night 1 and 2 of each treatment period. Participants placed the study drug under the tongue until it dissolved.
Placebo Placebo sublingual tablet administered between 2:15 and 3:15 a.m. on Night 1 and 2 of each treatment period. Participants placed the study drug under the tongue until it dissolved.

Measured Values
    Zolpidem 3.5 mg     Zolpidem 1.75 mg     Placebo  
Number of Participants Analyzed  
[units: participants]
  80     82     81  
Subjective Sleep Quality Rating  
[units: percentage of participants]
     
Poor     18.8     29.3     34.6  
Fair     38.8     37.8     42.0  
Good     36.3     30.5     19.8  
Excellent     6.3     2.4     3.7  


Statistical Analysis 1 for Subjective Sleep Quality Rating
Groups [1] All groups
Method [2] Cochran-Mantel-Haenszel
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The outcome noted above reflects the all-night sleep quality rating of study subjects who had a scheduled awakening after approximately 4 hours of sleep, were kept awake for 30 minutes and then allowed to return to bed and to sleep. After 4 hours, they were awakened again and disconnected from the PSG apparatus. Morning testing was conducted that included the Sleep Quality questionnaire. Evaluation of the results should reflect the nature of the study and the scheduled sleep disturbance.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Treatment effect



6.  Secondary:   Subjective Level of Refreshed Sleep   [ Time Frame: Days 1 and 2 for each treatment ]

7.  Secondary:   Subjective Ability to Function   [ Time Frame: Days 1 and 2 for each treatment ]

8.  Secondary:   Polysomnography Sleep Efficiency After Scheduled Middle-of-the-Night Awakening   [ Time Frame: Days 1 and 2 for each treatment ]

9.  Secondary:   Subjective Sleep Onset Latency After Middle-of-the-Night Awakening   [ Time Frame: Days 1 and 2 for each treatment ]

10.  Secondary:   Polysomnography Wake Time After Sleep Onset Following Middle-of-the-Night Awakening   [ Time Frame: Days 1 and 2 for each treatment ]

11.  Secondary:   Subjective Wake Time After Sleep Onset After Middle-of-the-Night Awakening   [ Time Frame: Days 1 and 2 for each treatment ]

12.  Secondary:   Polysomnography Number of Awakenings After Middle-of-the-Night Awakening   [ Time Frame: Days 1 and 2 for each treatment ]

13.  Other Pre-specified:   Total Sleep Time After Scheduled Middle-of-the-Night Awakening Measured by Polysomnography for Participants With More Severe Insomnia   [ Time Frame: Days 1 and 2 for each treatment ]

14.  Other Pre-specified:   Latency to Persistent Sleep After Middle-of-the-Night Awakening as Measured by Polysomnography for a Subpopulation of Participants With More Severe Insomnia   [ Time Frame: Days 1 and 2 for each treatment ]

15.  Post-Hoc:   Subjective Number of Awakenings After Middle-of-the-Night Awakening   [ Time Frame: Days 1 and 2 for each treatment ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Scheduled nocturnal awakening is an established method used to evaluate treatments for naturally occurring middle-of-the-night awakenings. Additional studies are needed to determine the generalizability of the findings to 'real world' conditions.


  More Information