Insomnia
Conditions
Keywords
Insomnia
Brief summary
The purpose of this study is to evaluate sleep onset following administration of Transcept zolpidem tartrate sublingual tablet versus placebo in adult insomnia patients.
Interventions
DRUGzolpidem tartrate sublingual tablet 3.5mg
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 and allowed it to dissolve there for about 2 minutes, then swallowed after dissolved.
DRUGzolpidem tartrate sublingual tablet 1.75mg
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 and allowed it to dissolve there for about 2 minutes, then swallowed after dissolved.
DRUGPlacebo
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 and allowed it to dissolve there for about 2 minutes, then swallowed after dissolved.
Sponsors
Transcept Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* Insomnia as defined by DSM-IV criteria and supported by subject diary * Male or female between the ages of 18-64 years * Body mass index (BMI) between 18-34 kg/m\^2 * Females of childbearing potential must use a medically acceptable method of contraception * Capable of understanding and willing to comply with study procedures and has provided informed consent
Exclusion criteria
* Females who are pregnant, breast-feeding or have a positive pregnancy test * Any circadian rhythm disorder including planned travel across several time zones during the study period * Known hypersensitivity to Zolpidem * Has performed regular shift work with the past several months prior to screening * An acute clinically significant illness or surgery as determined by the PI within 30 days of screening * Patients that have used any central nervous system (CNS) medication or other medication known to impact the sleep/wake cycle * A history of psychiatric disorder as defined by DSM-IV * A history of drug addiction or alcohol abuse * Any current significant disease, unless adequately controlled with a protocol allowed medication * Known history of HIV or Hepatitis B or C * Patients who have received an investigational drug within several months of screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Latency to Persistent Sleep After Middle-of-the-Night Awakening as Measured by Polysomnography | Days 1 and 2 for each treatment | Polysomnography was used to measure the time to return to persistent sleep after a middle-of-the-night (MOTN) awakening for each day of every two-day treatment period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Polysomnography Number of Awakenings After Middle-of-the-Night Awakening | Days 1 and 2 for each treatment | Number of times a participant awoke following sleep onset after the middle-of-the-night awakening, as measured by polysomnography for each day of every two-day treatment period. |
| Number of Treatment Responders Based on Polysomnography Latency to Persistent Sleep After Middle-of-the-Night Awakening | Days 1 and 2 for each treatment | Polysomnography was used to measure the time to return to persistent sleep after a middle-of-the-night (MOTN) awakening for each day of every two-day treatment period. A participant was considered to be a responder if the time to return to persistent sleep was less than twenty minutes. |
| Total Sleep Time After Scheduled Middle-of-the-Night Awakening Measured by Polysomnography | Days 1 and 2 for each treatment | Polysomnography was used to measure the time from return to persistent sleep after a middle-of-the-night (MOTN) awakening until final awakening for each day of every two-day treatment period. |
| Average Subjective Total Sleep Time After Scheduled Middle-of-the-Night Awakening | Days 1 and 2 for each treatment | The time from return to persistent sleep after a middle-of-the-night (MOTN) awakening until final awakening for each day of every two-day treatment period was recorded by each participant using the Treatment Morning Sleep Questionnaire. |
| Subjective Sleep Quality Rating | Days 1 and 2 for each treatment | 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. |
| Subjective Level of Refreshed Sleep | Days 1 and 2 for each treatment | Level of refreshed sleep 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. |
| Polysomnography Wake Time After Sleep Onset Following Middle-of-the-Night Awakening | Days 1 and 2 for each treatment | Amount of time awake after sleep onset following a middle-of-the-night awakening was measured by polysomnography for each day of every two-day treatment period. |
| Subjective Wake Time After Sleep Onset After Middle-of-the-Night Awakening | Days 1 and 2 for each treatment | Amount of time awake after sleep onset following a middle-of-the-night awakening was recorded by participants using the Treatment Morning Sleep Questionnaire for each day of every two-day treatment period. |
| Subjective Ability to Function | Days 1 and 2 for each treatment | Ability to function 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. |
| Polysomnography Sleep Efficiency After Scheduled Middle-of-the-Night Awakening | Days 1 and 2 for each treatment | Sleep efficiency is a measurement of the percentage of time asleep to the total time in bed. It was measured by polysomnography for each day of every two-day treatment period. |
| Subjective Sleep Onset Latency After Middle-of-the-Night Awakening | Days 1 and 2 for each treatment | Participants documented the time to return to sleep after a middle-of-the-night (MOTN) awakening for each day of every two-day treatment period using the Treatment Morning Sleep Questionnaire. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Total Sleep Time After Scheduled Middle-of-the-Night Awakening Measured by Polysomnography for Participants With More Severe Insomnia | Days 1 and 2 for each treatment | Polysomnography was used to measure the time from return to persistent sleep after a middle-of-the-night (MOTN) awakening until final awakening for each day of every two-day treatment period in the subpopulation of patients with greater than 60 minutes to fall asleep after a MOTN awakening at baseline. |
| Latency to Persistent Sleep After Middle-of-the-Night Awakening as Measured by Polysomnography for a Subpopulation of Participants With More Severe Insomnia | Days 1 and 2 for each treatment | Polysomnography was used to measure the time to return to persistent sleep after a middle-of-the-night (MOTN) awakening for each day of every two-day treatment period in a subpopulation of patients with greater than 60 minutes to fall asleep after a MOTN awakening at baseline. |
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Placebo/Zolpidem 3.5/Zolpidem 1.75 Cross-over interventions administered in the order listed. | 14 |
| Placebo/Zolpidem 1.75/Zolpidem 3.5 Cross-over interventions administered in the order listed. | 13 |
| Zolpidem 3.5/Placebo/Zolpidem 1.75 Cross-over interventions administered in the order listed. | 13 |
| Zolpidem 3.5/Zolpidem 1.75/Placebo Cross-over interventions administered in the order listed. | 15 |
| Zolpidem 1.75/Placebo/Zolpidem 3.5 Cross-over interventions administered in the order listed. | 13 |
| Zolpidem 1.75/Zolpidem 3.5/Placebo Cross-over interventions administered in the order listed. | 14 |
| Total | 82 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Family Emergency | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | 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 | Placebo/Zolpidem 3.5/Zolpidem 1.75 | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 13 Participants | 15 Participants | 13 Participants | 14 Participants | 14 Participants | 82 Participants |
| Age Continuous | 47.2 years STANDARD_DEVIATION 14.9 | 49.6 years STANDARD_DEVIATION 10.74 | 45.0 years STANDARD_DEVIATION 9.64 | 41.8 years STANDARD_DEVIATION 13.33 | 43.5 years STANDARD_DEVIATION 12.99 | 48.2 years STANDARD_DEVIATION 10.21 | 45.9 years STANDARD_DEVIATION 11.97 |
| Body Mass Index | 27.10 kilograms/square meters STANDARD_DEVIATION 4.164 | 27.27 kilograms/square meters STANDARD_DEVIATION 4.164 | 27.43 kilograms/square meters STANDARD_DEVIATION 3.717 | 25.92 kilograms/square meters STANDARD_DEVIATION 4.393 | 26.84 kilograms/square meters STANDARD_DEVIATION 2.681 | 27.72 kilograms/square meters STANDARD_DEVIATION 3.494 | 27.06 kilograms/square meters STANDARD_DEVIATION 3.718 |
| Height | 166.4 centimeters STANDARD_DEVIATION 7.574 | 172.4 centimeters STANDARD_DEVIATION 10.74 | 167.2 centimeters STANDARD_DEVIATION 10.246 | 167.4 centimeters STANDARD_DEVIATION 8.775 | 169.8 centimeters STANDARD_DEVIATION 9.955 | 174.6 centimeters STANDARD_DEVIATION 9.353 | 169.6 centimeters STANDARD_DEVIATION 9.7 |
| Number of Nights with Middle of the Night Awakening | 9.4 number of nights STANDARD_DEVIATION 1.19 | 8.9 number of nights STANDARD_DEVIATION 1.38 | 9.3 number of nights STANDARD_DEVIATION 0.98 | 9.3 number of nights STANDARD_DEVIATION 1.11 | 8.6 number of nights STANDARD_DEVIATION 1.5 | 9.3 number of nights STANDARD_DEVIATION 0.99 | 9.1 number of nights STANDARD_DEVIATION 1.2 |
| Race/Ethnicity, Customized Asian/Pacific | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants | 0 participants | 2 participants |
| Race/Ethnicity, Customized Black | 5 participants | 4 participants | 9 participants | 6 participants | 7 participants | 5 participants | 36 participants |
| Race/Ethnicity, Customized Caucasian | 8 participants | 7 participants | 6 participants | 7 participants | 6 participants | 8 participants | 42 participants |
| Race/Ethnicity, Customized Hispanic | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants | 2 participants |
| Region of Enrollment United States | 13 participants | 13 participants | 15 participants | 13 participants | 14 participants | 14 participants | 82 participants |
| Sex: Female, Male Female | 10 Participants | 10 Participants | 11 Participants | 10 Participants | 9 Participants | 8 Participants | 58 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 4 Participants | 3 Participants | 5 Participants | 6 Participants | 24 Participants |
| Weight | 75.10 kilograms STANDARD_DEVIATION 12.665 | 81.83 kilograms STANDARD_DEVIATION 17.816 | 77.46 kilograms STANDARD_DEVIATION 16.739 | 72.91 kilograms STANDARD_DEVIATION 14.421 | 77.50 kilograms STANDARD_DEVIATION 10.331 | 84.41 kilograms STANDARD_DEVIATION 11.409 | 78.25 kilograms STANDARD_DEVIATION 14.249 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 80 | 0 / 82 | 0 / 81 |
| serious Total, serious adverse events | 0 / 80 | 0 / 82 | 0 / 81 |
Outcome results
Primary
Latency to Persistent Sleep After Middle-of-the-Night Awakening as Measured by Polysomnography
Polysomnography was used to measure the time to return to persistent sleep after a middle-of-the-night (MOTN) awakening for each day of every two-day treatment period.
Time frame: Days 1 and 2 for each treatment
Population: Intent-to-treat population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Zolpidem 3.5 mg | Latency to Persistent Sleep After Middle-of-the-Night Awakening as Measured by Polysomnography | 9.69 minutes |
| Zolpidem 1.75 mg | Latency to Persistent Sleep After Middle-of-the-Night Awakening as Measured by Polysomnography | 16.89 minutes |
| Placebo | Latency to Persistent Sleep After Middle-of-the-Night Awakening as Measured by Polysomnography | 28.12 minutes |
p-value: <0.001ANCOVA
Secondary
Average Subjective Total Sleep Time After Scheduled Middle-of-the-Night Awakening
The time from return to persistent sleep after a middle-of-the-night (MOTN) awakening until final awakening for each day of every two-day treatment period was recorded by each participant using the Treatment Morning Sleep Questionnaire.
Time frame: Days 1 and 2 for each treatment
Population: Intent to treat population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Zolpidem 3.5 mg | Average Subjective Total Sleep Time After Scheduled Middle-of-the-Night Awakening | 172.51 minutes |
| Zolpidem 1.75 mg | Average Subjective Total Sleep Time After Scheduled Middle-of-the-Night Awakening | 162.36 minutes |
| Placebo | Average Subjective Total Sleep Time After Scheduled Middle-of-the-Night Awakening | 148.61 minutes |
p-value: <0.001ANCOVA
Secondary
Number of Treatment Responders Based on Polysomnography Latency to Persistent Sleep After Middle-of-the-Night Awakening
Polysomnography was used to measure the time to return to persistent sleep after a middle-of-the-night (MOTN) awakening for each day of every two-day treatment period. A participant was considered to be a responder if the time to return to persistent sleep was less than twenty minutes.
Time frame: Days 1 and 2 for each treatment
Population: Intent to treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zolpidem 3.5 mg | Number of Treatment Responders Based on Polysomnography Latency to Persistent Sleep After Middle-of-the-Night Awakening | 60 participants |
| Zolpidem 1.75 mg | Number of Treatment Responders Based on Polysomnography Latency to Persistent Sleep After Middle-of-the-Night Awakening | 46 participants |
| Placebo | Number of Treatment Responders Based on Polysomnography Latency to Persistent Sleep After Middle-of-the-Night Awakening | 23 participants |
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Polysomnography Number of Awakenings After Middle-of-the-Night Awakening
Number of times a participant awoke following sleep onset after the middle-of-the-night awakening, as measured by polysomnography for each day of every two-day treatment period.
Time frame: Days 1 and 2 for each treatment
Population: Intent to treat population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Zolpidem 3.5 mg | Polysomnography Number of Awakenings After Middle-of-the-Night Awakening | 3.71 number of awakenings |
| Zolpidem 1.75 mg | Polysomnography Number of Awakenings After Middle-of-the-Night Awakening | 3.70 number of awakenings |
| Placebo | Polysomnography Number of Awakenings After Middle-of-the-Night Awakening | 4.13 number of awakenings |
p-value: 0.072ANCOVA
p-value: <0.001ANCOVA
Secondary
Polysomnography Sleep Efficiency After Scheduled Middle-of-the-Night Awakening
Sleep efficiency is a measurement of the percentage of time asleep to the total time in bed. It was measured by polysomnography for each day of every two-day treatment period.
Time frame: Days 1 and 2 for each treatment
Population: Intent to treat population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Zolpidem 3.5 mg | Polysomnography Sleep Efficiency After Scheduled Middle-of-the-Night Awakening | 87.08 percentage of time asleep |
| Zolpidem 1.75 mg | Polysomnography Sleep Efficiency After Scheduled Middle-of-the-Night Awakening | 82.63 percentage of time asleep |
| Placebo | Polysomnography Sleep Efficiency After Scheduled Middle-of-the-Night Awakening | 76.31 percentage of time asleep |
p-value: <0.001ANCOVA
Secondary
Polysomnography Wake Time After Sleep Onset Following Middle-of-the-Night Awakening
Amount of time awake after sleep onset following a middle-of-the-night awakening was measured by polysomnography for each day of every two-day treatment period.
Time frame: Days 1 and 2 for each treatment
Population: Intent to treat population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Zolpidem 3.5 mg | Polysomnography Wake Time After Sleep Onset Following Middle-of-the-Night Awakening | 15.06 minutes |
| Zolpidem 1.75 mg | Polysomnography Wake Time After Sleep Onset Following Middle-of-the-Night Awakening | 15.81 minutes |
| Placebo | Polysomnography Wake Time After Sleep Onset Following Middle-of-the-Night Awakening | 15.71 minutes |
p-value: 0.79ANCOVA
Secondary
Subjective Ability to Function
Ability to function 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
Population: Intent to treat population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Zolpidem 3.5 mg | Subjective Ability to Function | Poor | 7.5 percentage of participants |
| Zolpidem 3.5 mg | Subjective Ability to Function | Fair | 41.3 percentage of participants |
| Zolpidem 3.5 mg | Subjective Ability to Function | Good | 45.0 percentage of participants |
| Zolpidem 3.5 mg | Subjective Ability to Function | Excellent | 6.3 percentage of participants |
| Zolpidem 1.75 mg | Subjective Ability to Function | Excellent | 6.1 percentage of participants |
| Zolpidem 1.75 mg | Subjective Ability to Function | Poor | 9.8 percentage of participants |
| Zolpidem 1.75 mg | Subjective Ability to Function | Good | 41.5 percentage of participants |
| Zolpidem 1.75 mg | Subjective Ability to Function | Fair | 42.7 percentage of participants |
| Placebo | Subjective Ability to Function | Excellent | 6.2 percentage of participants |
| Placebo | Subjective Ability to Function | Fair | 42.0 percentage of participants |
| Placebo | Subjective Ability to Function | Good | 33.3 percentage of participants |
| Placebo | Subjective Ability to Function | Poor | 18.5 percentage of participants |
p-value: 0.012Cochran-Mantel-Haenszel
Secondary
Subjective Level of Refreshed Sleep
Level of refreshed sleep 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
Population: Intent to treat population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Zolpidem 3.5 mg | Subjective Level of Refreshed Sleep | Excellent | 5.0 percentage of participants |
| Zolpidem 3.5 mg | Subjective Level of Refreshed Sleep | Good | 35.0 percentage of participants |
| Zolpidem 3.5 mg | Subjective Level of Refreshed Sleep | Fair | 42.5 percentage of participants |
| Zolpidem 3.5 mg | Subjective Level of Refreshed Sleep | Poor | 17.5 percentage of participants |
| Zolpidem 1.75 mg | Subjective Level of Refreshed Sleep | Poor | 22.0 percentage of participants |
| Zolpidem 1.75 mg | Subjective Level of Refreshed Sleep | Fair | 41.5 percentage of participants |
| Zolpidem 1.75 mg | Subjective Level of Refreshed Sleep | Good | 34.1 percentage of participants |
| Zolpidem 1.75 mg | Subjective Level of Refreshed Sleep | Excellent | 2.4 percentage of participants |
| Placebo | Subjective Level of Refreshed Sleep | Fair | 44.4 percentage of participants |
| Placebo | Subjective Level of Refreshed Sleep | Poor | 32.1 percentage of participants |
| Placebo | Subjective Level of Refreshed Sleep | Excellent | 3.7 percentage of participants |
| Placebo | Subjective Level of Refreshed Sleep | Good | 19.8 percentage of participants |
p-value: <0.004Cochran-Mantel-Haenszel
Secondary
Subjective Sleep Onset Latency After Middle-of-the-Night Awakening
Participants documented the time to return to sleep after a middle-of-the-night (MOTN) awakening for each day of every two-day treatment period using the Treatment Morning Sleep Questionnaire.
Time frame: Days 1 and 2 for each treatment
Population: Intent to treat population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Zolpidem 3.5 mg | Subjective Sleep Onset Latency After Middle-of-the-Night Awakening | 25.23 minutes |
| Zolpidem 1.75 mg | Subjective Sleep Onset Latency After Middle-of-the-Night Awakening | 28.58 minutes |
| Placebo | Subjective Sleep Onset Latency After Middle-of-the-Night Awakening | 40.43 minutes |
p-value: <0.001ANCOVA
Secondary
Subjective Sleep Quality Rating
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
Population: Intent to treat population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Zolpidem 3.5 mg | Subjective Sleep Quality Rating | Excellent | 6.3 percentage of participants |
| Zolpidem 3.5 mg | Subjective Sleep Quality Rating | Poor | 18.8 percentage of participants |
| Zolpidem 3.5 mg | Subjective Sleep Quality Rating | Fair | 38.8 percentage of participants |
| Zolpidem 3.5 mg | Subjective Sleep Quality Rating | Good | 36.3 percentage of participants |
| Zolpidem 1.75 mg | Subjective Sleep Quality Rating | Good | 30.5 percentage of participants |
| Zolpidem 1.75 mg | Subjective Sleep Quality Rating | Excellent | 2.4 percentage of participants |
| Zolpidem 1.75 mg | Subjective Sleep Quality Rating | Fair | 37.8 percentage of participants |
| Zolpidem 1.75 mg | Subjective Sleep Quality Rating | Poor | 29.3 percentage of participants |
| Placebo | Subjective Sleep Quality Rating | Good | 19.8 percentage of participants |
| Placebo | Subjective Sleep Quality Rating | Poor | 34.6 percentage of participants |
| Placebo | Subjective Sleep Quality Rating | Fair | 42.0 percentage of participants |
| Placebo | Subjective Sleep Quality Rating | Excellent | 3.7 percentage of participants |
Comparison: 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.p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Subjective Wake Time After Sleep Onset After Middle-of-the-Night Awakening
Amount of time awake after sleep onset following a middle-of-the-night awakening was recorded by participants using the Treatment Morning Sleep Questionnaire for each day of every two-day treatment period.
Time frame: Days 1 and 2 for each treatment
Population: Intent to treat population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Zolpidem 3.5 mg | Subjective Wake Time After Sleep Onset After Middle-of-the-Night Awakening | 28.69 minutes |
| Zolpidem 1.75 mg | Subjective Wake Time After Sleep Onset After Middle-of-the-Night Awakening | 29.43 minutes |
| Placebo | Subjective Wake Time After Sleep Onset After Middle-of-the-Night Awakening | 34.22 minutes |
p-value: 0.083ANCOVA
Secondary
Total Sleep Time After Scheduled Middle-of-the-Night Awakening Measured by Polysomnography
Polysomnography was used to measure the time from return to persistent sleep after a middle-of-the-night (MOTN) awakening until final awakening for each day of every two-day treatment period.
Time frame: Days 1 and 2 for each treatment
Population: Intent-to-treat population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Zolpidem 3.5 mg | Total Sleep Time After Scheduled Middle-of-the-Night Awakening Measured by Polysomnography | 208.99 minutes |
| Zolpidem 1.75 mg | Total Sleep Time After Scheduled Middle-of-the-Night Awakening Measured by Polysomnography | 197.80 minutes |
| Placebo | Total Sleep Time After Scheduled Middle-of-the-Night Awakening Measured by Polysomnography | 183.12 minutes |
p-value: <0.001ANCOVA
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
Polysomnography was used to measure the time to return to persistent sleep after a middle-of-the-night (MOTN) awakening for each day of every two-day treatment period in a subpopulation of patients with greater than 60 minutes to fall asleep after a MOTN awakening at baseline.
Time frame: Days 1 and 2 for each treatment
Population: Intent to treat population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Zolpidem 3.5 mg | Latency to Persistent Sleep After Middle-of-the-Night Awakening as Measured by Polysomnography for a Subpopulation of Participants With More Severe Insomnia | 12.62 minutes |
| Zolpidem 1.75 mg | Latency to Persistent Sleep After Middle-of-the-Night Awakening as Measured by Polysomnography for a Subpopulation of Participants With More Severe Insomnia | 23.28 minutes |
| Placebo | Latency to Persistent Sleep After Middle-of-the-Night Awakening as Measured by Polysomnography for a Subpopulation of Participants With More Severe Insomnia | 37.89 minutes |
p-value: <0.001ANCOVA
Post Hoc
Subjective Number of Awakenings After Middle-of-the-Night Awakening
Number of times a participant awoke following sleep onset after the middle-of-the-night awakening, as documented by the participant for each day of every two-day treatment period using the Treatment Morning Sleep Questionnaire.
Time frame: Days 1 and 2 for each treatment
Population: Intent to treat population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Zolpidem 3.5 mg | Subjective Number of Awakenings After Middle-of-the-Night Awakening | 0.86 number of awakenings |
| Zolpidem 1.75 mg | Subjective Number of Awakenings After Middle-of-the-Night Awakening | 1.03 number of awakenings |
| Placebo | Subjective Number of Awakenings After Middle-of-the-Night Awakening | 1.14 number of awakenings |
p-value: 0.017ANCOVA
Other Pre-specified
Total Sleep Time After Scheduled Middle-of-the-Night Awakening Measured by Polysomnography for Participants With More Severe Insomnia
Polysomnography was used to measure the time from return to persistent sleep after a middle-of-the-night (MOTN) awakening until final awakening for each day of every two-day treatment period in the subpopulation of patients with greater than 60 minutes to fall asleep after a MOTN awakening at baseline.
Time frame: Days 1 and 2 for each treatment
Population: Intent to treat population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Zolpidem 3.5 mg | Total Sleep Time After Scheduled Middle-of-the-Night Awakening Measured by Polysomnography for Participants With More Severe Insomnia | 194.58 minutes |
| Zolpidem 1.75 mg | Total Sleep Time After Scheduled Middle-of-the-Night Awakening Measured by Polysomnography for Participants With More Severe Insomnia | 179.98 minutes |
| Placebo | Total Sleep Time After Scheduled Middle-of-the-Night Awakening Measured by Polysomnography for Participants With More Severe Insomnia | 166.62 minutes |
p-value: <0.001ANCOVA