Insomnia
Conditions
Keywords
Insomnia
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.
Interventions
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.
DRUGPlacebo
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.
Sponsors
Transcept Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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? |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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? |
| 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? |
| 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? |
| 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? |
| 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. |
| 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. |
| 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? |
| 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? |
Countries
United States
Participant flow
Pre-assignment details
Seven hundred and three (703) subjects were screened. Three hundred (300) subjects were randomized, but 5 subjects never took drug.
Participants by arm
| Arm | Count |
|---|---|
| Zolpidem 3.5 mg Zolpidem tartrate sublingual tablet, 3.5 milligram, taken following a middle-of-the-night awakening. | 150 |
| Placebo Placebo sublingual tablet taken following a middle-of-the-night awakening. | 145 |
| Total | 295 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Lost to Follow-up | 2 | 4 |
| Overall Study | Patient refused Visit 4 procedures | 1 | 0 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Withdrawal by Subject | 7 | 2 |
Baseline characteristics
| Characteristic | Total | Zolpidem 3.5 mg | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 295 Participants | 150 Participants | 145 Participants |
| Age Continuous | 42.8 years STANDARD_DEVIATION 11.33 | 42.3 years STANDARD_DEVIATION 11.38 | 43.4 years STANDARD_DEVIATION 11.3 |
| Body Mass Index | 26.35 kilogram per square meter STANDARD_DEVIATION 3.807 | 26.17 kilogram per square meter STANDARD_DEVIATION 3.86 | 26.55 kilogram per square meter STANDARD_DEVIATION 3.754 |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 92 Participants | 47 Participants | 45 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 190 Participants | 96 Participants | 94 Participants |
| Region of Enrollment United States | 295 participants | 150 participants | 145 participants |
| Sex: Female, Male Female | 201 Participants | 107 Participants | 94 Participants |
| Sex: Female, Male Male | 94 Participants | 43 Participants | 51 Participants |
| Weight | 74.99 kilograms STANDARD_DEVIATION 14.273 | 74.27 kilograms STANDARD_DEVIATION 15.05 | 75.73 kilograms STANDARD_DEVIATION 13.434 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 150 | 0 / 145 |
| serious Total, serious adverse events | 0 / 150 | 0 / 145 |
Outcome results
Primary
Latency to Sleep Onset After Middle-of-the-Night Awakening at Baseline
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Zolpidem 3.5 mg | Latency to Sleep Onset After Middle-of-the-Night Awakening at Baseline | 68.13 minutes |
| Placebo | Latency to Sleep Onset After Middle-of-the-Night Awakening at Baseline | 69.42 minutes |
Primary
Latency to Sleep Onset After Middle-of-the-Night Awakening During Double-blind Treatment
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Zolpidem 3.5 mg | Latency to Sleep Onset After Middle-of-the-Night Awakening During Double-blind Treatment | 38.22 minutes |
| Placebo | Latency to Sleep Onset After Middle-of-the-Night Awakening During Double-blind Treatment | 56.37 minutes |
Secondary
Morning Sleepiness Rating Following Dosing Post Middle-of-the-Night Awakening at Baseline
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
Population: Safety population: participants who took at least one dose of study medication post-randomization.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Zolpidem 3.5 mg | Morning Sleepiness Rating Following Dosing Post Middle-of-the-Night Awakening at Baseline | 4.87 units on a scale |
| Placebo | Morning Sleepiness Rating Following Dosing Post Middle-of-the-Night Awakening at Baseline | 4.71 units on a scale |
Secondary
Morning Sleepiness Rating Following Dosing Post Middle-of-the-Night Awakening During Double-blind Treatment
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
Population: Safety population: participants who took at least one dose of study medication post-randomization.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Zolpidem 3.5 mg | Morning Sleepiness Rating Following Dosing Post Middle-of-the-Night Awakening During Double-blind Treatment | 5.59 units on a scale |
| Placebo | Morning Sleepiness Rating Following Dosing Post Middle-of-the-Night Awakening During Double-blind Treatment | 5.24 units on a scale |
p-value: 0.0041ANCOVA
Secondary
Subjective Number of Awakenings Following Middle-of-the-Night Awakening at Baseline.
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Zolpidem 3.5 mg | Subjective Number of Awakenings Following Middle-of-the-Night Awakening at Baseline. | 0 awakenings | 16.7 percentage of participants |
| Zolpidem 3.5 mg | Subjective Number of Awakenings Following Middle-of-the-Night Awakening at Baseline. | >0 and <=1 awakenings | 46.0 percentage of participants |
| Zolpidem 3.5 mg | Subjective Number of Awakenings Following Middle-of-the-Night Awakening at Baseline. | >1 and <=2 awakenings | 26.0 percentage of participants |
| Zolpidem 3.5 mg | Subjective Number of Awakenings Following Middle-of-the-Night Awakening at Baseline. | >2 awakenings | 11.3 percentage of participants |
| Placebo | Subjective Number of Awakenings Following Middle-of-the-Night Awakening at Baseline. | >2 awakenings | 16.0 percentage of participants |
| Placebo | Subjective Number of Awakenings Following Middle-of-the-Night Awakening at Baseline. | 0 awakenings | 11.8 percentage of participants |
| Placebo | Subjective Number of Awakenings Following Middle-of-the-Night Awakening at Baseline. | >1 and <=2 awakenings | 27.1 percentage of participants |
| Placebo | Subjective Number of Awakenings Following Middle-of-the-Night Awakening at Baseline. | >0 and <=1 awakenings | 45.1 percentage of participants |
Secondary
Subjective Number of Awakenings Following Middle-of-the-Night Awakening During Double-blind Treatment
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Zolpidem 3.5 mg | Subjective Number of Awakenings Following Middle-of-the-Night Awakening During Double-blind Treatment | 0 awakenings | 30.0 percentage of participants |
| Zolpidem 3.5 mg | Subjective Number of Awakenings Following Middle-of-the-Night Awakening During Double-blind Treatment | >0 and <=1 awakenings | 46.0 percentage of participants |
| Zolpidem 3.5 mg | Subjective Number of Awakenings Following Middle-of-the-Night Awakening During Double-blind Treatment | >1 and <=2 awakenings | 17.3 percentage of participants |
| Zolpidem 3.5 mg | Subjective Number of Awakenings Following Middle-of-the-Night Awakening During Double-blind Treatment | >2 awakenings | 6.7 percentage of participants |
| Placebo | Subjective Number of Awakenings Following Middle-of-the-Night Awakening During Double-blind Treatment | >2 awakenings | 15.3 percentage of participants |
| Placebo | Subjective Number of Awakenings Following Middle-of-the-Night Awakening During Double-blind Treatment | 0 awakenings | 16.7 percentage of participants |
| Placebo | Subjective Number of Awakenings Following Middle-of-the-Night Awakening During Double-blind Treatment | >1 and <=2 awakenings | 25.0 percentage of participants |
| Placebo | Subjective Number of Awakenings Following Middle-of-the-Night Awakening During Double-blind Treatment | >0 and <=1 awakenings | 43.1 percentage of participants |
p-value: <0.001ANCOVA
Secondary
Subjective Total Sleep Time Following Middle-of-the-Night Awakening at Baseline
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Zolpidem 3.5 mg | Subjective Total Sleep Time Following Middle-of-the-Night Awakening at Baseline | 241.2 minutes |
| Placebo | Subjective Total Sleep Time Following Middle-of-the-Night Awakening at Baseline | 222.9 minutes |
Secondary
Subjective Total Sleep Time Following Middle-of-the-Night Awakening During Double-blind Treatment
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Zolpidem 3.5 mg | Subjective Total Sleep Time Following Middle-of-the-Night Awakening During Double-blind Treatment | 264.1 minutes |
| Placebo | Subjective Total Sleep Time Following Middle-of-the-Night Awakening During Double-blind Treatment | 255.0 minutes |
Secondary
Subjective Wake Time After Sleep Onset Following Middle-of-the-Night Awakening at Baseline
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Zolpidem 3.5 mg | Subjective Wake Time After Sleep Onset Following Middle-of-the-Night Awakening at Baseline | No wake time | 16.7 percentage of participants |
| Zolpidem 3.5 mg | Subjective Wake Time After Sleep Onset Following Middle-of-the-Night Awakening at Baseline | >0 to 20 minutes | 18.7 percentage of participants |
| Zolpidem 3.5 mg | Subjective Wake Time After Sleep Onset Following Middle-of-the-Night Awakening at Baseline | 21 to 60 minutes | 25.3 percentage of participants |
| Zolpidem 3.5 mg | Subjective Wake Time After Sleep Onset Following Middle-of-the-Night Awakening at Baseline | >60 minutes | 39.3 percentage of participants |
| Placebo | Subjective Wake Time After Sleep Onset Following Middle-of-the-Night Awakening at Baseline | >60 minutes | 41.0 percentage of participants |
| Placebo | Subjective Wake Time After Sleep Onset Following Middle-of-the-Night Awakening at Baseline | No wake time | 11.8 percentage of participants |
| Placebo | Subjective Wake Time After Sleep Onset Following Middle-of-the-Night Awakening at Baseline | 21 to 60 minutes | 32.6 percentage of participants |
| Placebo | Subjective Wake Time After Sleep Onset Following Middle-of-the-Night Awakening at Baseline | >0 to 20 minutes | 14.6 percentage of participants |
Secondary
Subjective Wake Time After Sleep Onset Following Middle-of-the-Night Awakening During Double-blind Treatment
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Zolpidem 3.5 mg | Subjective Wake Time After Sleep Onset Following Middle-of-the-Night Awakening During Double-blind Treatment | No wake time | 30.0 percentage of participants |
| Zolpidem 3.5 mg | Subjective Wake Time After Sleep Onset Following Middle-of-the-Night Awakening During Double-blind Treatment | >0 to 20 minutes | 27.3 percentage of participants |
| Zolpidem 3.5 mg | Subjective Wake Time After Sleep Onset Following Middle-of-the-Night Awakening During Double-blind Treatment | 21 to 60 minutes | 26.0 percentage of participants |
| Zolpidem 3.5 mg | Subjective Wake Time After Sleep Onset Following Middle-of-the-Night Awakening During Double-blind Treatment | > 60 minutes | 16.7 percentage of participants |
| Placebo | Subjective Wake Time After Sleep Onset Following Middle-of-the-Night Awakening During Double-blind Treatment | > 60 minutes | 25.0 percentage of participants |
| Placebo | Subjective Wake Time After Sleep Onset Following Middle-of-the-Night Awakening During Double-blind Treatment | No wake time | 16.7 percentage of participants |
| Placebo | Subjective Wake Time After Sleep Onset Following Middle-of-the-Night Awakening During Double-blind Treatment | 21 to 60 minutes | 31.9 percentage of participants |
| Placebo | Subjective Wake Time After Sleep Onset Following Middle-of-the-Night Awakening During Double-blind Treatment | >0 to 20 minutes | 26.4 percentage of participants |
p-value: 0.006ANCOVA