Fibromyalgia, Sleep Disorders
Conditions
Keywords
Fibromyalgia sleep maintenance disturbance pregabalin
Brief summary
The purpose of the study is to demonstrate the effect of Lyrica on Wake after sleep onset in subjects with fibromyalgia with sleep maintenance disturbance (on polysomnogram)
Interventions
DRUGPregabalin
Capsule, flexible dosing double-blind. Treatment duration is approximately 4 weeks titrated to 300-450 mg/day
DRUGPlacebo
Capsule, flexible dosing double-blind. Treatment duration is approximately 4 weeks
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects must meet diagnostic criteria for fibromyalgia; * Subjects must report difficulty in maintaining sleep at least 3 times per week and meet Research Diagnostic Criteria (RDC) for insomnia disorder, corroborated by subject diary, and meet PSG inclusion criteria at visit 3.
Exclusion criteria
* History of active sleep disorder other than Research Diagnostic Criteria(RDC) insomnia criteria or any sleep or circadian rhythm disturbance; * Use of medications known to affect sleep wake function by Visit 2; * Involved in night or rotating shift work, or travel across \>4 time zones 14 days prior to screening and during study; regular daytime napping * PSG finding of apnea/hypopnea or periodic limb movement with arousal index \>10/hr on either night of PSG.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Wake After Sleep Onset (WASO) at Weeks 5 and 11 | Week 5 (End of Intervention Period 1) and Week 11 (End of Intervention Period 2) or Early Termination (ET) | WASO was the sum of wake time during sleep measured in epochs (30 seconds of polysomnography \[PSG\]) recording) after the onset of persistent sleep and prior to final awakening and wake time after sleep (the number of epochs after the final awakening until the end of PSG recording \[i.e. awake epoch immediately prior to the end of the recording\]) on 2 consecutive nights divided by 2 at the end of each intervention period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Wake Time After Sleep (WTAS) | Week 5 (End of Intervention Period 1) and Week 11 (End of Intervention Period 2) or ET | WTAS, as determined by PSG, was the total amount of time awake after the final awakening until the end of the 8 hours. WTAS was the sum of 2 consecutive nights of recordings divided by 2 at the end of each intervention period. |
| Total Sleep Time (TST) | Week 5 (End of Intervention Period 1) and Week 11 (End of Intervention Period 2) or ET | TST, as determined by PSG, was the number of non-wake epochs from the beginning of recording to the end of the recording. TST was the sum of 2 consecutive nights of recording divided by 2 at the end of each intervention period. |
| Sleep Efficiency (SE) | Week 5 (End of Intervention Period 1) and Week 11 (End of Intervention Period 2) or ET | SE, as determined by PSG, was the TST divided by the time in bed, multiplied by 100. The sum of 2 consecutive nights of recording divided by 2 at the end of each intervention period. |
| Number of Awakenings After Sleep Onset (NAASO 1) | Week 5 (End of Intervention Period 1) and Week 11 (End of Intervention Period 2) or ET | NAASO 1, as determined by PSG, was the number of times there was a wake period of at least one epoch in duration. Each entry counted was separated by a Stage 2 epoch, Stage 3 and 4 epoch, or Stage rapid eye movement (REM) epoch. The sum of 2 consecutive nights of recording was divided by 2 at the end of each intervention period. |
| Number of Awakenings After Sleep Onset (NAASO 2) | Week 5 (End of Intervention Period 1) and Week 11 (End of Intervention Period 2) or ET | NAASO 2, as determined by PSG, was the number of times that there was a wake period of at least two epochs in duration. Each entry counted was separated by a Stage 2 epoch, Stage 3 and 4 epoch, or Stage REM epoch. The sum of 2 consecutive nights of recording divided by 2 at the end of each intervention period. |
| Latency to Persistent Sleep (LPS) | Week 5 (End of Intervention Period 1) and Week 11 (End of Intervention Period 2) or ET | LPS, as determined by PSG, was the total number of epochs recorded on 2 consecutive nights divided by 2 at the end of each intervention period, from the beginning of the recording to the start of the first 20 consecutive non-wake epochs. |
| WASO by Hour of the Night | Week 5 (End of Intervention Period 1) and Week 11 (End of Intervention Period 2) or ET | WASO, as determined by PSG, was the wake time during sleep (number of wake epochs after the onset of persistent sleep and prior to final awakening) and wake time after sleep (the number of epochs after the final awakening until the end of PSG recording) on 2 consecutive nights divided by 2 at the end of each intervention period by each individual hour (8 hours total). |
| WASO by Each Quarter of the Night | Week 5 (End of Intervention Period 1) and Week 11 (End of Intervention Period 2) or ET | WASO, as determined by PSG, was the sum of wake time during sleep (number of wake epochs after the onset of persistent sleep and prior to final awakening) and wake time after sleep (the number of epochs after the final awakening until the end of PSG recording) on 2 consecutive nights divided by 2 at the end of each intervention period by each individual quarter of the night (eight hours in 2 hour increments). |
| Wake Time During Sleep (WTDS) | Week 5 (End of Intervention Period 1) and Week 11 (End of Intervention Period 2) or ET | WTDS, as determined by PSG, was the total amount of time awake the participant experienced after the onset of persistent sleep and prior to the final awakening, or at the end of 8 hours of recording. WTDS was the sum of 2 consecutive nights of recordings divided by 2 at the end of each intervention period. |
| Change From Baseline in MOS-SS Sleep Disturbance at Weeks 5 and 11 | Week 1 (Baseline Intervention Period 1), Week 5 (End of Intervention Period 1), Week 7 (Baseline Intervention Period 2) and Week 11 (End of Intervention Period 2) or ET | MOS-SS, a participant rated instrument used to assess sleep quantity and quality over the previous week, was comprised of 12 items yielding 7 subscale scores and 2 index composite index scores. Sleep Disturbance subscale score (4 items): individual scores were transformed (actual raw score minus lowest possible score divided by possible raw score range times 100) and ranged from 0 to 100; higher score indicated greater disturbance. Total score ranged=0 to 100; higher score indicates greater intensity of attribute. Change was score at week x minus score at baseline. |
| Change From Baseline in MOS-SS Sleep Problems Index II Weeks 5 and 11 | Week 1 (Baseline Intervention Period 1), Week 5 (End of Intervention Period 1), Week 7 (Baseline Intervention Period 2) and Week 11 (End of Intervention Period 2) or ET | MOS-SS, a participant rated instrument used to assess sleep quantity and quality over the previous week, was compromised of 12 items yielding 7 subscale scores and 2 index composite index scores. Composite index included Sleep Problems Index II (9 items), scores ranged from 0 to 100; higher scores indicated greater sleep problems. Change was score at week x minus score at baseline. |
| Sleep Quality | Weeks 1, 2, 3 and 4 of Each Intervention Period or ET | Sleep Quality as meassured by numeric rating scale (NRS), a participant rated scale 0 to 10, (0 = very poor sleep, 10 = excellent sleep). Weekly values were calculated as the average of the participants daily diary scores. |
| Subjective Wake After Sleep Onset (sWASO) | Weeks 1, 2, 3 and 4 of Each Intervention Period or ET | sWASO as reported on daily SSQ, a participant reported subjective estimate of the total amount of time the participant was awake after initial sleep onset until final awakening. Weekly values were calculated as the average of the participant's daily SSQ values. |
| Latency of Sleep Onset (LSO) | Weeks 1, 2, 3 and 4 of Each Intervention Period or ET | LSO as reported on daily Subjective Sleep Questionnaire (SSQ), a participant reported subjective estimate of the amount of time to fall asleep after lights out. Weekly values were calculated as the average minutes reported on the participant's daily SSQ. |
| Daily Pain Score | Daily up to Day 73 or ET | Pain intensity as measured by NRS; a participant rated scale 0 to 10 (0 = no pain to 10 = worst pain possible). Weekly values were calculated as the average of the participants daily pain scores. |
| Subjective Total Sleep Time (sTST) | Weeks 1, 2, 3 and 4 of Each Intervention Period or ET | sTST as reported on daily SSQ, a participant reported subjective estimate of the total amount of time the participant was asleep after lights out until final awakening. Weekly values were calculated as the average of the participants daily SSQ values. |
| Slow Wave Sleep (SWS) | Week 5 (End of Intervention Period 1) and Week 11 (End of Intervention Period 2) or ET | SWS, as determined by PSG, Stage 3 plus 4 sleep divided by TST times 100 was the percentage of TST. The sum of 2 consecutive nights of recording divided by 2 at the end of each intervention period. |
Countries
Canada, Germany, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population Includes groups randomized to receive matching placebo and Pregabalin, 75 up to 225 mg, twice per day in the first intervention and Pregabalin, 75 up to 225 mg, and matching placebo twice per day in the second intervention | 119 |
| Total | 119 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | Adverse Event | 1 | 2 |
| First Intervention | Lost to Follow-up | 1 | 0 |
| First Intervention | No longer willing to participate | 2 | 0 |
| First Intervention | Protocol Violation | 3 | 6 |
| Second Intervention | No longer willing to participate | 0 | 1 |
| Second Intervention | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age, Continuous | 48.4 Years STANDARD_DEVIATION 9.9 |
| Medical Outcome Study Sleep Scale (MOS-SS) Sleep Disturbance Baseline Measure (Weeks 1 and 7) Week 1 Sleep Disturbance Placebo | 69.32 Scores on a Scale STANDARD_DEVIATION 17.48 |
| Medical Outcome Study Sleep Scale (MOS-SS) Sleep Disturbance Baseline Measure (Weeks 1 and 7) Week 1 Sleep Disturbance Pregabalin | 69.29 Scores on a Scale STANDARD_DEVIATION 20.44 |
| Medical Outcome Study Sleep Scale (MOS-SS) Sleep Disturbance Baseline Measure (Weeks 1 and 7) Week 7 Sleep Disturbance Placebo | 52.75 Scores on a Scale STANDARD_DEVIATION 24.77 |
| Medical Outcome Study Sleep Scale (MOS-SS) Sleep Disturbance Baseline Measure (Weeks 1 and 7) Week 7 Sleep Disturbance Pregabalin | 51.51 Scores on a Scale STANDARD_DEVIATION 26.48 |
| MOS-SS Overall Sleep Index II Baseline Measure (Weeks 1 and 7) Week 1 Sleep Problems Index II Placebo | 62.82 Scores on a Scale STANDARD_DEVIATION 12.96 |
| MOS-SS Overall Sleep Index II Baseline Measure (Weeks 1 and 7) Week 1 Sleep Problems Index II Pregabalin | 63.21 Scores on a Scale STANDARD_DEVIATION 14.27 |
| MOS-SS Overall Sleep Index II Baseline Measure (Weeks 1 and 7) Week 7 Sleep Problems Index II Placebo | 47.22 Scores on a Scale STANDARD_DEVIATION 18.38 |
| MOS-SS Overall Sleep Index II Baseline Measure (Weeks 1 and 7) Week 7 Sleep Problems Index II Pregablin | 48.79 Scores on a Scale STANDARD_DEVIATION 19.89 |
| Sex: Female, Male Female | 103 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 21 / 111 | 51 / 112 |
| serious Total, serious adverse events | 0 / 111 | 0 / 112 |
Outcome results
Primary
Wake After Sleep Onset (WASO) at Weeks 5 and 11
WASO was the sum of wake time during sleep measured in epochs (30 seconds of polysomnography \[PSG\]) recording) after the onset of persistent sleep and prior to final awakening and wake time after sleep (the number of epochs after the final awakening until the end of PSG recording \[i.e. awake epoch immediately prior to the end of the recording\]) on 2 consecutive nights divided by 2 at the end of each intervention period.
Time frame: Week 5 (End of Intervention Period 1) and Week 11 (End of Intervention Period 2) or Early Termination (ET)
Population: Per Protocol Population (PP) = all randomized participants who received study medication at a dose of 300 or 450 mg/day and completed the study without any major protocol violations;
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Wake After Sleep Onset (WASO) at Weeks 5 and 11 | 70.69 Minutes | Standard Error 3.78 |
| Pregabalin | Wake After Sleep Onset (WASO) at Weeks 5 and 11 | 51.54 Minutes | Standard Error 3.78 |
p-value: <0.000195% CI: [-26.69, -11.61]linear mixed effects model
Secondary
Change From Baseline in MOS-SS Sleep Disturbance at Weeks 5 and 11
MOS-SS, a participant rated instrument used to assess sleep quantity and quality over the previous week, was comprised of 12 items yielding 7 subscale scores and 2 index composite index scores. Sleep Disturbance subscale score (4 items): individual scores were transformed (actual raw score minus lowest possible score divided by possible raw score range times 100) and ranged from 0 to 100; higher score indicated greater disturbance. Total score ranged=0 to 100; higher score indicates greater intensity of attribute. Change was score at week x minus score at baseline.
Time frame: Week 1 (Baseline Intervention Period 1), Week 5 (End of Intervention Period 1), Week 7 (Baseline Intervention Period 2) and Week 11 (End of Intervention Period 2) or ET
Population: ITT; n: number of participants at specific time points
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in MOS-SS Sleep Disturbance at Weeks 5 and 11 | Change Week 1 to Week 5 (n=59, 56) | -19.0 Units on a scale | Standard Error 2.98 |
| Placebo | Change From Baseline in MOS-SS Sleep Disturbance at Weeks 5 and 11 | Change Week 7 to Week 11 (n=50, 52) | -2.23 Units on a scale | Standard Error 3.1 |
| Pregabalin | Change From Baseline in MOS-SS Sleep Disturbance at Weeks 5 and 11 | Change Week 1 to Week 5 (n=59, 56) | -27.1 Units on a scale | Standard Error 3.06 |
| Pregabalin | Change From Baseline in MOS-SS Sleep Disturbance at Weeks 5 and 11 | Change Week 7 to Week 11 (n=50, 52) | -21.0 Units on a scale | Standard Error 3.04 |
Comparison: Week 5p-value: 0.059195% CI: [-16.59, 0.32]linear mixed effects model
Comparison: Week 11p-value: <0.000195% CI: [-27.43, -10.2]linear mixed effects model
Secondary
Change From Baseline in MOS-SS Sleep Problems Index II Weeks 5 and 11
MOS-SS, a participant rated instrument used to assess sleep quantity and quality over the previous week, was compromised of 12 items yielding 7 subscale scores and 2 index composite index scores. Composite index included Sleep Problems Index II (9 items), scores ranged from 0 to 100; higher scores indicated greater sleep problems. Change was score at week x minus score at baseline.
Time frame: Week 1 (Baseline Intervention Period 1), Week 5 (End of Intervention Period 1), Week 7 (Baseline Intervention Period 2) and Week 11 (End of Intervention Period 2) or ET
Population: ITT
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in MOS-SS Sleep Problems Index II Weeks 5 and 11 | Change Week 1 to Week 5 (n=59, 56) | -16.4 Units on a scale | Standard Error 2.37 |
| Placebo | Change From Baseline in MOS-SS Sleep Problems Index II Weeks 5 and 11 | Change Week 7 to Week 11 (50, 52) | -0.98 Units on a scale | Standard Error 2.51 |
| Pregabalin | Change From Baseline in MOS-SS Sleep Problems Index II Weeks 5 and 11 | Change Week 1 to Week 5 (n=59, 56) | -21.9 Units on a scale | Standard Error 2.43 |
| Pregabalin | Change From Baseline in MOS-SS Sleep Problems Index II Weeks 5 and 11 | Change Week 7 to Week 11 (50, 52) | -14.4 Units on a scale | Standard Error 2.46 |
Comparison: Week 5p-value: 0.110195% CI: [-12.2, 1.26]linear mixed effects model
Comparison: Week 11p-value: 0.000295% CI: [-20.36, -6.42]linear mixed effects model
Secondary
Daily Pain Score
Pain intensity as measured by NRS; a participant rated scale 0 to 10 (0 = no pain to 10 = worst pain possible). Weekly values were calculated as the average of the participants daily pain scores.
Time frame: Daily up to Day 73 or ET
Population: ITT; LOCF
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Daily Pain Score | Week 1 | 6.12 Units on a scale | Standard Error 0.18 |
| Placebo | Daily Pain Score | Week 2 | 5.81 Units on a scale | Standard Error 0.18 |
| Placebo | Daily Pain Score | Week 3 | 5.73 Units on a scale | Standard Error 0.19 |
| Placebo | Daily Pain Score | Week 4 | 5.44 Units on a scale | Standard Error 0.2 |
| Pregabalin | Daily Pain Score | Week 4 | 4.92 Units on a scale | Standard Error 0.2 |
| Pregabalin | Daily Pain Score | Week 1 | 5.42 Units on a scale | Standard Error 0.18 |
| Pregabalin | Daily Pain Score | Week 3 | 5.14 Units on a scale | Standard Error 0.19 |
| Pregabalin | Daily Pain Score | Week 2 | 5.10 Units on a scale | Standard Error 0.18 |
Comparison: Week 1p-value: <0.000195% CI: [-1.02, -0.37]linear mixed effects model
Comparison: Week 2p-value: 0.000195% CI: [-1.06, -0.36]linear mixed effects model
Comparison: Week 3p-value: 0.001495% CI: [-0.95, -0.24]linear mixed effects model
Comparison: Week 4p-value: 0.008495% CI: [-0.9, -0.14]linear mixed effects model
Secondary
Latency of Sleep Onset (LSO)
LSO as reported on daily Subjective Sleep Questionnaire (SSQ), a participant reported subjective estimate of the amount of time to fall asleep after lights out. Weekly values were calculated as the average minutes reported on the participant's daily SSQ.
Time frame: Weeks 1, 2, 3 and 4 of Each Intervention Period or ET
Population: ITT; LOCF
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Latency of Sleep Onset (LSO) | Week 3 | 48.92 Minutes | Standard Error 4.01 |
| Placebo | Latency of Sleep Onset (LSO) | Week 1 | 51.23 Minutes | Standard Error 2.61 |
| Placebo | Latency of Sleep Onset (LSO) | Week 4 | 46.70 Minutes | Standard Error 2.68 |
| Placebo | Latency of Sleep Onset (LSO) | Week 2 | 49.94 Minutes | Standard Error 2.92 |
| Pregabalin | Latency of Sleep Onset (LSO) | Week 4 | 40.51 Minutes | Standard Error 2.68 |
| Pregabalin | Latency of Sleep Onset (LSO) | Week 1 | 43.56 Minutes | Standard Error 2.61 |
| Pregabalin | Latency of Sleep Onset (LSO) | Week 3 | 43.24 Minutes | Standard Error 4.02 |
| Pregabalin | Latency of Sleep Onset (LSO) | Week 2 | 42.27 Minutes | Standard Error 2.92 |
Comparison: Week 1p-value: 0.000195% CI: [-11.44, -3.89]linear mixed effects model
Comparison: Week 2p-value: 0.007795% CI: [-13.27, -2.07]linear mixed effects model
Comparison: Week 3p-value: 0.219695% CI: [-14.81, 3.44]linear mixed effects model
Comparison: Week 4p-value: 0.008195% CI: [-10.73, -1.64]linear mixed effects model
Secondary
Latency to Persistent Sleep (LPS)
LPS, as determined by PSG, was the total number of epochs recorded on 2 consecutive nights divided by 2 at the end of each intervention period, from the beginning of the recording to the start of the first 20 consecutive non-wake epochs.
Time frame: Week 5 (End of Intervention Period 1) and Week 11 (End of Intervention Period 2) or ET
Population: ITT
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Latency to Persistent Sleep (LPS) | 41.63 Minutes | Standard Error 3.7 |
| Pregabalin | Latency to Persistent Sleep (LPS) | 34.45 Minutes | Standard Error 3.74 |
p-value: 0.044795% CI: [-14.18, -0.17]linear mixed effects model
Secondary
Number of Awakenings After Sleep Onset (NAASO 1)
NAASO 1, as determined by PSG, was the number of times there was a wake period of at least one epoch in duration. Each entry counted was separated by a Stage 2 epoch, Stage 3 and 4 epoch, or Stage rapid eye movement (REM) epoch. The sum of 2 consecutive nights of recording was divided by 2 at the end of each intervention period.
Time frame: Week 5 (End of Intervention Period 1) and Week 11 (End of Intervention Period 2) or ET
Population: ITT
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Number of Awakenings After Sleep Onset (NAASO 1) | 26.92 Awakenings | Standard Error 1 |
| Pregabalin | Number of Awakenings After Sleep Onset (NAASO 1) | 24.51 Awakenings | Standard Error 1 |
p-value: 0.013595% CI: [-4.31, -0.51]linear mixed effects model
Secondary
Number of Awakenings After Sleep Onset (NAASO 2)
NAASO 2, as determined by PSG, was the number of times that there was a wake period of at least two epochs in duration. Each entry counted was separated by a Stage 2 epoch, Stage 3 and 4 epoch, or Stage REM epoch. The sum of 2 consecutive nights of recording divided by 2 at the end of each intervention period.
Time frame: Week 5 (End of Intervention Period 1) and Week 11 (End of Intervention Period 2) or ET
Population: ITT
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Number of Awakenings After Sleep Onset (NAASO 2) | 10.16 Awakenings | Standard Error 0.44 |
| Pregabalin | Number of Awakenings After Sleep Onset (NAASO 2) | 8.63 Awakenings | Standard Error 0.45 |
p-value: 0.000895% CI: [-2.41, -0.66]linear mixed effects model
Secondary
Sleep Efficiency (SE)
SE, as determined by PSG, was the TST divided by the time in bed, multiplied by 100. The sum of 2 consecutive nights of recording divided by 2 at the end of each intervention period.
Time frame: Week 5 (End of Intervention Period 1) and Week 11 (End of Intervention Period 2) or ET
Population: ITT
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Sleep Efficiency (SE) | 77.21 Percentage of time asleep | Standard Error 0.97 |
| Pregabalin | Sleep Efficiency (SE) | 82.64 Percentage of time asleep | Standard Error 0.98 |
p-value: <0.000195% CI: [3.74, 7.11]linear mixed effects model
Secondary
Sleep Quality
Sleep Quality as meassured by numeric rating scale (NRS), a participant rated scale 0 to 10, (0 = very poor sleep, 10 = excellent sleep). Weekly values were calculated as the average of the participants daily diary scores.
Time frame: Weeks 1, 2, 3 and 4 of Each Intervention Period or ET
Population: ITT; Last observation carried forward (LOCF)
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Sleep Quality | Week 1 | 4.79 Unit on a scale | Standard Error 0.16 |
| Placebo | Sleep Quality | Week 2 | 4.95 Unit on a scale | Standard Error 0.18 |
| Placebo | Sleep Quality | Week 3 | 5.09 Unit on a scale | Standard Error 0.17 |
| Placebo | Sleep Quality | Week 4 | 5.17 Unit on a scale | Standard Error 0.17 |
| Pregabalin | Sleep Quality | Week 4 | 6.06 Unit on a scale | Standard Error 0.17 |
| Pregabalin | Sleep Quality | Week 1 | 5.70 Unit on a scale | Standard Error 0.17 |
| Pregabalin | Sleep Quality | Week 3 | 5.96 Unit on a scale | Standard Error 0.17 |
| Pregabalin | Sleep Quality | Week 2 | 6.09 Unit on a scale | Standard Error 0.18 |
Comparison: Week 1p-value: <0.000195% CI: [0.58, 1.24]linear mixed effects model
Comparison: Week 2p-value: <0.000195% CI: [0.76, 1.53]linear mixed effects model
Comparison: Week 3p-value: <0.000195% CI: [0.46, 1.28]linear mixed effects model
Comparison: Week 4p-value: <0.000195% CI: [0.51, 1.26]linear mixed effects model
Secondary
Slow Wave Sleep (SWS)
SWS, as determined by PSG, Stage 3 plus 4 sleep divided by TST times 100 was the percentage of TST. The sum of 2 consecutive nights of recording divided by 2 at the end of each intervention period.
Time frame: Week 5 (End of Intervention Period 1) and Week 11 (End of Intervention Period 2) or ET
Population: ITT
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Slow Wave Sleep (SWS) | 15.04 Percentage of total sleep time | Standard Error 1.01 |
| Pregabalin | Slow Wave Sleep (SWS) | 17.18 Percentage of total sleep time | Standard Error 1.01 |
p-value: 0.002495% CI: [0.78, 3.5]linear mixed effects model
Secondary
Subjective Total Sleep Time (sTST)
sTST as reported on daily SSQ, a participant reported subjective estimate of the total amount of time the participant was asleep after lights out until final awakening. Weekly values were calculated as the average of the participants daily SSQ values.
Time frame: Weeks 1, 2, 3 and 4 of Each Intervention Period or ET
Population: ITT; LOCF
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Subjective Total Sleep Time (sTST) | Week 1 | 336.8 Minutes | Standard Error 5.4 |
| Placebo | Subjective Total Sleep Time (sTST) | Week 2 | 341.9 Minutes | Standard Error 5.76 |
| Placebo | Subjective Total Sleep Time (sTST) | Week 3 | 344.1 Minutes | Standard Error 5.73 |
| Placebo | Subjective Total Sleep Time (sTST) | Week 4 | 352.5 Minutes | Standard Error 5.6 |
| Pregabalin | Subjective Total Sleep Time (sTST) | Week 4 | 377.9 Minutes | Standard Error 5.61 |
| Pregabalin | Subjective Total Sleep Time (sTST) | Week 1 | 361.7 Minutes | Standard Error 5.41 |
| Pregabalin | Subjective Total Sleep Time (sTST) | Week 3 | 370.9 Minutes | Standard Error 5.74 |
| Pregabalin | Subjective Total Sleep Time (sTST) | Week 2 | 371.3 Minutes | Standard Error 5.77 |
Comparison: Week 1p-value: <0.000195% CI: [13.25, 36.4]linear mixed effects model
Comparison: Week 2p-value: <0.000195% CI: [18.59, 40.21]linear mixed effects model
Comparison: Week 3p-value: <0.000195% CI: [15.37, 38.21]linear mixed effects model
Comparison: Week 4p-value: <0.000195% CI: [15.03, 35.86]linear mixed effects model
Secondary
Subjective Wake After Sleep Onset (sWASO)
sWASO as reported on daily SSQ, a participant reported subjective estimate of the total amount of time the participant was awake after initial sleep onset until final awakening. Weekly values were calculated as the average of the participant's daily SSQ values.
Time frame: Weeks 1, 2, 3 and 4 of Each Intervention Period or ET
Population: ITT; LOCF
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Subjective Wake After Sleep Onset (sWASO) | Week 1 | 80.86 Minutes | Standard Error 3.71 |
| Placebo | Subjective Wake After Sleep Onset (sWASO) | Week 2 | 75.48 Minutes | Standard Error 3.91 |
| Placebo | Subjective Wake After Sleep Onset (sWASO) | Week 3 | 74.97 Minutes | Standard Error 4.75 |
| Placebo | Subjective Wake After Sleep Onset (sWASO) | Week 4 | 69.65 Minutes | Standard Error 4.2 |
| Pregabalin | Subjective Wake After Sleep Onset (sWASO) | Week 4 | 59.40 Minutes | Standard Error 4.21 |
| Pregabalin | Subjective Wake After Sleep Onset (sWASO) | Week 1 | 62.59 Minutes | Standard Error 3.73 |
| Pregabalin | Subjective Wake After Sleep Onset (sWASO) | Week 3 | 61.73 Minutes | Standard Error 4.76 |
| Pregabalin | Subjective Wake After Sleep Onset (sWASO) | Week 2 | 59.43 Minutes | Standard Error 3.92 |
Comparison: Week 1p-value: <0.000195% CI: [-27.02, -9.52]linear mixed effects model
Comparison: Week 2p-value: 0.000295% CI: [-24.24, -7.87]linear mixed effects model
Comparison: Week 3p-value: 0.008595% CI: [-23.01, -3.46]linear mixed effects model
Comparison: Week 4p-value: 0.010295% CI: [-18.01, -2.48]linear mixed effects model
Secondary
Total Sleep Time (TST)
TST, as determined by PSG, was the number of non-wake epochs from the beginning of recording to the end of the recording. TST was the sum of 2 consecutive nights of recording divided by 2 at the end of each intervention period.
Time frame: Week 5 (End of Intervention Period 1) and Week 11 (End of Intervention Period 2) or ET
Population: ITT
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Total Sleep Time (TST) | 370.6 Minutes | Standard Error 4.65 |
| Pregabalin | Total Sleep Time (TST) | 396.2 Minutes | Standard Error 4.69 |
p-value: <0.000195% CI: [17.48, 33.61]linear mixed effects model
Secondary
Wake Time After Sleep (WTAS)
WTAS, as determined by PSG, was the total amount of time awake after the final awakening until the end of the 8 hours. WTAS was the sum of 2 consecutive nights of recordings divided by 2 at the end of each intervention period.
Time frame: Week 5 (End of Intervention Period 1) and Week 11 (End of Intervention Period 2) or ET
Population: ITT
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Wake Time After Sleep (WTAS) | 9.19 Minutes | Standard Error 1.55 |
| Pregabalin | Wake Time After Sleep (WTAS) | 7.38 Minutes | Standard Error 1.57 |
p-value: 0.384195% CI: [-5.92, 2.3]linear mixed effects model
Secondary
Wake Time During Sleep (WTDS)
WTDS, as determined by PSG, was the total amount of time awake the participant experienced after the onset of persistent sleep and prior to the final awakening, or at the end of 8 hours of recording. WTDS was the sum of 2 consecutive nights of recordings divided by 2 at the end of each intervention period.
Time frame: Week 5 (End of Intervention Period 1) and Week 11 (End of Intervention Period 2) or ET
Population: Intent to treat (ITT) population: randomized participants who received at least one dose of medication and had at least one efficacy evaluation
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Wake Time During Sleep (WTDS) | 63.38 Minutes | Standard Error 2.9 |
| Pregabalin | Wake Time During Sleep (WTDS) | 45.83 Minutes | Standard Error 2.93 |
p-value: <0.000195% CI: [-23.29, -11.8]linear mixed effects model
Secondary
WASO by Each Quarter of the Night
WASO, as determined by PSG, was the sum of wake time during sleep (number of wake epochs after the onset of persistent sleep and prior to final awakening) and wake time after sleep (the number of epochs after the final awakening until the end of PSG recording) on 2 consecutive nights divided by 2 at the end of each intervention period by each individual quarter of the night (eight hours in 2 hour increments).
Time frame: Week 5 (End of Intervention Period 1) and Week 11 (End of Intervention Period 2) or ET
Population: ITT
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | WASO by Each Quarter of the Night | Quarter 1 | 7.23 Minutes | Standard Error 0.63 |
| Placebo | WASO by Each Quarter of the Night | Quarter 2 | 16.04 Minutes | Standard Error 1.05 |
| Placebo | WASO by Each Quarter of the Night | Quarter 3 | 21.73 Minutes | Standard Error 1.58 |
| Placebo | WASO by Each Quarter of the Night | Quarter 4 | 28.04 Minutes | Standard Error 1.98 |
| Pregabalin | WASO by Each Quarter of the Night | Quarter 4 | 22.60 Minutes | Standard Error 2 |
| Pregabalin | WASO by Each Quarter of the Night | Quarter 1 | 5.98 Minutes | Standard Error 0.64 |
| Pregabalin | WASO by Each Quarter of the Night | Quarter 3 | 14.90 Minutes | Standard Error 1.6 |
| Pregabalin | WASO by Each Quarter of the Night | Quarter 2 | 10.04 Minutes | Standard Error 1.06 |
Comparison: Quarter 1p-value: 0.110695% CI: [-2.79, 0.29]linear mixed effects model
Comparison: Quarter 2p-value: <0.000195% CI: [-8.49, -3.51]linear mixed effects model
Comparison: Quarter 3p-value: 0.000495% CI: [-10.53, -3.13]linear mixed effects model
Comparison: Quarter 4p-value: 0.019995% CI: [-10, -0.88]linear mixed effects model
Secondary
WASO by Hour of the Night
WASO, as determined by PSG, was the wake time during sleep (number of wake epochs after the onset of persistent sleep and prior to final awakening) and wake time after sleep (the number of epochs after the final awakening until the end of PSG recording) on 2 consecutive nights divided by 2 at the end of each intervention period by each individual hour (8 hours total).
Time frame: Week 5 (End of Intervention Period 1) and Week 11 (End of Intervention Period 2) or ET
Population: ITT
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | WASO by Hour of the Night | Hour 5 | 10.55 Minutes | Standard Error 0.9 |
| Placebo | WASO by Hour of the Night | Hour 3 | 7.09 Minutes | Standard Error 0.54 |
| Placebo | WASO by Hour of the Night | Hour 6 | 11.26 Minutes | Standard Error 0.94 |
| Placebo | WASO by Hour of the Night | Hour 2 | 5.66 Minutes | Standard Error 0.52 |
| Placebo | WASO by Hour of the Night | Hour 7 | 10.96 Minutes | Standard Error 0.91 |
| Placebo | WASO by Hour of the Night | Hour 4 | 8.95 Minutes | Standard Error 0.75 |
| Placebo | WASO by Hour of the Night | Hour 8 | 17.08 Minutes | Standard Error 1.34 |
| Placebo | WASO by Hour of the Night | Hour 1 | 1.96 Minutes | Standard Error 0.27 |
| Pregabalin | WASO by Hour of the Night | Hour 8 | 14.23 Minutes | Standard Error 1.35 |
| Pregabalin | WASO by Hour of the Night | Hour 2 | 4.56 Minutes | Standard Error 0.53 |
| Pregabalin | WASO by Hour of the Night | Hour 3 | 4.65 Minutes | Standard Error 0.55 |
| Pregabalin | WASO by Hour of the Night | Hour 4 | 5.43 Minutes | Standard Error 0.75 |
| Pregabalin | WASO by Hour of the Night | Hour 5 | 7.54 Minutes | Standard Error 0.9 |
| Pregabalin | WASO by Hour of the Night | Hour 6 | 7.38 Minutes | Standard Error 0.95 |
| Pregabalin | WASO by Hour of the Night | Hour 7 | 8.38 Minutes | Standard Error 0.92 |
| Pregabalin | WASO by Hour of the Night | Hour 1 | 1.62 Minutes | Standard Error 0.28 |
Comparison: Hour 1p-value: 0.361395% CI: [-1.07, 0.39]linear mixed effects model
Comparison: Hour 2p-value: 0.068695% CI: [-2.29, 0.09]linear mixed effects model
Comparison: Hour 3p-value: 0.000995% CI: [-3.85, -1.03]linear mixed effects model
Comparison: Hour 4p-value: 0.000295% CI: [-5.33, -1.71]linear mixed effects model
Comparison: Hour 5p-value: 0.006595% CI: [-5.16, -0.86]linear mixed effects model
Comparison: Hour 6p-value: 0.002495% CI: [-6.36, -1.41]linear mixed effects model
Comparison: Hour 7p-value: 0.036695% CI: [-5.01, -0.16]linear mixed effects model
Comparison: Hour 8p-value: 0.059395% CI: [-5.82, 0.11]linear mixed effects model