Postherpetic Neuralgia ( PHN )
Conditions
Keywords
Pregabalin, Postherpetic Neuralgia ( PHN )
Brief summary
To prove pregabalin is effective in relieving pain compared with placebo in subjects with postherpetic neuralgia (PHN).
Interventions
Capsule, 300 mg/d, BID, 8 weeks treatment
DRUGPlacebo
Capsule, 300 mg/d, BID, 8 weeks treatment
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female Chinese subjects, ages ≥18 at screening * Subjects with symptoms of neuropathic pain associated with postherpetic neuralgia (PHN). Subjects must have pain present for ﹥3 months after healing of the acute herpes zoster skin rash * At screening (V1), subjects must have a score ≥40mm on the 100-mm visual analog scale (VAS) of the Short Form-McGill Pain Questionnaire (SF-MPQ, see Appendix 3) * At randomization (V2), subjects must have a score ≥40mm on the 100-mm visual analog scale (VAS) of the Short Form-McGill Pain Questionnaire (SF-MPQ, see Appendix 3) * At randomization (V2), subjects must have completed at least 5 daily pain diaries (DPRS, see Appendix 2) and have an average daily pain score ≥4 over the past 7 days
Exclusion criteria
* Subjects who demonstrate a high response to placebo, with 30% decrease on the Pain Visual Analog Scale (VAS) at randomization as compared to screening * Subjects who have a high variability in pain scores during the 1 week screening period, with any difference between two scores ﹥3
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Baseline Mean Pain Score | Baseline | The daily pain rating scale (DPRS) consists of an 11-point numeric scale ranging from 0 (no pain) to 10 (worst possible pain). Participants described their pain during the past 24 hours by choosing the appropriate number between 0 and 10. |
| Change From Baseline in Mean Pain Score at Endpoint | Baseline until end of fixed dose phase (Day 57/Week 8)/Early Termination (Study Endpoint) | The daily pain rating scale (DPRS) consists of an 11-point numeric scale ranging from 0 (no pain) to 10 (worst possible pain). Participants described their pain during the past 24 hours by choosing the appropriate number between 0 and 10. The mean endpoint pain score was obtained from the last 7 available DPRS scores of the daily pain diary while the participant was on study medication, up to and including the day after the last Week 8 (Day 57) dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in MOS-Sleep Scale, Quantity of Sleep Score at Endpoint | Baseline and Day 57 (Week 8)/Early Termination (Study Endpoint) | The MOS-Sleep Scale was a participant-rated questionnaire consisting of 12 items that assessed key constructs of sleep. Instrument scoring yielded 7 subscales (sleep disturbance, snoring, awaken short of breath or with a headache, quantity of sleep, optimal sleep, sleep adequacy, and somnolence) as well as a 9-item overall sleep problems index. The total score ranged from 0 to 100. The MOS Sleep Quantity sub-scale scores ranged from 0 to 24 (number of hours slept). |
| Change From Baseline in Mean Sleep Interference Score at Endpoint | Baseline until end of fixed dose phase (Day 57/Week 8)/Early Termination (Study Endpoint) | Pain-related sleep interference was assessed on an 11-point numerical rating scale ranging from 0 (did not interfere with sleep) to 10 (completely interfered \[unable to sleep due to pain\]). Participants were to describe how their pain had interfered with their sleep during the past 24 hours by choosing the appropriate number between 0 and 10. The mean endpoint score was obtained from the last 7 available scores of the daily diary while the participant was on study medication, up to and including the day after the last Week 8 (Day 57) dose. |
| Change From Baseline in Weekly Mean Sleep Interference Scores at Weeks 1 to 8 | Baseline and weekly from Weeks 1 to 8 | Pain-related sleep interference was assessed on an 11-point numerical rating scale ranging from 0 (did not interfere with sleep) to 10 (completely interfered \[unable to sleep due to pain\]). Participants were to describe how their pain had interfered with their sleep during the past 24 hours by choosing the appropriate number between 0 and 10. The weekly mean score was the sum of the daily scores divided by the number of diary entries during that week. |
| Percentage of 30 Percent (%) Responders at Endpoint | End of fixed dose phase (Day 57/Week 8)/Early Termination (Study Endpoint) | The DPRS consists of an 11-point numeric scale ranging from 0 (no pain) to 10 (worst possible pain). Participants described their pain during the past 24 hours by choosing the appropriate number between 0 and 10. A 30% responder was a participant who had 30% reduction or more in mean pain score at the end of the fixed dose phase (Day 57/Week 8)/Early Termination (Study Endpoint) compared to baseline. |
| Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 3, 5, and 8 | Baseline; Weeks 1, 3, 5, and 8 | SF-MPQ was assessed according to the participant's answer to the SF-MPQ questionnaire. The score for each composite scale (sensory, affective, and total) was derived by summing the reported intensity value for each item within a particular scale where None=0, Mild=1, Moderate=2, and Severe=3. The sensory score was the sum of the scores of the first 11 pain descriptors (throbbing, shooting, stabbing, sharp, cramping, gnawing, hot-burning, aching, heavy, tender, and splitting) and could range from 0-33. The affective score was the sum of the scores of the last 4 pain descriptors (tiring-exhausting, sickening, fearful, and punishing-cruel) and could range from 0-12. The total score was the sum of the scores of all 15 pain descriptors and could range from 0 to 45. Higher scores indicated greater pain. |
| Baseline Pain Visual Analogue Scale (VAS) and Present Pain Intensity (PPI) Scale | Baseline | The VAS was part of the Short Form McGill Pain Questionnaire (SF-MPQ) scale and reflected the overall pain intensity score, The pain VAS was a horizontal line; 100 millimeters (mm) in length, was self-administered by the participant in order to rate pain from 0 (no pain) to 100 (worst possible pain). The PPI was part of the SF-MPQ scale and measured the participant's present pain intensity on a 6-point scale ranging from 0 (no pain) to 5 (excruciating). |
| Change From Baseline in Pain VAS From the SF-MPQ at Endpoint | Baseline to Day 57 (Week 8)/Early Termination (Study Endpoint) | The VAS was part of the SF-MPQ scale and reflected the overall pain intensity score. The pain VAS was a horizontal line; 100 mm in length, was self-administered by the participant in order to rate pain from 0 (no pain) to 100 (worst possible pain). |
| Change From Baseline in PPI Scale From the SF-MPQ at Endpoint | Baseline to Day 57 (Week 8)/Early Termination (Study Endpoint) | The PPI was part of the SF-MPQ scale and measured the participant's present pain intensity on a 6-point scale ranging from 0 (no pain) to 5 (excruciating). |
| Baseline Medical Outcomes Study (MOS)-Sleep Scale Scores | Baseline | The MOS-Sleep Scale was a participant-rated questionnaire consisting of 12 items that assessed key constructs of sleep. Instrument scoring yielded 7 subscales (sleep disturbance, snoring, awaken short of breath or with a headache, quantity of sleep, optimal sleep, sleep adequacy, and somnolence) as well as a 9-item overall sleep problems index. The total score ranged from 0 to 100. With the exception of sleep adequacy, optimal sleep, and quantity, higher scores reflected greater impairment in the MOS-Sleep subscales. The MOS-Sleep Scale was used to evaluate sleep during the previous week. |
| Change From Baseline in MOS-Sleep Scale, Sleep Disturbance Score at Endpoint | Baseline and Day 57 (Week 8)/Early Termination (Study Endpoint) | The MOS-Sleep Scale was a participant-rated questionnaire consisting of 12 items that assessed key constructs of sleep. Instrument scoring yielded 7 subscales (sleep disturbance, snoring, awaken short of breath or with a headache, quantity of sleep, optimal sleep, sleep adequacy, and somnolence) as well as a 9-item overall sleep problems index. The total score ranged from 0 to 100. For sleep disturbance, the subscale score also ranged from 0 to 100, with higher scores representing greater sleep disturbance. |
| Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 8 | Baseline and weekly from Weeks 1 to 8 | The DPRS consists of an 11-point numeric scale ranging from 0 (no pain) to 10 (worst possible pain). Participants described their pain during the past 24 hours by choosing the appropriate number between 0 and 10. The weekly mean pain score was the sum of the daily scores divided by the number of diary entries during that week. |
| Change From Baseline in MOS-Sleep Scale, Awaken Short of Breath Score at Endpoint | Baseline and Day 57 (Week 8)/Early Termination (Study Endpoint) | The MOS-Sleep Scale was a participant-rated questionnaire consisting of 12 items that assessed key constructs of sleep. Instrument scoring yielded 7 subscales (sleep disturbance, snoring, awaken short of breath or with a headache, quantity of sleep, optimal sleep, sleep adequacy, and somnolence) as well as a 9-item overall sleep problems index. The total score ranged from 0 to 100. The awaken short of breath subscale also ranged from 0 to 100, with lower scores indicating less difficulty in breathing. |
| Percentage of Participants Who Had Optimal Sleep at Endpoint | Day 57 (Week 8)/Early Termination (Study Endpoint) | The MOS-Sleep Scale was a participant-rated questionnaire consisting of 12 items that assessed key constructs of sleep. Instrument scoring yielded 7 subscales (sleep disturbance, snoring, awaken short of breath or with a headache, quantity of sleep, optimal sleep, sleep adequacy, and somnolence) as well as a 9-item overall sleep problems index. The total score ranged from 0 to 100. The MOS optimal sleep subscale was a binary outcome derived from the sleep quantity responses: the response was YES if sleep quantity was 7 or 8 hours per night. |
| Change From Baseline in MOS-Sleep Scale, Sleep Adequacy Score at Endpoint | Baseline and Day 57 (Week 8)/Early Termination (Study Endpoint) | The MOS-Sleep Scale was a participant-rated questionnaire consisting of 12 items that assessed key constructs of sleep. Instrument scoring yielded 7 subscales (sleep disturbance, snoring, awaken short of breath or with a headache, quantity of sleep, optimal sleep, sleep adequacy, and somnolence) as well as a 9-item overall sleep problems index. The total score ranged from 0 to 100. The sleep adequacy subscale also ranged from 0 to 100, with higher scores indicating greater sleep adequacy. |
| Change From Baseline in MOS-Sleep Scale, Somnolence Score at Endpoint | Baseline and Day 57 (Week 8)/Early Termination (Study Endpoint) | The MOS-Sleep Scale was a participant-rated questionnaire consisting of 12 items that assessed key constructs of sleep. Instrument scoring yielded 7 subscales (sleep disturbance, snoring, awaken short of breath or with a headache, quantity of sleep, optimal sleep, sleep adequacy, and somnolence) as well as a 9-item overall sleep problems index. The total score ranged from 0 to 100. The somnolence subscale score also ranged from 0 to 100, with lower scores indicating less somnolence. |
| Change From Baseline in MOS-Sleep Scale, Sleep Problems Index Score at Endpoint | Baseline and Day 57 (Week 8)/Early Termination (Study Endpoint) | The MOS-Sleep Scale was a participant-rated questionnaire consisting of 12 items that assessed key constructs of sleep. Instrument scoring yielded 7 subscales (sleep disturbance, snoring, awaken short of breath or with a headache, quantity of sleep, optimal sleep, sleep adequacy, and somnolence) as well as a 9-item overall sleep problems index. The total score ranged from 0 to 100. The sleep problems index subscale score also ranged from 0 to 100, with lower scores indicating fewer sleep problems. |
| Clinical Global Impression of Change (CGIC) Score at Endpoint | Day 57 (Week 8)/Early Termination (Study Endpoint) | The CGIC was a clinician-rated global measure that provided a clinically relevant and easy to interpret account of a clinician's perception of the clinical importance of the participant's improvement or worsening during their involvement in a clinical study. Clinicians rated the participant's overall improvement on a 7-point scale where scores ranged from 1 (very much improved) to 7 (very much worse). |
| Patient Global Impression of Change (PGIC) Score at Endpoint | Day 57 (Week 8)/Early Termination (Study Endpoint) | The PGIC was a participant-rated global measure that provided a clinically relevant and easy to interpret account of a participant's perception of the clinical importance of their own improvement or worsening during their involvement in a clinical study. Participants rated their overall improvement on a 7-point scale where scores ranged from 1 (very much improved) to 7 (very much worse). |
| Baseline Hospital Anxiety and Depression Scale (HADS) Scores | Baseline | The HADS was a self-administered questionnaire that consisted of 2 subscales, 1 measuring anxiety (HADS-A Scale) and the other measuring depression (HADS-D Scale). Each subscale comprised of 7 items; participants assessed how each item applied to them on a scale of 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Subscores from HADS-A (Anxiety) and HADS-D (Depression) were not to be combined. The interpretation of each HADS subscales was as follows: 0-7 normal, 8-10 mild, 11-14 moderate and 15-21 severe. |
| Change From Baseline in HADS Anxiety Total Score at Endpoint | Baseline and Day 57 (Week 8)/Early Termination (Study Endpoint) | The HADS was a self-administered questionnaire that consisted of 2 subscales, 1 measuring anxiety (HADS-A Scale) and the other measuring depression (HADS-D Scale). Each subscale was comprised of 7 items; participants assessed how each item applied to them on a scale of 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Subscores from HADS-A (Anxiety) and HADS-D (Depression) were not to be combined. The interpretation of each HADS subscales was as follows: 0-7 normal, 8-10 mild, 11-14 moderate and 15-21 severe. |
| Change From Baseline in HADS Depression Total Score at Endpoint | Baseline and Day 57 (Week 8)/Early Termination (Study Endpoint) | The HADS was a self-administered questionnaire that consisted of 2 subscales, 1 measuring anxiety (HADS-A Scale) and the other measuring depression (HADS-D Scale). Each subscale was comprised of 7 items; participants assessed how each item applied to them on a scale of 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Subscores from HADS-A (Anxiety) and HADS-D (Depression) were not to be combined. The interpretation of each HADS subscales was as follows: 0-7 normal, 8-10 mild, 11-14 moderate and 15-21 severe. |
| Change From Baseline in MOS-Sleep Scale, Snoring Score at Endpoint | Baseline and Day 57 (Week 8)/Early Termination (Study Endpoint) | The MOS-Sleep Scale was a participant-rated questionnaire consisting of 12 items that assessed key constructs of sleep. Instrument scoring yielded 7 subscales (sleep disturbance, snoring, awaken short of breath or with a headache, quantity of sleep, optimal sleep, sleep adequacy, and somnolence) as well as a 9-item overall sleep problems index. The total score ranged from 0 to 100. The snoring subscale score also ranged from 0 to 100, with lower scores indicating less snoring. |
| Baseline Mean Sleep Interference Score | Baseline | Pain-related sleep interference was assessed on an 11-point numerical rating scale ranging from 0 (did not interfere with sleep) to 10 (completely interfered \[unable to sleep due to pain\]). Participants were to describe how their pain had interfered with their sleep during the past 24 hours by choosing the appropriate number between 0 and 10. |
Countries
China
Participant flow
Recruitment details
223 participants were randomized, as stated on clinicaltrials.gov. However, 1 was randomized by mistake, was considered a screen failure, and was not given any medication. As such, the actual number of participants randomized and assigned to treatment was 222.
Participants by arm
| Arm | Count |
|---|---|
| Pregabalin Participants received 1 matching placebo capsule twice a day (BID) for 1 week (run-in period), followed by an 8-week double-blind treatment phase (1-week dose-titration phase where participants received pregabalin 150 milligram \[mg\] per day in the form of 75 mg BID and a 7-week fixed dose phase where participants received pregabalin 300 mg per day in the form of 150 mg BID), and a 1-week taper-off phase where participants received pregabalin 150 mg per day (in the form of 75 mg BID). | 111 |
| Placebo Participants received matching placebo capsule(s) for a period of 10 weeks. | 109 |
| Total | 220 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 2 |
| Overall Study | Did not meet entrance criteria | 0 | 2 |
| Overall Study | Did not receive treatment | 1 | 1 |
| Overall Study | Insufficient clinical response | 0 | 2 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Other | 2 | 4 |
| Overall Study | Protocol Violation | 2 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 5 |
Baseline characteristics
| Characteristic | Pregabalin | Placebo | Total |
|---|---|---|---|
| Age, Customized 18-44 years | 4 participants | 3 participants | 7 participants |
| Age, Customized 45-64 years | 39 participants | 47 participants | 86 participants |
| Age, Customized More than or equal to (>=)65 years | 68 participants | 59 participants | 127 participants |
| Sex: Female, Male Female | 54 Participants | 47 Participants | 101 Participants |
| Sex: Female, Male Male | 57 Participants | 62 Participants | 119 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 40 / 111 | 21 / 109 |
| serious Total, serious adverse events | 2 / 111 | 0 / 109 |
Outcome results
Primary
Baseline Mean Pain Score
The daily pain rating scale (DPRS) consists of an 11-point numeric scale ranging from 0 (no pain) to 10 (worst possible pain). Participants described their pain during the past 24 hours by choosing the appropriate number between 0 and 10.
Time frame: Baseline
Population: All participants in the Full Analysis Set (FAS) population (all participants randomized to treatment that received at least 1 dose of study medication) who had available data for this outcome measure. The Last Observation Carried Forward (LOCF) method was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Baseline Mean Pain Score | 5.93 units on a scale | Standard Deviation 1.304 |
| Placebo | Baseline Mean Pain Score | 6.08 units on a scale | Standard Deviation 1.266 |
Primary
Change From Baseline in Mean Pain Score at Endpoint
The daily pain rating scale (DPRS) consists of an 11-point numeric scale ranging from 0 (no pain) to 10 (worst possible pain). Participants described their pain during the past 24 hours by choosing the appropriate number between 0 and 10. The mean endpoint pain score was obtained from the last 7 available DPRS scores of the daily pain diary while the participant was on study medication, up to and including the day after the last Week 8 (Day 57) dose.
Time frame: Baseline until end of fixed dose phase (Day 57/Week 8)/Early Termination (Study Endpoint)
Population: All participants in the Full Analysis Set (FAS) population (all participants randomized to treatment that received at least 1 dose of study medication) who had available data for this outcome measure. The Last Observation Carried Forward (LOCF) method was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Change From Baseline in Mean Pain Score at Endpoint | -1.81 units on a scale | Standard Error 0.137 |
| Placebo | Change From Baseline in Mean Pain Score at Endpoint | -1.09 units on a scale | Standard Error 0.142 |
Comparison: Analysis performed using a general linear model with treatment and center as factors, and baseline value as a covariate.p-value: 0.000295% CI: [-1.08, -0.34]ANCOVA
Secondary
Baseline Hospital Anxiety and Depression Scale (HADS) Scores
The HADS was a self-administered questionnaire that consisted of 2 subscales, 1 measuring anxiety (HADS-A Scale) and the other measuring depression (HADS-D Scale). Each subscale comprised of 7 items; participants assessed how each item applied to them on a scale of 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Subscores from HADS-A (Anxiety) and HADS-D (Depression) were not to be combined. The interpretation of each HADS subscales was as follows: 0-7 normal, 8-10 mild, 11-14 moderate and 15-21 severe.
Time frame: Baseline
Population: All participants in the FAS population (all participants randomized to treatment that received at least 1 dose of study medication) who had available data for this outcome measure. The LOCF method was used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Baseline Hospital Anxiety and Depression Scale (HADS) Scores | Anxiety total score | 3.22 units on a scale | Standard Deviation 3.921 |
| Pregabalin | Baseline Hospital Anxiety and Depression Scale (HADS) Scores | Depression total score | 3.45 units on a scale | Standard Deviation 3.963 |
| Placebo | Baseline Hospital Anxiety and Depression Scale (HADS) Scores | Anxiety total score | 3.37 units on a scale | Standard Deviation 3.466 |
| Placebo | Baseline Hospital Anxiety and Depression Scale (HADS) Scores | Depression total score | 3.47 units on a scale | Standard Deviation 3.387 |
Secondary
Baseline Mean Sleep Interference Score
Pain-related sleep interference was assessed on an 11-point numerical rating scale ranging from 0 (did not interfere with sleep) to 10 (completely interfered \[unable to sleep due to pain\]). Participants were to describe how their pain had interfered with their sleep during the past 24 hours by choosing the appropriate number between 0 and 10.
Time frame: Baseline
Population: All participants in the FAS population (all participants randomized to treatment that received at least 1 dose of study medication) who had available data for this outcome measure. The LOCF method was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Baseline Mean Sleep Interference Score | 3.81 units on a scale | Standard Deviation 2.436 |
| Placebo | Baseline Mean Sleep Interference Score | 4.54 units on a scale | Standard Deviation 2.027 |
Secondary
Baseline Medical Outcomes Study (MOS)-Sleep Scale Scores
The MOS-Sleep Scale was a participant-rated questionnaire consisting of 12 items that assessed key constructs of sleep. Instrument scoring yielded 7 subscales (sleep disturbance, snoring, awaken short of breath or with a headache, quantity of sleep, optimal sleep, sleep adequacy, and somnolence) as well as a 9-item overall sleep problems index. The total score ranged from 0 to 100. With the exception of sleep adequacy, optimal sleep, and quantity, higher scores reflected greater impairment in the MOS-Sleep subscales. The MOS-Sleep Scale was used to evaluate sleep during the previous week.
Time frame: Baseline
Population: The FAS population consisted of all participants randomized to treatment that received at least 1 dose of study medication. The LOCF method was used in the analysis of this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Baseline Medical Outcomes Study (MOS)-Sleep Scale Scores | Awaken short of breath score | 9.91 units on a scale | Standard Deviation 21.213 |
| Pregabalin | Baseline Medical Outcomes Study (MOS)-Sleep Scale Scores | Somnolence score | 32.25 units on a scale | Standard Deviation 19.95 |
| Pregabalin | Baseline Medical Outcomes Study (MOS)-Sleep Scale Scores | Quantity of sleep score | 6.05 units on a scale | Standard Deviation 1.534 |
| Pregabalin | Baseline Medical Outcomes Study (MOS)-Sleep Scale Scores | Sleep problems index score | 31.38 units on a scale | Standard Deviation 20.691 |
| Pregabalin | Baseline Medical Outcomes Study (MOS)-Sleep Scale Scores | Sleep disturbance score | 36.09 units on a scale | Standard Deviation 25.542 |
| Pregabalin | Baseline Medical Outcomes Study (MOS)-Sleep Scale Scores | Snoring score | 29.19 units on a scale | Standard Deviation 32.45 |
| Pregabalin | Baseline Medical Outcomes Study (MOS)-Sleep Scale Scores | Sleep adequacy score | 57.66 units on a scale | Standard Deviation 31.449 |
| Placebo | Baseline Medical Outcomes Study (MOS)-Sleep Scale Scores | Sleep disturbance score | 35.08 units on a scale | Standard Deviation 22.365 |
| Placebo | Baseline Medical Outcomes Study (MOS)-Sleep Scale Scores | Sleep problems index score | 29.27 units on a scale | Standard Deviation 17.292 |
| Placebo | Baseline Medical Outcomes Study (MOS)-Sleep Scale Scores | Awaken short of breath score | 8.07 units on a scale | Standard Deviation 18.282 |
| Placebo | Baseline Medical Outcomes Study (MOS)-Sleep Scale Scores | Snoring score | 30.83 units on a scale | Standard Deviation 35.017 |
| Placebo | Baseline Medical Outcomes Study (MOS)-Sleep Scale Scores | Quantity of sleep score | 5.97 units on a scale | Standard Deviation 1.524 |
| Placebo | Baseline Medical Outcomes Study (MOS)-Sleep Scale Scores | Sleep adequacy score | 60.46 units on a scale | Standard Deviation 29.008 |
| Placebo | Baseline Medical Outcomes Study (MOS)-Sleep Scale Scores | Somnolence score | 30.89 units on a scale | Standard Deviation 17.816 |
Secondary
Baseline Pain Visual Analogue Scale (VAS) and Present Pain Intensity (PPI) Scale
The VAS was part of the Short Form McGill Pain Questionnaire (SF-MPQ) scale and reflected the overall pain intensity score, The pain VAS was a horizontal line; 100 millimeters (mm) in length, was self-administered by the participant in order to rate pain from 0 (no pain) to 100 (worst possible pain). The PPI was part of the SF-MPQ scale and measured the participant's present pain intensity on a 6-point scale ranging from 0 (no pain) to 5 (excruciating).
Time frame: Baseline
Population: The FAS population consisted of all participants randomized to treatment that received at least 1 dose of study medication. The LOCF method was used in the analysis of this outcome measure. Number of participants evaluable for PPI=110, 108
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Baseline Pain Visual Analogue Scale (VAS) and Present Pain Intensity (PPI) Scale | VAS | 60.39 units on a scale | Standard Deviation 13.064 |
| Pregabalin | Baseline Pain Visual Analogue Scale (VAS) and Present Pain Intensity (PPI) Scale | PPI | 2.33 units on a scale | Standard Deviation 0.94 |
| Placebo | Baseline Pain Visual Analogue Scale (VAS) and Present Pain Intensity (PPI) Scale | PPI | 2.42 units on a scale | Standard Deviation 0.738 |
| Placebo | Baseline Pain Visual Analogue Scale (VAS) and Present Pain Intensity (PPI) Scale | VAS | 62.60 units on a scale | Standard Deviation 12.252 |
Secondary
Change From Baseline in HADS Anxiety Total Score at Endpoint
The HADS was a self-administered questionnaire that consisted of 2 subscales, 1 measuring anxiety (HADS-A Scale) and the other measuring depression (HADS-D Scale). Each subscale was comprised of 7 items; participants assessed how each item applied to them on a scale of 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Subscores from HADS-A (Anxiety) and HADS-D (Depression) were not to be combined. The interpretation of each HADS subscales was as follows: 0-7 normal, 8-10 mild, 11-14 moderate and 15-21 severe.
Time frame: Baseline and Day 57 (Week 8)/Early Termination (Study Endpoint)
Population: All participants in the FAS population (all participants randomized to treatment that received at least 1 dose of study medication) who had available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Change From Baseline in HADS Anxiety Total Score at Endpoint | -0.92 units on a scale | Standard Error 0.233 |
| Placebo | Change From Baseline in HADS Anxiety Total Score at Endpoint | -0.71 units on a scale | Standard Error 0.241 |
Comparison: Analysis was performed using a general linear model with treatment and center as factors, and the baseline value as a covariate.p-value: 0.50695% CI: [-0.83, 0.41]ANCOVA
Secondary
Change From Baseline in HADS Depression Total Score at Endpoint
The HADS was a self-administered questionnaire that consisted of 2 subscales, 1 measuring anxiety (HADS-A Scale) and the other measuring depression (HADS-D Scale). Each subscale was comprised of 7 items; participants assessed how each item applied to them on a scale of 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Subscores from HADS-A (Anxiety) and HADS-D (Depression) were not to be combined. The interpretation of each HADS subscales was as follows: 0-7 normal, 8-10 mild, 11-14 moderate and 15-21 severe.
Time frame: Baseline and Day 57 (Week 8)/Early Termination (Study Endpoint)
Population: All participants in the FAS population (all participants randomized to treatment that received at least 1 dose of study medication) who had available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Change From Baseline in HADS Depression Total Score at Endpoint | -0.65 units on a scale | Standard Error 0.209 |
| Placebo | Change From Baseline in HADS Depression Total Score at Endpoint | -0.55 units on a scale | Standard Error 0.217 |
Comparison: Analysis was performed using a general linear model with treatment and center as factors, and the baseline value as a covariate.p-value: 0.724795% CI: [-0.66, 0.46]ANCOVA
Secondary
Change From Baseline in Mean Sleep Interference Score at Endpoint
Pain-related sleep interference was assessed on an 11-point numerical rating scale ranging from 0 (did not interfere with sleep) to 10 (completely interfered \[unable to sleep due to pain\]). Participants were to describe how their pain had interfered with their sleep during the past 24 hours by choosing the appropriate number between 0 and 10. The mean endpoint score was obtained from the last 7 available scores of the daily diary while the participant was on study medication, up to and including the day after the last Week 8 (Day 57) dose.
Time frame: Baseline until end of fixed dose phase (Day 57/Week 8)/Early Termination (Study Endpoint)
Population: All participants in the FAS population (all participants randomized to treatment that received at least 1 dose of study medication) who had available data for this outcome measure. The LOCF method was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Change From Baseline in Mean Sleep Interference Score at Endpoint | -1.24 units on a scale | Standard Error 0.145 |
| Placebo | Change From Baseline in Mean Sleep Interference Score at Endpoint | -0.70 units on a scale | Standard Error 0.15 |
Comparison: Analysis performed using a general linear model with treatment and center as factors, and baseline value as a covariate.p-value: 0.007995% CI: [-0.93, -0.14]ANCOVA
Secondary
Change From Baseline in MOS-Sleep Scale, Awaken Short of Breath Score at Endpoint
The MOS-Sleep Scale was a participant-rated questionnaire consisting of 12 items that assessed key constructs of sleep. Instrument scoring yielded 7 subscales (sleep disturbance, snoring, awaken short of breath or with a headache, quantity of sleep, optimal sleep, sleep adequacy, and somnolence) as well as a 9-item overall sleep problems index. The total score ranged from 0 to 100. The awaken short of breath subscale also ranged from 0 to 100, with lower scores indicating less difficulty in breathing.
Time frame: Baseline and Day 57 (Week 8)/Early Termination (Study Endpoint)
Population: All participants in the FAS population (all participants randomized to treatment that received at least 1 dose of study medication) who had available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Change From Baseline in MOS-Sleep Scale, Awaken Short of Breath Score at Endpoint | -0.10 units on a scale | Standard Error 1.895 |
| Placebo | Change From Baseline in MOS-Sleep Scale, Awaken Short of Breath Score at Endpoint | 0.26 units on a scale | Standard Error 1.988 |
Comparison: Analysis performed using a general linear model with treatment and center as factors, and baseline value as a covariate.p-value: 0.889295% CI: [-5.45, 4.73]ANCOVA
Secondary
Change From Baseline in MOS-Sleep Scale, Quantity of Sleep Score at Endpoint
The MOS-Sleep Scale was a participant-rated questionnaire consisting of 12 items that assessed key constructs of sleep. Instrument scoring yielded 7 subscales (sleep disturbance, snoring, awaken short of breath or with a headache, quantity of sleep, optimal sleep, sleep adequacy, and somnolence) as well as a 9-item overall sleep problems index. The total score ranged from 0 to 100. The MOS Sleep Quantity sub-scale scores ranged from 0 to 24 (number of hours slept).
Time frame: Baseline and Day 57 (Week 8)/Early Termination (Study Endpoint)
Population: All participants in the FAS population (all participants randomized to treatment that received at least 1 dose of study medication) who had available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Change From Baseline in MOS-Sleep Scale, Quantity of Sleep Score at Endpoint | 0.69 units on a scale | Standard Error 0.108 |
| Placebo | Change From Baseline in MOS-Sleep Scale, Quantity of Sleep Score at Endpoint | 0.25 units on a scale | Standard Error 0.111 |
Comparison: Analysis performed using a general linear model with treatment and center as factors, and baseline value as a covariate.p-value: 0.003595% CI: [0.14, 0.72]ANCOVA
Secondary
Change From Baseline in MOS-Sleep Scale, Sleep Adequacy Score at Endpoint
The MOS-Sleep Scale was a participant-rated questionnaire consisting of 12 items that assessed key constructs of sleep. Instrument scoring yielded 7 subscales (sleep disturbance, snoring, awaken short of breath or with a headache, quantity of sleep, optimal sleep, sleep adequacy, and somnolence) as well as a 9-item overall sleep problems index. The total score ranged from 0 to 100. The sleep adequacy subscale also ranged from 0 to 100, with higher scores indicating greater sleep adequacy.
Time frame: Baseline and Day 57 (Week 8)/Early Termination (Study Endpoint)
Population: All participants in the FAS population (all participants randomized to treatment that received at least 1 dose of study medication) who had available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Change From Baseline in MOS-Sleep Scale, Sleep Adequacy Score at Endpoint | 10.44 units on a scale | Standard Error 2.325 |
| Placebo | Change From Baseline in MOS-Sleep Scale, Sleep Adequacy Score at Endpoint | 8.64 units on a scale | Standard Error 2.403 |
Comparison: Analysis performed using a general linear model with treatment and center as factors, and baseline value as a covariate.p-value: 0.570295% CI: [-4.44, 8.03]ANCOVA
Secondary
Change From Baseline in MOS-Sleep Scale, Sleep Disturbance Score at Endpoint
The MOS-Sleep Scale was a participant-rated questionnaire consisting of 12 items that assessed key constructs of sleep. Instrument scoring yielded 7 subscales (sleep disturbance, snoring, awaken short of breath or with a headache, quantity of sleep, optimal sleep, sleep adequacy, and somnolence) as well as a 9-item overall sleep problems index. The total score ranged from 0 to 100. For sleep disturbance, the subscale score also ranged from 0 to 100, with higher scores representing greater sleep disturbance.
Time frame: Baseline and Day 57 (Week 8)/Early Termination (Study Endpoint)
Population: All participants in the FAS population (all participants randomized to treatment that received at least 1 dose of study medication) who had available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Change From Baseline in MOS-Sleep Scale, Sleep Disturbance Score at Endpoint | -11.97 units on a scale | Standard Error 1.821 |
| Placebo | Change From Baseline in MOS-Sleep Scale, Sleep Disturbance Score at Endpoint | -4.76 units on a scale | Standard Error 1.871 |
Comparison: Analysis performed using a general linear model with treatment and center as factors, and baseline value as a covariate.p-value: 0.003995% CI: [-12.08, -2.35]ANCOVA
Secondary
Change From Baseline in MOS-Sleep Scale, Sleep Problems Index Score at Endpoint
The MOS-Sleep Scale was a participant-rated questionnaire consisting of 12 items that assessed key constructs of sleep. Instrument scoring yielded 7 subscales (sleep disturbance, snoring, awaken short of breath or with a headache, quantity of sleep, optimal sleep, sleep adequacy, and somnolence) as well as a 9-item overall sleep problems index. The total score ranged from 0 to 100. The sleep problems index subscale score also ranged from 0 to 100, with lower scores indicating fewer sleep problems.
Time frame: Baseline and Day 57 (Week 8)/Early Termination (Study Endpoint)
Population: All participants in the FAS population (all participants randomized to treatment that received at least 1 dose of study medication) who had available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Change From Baseline in MOS-Sleep Scale, Sleep Problems Index Score at Endpoint | -7.38 units on a scale | Standard Error 1.427 |
| Placebo | Change From Baseline in MOS-Sleep Scale, Sleep Problems Index Score at Endpoint | -4.54 units on a scale | Standard Error 1.471 |
Comparison: Analysis performed using a general linear model with treatment and center as factors, and baseline value as a covariate.p-value: 0.140395% CI: [-6.63, 0.94]ANCOVA
Secondary
Change From Baseline in MOS-Sleep Scale, Snoring Score at Endpoint
The MOS-Sleep Scale was a participant-rated questionnaire consisting of 12 items that assessed key constructs of sleep. Instrument scoring yielded 7 subscales (sleep disturbance, snoring, awaken short of breath or with a headache, quantity of sleep, optimal sleep, sleep adequacy, and somnolence) as well as a 9-item overall sleep problems index. The total score ranged from 0 to 100. The snoring subscale score also ranged from 0 to 100, with lower scores indicating less snoring.
Time frame: Baseline and Day 57 (Week 8)/Early Termination (Study Endpoint)
Population: All participants in the FAS population (all participants randomized to treatment that received at least 1 dose of study medication) who had available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Change From Baseline in MOS-Sleep Scale, Snoring Score at Endpoint | -2.00 units on a scale | Standard Error 2.043 |
| Placebo | Change From Baseline in MOS-Sleep Scale, Snoring Score at Endpoint | -3.73 units on a scale | Standard Error 2.131 |
Comparison: Analysis performed using a general linear model with treatment and center as factors, and baseline value as a covariate.p-value: 0.535195% CI: [-3.76, 7.22]ANCOVA
Secondary
Change From Baseline in MOS-Sleep Scale, Somnolence Score at Endpoint
The MOS-Sleep Scale was a participant-rated questionnaire consisting of 12 items that assessed key constructs of sleep. Instrument scoring yielded 7 subscales (sleep disturbance, snoring, awaken short of breath or with a headache, quantity of sleep, optimal sleep, sleep adequacy, and somnolence) as well as a 9-item overall sleep problems index. The total score ranged from 0 to 100. The somnolence subscale score also ranged from 0 to 100, with lower scores indicating less somnolence.
Time frame: Baseline and Day 57 (Week 8)/Early Termination (Study Endpoint)
Population: All participants in the FAS population (all participants randomized to treatment that received at least 1 dose of study medication) who had available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Change From Baseline in MOS-Sleep Scale, Somnolence Score at Endpoint | 0.33 units on a scale | Standard Error 1.613 |
| Placebo | Change From Baseline in MOS-Sleep Scale, Somnolence Score at Endpoint | -0.54 units on a scale | Standard Error 1.668 |
Comparison: Analysis performed using a general linear model with treatment and center as factors, and baseline value as a covariate.p-value: 0.692995% CI: [-3.46, 5.2]ANCOVA
Secondary
Change From Baseline in Pain VAS From the SF-MPQ at Endpoint
The VAS was part of the SF-MPQ scale and reflected the overall pain intensity score. The pain VAS was a horizontal line; 100 mm in length, was self-administered by the participant in order to rate pain from 0 (no pain) to 100 (worst possible pain).
Time frame: Baseline to Day 57 (Week 8)/Early Termination (Study Endpoint)
Population: All participants in the FAS population (all participants randomized to treatment that received at least 1 dose of study medication) who had available data for this outcome measure. The LOCF method was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Change From Baseline in Pain VAS From the SF-MPQ at Endpoint | -20.71 units on a scale | Standard Error 1.412 |
| Placebo | Change From Baseline in Pain VAS From the SF-MPQ at Endpoint | -12.53 units on a scale | Standard Error 1.451 |
Comparison: Analysis performed using a general linear model with treatment and center as factors, and baseline value as a covariate.p-value: <0.000195% CI: [-11.99, -4.37]ANCOVA
Secondary
Change From Baseline in PPI Scale From the SF-MPQ at Endpoint
The PPI was part of the SF-MPQ scale and measured the participant's present pain intensity on a 6-point scale ranging from 0 (no pain) to 5 (excruciating).
Time frame: Baseline to Day 57 (Week 8)/Early Termination (Study Endpoint)
Population: All participants in the FAS population (all participants randomized to treatment that received at least 1 dose of study medication) who had available data for this outcome measure. The LOCF method was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Change From Baseline in PPI Scale From the SF-MPQ at Endpoint | -0.79 units on a scale | Standard Error 0.078 |
| Placebo | Change From Baseline in PPI Scale From the SF-MPQ at Endpoint | -0.42 units on a scale | Standard Error 0.08 |
Comparison: Analysis performed using a general linear model with treatment and center as factors, and baseline value as a covariate.p-value: 0.000795% CI: [-0.58, -0.16]ANCOVA
Secondary
Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 3, 5, and 8
SF-MPQ was assessed according to the participant's answer to the SF-MPQ questionnaire. The score for each composite scale (sensory, affective, and total) was derived by summing the reported intensity value for each item within a particular scale where None=0, Mild=1, Moderate=2, and Severe=3. The sensory score was the sum of the scores of the first 11 pain descriptors (throbbing, shooting, stabbing, sharp, cramping, gnawing, hot-burning, aching, heavy, tender, and splitting) and could range from 0-33. The affective score was the sum of the scores of the last 4 pain descriptors (tiring-exhausting, sickening, fearful, and punishing-cruel) and could range from 0-12. The total score was the sum of the scores of all 15 pain descriptors and could range from 0 to 45. Higher scores indicated greater pain.
Time frame: Baseline; Weeks 1, 3, 5, and 8
Population: The FAS population consisted of all participants randomized to treatment that received at least 1 dose of study medication. N=the number of participants who were evaluable for this measure at the given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 3, 5, and 8 | Affective score, Week 5 change (N=102, 95) | -0.85 units on a scale | Standard Deviation 2.036 |
| Pregabalin | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 3, 5, and 8 | Sensory score, Baseline | 8.24 units on a scale | Standard Deviation 5.276 |
| Pregabalin | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 3, 5, and 8 | Sensory score, Week 1 change (N=111, 106) | -1.68 units on a scale | Standard Deviation 3.776 |
| Pregabalin | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 3, 5, and 8 | Sensory score, Week 3 change (N=107, 101) | -2.97 units on a scale | Standard Deviation 3.852 |
| Pregabalin | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 3, 5, and 8 | Sensory score, Week 5 change (N=102, 96) | -3.31 units on a scale | Standard Deviation 4.496 |
| Pregabalin | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 3, 5, and 8 | Sensory score, Week 8 change (N=98, 93) | -3.61 units on a scale | Standard Deviation 4.299 |
| Pregabalin | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 3, 5, and 8 | Affective score, Baseline | 1.25 units on a scale | Standard Deviation 2.038 |
| Pregabalin | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 3, 5, and 8 | Affective score, Week 1 change (N=111, 105) | -0.61 units on a scale | Standard Deviation 1.602 |
| Pregabalin | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 3, 5, and 8 | Affective score, Week 3 change (N=107, 100) | -0.80 units on a scale | Standard Deviation 1.772 |
| Pregabalin | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 3, 5, and 8 | Affective score, Week 8 change (N=97,90) | -0.96 units on a scale | Standard Deviation 1.941 |
| Pregabalin | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 3, 5, and 8 | Total score, Baseline | 9.50 units on a scale | Standard Deviation 6.621 |
| Pregabalin | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 3, 5, and 8 | Total score, Week 1 change (N=111, 106) | -2.29 units on a scale | Standard Deviation 4.486 |
| Pregabalin | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 3, 5, and 8 | Total score, Week 3 change (N=107, 101) | -3.77 units on a scale | Standard Deviation 4.761 |
| Pregabalin | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 3, 5, and 8 | Total score, Week 5 change (N=102, 96) | -4.17 units on a scale | Standard Deviation 5.632 |
| Pregabalin | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 3, 5, and 8 | Total score, Week 8 change (N=98, 93) | -4.57 units on a scale | Standard Deviation 5.117 |
| Placebo | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 3, 5, and 8 | Affective score, Week 1 change (N=111, 105) | -0.28 units on a scale | Standard Deviation 1.404 |
| Placebo | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 3, 5, and 8 | Total score, Week 8 change (N=98, 93) | -2.53 units on a scale | Standard Deviation 5.308 |
| Placebo | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 3, 5, and 8 | Total score, Week 3 change (N=107, 101) | -1.51 units on a scale | Standard Deviation 4.654 |
| Placebo | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 3, 5, and 8 | Sensory score, Baseline | 8.00 units on a scale | Standard Deviation 4.939 |
| Placebo | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 3, 5, and 8 | Affective score, Week 3 change (N=107, 100) | -0.46 units on a scale | Standard Deviation 1.507 |
| Placebo | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 3, 5, and 8 | Sensory score, Week 1 change (N=111, 106) | -0.29 units on a scale | Standard Deviation 3.009 |
| Placebo | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 3, 5, and 8 | Affective score, Week 5 change (N=102, 95) | -0.59 units on a scale | Standard Deviation 1.512 |
| Placebo | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 3, 5, and 8 | Sensory score, Week 3 change (N=107, 101) | -1.05 units on a scale | Standard Deviation 3.81 |
| Placebo | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 3, 5, and 8 | Total score, Week 1 change (N=111, 106) | -0.57 units on a scale | Standard Deviation 3.494 |
| Placebo | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 3, 5, and 8 | Sensory score, Week 5 change (N=102, 96) | -1.79 units on a scale | Standard Deviation 4.058 |
| Placebo | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 3, 5, and 8 | Affective score, Week 8 change (N=97,90) | -0.66 units on a scale | Standard Deviation 1.63 |
| Placebo | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 3, 5, and 8 | Sensory score, Week 8 change (N=98, 93) | -1.94 units on a scale | Standard Deviation 4.418 |
| Placebo | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 3, 5, and 8 | Total score, Week 5 change (N=102, 96) | -2.37 units on a scale | Standard Deviation 5.035 |
| Placebo | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 3, 5, and 8 | Affective score, Baseline | 1.31 units on a scale | Standard Deviation 2.124 |
| Placebo | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 3, 5, and 8 | Total score, Baseline | 9.29 units on a scale | Standard Deviation 6.465 |
Secondary
Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 8
The DPRS consists of an 11-point numeric scale ranging from 0 (no pain) to 10 (worst possible pain). Participants described their pain during the past 24 hours by choosing the appropriate number between 0 and 10. The weekly mean pain score was the sum of the daily scores divided by the number of diary entries during that week.
Time frame: Baseline and weekly from Weeks 1 to 8
Population: The FAS population consisted of all participants randomized to treatment that received at least 1 dose of study medication.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 8 | Week 4 change from baseline | -1.36 units on a scale | Standard Error 0.11 |
| Pregabalin | Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 8 | Week 7 change from baseline | -1.78 units on a scale | Standard Error 0.111 |
| Pregabalin | Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 8 | Week 5 change from baseline | -1.50 units on a scale | Standard Error 0.11 |
| Pregabalin | Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 8 | Week 2 change from baseline | -1.00 units on a scale | Standard Error 0.109 |
| Pregabalin | Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 8 | Week 6 change from baseline | -1.70 units on a scale | Standard Error 0.11 |
| Pregabalin | Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 8 | Week 1 change from baseline | -0.62 units on a scale | Standard Error 0.108 |
| Pregabalin | Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 8 | Week 8 change from baseline | -1.91 units on a scale | Standard Error 0.111 |
| Pregabalin | Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 8 | Week 3 change from baseline | -1.23 units on a scale | Standard Error 0.109 |
| Placebo | Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 8 | Week 8 change from baseline | -1.21 units on a scale | Standard Error 0.114 |
| Placebo | Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 8 | Week 6 change from baseline | -1.11 units on a scale | Standard Error 0.114 |
| Placebo | Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 8 | Week 1 change from baseline | -0.12 units on a scale | Standard Error 0.111 |
| Placebo | Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 8 | Week 2 change from baseline | -0.35 units on a scale | Standard Error 0.112 |
| Placebo | Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 8 | Week 4 change from baseline | -0.85 units on a scale | Standard Error 0.114 |
| Placebo | Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 8 | Week 5 change from baseline | -0.99 units on a scale | Standard Error 0.114 |
| Placebo | Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 8 | Week 7 change from baseline | -1.07 units on a scale | Standard Error 0.114 |
| Placebo | Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 8 | Week 3 change from baseline | -0.65 units on a scale | Standard Error 0.112 |
Comparison: Week 1 Modelled Results. The model used was a linear mixed model with treatment, week, center, and treatment by week interaction as factors, and the baseline value as a covariate. A compound symmetry covariance structure is specified.p-value: 0.00195% CI: [-0.79, -0.2]Mixed Model Repeated Measures Analysis
Comparison: Week 2 Modelled Results. The model used was a linear mixed model with treatment, week, center, and treatment by week interaction as factors, and the baseline value as a covariate. A compound symmetry covariance structure is specified.p-value: <0.000195% CI: [-0.94, -0.35]Mixed Model Repeated Measures Analysis
Comparison: Week 3 Modelled Results. The model used was a linear mixed model with treatment, week, center, and treatment by week interaction as factors, and the baseline value as a covariate. A compound symmetry covariance structure is specified.p-value: 0.000195% CI: [-0.88, -0.29]Mixed Model Repeated Measures Analysis
Comparison: Week 4 Modelled Results. The model used was a linear mixed model with treatment, week, center, and treatment by week interaction as factors, and the baseline value as a covariate. A compound symmetry covariance structure is specified.p-value: 0.000995% CI: [-0.81, -0.21]Mixed Model Repeated Measures Analysis
Comparison: Week 5 Modelled Results. The model used was a linear mixed model with treatment, week, center, and treatment by week interaction as factors, and the baseline value as a covariate. A compound symmetry covariance structure is specified.p-value: 0.000995% CI: [-0.81, -0.21]Mixed Model Repeated Measures Analysis
Comparison: Week 6 Modelled Results. The model used was a linear mixed model with treatment, week, center, and treatment by week interaction as factors, and the baseline value as a covariate. A compound symmetry covariance structure is specified.p-value: 0.000195% CI: [-0.89, -0.29]Mixed Model Repeated Measures Analysis
Comparison: Week 7 Modelled Results. The model used was a linear mixed model with treatment, week, center, and treatment by week interaction as factors, and the baseline value as a covariate. A compound symmetry covariance structure is specified.p-value: <0.000195% CI: [-1.01, -0.41]Mixed Model Repeated Measures Analysis
Comparison: Week 8 Modelled Results. The model used was a linear mixed model with treatment, week, center, and treatment by week interaction as factors, and the baseline value as a covariate. A compound symmetry covariance structure is specified.p-value: <0.000195% CI: [-1, -0.4]Mixed Model Repeated Measures Analysis
Secondary
Change From Baseline in Weekly Mean Sleep Interference Scores at Weeks 1 to 8
Pain-related sleep interference was assessed on an 11-point numerical rating scale ranging from 0 (did not interfere with sleep) to 10 (completely interfered \[unable to sleep due to pain\]). Participants were to describe how their pain had interfered with their sleep during the past 24 hours by choosing the appropriate number between 0 and 10. The weekly mean score was the sum of the daily scores divided by the number of diary entries during that week.
Time frame: Baseline and weekly from Weeks 1 to 8
Population: The FAS population consisted of all participants randomized to treatment that received at least 1 dose of study medication.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Change From Baseline in Weekly Mean Sleep Interference Scores at Weeks 1 to 8 | Week 1 change from baseline | -0.52 units on a scale | Standard Error 0.124 |
| Pregabalin | Change From Baseline in Weekly Mean Sleep Interference Scores at Weeks 1 to 8 | Week 2 change from baseline | -0.82 units on a scale | Standard Error 0.124 |
| Pregabalin | Change From Baseline in Weekly Mean Sleep Interference Scores at Weeks 1 to 8 | Week 3 change from baseline | -0.92 units on a scale | Standard Error 0.125 |
| Pregabalin | Change From Baseline in Weekly Mean Sleep Interference Scores at Weeks 1 to 8 | Week 4 change from baseline | -0.96 units on a scale | Standard Error 0.125 |
| Pregabalin | Change From Baseline in Weekly Mean Sleep Interference Scores at Weeks 1 to 8 | Week 5 change from baseline | -1.02 units on a scale | Standard Error 0.126 |
| Pregabalin | Change From Baseline in Weekly Mean Sleep Interference Scores at Weeks 1 to 8 | Week 6 change from baseline | -1.13 units on a scale | Standard Error 0.126 |
| Pregabalin | Change From Baseline in Weekly Mean Sleep Interference Scores at Weeks 1 to 8 | Week 7 change from baseline | -1.27 units on a scale | Standard Error 0.126 |
| Pregabalin | Change From Baseline in Weekly Mean Sleep Interference Scores at Weeks 1 to 8 | Week 8 change from baseline | -1.31 units on a scale | Standard Error 0.126 |
| Placebo | Change From Baseline in Weekly Mean Sleep Interference Scores at Weeks 1 to 8 | Week 8 change from baseline | -0.84 units on a scale | Standard Error 0.131 |
| Placebo | Change From Baseline in Weekly Mean Sleep Interference Scores at Weeks 1 to 8 | Week 1 change from baseline | 0.01 units on a scale | Standard Error 0.128 |
| Placebo | Change From Baseline in Weekly Mean Sleep Interference Scores at Weeks 1 to 8 | Week 5 change from baseline | -0.62 units on a scale | Standard Error 0.13 |
| Placebo | Change From Baseline in Weekly Mean Sleep Interference Scores at Weeks 1 to 8 | Week 2 change from baseline | -0.16 units on a scale | Standard Error 0.128 |
| Placebo | Change From Baseline in Weekly Mean Sleep Interference Scores at Weeks 1 to 8 | Week 7 change from baseline | -0.79 units on a scale | Standard Error 0.13 |
| Placebo | Change From Baseline in Weekly Mean Sleep Interference Scores at Weeks 1 to 8 | Week 3 change from baseline | -0.35 units on a scale | Standard Error 0.129 |
| Placebo | Change From Baseline in Weekly Mean Sleep Interference Scores at Weeks 1 to 8 | Week 6 change from baseline | -0.74 units on a scale | Standard Error 0.13 |
| Placebo | Change From Baseline in Weekly Mean Sleep Interference Scores at Weeks 1 to 8 | Week 4 change from baseline | -0.51 units on a scale | Standard Error 0.13 |
Comparison: Week 1 Modelled Results. The model used was a linear mixed model with treatment, week, center, and treatment by week interaction as factors, and the baseline value as a covariate. A compound symmetry covariance structure is specified.p-value: 0.002495% CI: [-0.86, -0.19]Mixed Model Repeated Measures Analysis
Comparison: Week 2 Modelled Results. The model used was a linear mixed model with treatment, week, center, and treatment by week interaction as factors, and the baseline value as a covariate. A compound symmetry covariance structure is specified.p-value: 0.000295% CI: [-0.99, -0.31]Mixed Model Repeated Measures Analysis
Comparison: Week 3 Modelled Results. The model used was a linear mixed model with treatment, week, center, and treatment by week interaction as factors, and the baseline value as a covariate. A compound symmetry covariance structure is specified.p-value: 0.001295% CI: [-0.91, -0.22]Mixed Model Repeated Measures Analysis
Comparison: Week 4 Modelled Results. The model used was a linear mixed model with treatment, week, center, and treatment by week interaction as factors, and the baseline value as a covariate. A compound symmetry covariance structure is specified.p-value: 0.010195% CI: [-0.79, -0.11]Mixed Model Repeated Measures Analysis
Comparison: Week 5 Modelled Results. The model used was a linear mixed model with treatment, week, center, and treatment by week interaction as factors, and the baseline value as a covariate. A compound symmetry covariance structure is specified.p-value: 0.025895% CI: [-0.73, -0.05]Mixed Model Repeated Measures Analysis
Comparison: Week 6 Modelled Results. The model used was a linear mixed model with treatment, week, center, and treatment by week interaction as factors, and the baseline value as a covariate. A compound symmetry covariance structure is specified.p-value: 0.02695% CI: [-0.74, -0.05]Mixed Model Repeated Measures Analysis
Comparison: Week 7 Modelled Results. The model used was a linear mixed model with treatment, week, center, and treatment by week interaction as factors, and the baseline value as a covariate. A compound symmetry covariance structure is specified.p-value: 0.006295% CI: [-0.83, -0.14]Mixed Model Repeated Measures Analysis
Comparison: Week 8 Modelled Results. The model used was a linear mixed model with treatment, week, center, and treatment by week interaction as factors, and the baseline value as a covariate. A compound symmetry covariance structure is specified.p-value: 0.008195% CI: [-0.81, -0.12]Mixed Model Repeated Measures Analysis
Secondary
Clinical Global Impression of Change (CGIC) Score at Endpoint
The CGIC was a clinician-rated global measure that provided a clinically relevant and easy to interpret account of a clinician's perception of the clinical importance of the participant's improvement or worsening during their involvement in a clinical study. Clinicians rated the participant's overall improvement on a 7-point scale where scores ranged from 1 (very much improved) to 7 (very much worse).
Time frame: Day 57 (Week 8)/Early Termination (Study Endpoint)
Population: All participants in the FAS population (all participants randomized to treatment that received at least 1 dose of study medication) who had available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Clinical Global Impression of Change (CGIC) Score at Endpoint | 2.55 units on a scale | Standard Error 0.086 |
| Placebo | Clinical Global Impression of Change (CGIC) Score at Endpoint | 3.18 units on a scale | Standard Error 0.09 |
Comparison: Analysis was performed using a general linear model with treatment and center as factors.p-value: <0.000195% CI: [-0.86, -0.39]ANOVA
Secondary
Patient Global Impression of Change (PGIC) Score at Endpoint
The PGIC was a participant-rated global measure that provided a clinically relevant and easy to interpret account of a participant's perception of the clinical importance of their own improvement or worsening during their involvement in a clinical study. Participants rated their overall improvement on a 7-point scale where scores ranged from 1 (very much improved) to 7 (very much worse).
Time frame: Day 57 (Week 8)/Early Termination (Study Endpoint)
Population: All participants in the FAS population (all participants randomized to treatment that received at least 1 dose of study medication) who had available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Patient Global Impression of Change (PGIC) Score at Endpoint | 2.68 units on a scale | Standard Error 0.083 |
| Placebo | Patient Global Impression of Change (PGIC) Score at Endpoint | 3.17 units on a scale | Standard Error 0.086 |
Comparison: Analysis was performed using a general linear model with treatment and center as factors.p-value: <0.000195% CI: [-0.72, -0.27]ANOVA
Secondary
Percentage of 30 Percent (%) Responders at Endpoint
The DPRS consists of an 11-point numeric scale ranging from 0 (no pain) to 10 (worst possible pain). Participants described their pain during the past 24 hours by choosing the appropriate number between 0 and 10. A 30% responder was a participant who had 30% reduction or more in mean pain score at the end of the fixed dose phase (Day 57/Week 8)/Early Termination (Study Endpoint) compared to baseline.
Time frame: End of fixed dose phase (Day 57/Week 8)/Early Termination (Study Endpoint)
Population: All participants in the FAS population (all participants randomized to treatment that received at least 1 dose of study medication) who had available data for this outcome measure. The LOCF method was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pregabalin | Percentage of 30 Percent (%) Responders at Endpoint | 52.3 percentage of participants |
| Placebo | Percentage of 30 Percent (%) Responders at Endpoint | 30.6 percentage of participants |
Comparison: Cochran-Mantel-Haenszel test comparing pregabalin to placebo adjusted for center.p-value: 0.0007Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Had Optimal Sleep at Endpoint
The MOS-Sleep Scale was a participant-rated questionnaire consisting of 12 items that assessed key constructs of sleep. Instrument scoring yielded 7 subscales (sleep disturbance, snoring, awaken short of breath or with a headache, quantity of sleep, optimal sleep, sleep adequacy, and somnolence) as well as a 9-item overall sleep problems index. The total score ranged from 0 to 100. The MOS optimal sleep subscale was a binary outcome derived from the sleep quantity responses: the response was YES if sleep quantity was 7 or 8 hours per night.
Time frame: Day 57 (Week 8)/Early Termination (Study Endpoint)
Population: All participants in the FAS population (consisted of all participants randomized to treatment that received at least 1 dose of study medication) with available data to contribute to the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pregabalin | Percentage of Participants Who Had Optimal Sleep at Endpoint | 49.5 percentage of participants |
| Placebo | Percentage of Participants Who Had Optimal Sleep at Endpoint | 40.6 percentage of participants |
Comparison: Analysis performed using a logistic regression model with treatment and center as factors, and baseline value as a covariate.p-value: 0.097295% CI: [0.9, 3.6]Regression, Logistic