Diabetic Neuropathy, Painful
Conditions
Keywords
Diabetic Neuropathies, Pain, Efficacy of pregabalin, Placebo controlled
Brief summary
Pregabalin has proven effective in previous clinical trails in other countries in relieving neuropathic pain associated with postherpetic neuralgia and painful diabetic neuropathy. This study is being conducted according to China registration requirement to submit a reapplication with new local diabetic peripheral neuropathy study as a commitment plus the existing data to apply for Lyrica pain associated with postherpetic neuralgia indication after Lyrica pain associated with postherpetic neuralgia is approved.
Interventions
DRUGPregabalin
Subjects in the pregabalin group will start treatment with pregabalin capsule 150 mg/day for 1 week, then their dose will be increased to 300mg/day. After 1-week titration period, dose must be stable during study, no dose adjustment is permitted, and subject who cannot tolerate 300 mg/day pregabalin will be withdrawn. At the completion of the dose maintenance phase subjects will taper off study medication over a 1-week period. 300 mg/ day subjects will taper to 150 mg/ day.
DRUGPlacebo matched with pregabalin
Subject will take placebo matched with pregabalin twice a day.
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 and female subjects aged 18 years or older * Diagnosis of painful, distal, symmetrical, sensorimotor polyneuropathy which is due to diabetes mellitus (Type 1 or 2), and symptoms of painful diabetic neuropathy for 6 months to 5 years (inclusive). * At the baseline and randomization visits, a score of ≥50 mm on the Visual Analogue Scale, at randomization, subjects must have completed at least 5 daily pain interference diaries, and have an average daily pain score of ≥5 over the past 7 days. * Patient who are willing and capable to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. * Women of childbearing potential are willing to use contraception during study.
Exclusion criteria
* Subjects with more than 30% decrease on the Pain Visual Analog Scale at randomization as compared to screening; and during the 1 week screening period, with more than one pain score \<3 in pain scores. * Subject has other kinds of neurological disorder, pain of other reason, or skin condition that could confuse the assessment. * Subject with any other serious or unstable condition which in the opinion of the investigator might compromise participation in the study.
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 and end of fixed dose phase (Day 63/Week 9)/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 Weekly Mean Pain Score at Weeks 1 to 9 | Baseline and weekly from Weeks 1 to 9 | 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. The overall change is the average change from Weeks 1 to 9. |
| 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. |
| Change From Baseline in Mean Sleep Interference Score at Endpoint | Baseline and end of fixed dose phase (Day 63/Week 9)/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 9 (Day 63) dose. |
| Change From Baseline in Weekly Mean Sleep Interference Score at Weeks 1 to 9 | Baseline and weekly from Weeks 1 to 9 | 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. The overall change is the average change from Weeks 1 to 9. |
| Percentage of 30 Percent (%) Responders at Endpoint | End of fixed dose phase (Day 63/Week 9)/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 63/Week 9) (Study Endpoint) compared to baseline. |
| Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 5, and 9 | Baseline; Weeks 1, 5, and 9 | 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). |
| Baseline Medical Outcomes Study (MOS)-Sleep Scale Scores | Baseline | The MOS-Sleep Scale was a participant-rated instrument which assesses sleep quantity and quality with 12 items (7 subscale scores: sleep disturbance, snoring, awakening short of breath/with headache, sleep adequacy, somnolence, sleep quantity, optimal sleep; and a 9-item overall sleep problems index). Subscale scores total range: 0-100 (except sleep quantity \[range 0-24 hours\], optimal sleep \[yes:1, no:0\]). Higher scores=poorer sleep outcomes (except sleep quantity, adequacy, and optimal sleep). |
| Change From Baseline in MOS-Sleep Scale, Sleep Disturbance Score at Endpoint | Baseline and Day 63 (Week 9)/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 MOS-Sleep Scale, Snoring Score at Endpoint | Baseline and Day 63 (Week 9)/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. |
| Change From Baseline in Pain VAS From the SF-MPQ at Endpoint | Baseline and Day 63 (Week 9)/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 MOS-Sleep Scale, Quantity of Sleep Score at Endpoint | Baseline and Day 63 (Week 9)/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). |
| Percentage of Participants Who Had Optimal Sleep at Endpoint | Day 63 (Week 9)/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 63 (Week 9)/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 63 (Week 9)/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 63 (Week 9)/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) at Endpoint | Day 63 (Week 9)/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 63 (Week 9)/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 63 (Week 9)/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 63 (Week 9)/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, Awaken Short of Breath Score at Endpoint | Baseline and Day 63 (Week 9)/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. |
| Change From Baseline in PPI Scale From the SF-MPQ at Endpoint | Baseline and Day 63 (Week 9)/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). |
Countries
China
Participant flow
Recruitment details
All participants were Chinese. 626 participants were randomized initially, as originally stated on clinicaltrials.gov. However, 3 participants discontinued right after randomization without any treatment information. As such, the actual number of participants randomized and assigned to treatment was 623 as stated in the Started Row below.
Participants by arm
| Arm | Count |
|---|---|
| Pregabalin Participants received 1 placebo capsule matched to pregabalin twice a day for 1 week (run-in period), followed by a 9-week double-blind treatment phase (1-week dose-escalation phase where participants received pregabalin 150 milligram \[mg\] per day in the form of 75 mg twice a day and an 8-week fixed dose phase where participants received pregabalin 300 mg per day in the form of 150 mg twice a day), and a 1-week taper-off phase where participants received pregabalin 150 mg per day (in the form of 75 mg twice a day). | 313 |
| Placebo Participants received matching placebo capsule(s) for a period of 11 weeks， which consisted of a 1-week run-in period, 9-week double-blind treatment phase and 1-week taper-off period. | 307 |
| Total | 620 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 11 | 9 |
| Overall Study | Did not meet entrance criteria | 3 | 4 |
| Overall Study | Insufficient clinical response | 4 | 7 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Other unspecified | 5 | 7 |
| Overall Study | Protocol Violation | 1 | 3 |
| Overall Study | Randomized but not treated | 1 | 2 |
| Overall Study | Withdrawal by Subject | 4 | 5 |
Baseline characteristics
| Characteristic | Pregabalin | Placebo | Total |
|---|---|---|---|
| Age, Customized 18-44 years | 25 participants 10.3 | 15 participants 9.5 | 40 participants |
| Age, Customized 45-64 years | 172 participants | 178 participants | 350 participants |
| Age, Customized More than or equal to (>=) 65 years | 116 participants | 114 participants | 230 participants |
| Sex: Female, Male Female | 159 Participants | 168 Participants | 327 Participants |
| Sex: Female, Male Male | 154 Participants | 139 Participants | 293 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 77 / 314 | 55 / 308 |
| serious Total, serious adverse events | 7 / 314 | 5 / 308 |
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, consisting of all participants randomized to treatment that received at least 1 dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Baseline Mean Pain Score | 6.65 units on a scale | Standard Deviation 1.117 |
| Placebo | Baseline Mean Pain Score | 6.67 units on a scale | Standard Deviation 1.15 |
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 and end of fixed dose phase (Day 63/Week 9)/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 | -2.14 units on a scale | Standard Error 0.115 |
| Placebo | Change From Baseline in Mean Pain Score at Endpoint | -1.86 units on a scale | Standard Error 0.117 |
p-value: 0.055995% CI: [-0.58, 0.01]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, consisting of all participants randomized to treatment that received at least 1 dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Baseline Hospital Anxiety and Depression Scale (HADS) Scores | Anxiety total score | 3.76 units on a scale | Standard Deviation 3.8 |
| Pregabalin | Baseline Hospital Anxiety and Depression Scale (HADS) Scores | Depression total score | 4.45 units on a scale | Standard Deviation 4.081 |
| Placebo | Baseline Hospital Anxiety and Depression Scale (HADS) Scores | Anxiety total score | 3.67 units on a scale | Standard Deviation 3.645 |
| Placebo | Baseline Hospital Anxiety and Depression Scale (HADS) Scores | Depression total score | 4.35 units on a scale | Standard Deviation 3.798 |
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 Full Analysis Set (FAS) population, consisting of all participants randomized to treatment that received at least 1 dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Baseline Mean Sleep Interference Score | 5.25 units on a scale | Standard Deviation 2.236 |
| Placebo | Baseline Mean Sleep Interference Score | 5.12 units on a scale | Standard Deviation 2.278 |
Secondary
Baseline Medical Outcomes Study (MOS)-Sleep Scale Scores
The MOS-Sleep Scale was a participant-rated instrument which assesses sleep quantity and quality with 12 items (7 subscale scores: sleep disturbance, snoring, awakening short of breath/with headache, sleep adequacy, somnolence, sleep quantity, optimal sleep; and a 9-item overall sleep problems index). Subscale scores total range: 0-100 (except sleep quantity \[range 0-24 hours\], optimal sleep \[yes:1, no:0\]). Higher scores=poorer sleep outcomes (except sleep quantity, adequacy, and optimal sleep).
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. N=number of evaluable participants for each category
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Baseline Medical Outcomes Study (MOS)-Sleep Scale Scores | Awaken short of breath score (N=313, 307) | 11.50 units on a scale | Standard Deviation 21.557 |
| Pregabalin | Baseline Medical Outcomes Study (MOS)-Sleep Scale Scores | Sleep adequacy score (N=313, 307) | 57.32 units on a scale | Standard Deviation 31.518 |
| Pregabalin | Baseline Medical Outcomes Study (MOS)-Sleep Scale Scores | Snoring score (N=312, 307) | 35.13 units on a scale | Standard Deviation 36.67 |
| Pregabalin | Baseline Medical Outcomes Study (MOS)-Sleep Scale Scores | Somnolence score (N=312, 307) | 33.87 units on a scale | Standard Deviation 20.459 |
| Pregabalin | Baseline Medical Outcomes Study (MOS)-Sleep Scale Scores | Quantity of sleep score (N=311, 304) | 6.07 units on a scale | Standard Deviation 2.882 |
| Pregabalin | Baseline Medical Outcomes Study (MOS)-Sleep Scale Scores | Sleep problems index score (N=312, 307) | 32.19 units on a scale | Standard Deviation 19.806 |
| Pregabalin | Baseline Medical Outcomes Study (MOS)-Sleep Scale Scores | Sleep disturbance score (N=313, 307) | 36.29 units on a scale | Standard Deviation 24.768 |
| Placebo | Baseline Medical Outcomes Study (MOS)-Sleep Scale Scores | Sleep problems index score (N=312, 307) | 31.21 units on a scale | Standard Deviation 20.388 |
| Placebo | Baseline Medical Outcomes Study (MOS)-Sleep Scale Scores | Sleep disturbance score (N=313, 307) | 35.13 units on a scale | Standard Deviation 26.915 |
| Placebo | Baseline Medical Outcomes Study (MOS)-Sleep Scale Scores | Snoring score (N=312, 307) | 37.59 units on a scale | Standard Deviation 37.163 |
| Placebo | Baseline Medical Outcomes Study (MOS)-Sleep Scale Scores | Awaken short of breath score (N=313, 307) | 10.75 units on a scale | Standard Deviation 21.883 |
| Placebo | Baseline Medical Outcomes Study (MOS)-Sleep Scale Scores | Quantity of sleep score (N=311, 304) | 5.98 units on a scale | Standard Deviation 1.451 |
| Placebo | Baseline Medical Outcomes Study (MOS)-Sleep Scale Scores | Sleep adequacy score (N=313, 307) | 60.88 units on a scale | Standard Deviation 30.274 |
| Placebo | Baseline Medical Outcomes Study (MOS)-Sleep Scale Scores | Somnolence score (N=312, 307) | 36.03 units on a scale | Standard Deviation 21.491 |
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: All participants in the FAS population, consisting of all participants randomized to treatment that received at least 1 dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Baseline Pain Visual Analogue Scale (VAS) and Present Pain Intensity (PPI) Scale | VAS | 69.08 units on a scale | Standard Deviation 11.474 |
| Pregabalin | Baseline Pain Visual Analogue Scale (VAS) and Present Pain Intensity (PPI) Scale | PPI | 2.28 units on a scale | Standard Deviation 0.784 |
| Placebo | Baseline Pain Visual Analogue Scale (VAS) and Present Pain Intensity (PPI) Scale | VAS | 69.06 units on a scale | Standard Deviation 11.811 |
| Placebo | Baseline Pain Visual Analogue Scale (VAS) and Present Pain Intensity (PPI) Scale | PPI | 2.27 units on a scale | Standard Deviation 0.83 |
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 63 (Week 9)/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 HADS Anxiety Total Score at Endpoint | -0.48 units on a scale | Standard Error 0.161 |
| Placebo | Change From Baseline in HADS Anxiety Total Score at Endpoint | -0.31 units on a scale | Standard Error 0.163 |
p-value: 0.417295% CI: [-0.57, 0.24]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 63 (Week 9)/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 HADS Depression Total Score at Endpoint | -0.57 units on a scale | Standard Error 0.169 |
| Placebo | Change From Baseline in HADS Depression Total Score at Endpoint | -0.38 units on a scale | Standard Error 0.172 |
p-value: 0.372495% CI: [-0.62, 0.23]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 9 (Day 63) dose.
Time frame: Baseline and end of fixed dose phase (Day 63/Week 9)/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 | -1.52 units on a scale | Standard Error 0.11 |
| Placebo | Change From Baseline in Mean Sleep Interference Score at Endpoint | -1.30 units on a scale | Standard Error 0.112 |
p-value: 0.13495% CI: [-0.49, 0.07]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 63 (Week 9)/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 MOS-Sleep Scale, Awaken Short of Breath Score at Endpoint | -2.10 units on a scale | Standard Error 1.061 |
| Placebo | Change From Baseline in MOS-Sleep Scale, Awaken Short of Breath Score at Endpoint | -2.31 units on a scale | Standard Error 1.078 |
p-value: 0.880895% CI: [-2.49, 2.9]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 63 (Week 9)/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 MOS-Sleep Scale, Quantity of Sleep Score at Endpoint | 0.33 units on a scale | Standard Error 0.085 |
| Placebo | Change From Baseline in MOS-Sleep Scale, Quantity of Sleep Score at Endpoint | 0.14 units on a scale | Standard Error 0.087 |
p-value: 0.088795% CI: [-0.03, 0.4]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 63 (Week 9)/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 MOS-Sleep Scale, Sleep Adequacy Score at Endpoint | 8.87 units on a scale | Standard Error 1.532 |
| Placebo | Change From Baseline in MOS-Sleep Scale, Sleep Adequacy Score at Endpoint | 7.82 units on a scale | Standard Error 1.552 |
p-value: 0.59695% CI: [-2.83, 4.92]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 63 (Week 9)/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 MOS-Sleep Scale, Sleep Disturbance Score at Endpoint | -9.11 units on a scale | Standard Error 1.222 |
| Placebo | Change From Baseline in MOS-Sleep Scale, Sleep Disturbance Score at Endpoint | -7.98 units on a scale | Standard Error 1.244 |
p-value: 0.475895% CI: [-4.22, 1.97]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 63 (Week 9)/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 MOS-Sleep Scale, Sleep Problems Index Score at Endpoint | -6.71 units on a scale | Standard Error 0.914 |
| Placebo | Change From Baseline in MOS-Sleep Scale, Sleep Problems Index Score at Endpoint | -5.88 units on a scale | Standard Error 0.927 |
p-value: 0.482995% CI: [-3.14, 1.49]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 63 (Week 9)/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 MOS-Sleep Scale, Snoring Score at Endpoint | 2.78 units on a scale | Standard Error 1.716 |
| Placebo | Change From Baseline in MOS-Sleep Scale, Snoring Score at Endpoint | -0.53 units on a scale | Standard Error 1.743 |
p-value: 0.136395% CI: [-1.05, 7.67]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 63 (Week 9)/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 MOS-Sleep Scale, Somnolence Score at Endpoint | -1.22 units on a scale | Standard Error 1.187 |
| Placebo | Change From Baseline in MOS-Sleep Scale, Somnolence Score at Endpoint | -0.88 units on a scale | Standard Error 1.208 |
p-value: 0.821695% CI: [-3.36, 2.67]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 and Day 63 (Week 9)/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 | -25.07 units on a scale | Standard Error 1.26 |
| Placebo | Change From Baseline in Pain VAS From the SF-MPQ at Endpoint | -21.82 units on a scale | Standard Error 1.279 |
p-value: 0.046395% CI: [-6.45, -0.05]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 and Day 63 (Week 9)/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 | -0.80 units on a scale | Standard Error 0.047 |
| Placebo | Change From Baseline in PPI Scale From the SF-MPQ at Endpoint | -0.73 units on a scale | Standard Error 0.048 |
p-value: 0.274895% CI: [-0.19, 0.05]ANCOVA
Secondary
Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 5, and 9
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, 5, and 9
Population: The FAS population consisted of all participants randomized to treatment that received at least 1 dose of study medication. N=number of evaluable participants at the specified time point. No inferential analyses were performed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 5, and 9 | Sensory score, Week 9 change (N=288, 274) | -3.87 units on a scale | Standard Deviation 4.432 |
| Pregabalin | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 5, and 9 | Affective score, Week 5 change (N=297, 289) | -0.72 units on a scale | Standard Deviation 1.724 |
| Pregabalin | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 5, and 9 | Sensory score, Baseline (N=313, 306) | 7.90 units on a scale | Standard Deviation 5.101 |
| Pregabalin | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 5, and 9 | Affective score, Week 9 change (N=287, 274) | -0.75 units on a scale | Standard Deviation 1.744 |
| Pregabalin | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 5, and 9 | Affective score, Baseline (N=313, 307) | 1.25 units on a scale | Standard Deviation 1.809 |
| Pregabalin | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 5, and 9 | Total score, Baseline (N=313, 307) | 9.15 units on a scale | Standard Deviation 6.118 |
| Pregabalin | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 5, and 9 | Sensory score, Week 1 change (N=311, 304) | -1.50 units on a scale | Standard Deviation 3.422 |
| Pregabalin | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 5, and 9 | Total score, Week 1 change (N=311, 305) | -1.92 units on a scale | Standard Deviation 4.26 |
| Pregabalin | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 5, and 9 | Affective score, Week 1 change (N=311, 304) | -0.41 units on a scale | Standard Deviation 1.569 |
| Pregabalin | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 5, and 9 | Total score, Week 5 change (N=297, 289) | -3.61 units on a scale | Standard Deviation 5.084 |
| Pregabalin | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 5, and 9 | Total score, Week 9 change (N=288, 274) | -4.62 units on a scale | Standard Deviation 5.272 |
| Pregabalin | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 5, and 9 | Sensory score, Week 5 change (N=297, 288) | -2.89 units on a scale | Standard Deviation 4.244 |
| Placebo | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 5, and 9 | Total score, Week 9 change (N=288, 274) | -4.00 units on a scale | Standard Deviation 5.512 |
| Placebo | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 5, and 9 | Total score, Week 5 change (N=297, 289) | -3.07 units on a scale | Standard Deviation 4.893 |
| Placebo | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 5, and 9 | Sensory score, Baseline (N=313, 306) | 8.11 units on a scale | Standard Deviation 5.098 |
| Placebo | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 5, and 9 | Sensory score, Week 1 change (N=311, 304) | -1.34 units on a scale | Standard Deviation 3.134 |
| Placebo | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 5, and 9 | Sensory score, Week 5 change (N=297, 288) | -2.47 units on a scale | Standard Deviation 3.925 |
| Placebo | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 5, and 9 | Sensory score, Week 9 change (N=288, 274) | -3.37 units on a scale | Standard Deviation 4.348 |
| Placebo | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 5, and 9 | Affective score, Baseline (N=313, 307) | 1.20 units on a scale | Standard Deviation 1.817 |
| Placebo | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 5, and 9 | Affective score, Week 1 change (N=311, 304) | -0.37 units on a scale | Standard Deviation 1.41 |
| Placebo | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 5, and 9 | Affective score, Week 5 change (N=297, 289) | -0.62 units on a scale | Standard Deviation 1.652 |
| Placebo | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 5, and 9 | Affective score, Week 9 change (N=287, 274) | -0.62 units on a scale | Standard Deviation 1.792 |
| Placebo | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 5, and 9 | Total score, Baseline (N=313, 307) | 9.28 units on a scale | Standard Deviation 6.445 |
| Placebo | Change From Baseline in Short Form McGill Pain Questionnaire (SF-MPQ) Score at Weeks 1, 5, and 9 | Total score, Week 1 change (N=311, 305) | -1.70 units on a scale | Standard Deviation 3.908 |
Secondary
Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 9
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. The overall change is the average change from Weeks 1 to 9.
Time frame: Baseline and weekly from Weeks 1 to 9
Population: The FAS population consisted of all participants randomized to treatment that received at least 1 dose of study medication. N=number of evaluable participants at the specified time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 9 | Week 3 change from baseline (N=298, 291) | -1.25 units on a scale | Standard Error 0.092 |
| Pregabalin | Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 9 | Week 6 change from baseline (N=293, 278) | -1.84 units on a scale | Standard Error 0.092 |
| Pregabalin | Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 9 | Week 2 change from baseline (N=304, 295) | -0.97 units on a scale | Standard Error 0.092 |
| Pregabalin | Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 9 | Week 4 change from baseline (N=297, 289) | -1.47 units on a scale | Standard Error 0.092 |
| Pregabalin | Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 9 | Week 8 change from baseline (N=290, 275) | -2.18 units on a scale | Standard Error 0.092 |
| Pregabalin | Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 9 | Week 1 change from baseline (N=312, 307) | -0.60 units on a scale | Standard Error 0.091 |
| Pregabalin | Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 9 | Week 9 change from baseline (N=287, 273) | -2.32 units on a scale | Standard Error 0.092 |
| Pregabalin | Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 9 | Week 5 change from baseline (N=296, 287) | -1.61 units on a scale | Standard Error 0.092 |
| Pregabalin | Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 9 | Overall change from baseline | -1.59 units on a scale | Standard Error 0.082 |
| Pregabalin | Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 9 | Week 7 change from baseline (N=290, 275) | -2.04 units on a scale | Standard Error 0.092 |
| Placebo | Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 9 | Overall change from baseline | -1.33 units on a scale | Standard Error 0.083 |
| Placebo | Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 9 | Week 1 change from baseline (N=312, 307) | -0.36 units on a scale | Standard Error 0.092 |
| Placebo | Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 9 | Week 2 change from baseline (N=304, 295) | -0.71 units on a scale | Standard Error 0.093 |
| Placebo | Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 9 | Week 3 change from baseline (N=298, 291) | -1.01 units on a scale | Standard Error 0.093 |
| Placebo | Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 9 | Week 4 change from baseline (N=297, 289) | -1.21 units on a scale | Standard Error 0.093 |
| Placebo | Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 9 | Week 5 change from baseline (N=296, 287) | -1.39 units on a scale | Standard Error 0.093 |
| Placebo | Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 9 | Week 6 change from baseline (N=293, 278) | -1.59 units on a scale | Standard Error 0.094 |
| Placebo | Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 9 | Week 7 change from baseline (N=290, 275) | -1.77 units on a scale | Standard Error 0.094 |
| Placebo | Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 9 | Week 8 change from baseline (N=290, 275) | -1.88 units on a scale | Standard Error 0.094 |
| Placebo | Change From Baseline in Weekly Mean Pain Score at Weeks 1 to 9 | Week 9 change from baseline (N=287, 273) | -2.07 units on a scale | Standard Error 0.094 |
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: 0.052795% CI: [-0.47, 0]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: 0.027995% CI: [-0.5, -0.03]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: 0.050895% CI: [-0.48, 0]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: 0.034995% CI: [-0.49, -0.02]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: 0.067295% CI: [-0.46, 0.02]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: 0.046995% CI: [-0.48, 0]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: 0.02895% CI: [-0.51, -0.03]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: 0.01495% CI: [-0.54, -0.06]Mixed Model Repeated Measures Analysis
Comparison: Week 9 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: 0.037595% CI: [-0.49, -0.01]Mixed Model Repeated Measures Analysis
Comparison: Overall change from baseline analysis. 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: 0.016495% CI: [-0.46, -0.05]Mixed Model Repeated Measures Analysis
Secondary
Change From Baseline in Weekly Mean Sleep Interference Score at Weeks 1 to 9
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. The overall change is the average change from Weeks 1 to 9.
Time frame: Baseline and weekly from Weeks 1 to 9
Population: The FAS population consisted of all participants randomized to treatment that received at least 1 dose of study medication. N=number of evaluable participants at the specified time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Change From Baseline in Weekly Mean Sleep Interference Score at Weeks 1 to 9 | Week 1 change from baseline (N=311, 307) | -0.38 units on a scale | Standard Error 0.096 |
| Pregabalin | Change From Baseline in Weekly Mean Sleep Interference Score at Weeks 1 to 9 | Week 2 change from baseline (N=303, 295) | -0.66 units on a scale | Standard Error 0.097 |
| Pregabalin | Change From Baseline in Weekly Mean Sleep Interference Score at Weeks 1 to 9 | Week 3 change from baseline (N=297, 291) | -0.88 units on a scale | Standard Error 0.097 |
| Pregabalin | Change From Baseline in Weekly Mean Sleep Interference Score at Weeks 1 to 9 | Week 4 change from baseline (N=296, 289) | -1.06 units on a scale | Standard Error 0.097 |
| Pregabalin | Change From Baseline in Weekly Mean Sleep Interference Score at Weeks 1 to 9 | Week 5 change from baseline (N=295, 287) | -1.14 units on a scale | Standard Error 0.097 |
| Pregabalin | Change From Baseline in Weekly Mean Sleep Interference Score at Weeks 1 to 9 | Week 6 change from baseline (N=292, 278) | -1.32 units on a scale | Standard Error 0.098 |
| Pregabalin | Change From Baseline in Weekly Mean Sleep Interference Score at Weeks 1 to 9 | Week 7 change from baseline (N=289, 275) | -1.43 units on a scale | Standard Error 0.098 |
| Pregabalin | Change From Baseline in Weekly Mean Sleep Interference Score at Weeks 1 to 9 | Week 8 change from baseline (N=289, 275) | -1.59 units on a scale | Standard Error 0.098 |
| Pregabalin | Change From Baseline in Weekly Mean Sleep Interference Score at Weeks 1 to 9 | Week 9 change from baseline (N=286, 273) | -1.67 units on a scale | Standard Error 0.098 |
| Pregabalin | Change From Baseline in Weekly Mean Sleep Interference Score at Weeks 1 to 9 | Overall change from baseline | -1.13 units on a scale | Standard Error 0.085 |
| Placebo | Change From Baseline in Weekly Mean Sleep Interference Score at Weeks 1 to 9 | Week 8 change from baseline (N=289, 275) | -1.36 units on a scale | Standard Error 0.099 |
| Placebo | Change From Baseline in Weekly Mean Sleep Interference Score at Weeks 1 to 9 | Week 1 change from baseline (N=311, 307) | -0.26 units on a scale | Standard Error 0.098 |
| Placebo | Change From Baseline in Weekly Mean Sleep Interference Score at Weeks 1 to 9 | Week 6 change from baseline (N=292, 278) | -1.07 units on a scale | Standard Error 0.099 |
| Placebo | Change From Baseline in Weekly Mean Sleep Interference Score at Weeks 1 to 9 | Week 2 change from baseline (N=303, 295) | -0.51 units on a scale | Standard Error 0.098 |
| Placebo | Change From Baseline in Weekly Mean Sleep Interference Score at Weeks 1 to 9 | Overall change from baseline | -0.94 units on a scale | Standard Error 0.087 |
| Placebo | Change From Baseline in Weekly Mean Sleep Interference Score at Weeks 1 to 9 | Week 3 change from baseline (N=297, 291) | -0.72 units on a scale | Standard Error 0.099 |
| Placebo | Change From Baseline in Weekly Mean Sleep Interference Score at Weeks 1 to 9 | Week 7 change from baseline (N=289, 275) | -1.25 units on a scale | Standard Error 0.099 |
| Placebo | Change From Baseline in Weekly Mean Sleep Interference Score at Weeks 1 to 9 | Week 4 change from baseline (N=296, 289) | -0.86 units on a scale | Standard Error 0.099 |
| Placebo | Change From Baseline in Weekly Mean Sleep Interference Score at Weeks 1 to 9 | Week 9 change from baseline (N=286, 273) | -1.49 units on a scale | Standard Error 0.1 |
| Placebo | Change From Baseline in Weekly Mean Sleep Interference Score at Weeks 1 to 9 | Week 5 change from baseline (N=295, 287) | -0.98 units on a scale | Standard Error 0.099 |
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: 0.343895% CI: [-0.37, 0.13]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: 0.248295% CI: [-0.4, 0.1]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: 0.224995% CI: [-0.41, 0.1]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: 0.109495% CI: [-0.46, 0.05]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: 0.209595% CI: [-0.41, 0.09]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: 0.053195% CI: [-0.5, 0]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: 0.162895% CI: [-0.44, 0.07]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: 0.07795% CI: [-0.48, 0.02]Mixed Model Repeated Measures Analysis
Comparison: Week 9 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: 0.165195% CI: [-0.43, 0.07]Mixed Model Repeated Measures Analysis
Comparison: Overall change from baseline analysis. 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: 0.100695% CI: [-0.4, 0.04]Mixed Model Repeated Measures Analysis
Secondary
Clinical Global Impression of Change (CGIC) 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 63 (Week 9)/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 | Clinical Global Impression of Change (CGIC) at Endpoint | 2.58 units on a scale | Standard Error 0.057 |
| Placebo | Clinical Global Impression of Change (CGIC) at Endpoint | 2.73 units on a scale | Standard Error 0.058 |
Comparison: Analysis performed using a general linear model with treatment and center as factors.p-value: 0.043195% CI: [-0.29, 0]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 63 (Week 9)/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 | Patient Global Impression of Change (PGIC) Score at Endpoint | 2.60 units on a scale | Standard Error 0.057 |
| Placebo | Patient Global Impression of Change (PGIC) Score at Endpoint | 2.74 units on a scale | Standard Error 0.058 |
Comparison: Analysis performed using a general linear model with treatment and center as factors.p-value: 0.060295% CI: [-0.28, 0.01]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 63/Week 9) (Study Endpoint) compared to baseline.
Time frame: End of fixed dose phase (Day 63/Week 9)/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) | Dispersion |
|---|---|---|---|
| Pregabalin | Percentage of 30 Percent (%) Responders at Endpoint | 50.3 percentage of participants | 0.115 |
| Placebo | Percentage of 30 Percent (%) Responders at Endpoint | 44.3 percentage of participants | 0.117 |
p-value: 0.130995% CI: [0.93, 1.74]Cochran-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 63 (Week 9)/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) | Dispersion |
|---|---|---|---|
| Pregabalin | Percentage of Participants Who Had Optimal Sleep at Endpoint | 43.8 percentage of participants | 0.085 |
| Placebo | Percentage of Participants Who Had Optimal Sleep at Endpoint | 45.0 percentage of participants | 0.087 |
Comparison: Analysis performed using a logistic regression model with treatment and center as factors, and baseline value as a covariate.p-value: 0.792995% CI: [0.72, 1.53]Regression, Logistic