Neuropathic Pain
Conditions
Brief summary
This study will measure the impact of treatment with pregabalin in adult men and women who have a diagnosis of peripheral neuropathic pain (pain caused by a primary lesion of the peripheral nervous system such as Diabetic peripheral Neuropathy and Postherpetic Neuralgia).
Interventions
pregabalin 150mg/day (75mg BID)
DRUGPlacebo
Placebo
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
* Subjects presenting a diagnosis of peripheral neuropathic pain, defined as pain caused by a lesion of the peripheral nervous system manifesting with sensory symptoms and signs, for at least 6 months at screening. * At baseline, subjects must have completed at least 4 daily pain diaries and must have a mean weekly pain score equal or greater than 4.
Exclusion criteria
* Presence of any of the following diagnoses: Cervical or lumbo-sacral radiculopathy; Operated or non-operated chronic low back pain Carpal tunnel syndrome or any other entrapment-related neuropathic pain (defined as pain associated with focal nerve lesion produced by constriction or mechanical distortion of the nerve, within a fibrous or fibro-osseous tunnel, or by a fibrous band) ; Complex regional pain syndrome (type 1 and 2); Fibromyalgia.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Neuropathic Pain in Subjects With Peripheral Neuropathic Pain Conditions During the Double-blind Phase | 9 weeks | Pain score end of Double-Blind treatment = mean of last 7 available pain scores from daily pain diary while on Double-Blind treatment. A Daily Pain Rating Score : 11- point numerical scale ranging from 0 (no pain) to 10 (worst possible pain). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Weekly Mean Pain Scores During the Double Blind Treatment Phase | Week 4 - 9 | Mean Pain scores for weeks 4, 5, 6, 7, 8 and 9. Mean of last 7 available pain scores from daily pain diary while on single-blind treatment. A Daily Pain Rating Score : 11-point numerical scale ranging from 0 (no pain) to 10 (worst possible pain). |
| Change in Pain Scores During Double Blind Treatment Phase | 9 weeks | Change in Mean Pain score = Mean of last 7 available pain scores from daily pain diary while on single-blind treatment. A Daily Pain Rating Score : 11-point numerical scale ranging from 0 (no pain) to 10 (worst possible pain). |
| Number of Subjects With >= 30% Reduction in Mean Pain Score During Single-blind Treatment | Week 4 (end of single-blind treatment phase) | Responders = ≥30% reduction in mean pain score at end of single-blind treatment phase compared to weekly mean pain score at baseline. Mean of last 7 available pain scores from daily pain diary while on single-blind treatment. A Daily Pain Rating Score : 11-point numerical scale ranging from 0 (no pain) to 10 (worst possible pain). |
| Mean Pain Score for Responders at End of Single-blind Treatment Phase. Change From Baseline of Mean of Last 7 Available Pain Scores From Daily Pain Diary While on Single-blind Treatment. | Week 4 | Daily Pain Rating Score:11-point numerical scale 0 (no pain) to 10 (worst possible pain). Responders = ≥30% reduction in mean pain score at end of single-blind treatment phase compared to weekly mean pain score at baseline. |
| Mean Pain Score for Non-responders at End of Single-blind Treatment Phase | Week 4 | Change from baseline of mean of last 7 available pain scores from daily pain diary while on single-blind treatment. Daily Pain Rating Score:11-point numerical scale 0 (no pain) to 10 (worst possible pain). Non-Responders = \<30% reduction in mean pain score at end of single-blind treatment phase compared to weekly mean pain score at baseline. |
| Categorized Daily Pain Score | Week 9 | Mean number of days in each pain category. DPRS Daily Pain Rating Score Categories: No pain (score 0), Mild pain (scores 1-3), Moderate pain (scores 4-6), Severe pain (scores 7-10) |
| Time to Meaningful Increase in Pain During Double-blind Treatment Phase (Number of Participants) | Week 9 | Number of participants who experienced a meaningful increase in pain also includes participants who took rescue medication for pain due to peripheral neuropathic pain or discontinued from the study . |
| Mean Sleep Interference Score | Week 9 | Mean Sleep Interference (SI) score at end of Double-Blind treatment = mean of last 7 available SI scores from daily SI diary while on Double-Blind treatment. Daily SI rating scale (DSIS) consists of an 11-point numerical scale : Zero means pain does not interfere with sleep and 10 means pain completely interferes with sleep. |
| Weekly Mean Pain Scores During the Single-blind Treatment Phase | 0 and 4 weeks | Pain score at Week 0 and Week 4, end of single-bind treatment. Mean of last 7 available pain scores from daily pain diary while on single-blind treatment. A Daily Pain Rating Score : 11- point numerical scale ranging from 0 (no pain) to 10 (worst possible pain). |
| Weekly Mean Sleep Interference Scores During the Double Blind Treatment Phase | Week 9 | Mean Sleep Interference scores for weeks 4, 5, 6, 7, 8 and 9. Mean of last 7 available SI scores from daily SI diary while on single-blind treatment. Daily SI rating scale (DSIS) consists of an 11-point numerical scale : Zero means pain does not interfere with sleep and 10 means pain completely interferes with sleep. |
| Change in Sleep Interference Scores During Double Blind Treatment Phase | 9 weeks | Change in Mean SI score: Mean SI score at observation minus mean SI score at week 4. Mean SI Score = mean of last 7 available SI scores from daily SI diary while on single-blind treatment. Daily SI rating scale (DSIS) is 11-point numerical scale : Zero means pain does not interfere with sleep and 10 means pain completely interferes with sleep. |
| Intensity of Neuropathic Pain -Visual Analog Scale (NeP - VAS) | Week 4, Week 9 | Change in Scale from randomization to Week 9. Scale to measure Neuropathic Pain -Visual Analog Scale (NeP - VAS): the subject places a mark on the VAS scale (0 to 100) where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. |
| Change in Hospital Anxiety and Depression Scale Responses | Week 9 | Mean Change from Randomization in Score from Hospital Anxiety and Depression Scale (HADS): 2 subscales, measuring anxiety (HADS-A)and depression (HADS-D). 7 items in each subscale assessed on a scale of 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). which yields the score ranging 0-21. |
| Change in Pain Treatment Satisfaction Scale (PTSS) | Week 9 | Mean Change: score from observation minus score from randomization: PTSS Impact module of 8-items & Satisfaction module of 6-items; item scores 1-5. Mean score for each module transformed onto scale 0- 100, where score 0 =worst possible response and score 100 =best possible response: Score =\[(5 - mean non-missing items)\*100\]/4. |
| Patient Global Impression of Change (PGIC) Categories by Number of Subjects | Week 9 | Number of subjects that responded to PGIC Categories. PGIC is a subject-rated instrument that measures change in the subject's overall status on a 7-point scale. Scores range from 1 (very much improved) to 7 (very much worse). |
| Change in Modified Brief Pain Inventory (mBPI) for Pain Interference or Pain Severity. | Week 9 | Mean Change from Randomization: score at mBPI observation minus score at randomization. mBPI is extent to which pain interferes with daily activities on a 0 (no interference) to 10 (completely interfered) scale. |
| Change in Euro Quality of Life (EQ-5D) Health State Profile and Visual Analog Scale Components | Week 9 | two components to the EQ-5D: a Health State Profile (scores from five domains are used to calculate the utility score :0 refers to dead and a score of 1 refers to perfect health) and a Visual Analogue Scale (VAS) (0 represents the worst imaginable health state and 100 represents the best imaginable health state) |
| Weekly Mean Sleep Interference Scores During the Single-Blind Treatment Phase | 0 and 4 weeks | Sleep Interference (SI) score at Week 0 and Week 4, end of single-bind treatment. Mean of last 7 available SI scores from daily SI diary while on single-blind treatment. Daily SI rating scale (DSIS) consists of an 11-point numerical scale : Zero means pain does not interfere with sleep and 10 means pain completely interferes with sleep. |
Countries
Canada
Participant flow
Recruitment details
This study was conducted in Canada.
Pre-assignment details
405 subjects enrolled - 234 completed the single-blind phase. Subjects who responded (≥30% decrease in weekly mean pain score) during single-blind entered double-blind. 158 subjects assigned to study drug in double-blind phase. One subject in placebo group was randomized in error, not treated, not included as discontinuation;157 received treatment.
Participants by arm
| Arm | Count |
|---|---|
| Pregabalin subjects entered single-blind phase with 28 days of single-blind flexible pregabalin doses (150 to 600 mg/day), starting at 150 mg/day for ≥4 days, then dose adjustment as needed. Subjects who responded during the single-blind phase and were randomized to pregabalin entered the double-blind phase with 35 days of dose achieved at the end of the single-blind treatment phase. | 256 |
| Total | 256 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Single Blind Treatment Period | Adverse Event | 9 | 0 |
| Single Blind Treatment Period | Investigator decision to withdraw | 1 | 0 |
| Single Blind Treatment Period | Lack of Efficacy | 5 | 0 |
| Single Blind Treatment Period | Lost to Follow-up | 2 | 0 |
| Single Blind Treatment Period | Protocol Violation | 4 | 0 |
| Single Blind Treatment Period | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Pregabalin |
|---|---|
| Age, Continuous | 58.4 years STANDARD_DEVIATION 10.4 |
| Sex: Female, Male Female | 128 Participants |
| Sex: Female, Male Male | 128 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 196 / — | 33 / — | 29 / — |
| serious Total, serious adverse events | 1 / — | 0 / — | 0 / — |
Outcome results
Primary
Neuropathic Pain in Subjects With Peripheral Neuropathic Pain Conditions During the Double-blind Phase
Pain score end of Double-Blind treatment = mean of last 7 available pain scores from daily pain diary while on Double-Blind treatment. A Daily Pain Rating Score : 11- point numerical scale ranging from 0 (no pain) to 10 (worst possible pain).
Time frame: 9 weeks
Population: Full Analysis Set (FAS) = Intent-to-Treat (ITT) population, defined as all subjects who are randomized into the Double-Blind treatment phase, who receive at least one dose of Double-Blind study medication and complete at least one postrandomization efficacy assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Neuropathic Pain in Subjects With Peripheral Neuropathic Pain Conditions During the Double-blind Phase | 2.84 score on scale | Standard Error 0.18 |
| Placebo | Neuropathic Pain in Subjects With Peripheral Neuropathic Pain Conditions During the Double-blind Phase | 3.62 score on scale | Standard Error 0.18 |
Comparison: The study is powered to detect clinically significant difference of 1.2 between treatment groups in mean pain score at end of treatment. The statistical sample size calculation requires a total of 144 subjects to complete the Double-Blind phase of the study: a sample size of 72 in each treatment group will have 90% power to detect a difference in treatment mean pain scores of 1.2 assuming that the common standard deviation is 2.2 using a two group t-test with a 0.05 two-sided significance level.p-value: 0.001895% CI: [-1.27, -0.3]ANCOVA
Secondary
Categorized Daily Pain Score
Mean number of days in each pain category. DPRS Daily Pain Rating Score Categories: No pain (score 0), Mild pain (scores 1-3), Moderate pain (scores 4-6), Severe pain (scores 7-10)
Time frame: Week 9
Population: Number of subjects analyzed for each pain category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Categorized Daily Pain Score | No pain | 3.3 days | Standard Deviation 7.6 |
| Pregabalin | Categorized Daily Pain Score | Mild pain | 19.5 days | Standard Deviation 12.1 |
| Pregabalin | Categorized Daily Pain Score | Moderate pain | 7.4 days | Standard Deviation 9.5 |
| Pregabalin | Categorized Daily Pain Score | Severe pain | 1.2 days | Standard Deviation 2.8 |
| Placebo | Categorized Daily Pain Score | Severe pain | 1.7 days | Standard Deviation 4.5 |
| Placebo | Categorized Daily Pain Score | No pain | 0.9 days | Standard Deviation 3.1 |
| Placebo | Categorized Daily Pain Score | Moderate pain | 8.6 days | Standard Deviation 8.3 |
| Placebo | Categorized Daily Pain Score | Mild pain | 17.4 days | Standard Deviation 11.9 |
Secondary
Change in Euro Quality of Life (EQ-5D) Health State Profile and Visual Analog Scale Components
two components to the EQ-5D: a Health State Profile (scores from five domains are used to calculate the utility score :0 refers to dead and a score of 1 refers to perfect health) and a Visual Analogue Scale (VAS) (0 represents the worst imaginable health state and 100 represents the best imaginable health state)
Time frame: Week 9
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Change in Euro Quality of Life (EQ-5D) Health State Profile and Visual Analog Scale Components | Visual Analog Scale | -0.03 score on scale | Standard Error 1.83 |
| Pregabalin | Change in Euro Quality of Life (EQ-5D) Health State Profile and Visual Analog Scale Components | Health State Profile | -0.01 score on scale | Standard Error 0.02 |
| Placebo | Change in Euro Quality of Life (EQ-5D) Health State Profile and Visual Analog Scale Components | Health State Profile | -0.07 score on scale | Standard Error 0.02 |
| Placebo | Change in Euro Quality of Life (EQ-5D) Health State Profile and Visual Analog Scale Components | Visual Analog Scale | -2.09 score on scale | Standard Error 1.89 |
Comparison: Health State Profilep-value: 0.071995% CI: [0, 0.11]ANCOVA
Comparison: Visual Analog Scalep-value: 0.41895% CI: [-2.96, 7.1]ANCOVA
Secondary
Change in Hospital Anxiety and Depression Scale Responses
Mean Change from Randomization in Score from Hospital Anxiety and Depression Scale (HADS): 2 subscales, measuring anxiety (HADS-A)and depression (HADS-D). 7 items in each subscale assessed on a scale of 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). which yields the score ranging 0-21.
Time frame: Week 9
Population: FAS population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Change in Hospital Anxiety and Depression Scale Responses | HADS-A | -0.1 score on scale | Standard Error 0.3 |
| Pregabalin | Change in Hospital Anxiety and Depression Scale Responses | HADS-D | -0.4 score on scale | Standard Error 0.3 |
| Placebo | Change in Hospital Anxiety and Depression Scale Responses | HADS-A | 1.2 score on scale | Standard Error 0.3 |
| Placebo | Change in Hospital Anxiety and Depression Scale Responses | HADS-D | 0.8 score on scale | Standard Error 0.3 |
Comparison: HADS-Ap-value: 0.002395% CI: [-2.1, -0.5]ANCOVA
Comparison: HADS-Dp-value: 0.001395% CI: [-1.9, -0.5]ANCOVA
Secondary
Change in Modified Brief Pain Inventory (mBPI) for Pain Interference or Pain Severity.
Mean Change from Randomization: score at mBPI observation minus score at randomization. mBPI is extent to which pain interferes with daily activities on a 0 (no interference) to 10 (completely interfered) scale.
Time frame: Week 9
Population: FAS population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Change in Modified Brief Pain Inventory (mBPI) for Pain Interference or Pain Severity. | Pain interference | 0.16 score on scale | Standard Error 0.19 |
| Pregabalin | Change in Modified Brief Pain Inventory (mBPI) for Pain Interference or Pain Severity. | Pain severity | 0.29 score on scale | Standard Error 0.19 |
| Placebo | Change in Modified Brief Pain Inventory (mBPI) for Pain Interference or Pain Severity. | Pain interference | 0.92 score on scale | Standard Error 0.2 |
| Placebo | Change in Modified Brief Pain Inventory (mBPI) for Pain Interference or Pain Severity. | Pain severity | 1.06 score on scale | Standard Error 0.19 |
Comparison: Pain interferencep-value: 0.004995% CI: [-1.28, -0.23]ANCOVA
Comparison: Pain severityp-value: 0.003795% CI: [-1.29, -0.25]ANCOVA
Secondary
Change in Pain Scores During Double Blind Treatment Phase
Change in Mean Pain score = Mean of last 7 available pain scores from daily pain diary while on single-blind treatment. A Daily Pain Rating Score : 11-point numerical scale ranging from 0 (no pain) to 10 (worst possible pain).
Time frame: 9 weeks
Population: Full Analysis Set (FAS)
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Change in Pain Scores During Double Blind Treatment Phase | Change from randomization to Week 6 (n=66, 63) | 0.08 score on scale | Standard Error 0.16 |
| Pregabalin | Change in Pain Scores During Double Blind Treatment Phase | Change from randomization to Week 8 (n=63,53) | -0.10 score on scale | Standard Error 0.16 |
| Pregabalin | Change in Pain Scores During Double Blind Treatment Phase | Change from randomization to Week 7 (n=60, 56) | -0.06 score on scale | Standard Error 0.16 |
| Pregabalin | Change in Pain Scores During Double Blind Treatment Phase | Change from randomization to Week 9 (n=67,58) | 0.14 score on scale | Standard Error 0.15 |
| Pregabalin | Change in Pain Scores During Double Blind Treatment Phase | Change from randomization to Week 5 (n=70, 64) | -0.01 score on scale | Standard Error 0.15 |
| Placebo | Change in Pain Scores During Double Blind Treatment Phase | Change from randomization to Week 9 (n=67,58) | 0.84 score on scale | Standard Error 0.17 |
| Placebo | Change in Pain Scores During Double Blind Treatment Phase | Change from randomization to Week 5 (n=70, 64) | 0.71 score on scale | Standard Error 0.16 |
| Placebo | Change in Pain Scores During Double Blind Treatment Phase | Change from randomization to Week 6 (n=66, 63) | 1.05 score on scale | Standard Error 0.16 |
| Placebo | Change in Pain Scores During Double Blind Treatment Phase | Change from randomization to Week 7 (n=60, 56) | 0.87 score on scale | Standard Error 0.17 |
| Placebo | Change in Pain Scores During Double Blind Treatment Phase | Change from randomization to Week 8 (n=63,53) | 0.83 score on scale | Standard Error 0.17 |
Comparison: Week 5p-value: 0.00195% CI: [-1.15, -0.3]ANCOVA
Comparison: Week 6p-value: <0.000195% CI: [-1.41, -0.53]ANCOVA
Comparison: Week 7p-value: <0.000195% CI: [-1.39, -0.47]ANCOVA
Comparison: Week 8p-value: <0.000195% CI: [-1.39, -0.47]ANCOVA
Comparison: Week 9p-value: 0.002295% CI: [-1.14, -0.25]ANCOVA
Secondary
Change in Pain Treatment Satisfaction Scale (PTSS)
Mean Change: score from observation minus score from randomization: PTSS Impact module of 8-items & Satisfaction module of 6-items; item scores 1-5. Mean score for each module transformed onto scale 0- 100, where score 0 =worst possible response and score 100 =best possible response: Score =\[(5 - mean non-missing items)\*100\]/4.
Time frame: Week 9
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Change in Pain Treatment Satisfaction Scale (PTSS) | impact of current pain medication | -1.96 score on scale | Standard Error 2.53 |
| Pregabalin | Change in Pain Treatment Satisfaction Scale (PTSS) | satisfaction with current pain medication | -1.86 score on scale | Standard Error 2.04 |
| Placebo | Change in Pain Treatment Satisfaction Scale (PTSS) | impact of current pain medication | -7.95 score on scale | Standard Error 2.6 |
| Placebo | Change in Pain Treatment Satisfaction Scale (PTSS) | satisfaction with current pain medication | -8.35 score on scale | Standard Error 2.09 |
Comparison: Impactp-value: 0.082895% CI: [-0.79, 12.75]ANCOVA
Comparison: Satisfactionp-value: 0.019795% CI: [1.05, 11.94]ANCOVA
Secondary
Change in Sleep Interference Scores During Double Blind Treatment Phase
Change in Mean SI score: Mean SI score at observation minus mean SI score at week 4. Mean SI Score = mean of last 7 available SI scores from daily SI diary while on single-blind treatment. Daily SI rating scale (DSIS) is 11-point numerical scale : Zero means pain does not interfere with sleep and 10 means pain completely interferes with sleep.
Time frame: 9 weeks
Population: Full Analysis Set (FAS)
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Change in Sleep Interference Scores During Double Blind Treatment Phase | Change from randomization to Week 8 (n=63,53) | -0.13 score on scale | Standard Error 0.16 |
| Pregabalin | Change in Sleep Interference Scores During Double Blind Treatment Phase | Change from randomization to Week 5 (n=70, 64) | 0.07 score on scale | Standard Error 0.15 |
| Pregabalin | Change in Sleep Interference Scores During Double Blind Treatment Phase | Change from randomization to Week 9 (n=67,58) | -0.01 score on scale | Standard Error 0.15 |
| Pregabalin | Change in Sleep Interference Scores During Double Blind Treatment Phase | Change from randomization to Week 6 (n=66, 63) | 0.10 score on scale | Standard Error 0.16 |
| Pregabalin | Change in Sleep Interference Scores During Double Blind Treatment Phase | Change from randomization to Week 7 (n=60, 56) | -0.03 score on scale | Standard Error 0.16 |
| Placebo | Change in Sleep Interference Scores During Double Blind Treatment Phase | Change from randomization to Week 6 (n=66, 63) | 0.97 score on scale | Standard Error 0.16 |
| Placebo | Change in Sleep Interference Scores During Double Blind Treatment Phase | Change from randomization to Week 7 (n=60, 56) | 0.78 score on scale | Standard Error 0.17 |
| Placebo | Change in Sleep Interference Scores During Double Blind Treatment Phase | Change from randomization to Week 8 (n=63,53) | 0.72 score on scale | Standard Error 0.17 |
| Placebo | Change in Sleep Interference Scores During Double Blind Treatment Phase | Change from randomization to Week 9 (n=67,58) | 0.73 score on scale | Standard Error 0.17 |
| Placebo | Change in Sleep Interference Scores During Double Blind Treatment Phase | Change from randomization to Week 5 (n=70, 64) | 0.59 score on scale | Standard Error 0.16 |
Comparison: Week 5p-value: 0.017795% CI: [-0.94, -0.09]ANCOVA
Comparison: Week 6p-value: <0.000195% CI: [-1.31, -0.44]ANCOVA
Comparison: Week 7p-value: 0.000595% CI: [-1.28, -0.36]ANCOVA
Comparison: Week 8p-value: 0.000395% CI: [-1.31, -0.39]ANCOVA
Comparison: Week 9p-value: 0.001195% CI: [-1.18, -0.3]ANCOVA
Secondary
Intensity of Neuropathic Pain -Visual Analog Scale (NeP - VAS)
Change in Scale from randomization to Week 9. Scale to measure Neuropathic Pain -Visual Analog Scale (NeP - VAS): the subject places a mark on the VAS scale (0 to 100) where 0 represents the worst imaginable health state and 100 represents the best imaginable health state.
Time frame: Week 4, Week 9
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Intensity of Neuropathic Pain -Visual Analog Scale (NeP - VAS) | 6.9 scores on a scale | Standard Error 2.4 |
| Placebo | Intensity of Neuropathic Pain -Visual Analog Scale (NeP - VAS) | 15.9 scores on a scale | Standard Error 2.5 |
p-value: 0.006995% CI: [-15.5, -2.5]ANCOVA
Secondary
Mean Pain Score for Non-responders at End of Single-blind Treatment Phase
Change from baseline of mean of last 7 available pain scores from daily pain diary while on single-blind treatment. Daily Pain Rating Score:11-point numerical scale 0 (no pain) to 10 (worst possible pain). Non-Responders = \<30% reduction in mean pain score at end of single-blind treatment phase compared to weekly mean pain score at baseline.
Time frame: Week 4
Population: number of subjects that can be analyzed for Change from Baseline at End of Single Blind.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Mean Pain Score for Non-responders at End of Single-blind Treatment Phase | -0.49 score on scale | Standard Deviation 0.95 |
Secondary
Mean Pain Score for Responders at End of Single-blind Treatment Phase. Change From Baseline of Mean of Last 7 Available Pain Scores From Daily Pain Diary While on Single-blind Treatment.
Daily Pain Rating Score:11-point numerical scale 0 (no pain) to 10 (worst possible pain). Responders = ≥30% reduction in mean pain score at end of single-blind treatment phase compared to weekly mean pain score at baseline.
Time frame: Week 4
Population: number of subjects that can be analyzed for Change from Baseline at End of Single Blind.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Mean Pain Score for Responders at End of Single-blind Treatment Phase. Change From Baseline of Mean of Last 7 Available Pain Scores From Daily Pain Diary While on Single-blind Treatment. | -3.60 score on scale | Standard Deviation 1.32 |
Secondary
Mean Sleep Interference Score
Mean Sleep Interference (SI) score at end of Double-Blind treatment = mean of last 7 available SI scores from daily SI diary while on Double-Blind treatment. Daily SI rating scale (DSIS) consists of an 11-point numerical scale : Zero means pain does not interfere with sleep and 10 means pain completely interferes with sleep.
Time frame: Week 9
Population: FAS population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Mean Sleep Interference Score | 1.81 score on scale | Standard Error 0.17 |
| Placebo | Mean Sleep Interference Score | 2.52 score on scale | Standard Error 0.18 |
p-value: 0.003195% CI: [-1.18, -0.24]ANCOVA
Secondary
Number of Subjects With >= 30% Reduction in Mean Pain Score During Single-blind Treatment
Responders = ≥30% reduction in mean pain score at end of single-blind treatment phase compared to weekly mean pain score at baseline. Mean of last 7 available pain scores from daily pain diary while on single-blind treatment. A Daily Pain Rating Score : 11-point numerical scale ranging from 0 (no pain) to 10 (worst possible pain).
Time frame: Week 4 (end of single-blind treatment phase)
Population: 256 subjects entered the single-blind treatment phase, one subject did not have enough DPRS assessments for calculation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pregabalin | Number of Subjects With >= 30% Reduction in Mean Pain Score During Single-blind Treatment | Responders | 165 participants |
| Pregabalin | Number of Subjects With >= 30% Reduction in Mean Pain Score During Single-blind Treatment | Non-Responders | 90 participants |
Secondary
Patient Global Impression of Change (PGIC) Categories by Number of Subjects
Number of subjects that responded to PGIC Categories. PGIC is a subject-rated instrument that measures change in the subject's overall status on a 7-point scale. Scores range from 1 (very much improved) to 7 (very much worse).
Time frame: Week 9
Population: FAS Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pregabalin | Patient Global Impression of Change (PGIC) Categories by Number of Subjects | Very much improved | 21 participants |
| Pregabalin | Patient Global Impression of Change (PGIC) Categories by Number of Subjects | Minimally worse | 0 participants |
| Pregabalin | Patient Global Impression of Change (PGIC) Categories by Number of Subjects | Minimally improved | 15 participants |
| Pregabalin | Patient Global Impression of Change (PGIC) Categories by Number of Subjects | Much worse | 1 participants |
| Pregabalin | Patient Global Impression of Change (PGIC) Categories by Number of Subjects | Much improved | 35 participants |
| Pregabalin | Patient Global Impression of Change (PGIC) Categories by Number of Subjects | Very much worse | 0 participants |
| Pregabalin | Patient Global Impression of Change (PGIC) Categories by Number of Subjects | No change | 6 participants |
| Placebo | Patient Global Impression of Change (PGIC) Categories by Number of Subjects | Very much worse | 1 participants |
| Placebo | Patient Global Impression of Change (PGIC) Categories by Number of Subjects | Very much improved | 12 participants |
| Placebo | Patient Global Impression of Change (PGIC) Categories by Number of Subjects | Much improved | 32 participants |
| Placebo | Patient Global Impression of Change (PGIC) Categories by Number of Subjects | Minimally improved | 17 participants |
| Placebo | Patient Global Impression of Change (PGIC) Categories by Number of Subjects | No change | 7 participants |
| Placebo | Patient Global Impression of Change (PGIC) Categories by Number of Subjects | Minimally worse | 6 participants |
| Placebo | Patient Global Impression of Change (PGIC) Categories by Number of Subjects | Much worse | 0 participants |
Comparison: The distribution of the responses to the PGIC at EOT was compared between the 2 treatment groups using the 7 categories of the PGIC.p-value: 0.0278Mantel Haenszel
Secondary
Time to Meaningful Increase in Pain During Double-blind Treatment Phase (Number of Participants)
Number of participants who experienced a meaningful increase in pain also includes participants who took rescue medication for pain due to peripheral neuropathic pain or discontinued from the study .
Time frame: Week 9
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pregabalin | Time to Meaningful Increase in Pain During Double-blind Treatment Phase (Number of Participants) | 28 participants |
| Placebo | Time to Meaningful Increase in Pain During Double-blind Treatment Phase (Number of Participants) | 28 participants |
Secondary
Weekly Mean Pain Scores During the Double Blind Treatment Phase
Mean Pain scores for weeks 4, 5, 6, 7, 8 and 9. Mean of last 7 available pain scores from daily pain diary while on single-blind treatment. A Daily Pain Rating Score : 11-point numerical scale ranging from 0 (no pain) to 10 (worst possible pain).
Time frame: Week 4 - 9
Population: FAS population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Weekly Mean Pain Scores During the Double Blind Treatment Phase | Week 4 (n=73, 70) | 2.68 score on scale | Standard Deviation 1.29 |
| Pregabalin | Weekly Mean Pain Scores During the Double Blind Treatment Phase | Week 5 (n=70,64) | 2.62 score on scale | Standard Deviation 1.48 |
| Pregabalin | Weekly Mean Pain Scores During the Double Blind Treatment Phase | Week 6 (n=66,63) | 2.75 score on scale | Standard Deviation 1.76 |
| Pregabalin | Weekly Mean Pain Scores During the Double Blind Treatment Phase | Week 7 (n=60,56) | 2.53 score on scale | Standard Deviation 1.8 |
| Pregabalin | Weekly Mean Pain Scores During the Double Blind Treatment Phase | Week 8 (n=63,53) | 2.51 score on scale | Standard Deviation 1.59 |
| Pregabalin | Weekly Mean Pain Scores During the Double Blind Treatment Phase | Week 9 (n=67,58) | 2.80 score on scale | Standard Deviation 1.8 |
| Placebo | Weekly Mean Pain Scores During the Double Blind Treatment Phase | Week 8 (n=63,53) | 3.16 score on scale | Standard Deviation 1.54 |
| Placebo | Weekly Mean Pain Scores During the Double Blind Treatment Phase | Week 4 (n=73, 70) | 2.49 score on scale | Standard Deviation 1.23 |
| Placebo | Weekly Mean Pain Scores During the Double Blind Treatment Phase | Week 7 (n=60,56) | 3.20 score on scale | Standard Deviation 1.45 |
| Placebo | Weekly Mean Pain Scores During the Double Blind Treatment Phase | Week 5 (n=70,64) | 3.14 score on scale | Standard Deviation 1.41 |
| Placebo | Weekly Mean Pain Scores During the Double Blind Treatment Phase | Week 9 (n=67,58) | 3.29 score on scale | Standard Deviation 1.52 |
| Placebo | Weekly Mean Pain Scores During the Double Blind Treatment Phase | Week 6 (n=66,63) | 3.40 score on scale | Standard Deviation 1.49 |
Secondary
Weekly Mean Pain Scores During the Single-blind Treatment Phase
Pain score at Week 0 and Week 4, end of single-bind treatment. Mean of last 7 available pain scores from daily pain diary while on single-blind treatment. A Daily Pain Rating Score : 11- point numerical scale ranging from 0 (no pain) to 10 (worst possible pain).
Time frame: 0 and 4 weeks
Population: Full Analysis Set (FAS)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Weekly Mean Pain Scores During the Single-blind Treatment Phase | Week 0 - Baseline | 6.29 score on scale | Standard Deviation 1.43 |
| Pregabalin | Weekly Mean Pain Scores During the Single-blind Treatment Phase | Week 4 - end of single-blind treatment | 3.79 score on scale | Standard Deviation 2.11 |
Secondary
Weekly Mean Sleep Interference Scores During the Double Blind Treatment Phase
Mean Sleep Interference scores for weeks 4, 5, 6, 7, 8 and 9. Mean of last 7 available SI scores from daily SI diary while on single-blind treatment. Daily SI rating scale (DSIS) consists of an 11-point numerical scale : Zero means pain does not interfere with sleep and 10 means pain completely interferes with sleep.
Time frame: Week 9
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Weekly Mean Sleep Interference Scores During the Double Blind Treatment Phase | Week 4 (n=73, 70) | 1.68 score on scale | Standard Deviation 1.57 |
| Pregabalin | Weekly Mean Sleep Interference Scores During the Double Blind Treatment Phase | Week 5 (n=70,64) | 1.76 score on scale | Standard Deviation 1.61 |
| Pregabalin | Weekly Mean Sleep Interference Scores During the Double Blind Treatment Phase | Week 6 (n=66,63) | 1.85 score on scale | Standard Deviation 1.81 |
| Pregabalin | Weekly Mean Sleep Interference Scores During the Double Blind Treatment Phase | Week 7 (n=60,56) | 1.66 score on scale | Standard Deviation 1.63 |
| Pregabalin | Weekly Mean Sleep Interference Scores During the Double Blind Treatment Phase | Week 8 (n=63,53) | 1.59 score on scale | Standard Deviation 1.57 |
| Pregabalin | Weekly Mean Sleep Interference Scores During the Double Blind Treatment Phase | Week 9 (n=67,58) | 1.66 score on scale | Standard Deviation 1.74 |
| Placebo | Weekly Mean Sleep Interference Scores During the Double Blind Treatment Phase | Week 8 (n=63,53) | 2.36 score on scale | Standard Deviation 1.79 |
| Placebo | Weekly Mean Sleep Interference Scores During the Double Blind Treatment Phase | Week 4 (n=73, 70) | 1.62 score on scale | Standard Deviation 1.61 |
| Placebo | Weekly Mean Sleep Interference Scores During the Double Blind Treatment Phase | Week 7 (n=60,56) | 2.38 score on scale | Standard Deviation 1.75 |
| Placebo | Weekly Mean Sleep Interference Scores During the Double Blind Treatment Phase | Week 5 (n=70,64) | 2.24 score on scale | Standard Deviation 1.79 |
| Placebo | Weekly Mean Sleep Interference Scores During the Double Blind Treatment Phase | Week 9 (n=67,58) | 2.40 score on scale | Standard Deviation 1.86 |
| Placebo | Weekly Mean Sleep Interference Scores During the Double Blind Treatment Phase | Week 6 (n=66,63) | 2.53 score on scale | Standard Deviation 1.69 |
Secondary
Weekly Mean Sleep Interference Scores During the Single-Blind Treatment Phase
Sleep Interference (SI) score at Week 0 and Week 4, end of single-bind treatment. Mean of last 7 available SI scores from daily SI diary while on single-blind treatment. Daily SI rating scale (DSIS) consists of an 11-point numerical scale : Zero means pain does not interfere with sleep and 10 means pain completely interferes with sleep.
Time frame: 0 and 4 weeks
Population: Last observation carried forward (LOCF) approach for patients who do not complete the study will be adopted. This is defined as the mean of the last 7 diary scores while on Double-Blind study drug, up to and including the day after the last day on drug (excluding the taper phase).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Weekly Mean Sleep Interference Scores During the Single-Blind Treatment Phase | Week 0 - Baseline | 4.80 score on scale | Standard Deviation 2.44 |
| Pregabalin | Weekly Mean Sleep Interference Scores During the Single-Blind Treatment Phase | Week 4 - end of single-blind treatment | 2.72 score on scale | Standard Deviation 2.42 |