Central Neuropathic Pain
Conditions
Keywords
Post-stroke pain, pregabalin
Brief summary
Efficacy and Safety of flexibly dosed pregabalin compared to placebo among subjects with central post stroke pain (CPSP)
Interventions
DRUGPregabalin
Eligible subjects with post-stroke central pain will be randomized to receive double blinded treatment using pregabalin or matched placebo. The effects of pregabalin as compared to placebo on pain pain symptoms will be compared over the 13 week clinical trial. At baseline following pain ratings and clinical measures, subjects randomized to pregabalin receive instructions to take 75mg twice a day for 7days. The dosing of pregabalin or matching placebo will be titrated over the first 4 weeks (based on tolerability and pain scores). (Range 150-600mg) After the 4th week, the dose of medication will be maintained until week 12 (when tapering of medication begins) Ratings of Pain severity, review of pain/sleep diaries as well as medication tolerance occur bi-weekly throughout the study. Tapering off med occurs from week 12-13.
DRUGPlacebo
Eligible subjects with post-stroke central pain will be randomized to receive double blinded treatment using pregabalin or matched placebo. The effects of pregabalin as compared to placebo on pain pain symptoms will be compared over the 13 week clinical trial. At baseline following pain ratings and clinical measures, subjects randomized to pregabalin receive instructions to take 75mg twice a day for 7days. The dosing of pregabalin or matching placebo will be titrated over the first 4 weeks (based on tolerability and pain scores). (Range 150-600mg) After the 4th week, the dose of medication will be maintained until week 12 (when tapering of medication begins) Ratings of Pain severity, review of pain/sleep diaries as well as medication tolerance occur bi-weekly throughout the study. Tapering off med occurs from week 12-13.
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Positive history of clinical stroke at least 4 months prior to randomization CPSP--3 months prior to screening
Exclusion criteria
* History of dementia or any other severe cognitive impairment * Diabetic Peripheral Neuropathy (DPN)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Pain Score at Endpoint as Measured by Daily Pain Rating Scale (DPRS) | Up to Week 12 | Mean pain score obtained from last 7 available DPRS scores up to and including day of Week 12 visit or early termination (ET) equivalent. DPRS: subject rated 11-point numeric scale ranging from 0 (no pain) to 10 (worst possible pain) during past 24-hour period. Higher score indicates greater level of pain. Self-assessment performed daily on awakening prior to taking study medication. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With at Least a 30% Reduction From Baseline in Mean Pain Score at Endpoint | Baseline, Week 12 | 30% Responder Yes = number of subjects with 30% reduction in mean pain score from baseline to observation; 30% reduction calculated as \[(T minus B) divided by B multiplied by 100\] \< = negative 30. T = endpoint mean pain score (obtained from last 7 available scores from DPRS); B = baseline mean pain score (obtained from average of last 7 daily scores from DPRS). 30% Responder No indicates number of subjects that did not reach 30% reduction in mean pain score. |
| Number of Subjects With at Least a 50% Reduction From Baseline in Mean Pain Score at Endpoint | Baseline, Week 12 | 50% Responder Yes = number of subjects with 50% reduction in mean pain score from baseline to observation; 50% reduction calculated as \[(T minus B) divided by B multiplied by 100\] \< = negative 50. T = endpoint mean pain score (obtained from last 7 available scores from DPRS); B = baseline mean pain score (obtained from average of last 7 daily scores from DPRS). 50% Responder No indicates number of subjects that did not reach 50% reduction in mean pain score. |
| Weekly Mean Sleep Interference Score From Daily Sleep Diary (Daily Sleep Interference Scale [DSIS]) | Week 1, Week 2, Week 3, Week 6, Week 9, and Week 12 | DSIS: subject rated 11-point numeric scale ranging from 0 (pain does not interfere with sleep) to 10 (pain completely interferes with sleep) during past 24-hour period. Higher score indicates a greater level of sleep disturbance. Self-assessment performed daily on awakening prior to taking study medication. Endpoint calculated as mean of last 7 available scores. |
| Short Form-McGill Pain Questionnaire (SF-MPQ Visual Analog Scale [VAS]) - Part B Only | Week 12 | SF-MPQ Part B VAS consists of a line 0 to 100 millimeters (mm) in length; range is (no pain) to 100 mm (worst possible pain). Subjects placed a mark indicating the intensity of their pain. Distance from left-hand end of line was measured and entered on Case Report Form (CRF) as score in mm. Higher score indicates greater level of pain. |
| Neuropathic Pain Symptom Inventory (NPSI) | Week 12 | NPSI: subject rated questionnaire to evaluate different symptoms of neuropathic pain (dimensions: burning \[superficial\] spontaneous pain, pressing \[deep\] spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dyesthesia \[P/D\]). Includes 10 descriptors quantified on a 0 (no symptoms) to 10 (worst symptoms imaginable) and 2 temporal items assessing duration of spontaneous ongoing and paroxysmal pain. Questionnaire generates a score in each of the relevant dimensions and a total score (0 to 100). Higher score indicates a greater intensity of pain. |
| Medical Outcome Study (MOS) Sleep Scale | Week 12 | MOS: subject rated questionnaire to assess sleep quality and quantity. Consists of a 9-item overall sleep problems index (length of time to fall asleep, how many hours of sleep each night during past 4 weeks); 7 subscales rated 1 (all the time) to 6 (none of the time): sleep disturbance, snoring, awaken short of breath (SOB) or with a headache, somnolence adequacy, and sleep quantity. Scores are transformed (actual raw score minus lowest possible score divided by possible raw score range multiplied by 100); total score range = 0 to 100; higher score indicates greater intensity of attribute. |
| Number of Subjects With Yes or No Response for Medical Outcome Study (MOS) Sleep Scale - Optimal Sleep | Week 12 | MOS: subject rated questionnaire to assess sleep quality and quantity. Optimal sleep component is derived from Sleep Quantity average hours of sleep each night during the past 4 weeks. Number of subjects with response = YES if sleep quantity is 7 or 8 hours per night or response = NO if sleep quantity is \< 7 hours per night. |
| Pain Score as Measured by DPRS | Week 1, Week 2, Week 3, Week 6, Week 9, and Week 12 | Weekly mean pain score measured by DPRS: subject rated 11-point numeric scale ranging from 0 (no pain) to 10 (worst possible pain) during past 24-hour period. Higher score indicates greater level of pain. Self-assessment performed daily on awakening prior to taking study medication. |
| Euro Quality of Life (EQ-5D)- Health State Profile Utility Score | Week 12 | EQ-5D: subject rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (eg, confined to bed). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. |
| EQ-5D - VAS | Week 12 | EQ-5D: subject rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state. |
| Patient Global Impression of Change (PGIC) | Week 12 | PGIC: subject rated instrument to measure subject's change in overall status on a 7-point scale; range from 1 (very much improved) to 7 (very much worse). |
| Clinical Global Impression of Change (CGIC) | Week 12 | CGIC: clinician rated instrument that measures change in a subject's ovall status on a 7-point scale; range from 1 (very much improved) to 7 (very much worse). |
| Quantitative Assessment of Neuropathic Pain (QANeP) - Sensory Threshold | Baseline, Week 12 | QANeP: assessment of sensory threshold: subject responds yes when monofilament stimulus is felt on area of maximum pain: 1 (lowest/softest 0.07 gram \[g\]) to 6 (highest 300 g) or 7 (not perceived); rated by lowest/softest filament felt when in contact with the skin. Summarized as change from baseline (mean at observation minus mean at baseline). |
| QANeP - Pain Rating Scales | Baseline, Week 12 | Subject rated pain scale: static mechanical allodynia (SMA) gentle constant mechanical pressure; dynamic mechanical allodynia (DMA) gentle stroking with foam brush; punctate hyperalgesia (PH) pinprick; cold allodynia (CA) touch with cool metal rod 13-17° celsius (C); cold hyperalgesia (CH) touch with cold metal rod 4° C; temporal summation to tactile stimuli (TSTS) repeated touching/tapping. 11-point numeric scale; range 0 (no pain) to 10 (worst possible pain). Reference area=mirror image of pain site (test area). Summarized as change from baseline (mean at observation minus mean at baseline). |
| Hospital Anxiety and Depression Scale (HADS) - ITT Population | Week 12 | HADS is subject rated questionnaire with 2 subscales. HADS-A assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale comprised of 7 items with range 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score 0 to 21 for each subscale; higher score indicates greater severity of anxiety and depression symptoms. |
Countries
Australia, China, Hong Kong, India, Indonesia, Malaysia, Pakistan, Philippines, South Korea, Taiwan, Thailand
Participant flow
Pre-assignment details
Two-week screening and washout phase prior to randomization.
Participants by arm
| Arm | Count |
|---|---|
| Pregabalin 75 milligram (mg) capsule by mouth (PO) twice a day (BID) for 7 days. Pregabalin was titrated over the first 4 weeks based on tolerability and pain scores. Range was 150 mg total daily dose to a maximum of 600 mg total daily dose. Week 1: 150 mg BID for 7 days; Weeks 2 through 4: maintained at previous dose level or dose increased or reduced based on tolerability and pain scores (150 mg or 300 mg or 600 mg total daily dose). After the fourth week, dose was maintained until week 12 when dose was tapered to 75 mg BID. | 110 |
| Placebo 75 milligram (mg) capsule PO BID for 7 days. Placebo was titrated over the first 4 weeks based on tolerability and pain scores. Range was 150 mg total daily dose to a maximum of 600 mg total daily dose. Week 1: 150 mg BID for 7 days; Weeks 2 through 4: maintained at previous dose level or dose increased or reduced based on tolerability and pain scores (150 mg or 300 mg or 600 mg total daily dose). After the fourth week, dose was maintained until week 12 when dose was tapered to 75 mg BID. | 109 |
| Total | 219 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Assigned to Treatment | Other | 1 | 0 |
| Pregabalin or Placebo Treatment Period | Adverse Event | 9 | 4 |
| Pregabalin or Placebo Treatment Period | Lack of Efficacy | 0 | 1 |
| Pregabalin or Placebo Treatment Period | Lost to Follow-up | 0 | 7 |
| Pregabalin or Placebo Treatment Period | Other | 2 | 3 |
| Pregabalin or Placebo Treatment Period | Withdrawal by Subject | 6 | 4 |
Baseline characteristics
| Characteristic | Pregabalin | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 59.4 years STANDARD_DEVIATION 9.8 | 57.1 years STANDARD_DEVIATION 10.2 | 58.2 years STANDARD_DEVIATION 10 |
| Sex: Female, Male Female | 43 Participants | 39 Participants | 82 Participants |
| Sex: Female, Male Male | 67 Participants | 70 Participants | 137 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 59 / 110 | 25 / 109 |
| serious Total, serious adverse events | 6 / 110 | 2 / 109 |
Outcome results
Primary
Mean Pain Score at Endpoint as Measured by Daily Pain Rating Scale (DPRS)
Mean pain score obtained from last 7 available DPRS scores up to and including day of Week 12 visit or early termination (ET) equivalent. DPRS: subject rated 11-point numeric scale ranging from 0 (no pain) to 10 (worst possible pain) during past 24-hour period. Higher score indicates greater level of pain. Self-assessment performed daily on awakening prior to taking study medication.
Time frame: Up to Week 12
Population: Intent to Treat (ITT): received at least 1 dose study medication and completed at least 1 post-baseline assessment. Endpoint = Week 12 or ET
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Mean Pain Score at Endpoint as Measured by Daily Pain Rating Scale (DPRS) | 4.8 scores on scale | Standard Error 0.21 |
| Placebo | Mean Pain Score at Endpoint as Measured by Daily Pain Rating Scale (DPRS) | 5.0 scores on scale | Standard Error 0.21 |
Comparison: Modelled Results: Endpoint Mean Pain Score Pregabalin vs Placebop-value: 0.57895% CI: [-0.7, 0.4]ANCOVA
Comparison: Modelled Results: Treatment by country interactionp-value: 0.294ANCOVA
Secondary
Clinical Global Impression of Change (CGIC)
CGIC: clinician rated instrument that measures change in a subject's ovall status on a 7-point scale; range from 1 (very much improved) to 7 (very much worse).
Time frame: Week 12
Population: ITT
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Clinical Global Impression of Change (CGIC) | 2.8 scores on scale | Standard Error 0.1 |
| Placebo | Clinical Global Impression of Change (CGIC) | 3.1 scores on scale | Standard Error 0.11 |
Comparison: Modelled Resultsp-value: 0.04995% CI: [-0.6, 0]ANCOVA
Secondary
EQ-5D - VAS
EQ-5D: subject rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state.
Time frame: Week 12
Population: ITT
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | EQ-5D - VAS | 65.7 scores on scale | Standard Error 1.78 |
| Placebo | EQ-5D - VAS | 62.7 scores on scale | Standard Error 1.81 |
Comparison: Modelled Resultsp-value: 0.2295% CI: [-1.8, 7.9]ANCOVA
Secondary
Euro Quality of Life (EQ-5D)- Health State Profile Utility Score
EQ-5D: subject rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (eg, confined to bed). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.
Time frame: Week 12
Population: ITT
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Euro Quality of Life (EQ-5D)- Health State Profile Utility Score | 0.5 scores on scale | Standard Error 0.03 |
| Placebo | Euro Quality of Life (EQ-5D)- Health State Profile Utility Score | 0.5 scores on scale | Standard Error 0.03 |
Comparison: Modelled Resultsp-value: 0.56695% CI: [-0.1, 0.1]ANCOVA
Secondary
Hospital Anxiety and Depression Scale (HADS) - ITT Population
HADS is subject rated questionnaire with 2 subscales. HADS-A assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale comprised of 7 items with range 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score 0 to 21 for each subscale; higher score indicates greater severity of anxiety and depression symptoms.
Time frame: Week 12
Population: ITT; Week 12 \[LOCF\]
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Hospital Anxiety and Depression Scale (HADS) - ITT Population | Week 12 [LOCF] Anxiety score | 5.5 scores on scale | Standard Error 0.29 |
| Pregabalin | Hospital Anxiety and Depression Scale (HADS) - ITT Population | Week 12 [LOCF] Depression score | 6.7 scores on scale | Standard Error 0.3 |
| Placebo | Hospital Anxiety and Depression Scale (HADS) - ITT Population | Week 12 [LOCF] Depression score | 6.5 scores on scale | Standard Error 0.3 |
| Placebo | Hospital Anxiety and Depression Scale (HADS) - ITT Population | Week 12 [LOCF] Anxiety score | 6.5 scores on scale | Standard Error 0.3 |
Comparison: Week 12 \[LOCF\] Anxiety score; Modelled Resultsp-value: 0.01595% CI: [-1.8, -0.2]ANCOVA
Comparison: Week 12 \[LOCF\] Depression score; Modelled Resultsp-value: 0.695% CI: [-0.6, 1]ANCOVA
Secondary
Medical Outcome Study (MOS) Sleep Scale
MOS: subject rated questionnaire to assess sleep quality and quantity. Consists of a 9-item overall sleep problems index (length of time to fall asleep, how many hours of sleep each night during past 4 weeks); 7 subscales rated 1 (all the time) to 6 (none of the time): sleep disturbance, snoring, awaken short of breath (SOB) or with a headache, somnolence adequacy, and sleep quantity. Scores are transformed (actual raw score minus lowest possible score divided by possible raw score range multiplied by 100); total score range = 0 to 100; higher score indicates greater intensity of attribute.
Time frame: Week 12
Population: ITT; (n) = number of subjects with analyzable data at observation for pregabalin and placebo, respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Medical Outcome Study (MOS) Sleep Scale | Awaken SOB or headache (n=99, 97) | 11.3 scores on scale | Standard Error 1.95 |
| Pregabalin | Medical Outcome Study (MOS) Sleep Scale | Sleep adequacy (n=99, 97) | 67.5 scores on scale | Standard Error 2.48 |
| Pregabalin | Medical Outcome Study (MOS) Sleep Scale | Snoring score (n=98, 97) | 40.6 scores on scale | Standard Error 2.68 |
| Pregabalin | Medical Outcome Study (MOS) Sleep Scale | Somnolence (n=99, 97) | 39.9 scores on scale | Standard Error 1.81 |
| Pregabalin | Medical Outcome Study (MOS) Sleep Scale | Sleep quantity (100, 97) | 7.0 scores on scale | Standard Error 0.12 |
| Pregabalin | Medical Outcome Study (MOS) Sleep Scale | Overall sleep problems index (n=100, 97) | 28.2 scores on scale | Standard Error 1.53 |
| Pregabalin | Medical Outcome Study (MOS) Sleep Scale | Sleep disturbance (n=100, 97) | 27.1 scores on scale | Standard Error 2 |
| Placebo | Medical Outcome Study (MOS) Sleep Scale | Overall sleep problems index (n=100, 97) | 32.4 scores on scale | Standard Error 1.57 |
| Placebo | Medical Outcome Study (MOS) Sleep Scale | Sleep disturbance (n=100, 97) | 31.9 scores on scale | Standard Error 2.05 |
| Placebo | Medical Outcome Study (MOS) Sleep Scale | Snoring score (n=98, 97) | 32.9 scores on scale | Standard Error 2.75 |
| Placebo | Medical Outcome Study (MOS) Sleep Scale | Awaken SOB or headache (n=99, 97) | 15.0 scores on scale | Standard Error 1.99 |
| Placebo | Medical Outcome Study (MOS) Sleep Scale | Sleep quantity (100, 97) | 6.6 scores on scale | Standard Error 0.12 |
| Placebo | Medical Outcome Study (MOS) Sleep Scale | Sleep adequacy (n=99, 97) | 58.9 scores on scale | Standard Error 2.51 |
| Placebo | Medical Outcome Study (MOS) Sleep Scale | Somnolence (n=99, 97) | 37.8 scores on scale | Standard Error 1.84 |
Comparison: Sleep disturbance; Modelled Resultsp-value: 0.08695% CI: [-10.3, 0.7]ANCOVA
Comparison: Snoring score; Modelled Resultsp-value: 0.03995% CI: [0.4, 15.1]ANCOVA
Comparison: Awaken SOB or headache; Modelled Resultsp-value: 0.16995% CI: [-9.1, 1.6]ANCOVA
Comparison: Sleep quantity; Modelled Resultsp-value: 0.0395% CI: [0, 0.7]ANCOVA
Comparison: Sleep adequacy; Modelled Resultsp-value: 0.01395% CI: [1.8, 15.4]ANCOVA
Comparison: Somnolence; Modelled Resultsp-value: 0.39995% CI: [-2.8, 7.1]ANCOVA
Comparison: Overall sleep problems index; Modelled Resultsp-value: 0.04995% CI: [-8.4, 0]ANCOVA
Secondary
Neuropathic Pain Symptom Inventory (NPSI)
NPSI: subject rated questionnaire to evaluate different symptoms of neuropathic pain (dimensions: burning \[superficial\] spontaneous pain, pressing \[deep\] spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dyesthesia \[P/D\]). Includes 10 descriptors quantified on a 0 (no symptoms) to 10 (worst symptoms imaginable) and 2 temporal items assessing duration of spontaneous ongoing and paroxysmal pain. Questionnaire generates a score in each of the relevant dimensions and a total score (0 to 100). Higher score indicates a greater intensity of pain.
Time frame: Week 12
Population: ITT; (N) = number of subjects with analyzable data at observation for pregabalin and placebo, respectively; Week 12/Last observation carried forward (LOCF).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Neuropathic Pain Symptom Inventory (NPSI) | Burning Pain (n=108, 108) | 2.6 scores on scale | Standard Error 0.22 |
| Pregabalin | Neuropathic Pain Symptom Inventory (NPSI) | Pressing Pain (n=108, 107) | 2.7 scores on scale | Standard Error 0.18 |
| Pregabalin | Neuropathic Pain Symptom Inventory (NPSI) | Paroxysmal Pain (n=108, 108) | 1.9 scores on scale | Standard Error 0.18 |
| Pregabalin | Neuropathic Pain Symptom Inventory (NPSI) | Evoked Pain (n=108, 108) | 2.8 scores on scale | Standard Error 0.19 |
| Pregabalin | Neuropathic Pain Symptom Inventory (NPSI) | P/D (n=108, 108) | 2.7 scores on scale | Standard Error 0.2 |
| Pregabalin | Neuropathic Pain Symptom Inventory (NPSI) | Total Score (n=108, 107) | 25.7 scores on scale | Standard Error 1.36 |
| Placebo | Neuropathic Pain Symptom Inventory (NPSI) | P/D (n=108, 108) | 3.1 scores on scale | Standard Error 0.2 |
| Placebo | Neuropathic Pain Symptom Inventory (NPSI) | Burning Pain (n=108, 108) | 2.9 scores on scale | Standard Error 0.23 |
| Placebo | Neuropathic Pain Symptom Inventory (NPSI) | Evoked Pain (n=108, 108) | 3.2 scores on scale | Standard Error 0.19 |
| Placebo | Neuropathic Pain Symptom Inventory (NPSI) | Pressing Pain (n=108, 107) | 2.6 scores on scale | Standard Error 0.19 |
| Placebo | Neuropathic Pain Symptom Inventory (NPSI) | Total Score (n=108, 107) | 28.5 scores on scale | Standard Error 1.4 |
| Placebo | Neuropathic Pain Symptom Inventory (NPSI) | Paroxysmal Pain (n=108, 108) | 2.1 scores on scale | Standard Error 0.18 |
Comparison: Burning Pain Week 12 \[LOCF\]; Modelled Resultsp-value: 0.21695% CI: [-1, 0.2]ANCOVA
Comparison: Pressing Pain Week 12 \[LOCF\]; Modelled Resultsp-value: 0.7695% CI: [-0.4, 0.6]ANCOVA
Comparison: Paroxysmal Pain Week 12 \[LOCF\]; Modelled Resultsp-value: 0.3695% CI: [-0.7, 0.3]ANCOVA
Comparison: Evoked Pain Week 12 \[LOCF\]; Modelled Resultsp-value: 0.23995% CI: [-0.8, 0.2]ANCOVA
Comparison: P/D Week 12 \[LOCF\]; Modelled Resultsp-value: 0.11895% CI: [-1, 0.1]ANCOVA
Comparison: Total Score Week 12 \[LOCF\]; Modelled Resultsp-value: 0.13895% CI: [-6.5, 0.9]ANCOVA
Secondary
Number of Subjects With at Least a 30% Reduction From Baseline in Mean Pain Score at Endpoint
30% Responder Yes = number of subjects with 30% reduction in mean pain score from baseline to observation; 30% reduction calculated as \[(T minus B) divided by B multiplied by 100\] \< = negative 30. T = endpoint mean pain score (obtained from last 7 available scores from DPRS); B = baseline mean pain score (obtained from average of last 7 daily scores from DPRS). 30% Responder No indicates number of subjects that did not reach 30% reduction in mean pain score.
Time frame: Baseline, Week 12
Population: ITT; endpoint = Week 12 or ET
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pregabalin | Number of Subjects With at Least a 30% Reduction From Baseline in Mean Pain Score at Endpoint | 30% Responders Yes | 48 participants |
| Pregabalin | Number of Subjects With at Least a 30% Reduction From Baseline in Mean Pain Score at Endpoint | 30% Responders No | 60 participants |
| Placebo | Number of Subjects With at Least a 30% Reduction From Baseline in Mean Pain Score at Endpoint | 30% Responders Yes | 35 participants |
| Placebo | Number of Subjects With at Least a 30% Reduction From Baseline in Mean Pain Score at Endpoint | 30% Responders No | 73 participants |
Comparison: 30% Respondersp-value: 0.087Cochran-Mantel-Haenszel
Secondary
Number of Subjects With at Least a 50% Reduction From Baseline in Mean Pain Score at Endpoint
50% Responder Yes = number of subjects with 50% reduction in mean pain score from baseline to observation; 50% reduction calculated as \[(T minus B) divided by B multiplied by 100\] \< = negative 50. T = endpoint mean pain score (obtained from last 7 available scores from DPRS); B = baseline mean pain score (obtained from average of last 7 daily scores from DPRS). 50% Responder No indicates number of subjects that did not reach 50% reduction in mean pain score.
Time frame: Baseline, Week 12
Population: ITT; endpoint = Week 12 or ET
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pregabalin | Number of Subjects With at Least a 50% Reduction From Baseline in Mean Pain Score at Endpoint | 50 % Responders Yes | 26 participants |
| Pregabalin | Number of Subjects With at Least a 50% Reduction From Baseline in Mean Pain Score at Endpoint | 50 % Responders No | 82 participants |
| Placebo | Number of Subjects With at Least a 50% Reduction From Baseline in Mean Pain Score at Endpoint | 50 % Responders Yes | 22 participants |
| Placebo | Number of Subjects With at Least a 50% Reduction From Baseline in Mean Pain Score at Endpoint | 50 % Responders No | 86 participants |
Comparison: 50% Respondersp-value: 0.622Cochran-Mantel-Haenszel
Secondary
Number of Subjects With Yes or No Response for Medical Outcome Study (MOS) Sleep Scale - Optimal Sleep
MOS: subject rated questionnaire to assess sleep quality and quantity. Optimal sleep component is derived from Sleep Quantity average hours of sleep each night during the past 4 weeks. Number of subjects with response = YES if sleep quantity is 7 or 8 hours per night or response = NO if sleep quantity is \< 7 hours per night.
Time frame: Week 12
Population: ITT
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pregabalin | Number of Subjects With Yes or No Response for Medical Outcome Study (MOS) Sleep Scale - Optimal Sleep | Optimal sleep = Yes | 51 participants |
| Pregabalin | Number of Subjects With Yes or No Response for Medical Outcome Study (MOS) Sleep Scale - Optimal Sleep | Optimal sleep = No | 49 participants |
| Placebo | Number of Subjects With Yes or No Response for Medical Outcome Study (MOS) Sleep Scale - Optimal Sleep | Optimal sleep = Yes | 42 participants |
| Placebo | Number of Subjects With Yes or No Response for Medical Outcome Study (MOS) Sleep Scale - Optimal Sleep | Optimal sleep = No | 55 participants |
Comparison: Modelled Resultsp-value: 0.20195% CI: [0.8, 2.9]Regression, Logistic
Secondary
Pain Score as Measured by DPRS
Weekly mean pain score measured by DPRS: subject rated 11-point numeric scale ranging from 0 (no pain) to 10 (worst possible pain) during past 24-hour period. Higher score indicates greater level of pain. Self-assessment performed daily on awakening prior to taking study medication.
Time frame: Week 1, Week 2, Week 3, Week 6, Week 9, and Week 12
Population: ITT; (n) = number of participants with analyzable data at observation for pregabalin and placebo, respectively; weeks as specified in timeframe through Week 12 \[ET\]
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Pain Score as Measured by DPRS | Week 1 (n=108, 108) | 5.6 scores on scale | Standard Error 0.18 |
| Pregabalin | Pain Score as Measured by DPRS | Week 2 (n=104, 106) | 5.3 scores on scale | Standard Error 0.18 |
| Pregabalin | Pain Score as Measured by DPRS | Week 3 (n=102, 105) | 5.1 scores on scale | Standard Error 0.18 |
| Pregabalin | Pain Score as Measured by DPRS | Week 6 (n=97, 102) | 4.9 scores on scale | Standard Error 0.18 |
| Pregabalin | Pain Score as Measured by DPRS | Week 9 (n=98, 97) | 4.8 scores on scale | Standard Error 0.18 |
| Pregabalin | Pain Score as Measured by DPRS | Week 12 [ET] (n=92, 92) | 4.7 scores on scale | Standard Error 0.18 |
| Placebo | Pain Score as Measured by DPRS | Week 9 (n=98, 97) | 5.2 scores on scale | Standard Error 0.18 |
| Placebo | Pain Score as Measured by DPRS | Week 1 (n=108, 108) | 6.0 scores on scale | Standard Error 0.18 |
| Placebo | Pain Score as Measured by DPRS | Week 6 (n=97, 102) | 5.4 scores on scale | Standard Error 0.18 |
| Placebo | Pain Score as Measured by DPRS | Week 2 (n=104, 106) | 5.8 scores on scale | Standard Error 0.18 |
| Placebo | Pain Score as Measured by DPRS | Week 12 [ET] (n=92, 92) | 4.9 scores on scale | Standard Error 0.19 |
| Placebo | Pain Score as Measured by DPRS | Week 3 (n=102, 105) | 5.6 scores on scale | Standard Error 0.18 |
Comparison: Week 1 Modelled Resultsp-value: 0.16195% CI: [-0.8, 0.1]Mixed Models Analysis
Comparison: Week 2 Modelled Resultsp-value: 0.06295% CI: [-1, 0]Mixed Models Analysis
Comparison: Week 3 Modelled Resultsp-value: 0.02495% CI: [-1.1, -0.1]Mixed Models Analysis
Comparison: Week 6 Modelled Resultsp-value: 0.02695% CI: [-1.1, -0.1]Mixed Models Analysis
Comparison: Week 9 Modelled Resultsp-value: 0.10595% CI: [-0.9, 0.1]Mixed Models Analysis
Comparison: Week 12 Modelled Resultsp-value: 0.59295% CI: [-0.6, 0.4]Mixed Models Analysis
Secondary
Patient Global Impression of Change (PGIC)
PGIC: subject rated instrument to measure subject's change in overall status on a 7-point scale; range from 1 (very much improved) to 7 (very much worse).
Time frame: Week 12
Population: ITT
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Patient Global Impression of Change (PGIC) | 2.9 scores on scale | Standard Error 0.1 |
| Placebo | Patient Global Impression of Change (PGIC) | 3.1 scores on scale | Standard Error 0.1 |
Comparison: Modelled Resultsp-value: 0.14495% CI: [-0.5, 0.1]ANCOVA
Secondary
QANeP - Pain Rating Scales
Subject rated pain scale: static mechanical allodynia (SMA) gentle constant mechanical pressure; dynamic mechanical allodynia (DMA) gentle stroking with foam brush; punctate hyperalgesia (PH) pinprick; cold allodynia (CA) touch with cool metal rod 13-17° celsius (C); cold hyperalgesia (CH) touch with cold metal rod 4° C; temporal summation to tactile stimuli (TSTS) repeated touching/tapping. 11-point numeric scale; range 0 (no pain) to 10 (worst possible pain). Reference area=mirror image of pain site (test area). Summarized as change from baseline (mean at observation minus mean at baseline).
Time frame: Baseline, Week 12
Population: ITT; (n) = number of subjects with analyzable data at observation for pregabalin and placebo, respectively; Week 12 \[LOCF\].
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | QANeP - Pain Rating Scales | SMA (n=108, 107) | -0.7 scores on scale | Standard Deviation 2.14 |
| Pregabalin | QANeP - Pain Rating Scales | DMA (n=108, 107) | -0.8 scores on scale | Standard Deviation 1.96 |
| Pregabalin | QANeP - Pain Rating Scales | PH reference area (n=108, 107) | -0.2 scores on scale | Standard Deviation 2.6 |
| Pregabalin | QANeP - Pain Rating Scales | PH test area (n=108, 107) | -0.7 scores on scale | Standard Deviation 2.27 |
| Pregabalin | QANeP - Pain Rating Scales | TSTS (n=108, 106) | -1.0 scores on scale | Standard Deviation 2.47 |
| Pregabalin | QANeP - Pain Rating Scales | CA (n=108, 106) | -1.1 scores on scale | Standard Deviation 2.36 |
| Pregabalin | QANeP - Pain Rating Scales | CH reference area (n=107, 107) | 0.0 scores on scale | Standard Deviation 2.56 |
| Pregabalin | QANeP - Pain Rating Scales | CH test area (n=107, 106) | -0.9 scores on scale | Standard Deviation 2.47 |
| Placebo | QANeP - Pain Rating Scales | CH test area (n=107, 106) | -0.9 scores on scale | Standard Deviation 2.14 |
| Placebo | QANeP - Pain Rating Scales | SMA (n=108, 107) | -0.5 scores on scale | Standard Deviation 1.93 |
| Placebo | QANeP - Pain Rating Scales | TSTS (n=108, 106) | -0.5 scores on scale | Standard Deviation 2.25 |
| Placebo | QANeP - Pain Rating Scales | DMA (n=108, 107) | -0.6 scores on scale | Standard Deviation 1.83 |
| Placebo | QANeP - Pain Rating Scales | CH reference area (n=107, 107) | -0.2 scores on scale | Standard Deviation 1.74 |
| Placebo | QANeP - Pain Rating Scales | PH reference area (n=108, 107) | -0.2 scores on scale | Standard Deviation 2.41 |
| Placebo | QANeP - Pain Rating Scales | CA (n=108, 106) | -0.3 scores on scale | Standard Deviation 1.95 |
| Placebo | QANeP - Pain Rating Scales | PH test area (n=108, 107) | -0.0 scores on scale | Standard Deviation 2.37 |
Secondary
Quantitative Assessment of Neuropathic Pain (QANeP) - Sensory Threshold
QANeP: assessment of sensory threshold: subject responds yes when monofilament stimulus is felt on area of maximum pain: 1 (lowest/softest 0.07 gram \[g\]) to 6 (highest 300 g) or 7 (not perceived); rated by lowest/softest filament felt when in contact with the skin. Summarized as change from baseline (mean at observation minus mean at baseline).
Time frame: Baseline, Week 12
Population: ITT; Week 12 \[LOCF\].
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Quantitative Assessment of Neuropathic Pain (QANeP) - Sensory Threshold | 0.0 scores on scale | Standard Deviation 0.89 |
| Placebo | Quantitative Assessment of Neuropathic Pain (QANeP) - Sensory Threshold | -0.1 scores on scale | Standard Deviation 0.83 |
Secondary
Short Form-McGill Pain Questionnaire (SF-MPQ Visual Analog Scale [VAS]) - Part B Only
SF-MPQ Part B VAS consists of a line 0 to 100 millimeters (mm) in length; range is (no pain) to 100 mm (worst possible pain). Subjects placed a mark indicating the intensity of their pain. Distance from left-hand end of line was measured and entered on Case Report Form (CRF) as score in mm. Higher score indicates greater level of pain.
Time frame: Week 12
Population: ITT
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Short Form-McGill Pain Questionnaire (SF-MPQ Visual Analog Scale [VAS]) - Part B Only | 48.5 millimeters | Standard Error 2.19 |
| Placebo | Short Form-McGill Pain Questionnaire (SF-MPQ Visual Analog Scale [VAS]) - Part B Only | 49.5 millimeters | Standard Error 2.23 |
Comparison: Modelled Resultsp-value: 0.74195% CI: [-7, 5]ANCOVA
Secondary
Weekly Mean Sleep Interference Score From Daily Sleep Diary (Daily Sleep Interference Scale [DSIS])
DSIS: subject rated 11-point numeric scale ranging from 0 (pain does not interfere with sleep) to 10 (pain completely interferes with sleep) during past 24-hour period. Higher score indicates a greater level of sleep disturbance. Self-assessment performed daily on awakening prior to taking study medication. Endpoint calculated as mean of last 7 available scores.
Time frame: Week 1, Week 2, Week 3, Week 6, Week 9, and Week 12
Population: ITT; (n) = number of subjects with analyzable data at observation for pregabalin and placebo, respectively; endpoint = Week 12 or ET.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Weekly Mean Sleep Interference Score From Daily Sleep Diary (Daily Sleep Interference Scale [DSIS]) | Week 3 (n=102, 105) | 3.2 scores on scale | Standard Error 0.17 |
| Pregabalin | Weekly Mean Sleep Interference Score From Daily Sleep Diary (Daily Sleep Interference Scale [DSIS]) | Week 9 (n=98, 97) | 3.0 scores on scale | Standard Error 0.17 |
| Pregabalin | Weekly Mean Sleep Interference Score From Daily Sleep Diary (Daily Sleep Interference Scale [DSIS]) | Week 2 (n=104, 106) | 3.5 scores on scale | Standard Error 0.17 |
| Pregabalin | Weekly Mean Sleep Interference Score From Daily Sleep Diary (Daily Sleep Interference Scale [DSIS]) | Week 12 (n=92, 92) | 3.1 scores on scale | Standard Error 0.18 |
| Pregabalin | Weekly Mean Sleep Interference Score From Daily Sleep Diary (Daily Sleep Interference Scale [DSIS]) | Week 6 (n=98, 102) | 3.0 scores on scale | Standard Error 0.17 |
| Pregabalin | Weekly Mean Sleep Interference Score From Daily Sleep Diary (Daily Sleep Interference Scale [DSIS]) | Endpoint [Week 12 or ET] (n=108, 108) | 3.0 scores on scale | Standard Error 0.19 |
| Pregabalin | Weekly Mean Sleep Interference Score From Daily Sleep Diary (Daily Sleep Interference Scale [DSIS]) | Week 1 (n=108, 108) | 3.6 scores on scale | Standard Error 0.17 |
| Placebo | Weekly Mean Sleep Interference Score From Daily Sleep Diary (Daily Sleep Interference Scale [DSIS]) | Endpoint [Week 12 or ET] (n=108, 108) | 3.1 scores on scale | Standard Error 0.19 |
| Placebo | Weekly Mean Sleep Interference Score From Daily Sleep Diary (Daily Sleep Interference Scale [DSIS]) | Week 1 (n=108, 108) | 4.2 scores on scale | Standard Error 0.17 |
| Placebo | Weekly Mean Sleep Interference Score From Daily Sleep Diary (Daily Sleep Interference Scale [DSIS]) | Week 2 (n=104, 106) | 4.0 scores on scale | Standard Error 0.17 |
| Placebo | Weekly Mean Sleep Interference Score From Daily Sleep Diary (Daily Sleep Interference Scale [DSIS]) | Week 3 (n=102, 105) | 3.9 scores on scale | Standard Error 0.17 |
| Placebo | Weekly Mean Sleep Interference Score From Daily Sleep Diary (Daily Sleep Interference Scale [DSIS]) | Week 6 (n=98, 102) | 3.7 scores on scale | Standard Error 0.17 |
| Placebo | Weekly Mean Sleep Interference Score From Daily Sleep Diary (Daily Sleep Interference Scale [DSIS]) | Week 9 (n=98, 97) | 3.4 scores on scale | Standard Error 0.17 |
| Placebo | Weekly Mean Sleep Interference Score From Daily Sleep Diary (Daily Sleep Interference Scale [DSIS]) | Week 12 (n=92, 92) | 3.2 scores on scale | Standard Error 0.18 |
Comparison: Week 1; Modelled Resultsp-value: 0.02795% CI: [-1, -0.1]Mixed Models Analysis
Comparison: Week 2; Modelled Resultsp-value: 0.03895% CI: [-1, 0]Mixed Models Analysis
Comparison: Week 3; Modelled Resultsp-value: 0.00495% CI: [-1.2, -0.2]Mixed Models Analysis
Comparison: Week 6; Modelled Resultsp-value: 0.00595% CI: [-1.1, -0.2]Mixed Models Analysis
Comparison: Week 9; Modelled Resultsp-value: 0.07895% CI: [-0.9, 0]Mixed Models Analysis
Comparison: Week 12; Modelled Resultsp-value: 0.66395% CI: [-0.6, 0.4]Mixed Models Analysis
Comparison: Endpoint \[Week 12 or ET\]; Modelled Resultsp-value: 0.62795% CI: [-0.6, 0.4]Mixed Models Analysis