Neuropathic Pain
Conditions
Keywords
Methodology, Quantitative Sensory Testing, Neuropathies Pain, Pregabalin
Brief summary
Conventional pain efficacy measures such as Visual Analogue Scores (VAS) are often unable to detect treatment efficacy in small-scale clinical trials. Combining conventional pain efficacy measures with quantitative sensory testing (QST) may provide more sensitive and informative outcome measures in clinical trials.
Detailed description
Methodology to assess reproducibility and sensitivity of quantitative sensory testing
Interventions
DRUGPregabalin
Dose titration according to following regimen: 75mg BID for 3 days; 150mg for 4 days; 225mg BID for 4 days; 300mg BID for 17 days. Dose reduced for renally impaired patients
DRUGPlacebo
BID dosing for 28 days
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Neuropathic pain of peripheral origin demonstrating spontaneous ongoing pain and dynamic mechanical allodynia to brush stimuli. * A present pain intensity score of 4 or more (out of 10) for spontaneous ongoing pain and brush-evoked allodynia at the skin area at screen. * Stable analgesic medication (excluding pregabalin) for a minimum of 1 month prior to the start of study.
Exclusion criteria
* Patients who have undergone neurolytic or neurosurgical therapy. * Patients who have trigeminal neuralgia, central pain (due to cerebrovascular lesions, multiple sclerosis and traumatic spinal cord injuries), complex regional pain syndrome (Type I and II), and phantom limb pain. * Patients who have previously been treated with pregabalin.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Heat Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) and Week 4 (Visits 4 and 7) of each period | Duration of thermal stimuli was 2 seconds and an intensity that is increased in steps of 4 degrees celsius for heat stimuli (between 40 and 50 degrees celsius). Thermal pain sensitivity was participant-rated using 11-point NRS where 0=no pain and 10=worst pain imaginable. The average of 2 ratings was calculated to get the mean score. |
| Mean Change From Baseline in Dynamic Allodynia Area at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) and Week 4 (Visits 4 and 7) of each period | Dynamic area brush in cm\^2: calculated from 8 measured distances by calculating the area of an octagon. The angle between each pair of lines was 45 degrees at point c. The area of the octagon was found by totaling the areas of the 8 triangles. Octagon with 8 radial lengths from center to the outside. Area = Σ ( ½ length \* perpendicular height); Σ ( ½ ri \* sin(45) r(i+1) ) = Σ ( (ri \* r(i+1) )/2√2)). (where ri, i=1 to 8, were the eight radial lengths) |
| Mean Change From Baseline in Mechanical Pain Sensitivity (Von Frey) at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) and Week 4 (Visits 4 and 7) of each period | Sensitivity to mechanical pain stimuli was tested using calibrated Von Frey monofilaments. To obtain a stimulus-response-function, seven different Von Frey monofilaments (size 8 to 512 mN, force increased by a factor of two from filament to filament) applied three times each; each stimulus was participant-rated using 11-point NRS where 0=no pain and 10=worst pain imaginable. If a score of 8 or more was reported for a given intensity no stronger stimuli was applied. Von Frey stimulus was applied to the skin for 1 to 2 seconds. The average of 3 ratings was calculated for the mean score. |
| Mean Change From Baseline in Punctate Allodynia Area (Von Frey) at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) and Week 4 (Visits 4 and 7) of each period | Punctate allodynia area in cm\^2: calculated from 8 measured distances by calculating the area of an octagon. The angle between each pair of lines was 45 degrees at point c. The area of the octagon was found by totaling the areas of the 8 triangles. Octagon with 8 radial lengths from center to the outside. Area = Σ ( ½ length \* perpendicular height); Σ ( ½ ri \* sin(45) r(i+1) ) = Σ ( (ri \* r(i+1) )/2√2)). (where ri, i=1 to 8, were the eight radial lengths) |
| Mean Change From Baseline in Cold Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) and Week 4 (Visits 4 and 7) of each period | Duration of thermal stimuli was 2 seconds and an intensity that is increased in steps of 5 degrees celsius for cold stimuli (between 5 and 20 degrees celsius). Thermal pain sensitivity was participant-rated using 11-point NRS where 0=no pain and 10=worst pain imaginable. The average of 2 ratings was calculated to get the mean score. |
| Mean Change From Baseline in Dynamic Allodynia Intensity at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) and Week 4 (Visits 4 and 7) of each period | Five strokes applied with a standardized brush (somedic) across the painful site, 6cm long and at a control site to allow the participants to appreciate any difference. A painful and clearly dysaesthetic (unpleasant) sensation was considered as representing brush allodynia (whereas a strange or tickly sensation provoked by the brush was not). After each brush stimuli participants were asked to give a pain rating using 11-point numerical rating scale (NRS) where 0=no pain and 10=worst pain imaginable. The average of 5 brush strokes was calculated to obtain the mean score. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Patient's Global Impression of Change (PGIC) at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) and Week 4 (Visits 4 and 7) of each period | PGIC: participant-rated assessment measuring change in participant's overall status on a 7-point scale from 1=very much improved to 7=very much worse. |
| Mean Change From Baseline in Test-Day Global Pain Intensity at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) and Week 4 (Visits 4 and 7) of each period | Global pain: participant-rated pain using the test-day global pain scale, consisting of an 11-point NRS where 0 = no pain and 10 = worst possible pain. Participants described intensity of pain in response to How intense is your pain today? |
| Mean Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) Total Score at Visits 4 and 7 | Week 4 (Visits 4 and 7) of each period | NPSI: 10-item self-administered questionnaire assessing 5 dimensions of pain (burning superficial spontaneous pain, pressing deep spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dysesthesia). Each item consists of a question about the specific qualities of pain and an 11-point numerical scale range: 0 (absence of pain) to 10 (maximum intensity imaginable), and 2 temporal items related to spontaneous and paroxysmal pain. Maximum total score possible = 100. |
| Mean Change From Baseline in Weekly Pain Score From the Daily Diary at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) and Week 4 (Visits 4 and 7) of each period | Daily pain diary: participant-rated pain during the past 24 hours rated on an 11 point NRS scale where 0=no pain and 10=worst possible pain. For a given week, the pain response was the average of the 7 daily entries for that week, or average of the available data for that week if fewer than 7 entries were recorded (\>=1 daily pain score for any given week required). The endpoint for each week consisted of the change from baseline in average pain score (follow-up value minus baseline). |
Countries
Austria, Belgium, France, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants Includes all participants randomized to receive pregabalin first and placebo first. | 31 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | Adverse Event | 0 | 1 |
| First Intervention | Protocol Violation | 1 | 0 |
| Second Intervention | Adverse Event | 0 | 2 |
| Second Intervention | Lost to Follow-up | 1 | 0 |
| Second Intervention | Other | 1 | 2 |
| Second Intervention | Withdrawal by Subject | 0 | 1 |
| Washout Period | Protocol Violation | 0 | 2 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Customized 18 to 44 years | 9 participants |
| Age, Customized 45 to 64 years | 12 participants |
| Age, Customized >=65 years | 10 participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 20 / 28 | 15 / 30 |
| serious Total, serious adverse events | 1 / 28 | 1 / 30 |
Outcome results
Primary
Mean Change From Baseline in Cold Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7
Duration of thermal stimuli was 2 seconds and an intensity that is increased in steps of 5 degrees celsius for cold stimuli (between 5 and 20 degrees celsius). Thermal pain sensitivity was participant-rated using 11-point NRS where 0=no pain and 10=worst pain imaginable. The average of 2 ratings was calculated to get the mean score.
Time frame: Week 3 (Visits 3 and 6) and Week 4 (Visits 4 and 7) of each period
Population: FAS. n=number of participants contributing to the mean. Missing values were imputed using a single imputation regression method.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Mean Change From Baseline in Cold Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (5 degrees, n=15,16) | -0.821 scores on a scale | Standard Deviation 1.2039 |
| Pregabalin | Mean Change From Baseline in Cold Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (10 degrees, n=15,16) | -0.333 scores on a scale | Standard Deviation 1.3318 |
| Pregabalin | Mean Change From Baseline in Cold Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (15 degrees, n=15,16) | -0.567 scores on a scale | Standard Deviation 2.3442 |
| Pregabalin | Mean Change From Baseline in Cold Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (20 degrees, n=15,16) | -0.500 scores on a scale | Standard Deviation 1.9365 |
| Pregabalin | Mean Change From Baseline in Cold Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (5 degrees, n=18,21) | -0.726 scores on a scale | Standard Deviation 1.3375 |
| Pregabalin | Mean Change From Baseline in Cold Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (10 degrees, n=18,21) | -0.278 scores on a scale | Standard Deviation 1.3086 |
| Pregabalin | Mean Change From Baseline in Cold Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (15 degrees, n=18,21) | -0.583 scores on a scale | Standard Deviation 1.2632 |
| Pregabalin | Mean Change From Baseline in Cold Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (20 degrees, n=18,21) | -0.111 scores on a scale | Standard Deviation 1.4507 |
| Placebo | Mean Change From Baseline in Cold Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (20 degrees, n=18,21) | -0.333 scores on a scale | Standard Deviation 0.713 |
| Placebo | Mean Change From Baseline in Cold Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (5 degrees, n=15,16) | -1.402 scores on a scale | Standard Deviation 3.0295 |
| Placebo | Mean Change From Baseline in Cold Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (5 degrees, n=18,21) | -0.703 scores on a scale | Standard Deviation 2.4746 |
| Placebo | Mean Change From Baseline in Cold Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (10 degrees, n=15,16) | -1.313 scores on a scale | Standard Deviation 2.0402 |
| Placebo | Mean Change From Baseline in Cold Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (15 degrees, n=18,21) | 0.095 scores on a scale | Standard Deviation 1.5622 |
| Placebo | Mean Change From Baseline in Cold Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (15 degrees, n=15,16) | 0.125 scores on a scale | Standard Deviation 1.3478 |
| Placebo | Mean Change From Baseline in Cold Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (10 degrees, n=18,21) | -0.810 scores on a scale | Standard Deviation 1.6239 |
| Placebo | Mean Change From Baseline in Cold Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (20 degrees, n=15,16) | 0.031 scores on a scale | Standard Deviation 1.4314 |
Comparison: Week 3 (Visits 3 and 6)p-value: 0.750695% CI: [-0.83, 1.14]ANCOVA
Comparison: Week 4 (Visits 4 and 7)p-value: 0.967395% CI: [-0.61, 0.64]ANCOVA
Primary
Mean Change From Baseline in Dynamic Allodynia Area at Visits 3 and 6 and Visits 4 and 7
Dynamic area brush in cm\^2: calculated from 8 measured distances by calculating the area of an octagon. The angle between each pair of lines was 45 degrees at point c. The area of the octagon was found by totaling the areas of the 8 triangles. Octagon with 8 radial lengths from center to the outside. Area = Σ ( ½ length \* perpendicular height); Σ ( ½ ri \* sin(45) r(i+1) ) = Σ ( (ri \* r(i+1) )/2√2)). (where ri, i=1 to 8, were the eight radial lengths)
Time frame: Week 3 (Visits 3 and 6) and Week 4 (Visits 4 and 7) of each period
Population: FAS. n=number of participants contributing to the mean.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Mean Change From Baseline in Dynamic Allodynia Area at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (n=16,17) | -53.441 cm2 | Standard Deviation 114.7084 |
| Pregabalin | Mean Change From Baseline in Dynamic Allodynia Area at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (n=17,20) | -49.808 cm2 | Standard Deviation 100.2094 |
| Placebo | Mean Change From Baseline in Dynamic Allodynia Area at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (n=16,17) | -49.180 cm2 | Standard Deviation 94.3329 |
| Placebo | Mean Change From Baseline in Dynamic Allodynia Area at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (n=17,20) | -18.921 cm2 | Standard Deviation 104.3942 |
Comparison: Week 3 (Visits 3 and 6)p-value: 0.653995% CI: [-70.2, 45.56]ANCOVA
Comparison: Week 4 (Visits 4 and 7)p-value: 0.367895% CI: [-78.54, 30.72]ANCOVA
Primary
Mean Change From Baseline in Dynamic Allodynia Intensity at Visits 3 and 6 and Visits 4 and 7
Five strokes applied with a standardized brush (somedic) across the painful site, 6cm long and at a control site to allow the participants to appreciate any difference. A painful and clearly dysaesthetic (unpleasant) sensation was considered as representing brush allodynia (whereas a strange or tickly sensation provoked by the brush was not). After each brush stimuli participants were asked to give a pain rating using 11-point numerical rating scale (NRS) where 0=no pain and 10=worst pain imaginable. The average of 5 brush strokes was calculated to obtain the mean score.
Time frame: Week 3 (Visits 3 and 6) and Week 4 (Visits 4 and 7) of each period
Population: Full analysis set (FAS)=participants with present pain intensity score \>=4 out of 10 for brush evoked allodynia at screening and randomization, \>=4 out of 7 non missing values in week prior to randomization, \>4 for weekly average daily pain score, and who did not withdraw/discontinue. n=number of participants contributing to the mean.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Mean Change From Baseline in Dynamic Allodynia Intensity at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (n=15,16) | -1.09 scores on a scale | Standard Deviation 1.735 |
| Pregabalin | Mean Change From Baseline in Dynamic Allodynia Intensity at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (n=18,21) | -1.31 scores on a scale | Standard Deviation 1.924 |
| Placebo | Mean Change From Baseline in Dynamic Allodynia Intensity at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (n=15,16) | -1.16 scores on a scale | Standard Deviation 1.73 |
| Placebo | Mean Change From Baseline in Dynamic Allodynia Intensity at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (n=18,21) | -0.67 scores on a scale | Standard Deviation 1.984 |
Comparison: Week 3 (Visits 3 and 6)p-value: 0.731995% CI: [-1.29, 0.92]ANCOVA
Comparison: Week 4 (Visits 4 and 7)p-value: 0.340495% CI: [-1.61, 0.57]ANCOVA
Primary
Mean Change From Baseline in Heat Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7
Duration of thermal stimuli was 2 seconds and an intensity that is increased in steps of 4 degrees celsius for heat stimuli (between 40 and 50 degrees celsius). Thermal pain sensitivity was participant-rated using 11-point NRS where 0=no pain and 10=worst pain imaginable. The average of 2 ratings was calculated to get the mean score.
Time frame: Week 3 (Visits 3 and 6) and Week 4 (Visits 4 and 7) of each period
Population: FAS. n=number of participants contributing to the mean. Missing values were imputed using a single imputation regression method.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Mean Change From Baseline in Heat Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (40 degrees, n=15,16) | -1.100 scores on a scale | Standard Deviation 2.2216 |
| Pregabalin | Mean Change From Baseline in Heat Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (44 degrees, n=15,16) | 0.400 scores on a scale | Standard Deviation 3.4959 |
| Pregabalin | Mean Change From Baseline in Heat Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (47 degrees, n=15,16) | -0.908 scores on a scale | Standard Deviation 2.5249 |
| Pregabalin | Mean Change From Baseline in Heat Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (50 degrees, n=15,16) | -1.385 scores on a scale | Standard Deviation 2.8981 |
| Pregabalin | Mean Change From Baseline in Heat Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (40 degrees, n=18,21) | -0.639 scores on a scale | Standard Deviation 2.5771 |
| Pregabalin | Mean Change From Baseline in Heat Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (44 degrees, n=18,21) | -0.444 scores on a scale | Standard Deviation 4.1084 |
| Pregabalin | Mean Change From Baseline in Heat Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (47 degrees, n=18,21) | -0.337 scores on a scale | Standard Deviation 3.0065 |
| Pregabalin | Mean Change From Baseline in Heat Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (50 degrees, n=18,21) | -0.566 scores on a scale | Standard Deviation 2.2423 |
| Placebo | Mean Change From Baseline in Heat Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (50 degrees, n=18,21) | -0.387 scores on a scale | Standard Deviation 2.6689 |
| Placebo | Mean Change From Baseline in Heat Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (40 degrees, n=15,16) | -0.625 scores on a scale | Standard Deviation 2.313 |
| Placebo | Mean Change From Baseline in Heat Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (40 degrees, n=18,21) | -0.143 scores on a scale | Standard Deviation 0.9506 |
| Placebo | Mean Change From Baseline in Heat Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (44 degrees, n=15,16) | -0.938 scores on a scale | Standard Deviation 2.8395 |
| Placebo | Mean Change From Baseline in Heat Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (47 degrees, n=18,21) | -0.083 scores on a scale | Standard Deviation 2.7679 |
| Placebo | Mean Change From Baseline in Heat Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (47 degrees, n=15,16) | -0.578 scores on a scale | Standard Deviation 3.3112 |
| Placebo | Mean Change From Baseline in Heat Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (44 degrees, n=18,21) | -0.495 scores on a scale | Standard Deviation 2.9959 |
| Placebo | Mean Change From Baseline in Heat Pain Sensitivity at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (50 degrees, n=15,16) | -0.865 scores on a scale | Standard Deviation 2.105 |
Comparison: Week 3 (Visits 3 and 6)p-value: 0.550295% CI: [-0.99, 1.78]ANCOVA
Comparison: Week 4 (Visits 4 and 7)p-value: 0.853695% CI: [-1.15, 0.96]ANCOVA
Primary
Mean Change From Baseline in Mechanical Pain Sensitivity (Von Frey) at Visits 3 and 6 and Visits 4 and 7
Sensitivity to mechanical pain stimuli was tested using calibrated Von Frey monofilaments. To obtain a stimulus-response-function, seven different Von Frey monofilaments (size 8 to 512 mN, force increased by a factor of two from filament to filament) applied three times each; each stimulus was participant-rated using 11-point NRS where 0=no pain and 10=worst pain imaginable. If a score of 8 or more was reported for a given intensity no stronger stimuli was applied. Von Frey stimulus was applied to the skin for 1 to 2 seconds. The average of 3 ratings was calculated for the mean score.
Time frame: Week 3 (Visits 3 and 6) and Week 4 (Visits 4 and 7) of each period
Population: FAS. n=number of participants contributing to the mean. Missing values were imputed using a single imputation regression method.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Mean Change From Baseline in Mechanical Pain Sensitivity (Von Frey) at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (Size 8, n=15,16) | -0.133 scores on a scale | Standard Deviation 1.7494 |
| Pregabalin | Mean Change From Baseline in Mechanical Pain Sensitivity (Von Frey) at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (Size 16, n=15,16) | -1.356 scores on a scale | Standard Deviation 2.48 |
| Pregabalin | Mean Change From Baseline in Mechanical Pain Sensitivity (Von Frey) at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (Size 32, n=15,16) | -0.200 scores on a scale | Standard Deviation 1.8551 |
| Pregabalin | Mean Change From Baseline in Mechanical Pain Sensitivity (Von Frey) at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (Size 64, n=15,16) | -1.128 scores on a scale | Standard Deviation 2.0304 |
| Pregabalin | Mean Change From Baseline in Mechanical Pain Sensitivity (Von Frey) at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (Size 128, n=15,16) | -1.267 scores on a scale | Standard Deviation 1.6868 |
| Pregabalin | Mean Change From Baseline in Mechanical Pain Sensitivity (Von Frey) at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (Size 256, n=15,16) | -0.773 scores on a scale | Standard Deviation 2.242 |
| Pregabalin | Mean Change From Baseline in Mechanical Pain Sensitivity (Von Frey) at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (Size 512, n=15,16) | -1.533 scores on a scale | Standard Deviation 1.7873 |
| Pregabalin | Mean Change From Baseline in Mechanical Pain Sensitivity (Von Frey) at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (Size 8, n=18,21) | -0.370 scores on a scale | Standard Deviation 1.2674 |
| Pregabalin | Mean Change From Baseline in Mechanical Pain Sensitivity (Von Frey) at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (Size 16, n=18,21) | -0.611 scores on a scale | Standard Deviation 1.2693 |
| Pregabalin | Mean Change From Baseline in Mechanical Pain Sensitivity (Von Frey) at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (Size 32, n=18,21) | -0.333 scores on a scale | Standard Deviation 1.4597 |
| Pregabalin | Mean Change From Baseline in Mechanical Pain Sensitivity (Von Frey) at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (Size 64, n=18,21) | -1.116 scores on a scale | Standard Deviation 1.6152 |
| Pregabalin | Mean Change From Baseline in Mechanical Pain Sensitivity (Von Frey) at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (Size 128, n=18,21) | -1.315 scores on a scale | Standard Deviation 1.9322 |
| Pregabalin | Mean Change From Baseline in Mechanical Pain Sensitivity (Von Frey) at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (Size 256, n=18,21) | -1.322 scores on a scale | Standard Deviation 1.8729 |
| Pregabalin | Mean Change From Baseline in Mechanical Pain Sensitivity (Von Frey) at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (Size 512, n=18,21) | -1.836 scores on a scale | Standard Deviation 1.7249 |
| Placebo | Mean Change From Baseline in Mechanical Pain Sensitivity (Von Frey) at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (Size 64, n=18,21) | -0.462 scores on a scale | Standard Deviation 3.1381 |
| Placebo | Mean Change From Baseline in Mechanical Pain Sensitivity (Von Frey) at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (Size 8, n=15,16) | 0.417 scores on a scale | Standard Deviation 2.6063 |
| Placebo | Mean Change From Baseline in Mechanical Pain Sensitivity (Von Frey) at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (Size 8, n=18,21) | -0.429 scores on a scale | Standard Deviation 1.7132 |
| Placebo | Mean Change From Baseline in Mechanical Pain Sensitivity (Von Frey) at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (Size 16, n=15,16) | 0.208 scores on a scale | Standard Deviation 2.6412 |
| Placebo | Mean Change From Baseline in Mechanical Pain Sensitivity (Von Frey) at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (Size 256, n=18,21) | -0.751 scores on a scale | Standard Deviation 2.5072 |
| Placebo | Mean Change From Baseline in Mechanical Pain Sensitivity (Von Frey) at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (Size 32, n=15,16) | -0.188 scores on a scale | Standard Deviation 2.1636 |
| Placebo | Mean Change From Baseline in Mechanical Pain Sensitivity (Von Frey) at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (Size 16, n=18,21) | -0.889 scores on a scale | Standard Deviation 2.2616 |
| Placebo | Mean Change From Baseline in Mechanical Pain Sensitivity (Von Frey) at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (Size 64, n=15,16) | 0.561 scores on a scale | Standard Deviation 2.9543 |
| Placebo | Mean Change From Baseline in Mechanical Pain Sensitivity (Von Frey) at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (Size 128, n=18,21) | -0.841 scores on a scale | Standard Deviation 2.2843 |
| Placebo | Mean Change From Baseline in Mechanical Pain Sensitivity (Von Frey) at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (Size 128, n=15,16) | -0.097 scores on a scale | Standard Deviation 1.3385 |
| Placebo | Mean Change From Baseline in Mechanical Pain Sensitivity (Von Frey) at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (Size 32, n=18,21) | -0.825 scores on a scale | Standard Deviation 2.1386 |
| Placebo | Mean Change From Baseline in Mechanical Pain Sensitivity (Von Frey) at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (Size 256, n=15,16) | -0.171 scores on a scale | Standard Deviation 1.4133 |
| Placebo | Mean Change From Baseline in Mechanical Pain Sensitivity (Von Frey) at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (Size 512, n=18,21) | -0.420 scores on a scale | Standard Deviation 2.0238 |
| Placebo | Mean Change From Baseline in Mechanical Pain Sensitivity (Von Frey) at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (Size 512, n=15,16) | -0.480 scores on a scale | Standard Deviation 1.1183 |
Comparison: Week 3 (Visits 3 and 6)p-value: 0.007195% CI: [-1.84, -0.35]ANCOVA
Comparison: Week 4 (Visits 4 and 7)p-value: 0.129495% CI: [-1.36, 0.19]ANCOVA
Primary
Mean Change From Baseline in Punctate Allodynia Area (Von Frey) at Visits 3 and 6 and Visits 4 and 7
Punctate allodynia area in cm\^2: calculated from 8 measured distances by calculating the area of an octagon. The angle between each pair of lines was 45 degrees at point c. The area of the octagon was found by totaling the areas of the 8 triangles. Octagon with 8 radial lengths from center to the outside. Area = Σ ( ½ length \* perpendicular height); Σ ( ½ ri \* sin(45) r(i+1) ) = Σ ( (ri \* r(i+1) )/2√2)). (where ri, i=1 to 8, were the eight radial lengths)
Time frame: Week 3 (Visits 3 and 6) and Week 4 (Visits 4 and 7) of each period
Population: FAS. n=number of participants contributing to the mean.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Mean Change From Baseline in Punctate Allodynia Area (Von Frey) at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (n=16,17) | -75.571 cm2 | Standard Deviation 148.8301 |
| Pregabalin | Mean Change From Baseline in Punctate Allodynia Area (Von Frey) at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (n=17,20) | -75.834 cm2 | Standard Deviation 133.953 |
| Placebo | Mean Change From Baseline in Punctate Allodynia Area (Von Frey) at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (n=16,17) | -3.232 cm2 | Standard Deviation 125.8041 |
| Placebo | Mean Change From Baseline in Punctate Allodynia Area (Von Frey) at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (n=17,20) | -4.130 cm2 | Standard Deviation 129.8261 |
Comparison: Week 3 (Visits 3 and 6)p-value: 0.0395% CI: [-116.12, -6.96]ANCOVA
Comparison: Week 4 (Visits 4 and 7)p-value: 0.084495% CI: [-105.67, 7.55]ANCOVA
Secondary
Mean Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) Total Score at Visits 4 and 7
NPSI: 10-item self-administered questionnaire assessing 5 dimensions of pain (burning superficial spontaneous pain, pressing deep spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dysesthesia). Each item consists of a question about the specific qualities of pain and an 11-point numerical scale range: 0 (absence of pain) to 10 (maximum intensity imaginable), and 2 temporal items related to spontaneous and paroxysmal pain. Maximum total score possible = 100.
Time frame: Week 4 (Visits 4 and 7) of each period
Population: FAS. n=18, 18; number of participants contributing to the mean.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Mean Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) Total Score at Visits 4 and 7 | -10.67 scores on a scale | Standard Deviation 21.404 |
| Placebo | Mean Change From Baseline in Neuropathic Pain Symptom Inventory (NPSI) Total Score at Visits 4 and 7 | -7.72 scores on a scale | Standard Deviation 19.384 |
p-value: 0.499995% CI: [-17.13, 8.54]ANCOVA
Secondary
Mean Change From Baseline in Patient's Global Impression of Change (PGIC) at Visits 3 and 6 and Visits 4 and 7
PGIC: participant-rated assessment measuring change in participant's overall status on a 7-point scale from 1=very much improved to 7=very much worse.
Time frame: Week 3 (Visits 3 and 6) and Week 4 (Visits 4 and 7) of each period
Population: FAS. n=number of participants contributing to the mean.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Mean Change From Baseline in Patient's Global Impression of Change (PGIC) at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (n=15,16) | 3.3 scores on a scale | Standard Deviation 1.87 |
| Pregabalin | Mean Change From Baseline in Patient's Global Impression of Change (PGIC) at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (n=18,21) | 2.4 scores on a scale | Standard Deviation 1.2 |
| Placebo | Mean Change From Baseline in Patient's Global Impression of Change (PGIC) at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (n=15,16) | 3.4 scores on a scale | Standard Deviation 1.15 |
| Placebo | Mean Change From Baseline in Patient's Global Impression of Change (PGIC) at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (n=18,21) | 3.8 scores on a scale | Standard Deviation 1.63 |
Comparison: Week 3 (Visits 3 and 6)p-value: 0.663195% CI: [-1.12, 0.74]ANCOVA
Comparison: Week 4 (Visits 4 and 7)p-value: 0.002295% CI: [-2.48, -0.59]ANCOVA
Secondary
Mean Change From Baseline in Test-Day Global Pain Intensity at Visits 3 and 6 and Visits 4 and 7
Global pain: participant-rated pain using the test-day global pain scale, consisting of an 11-point NRS where 0 = no pain and 10 = worst possible pain. Participants described intensity of pain in response to How intense is your pain today?
Time frame: Week 3 (Visits 3 and 6) and Week 4 (Visits 4 and 7) of each period
Population: FAS. n=number of participants contributing to the mean.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Mean Change From Baseline in Test-Day Global Pain Intensity at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (n=7,10) | -1.5 scores on a scale | Standard Deviation 2.39 |
| Pregabalin | Mean Change From Baseline in Test-Day Global Pain Intensity at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (n=11,11) | -1.6 scores on a scale | Standard Deviation 1.95 |
| Placebo | Mean Change From Baseline in Test-Day Global Pain Intensity at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (n=7,10) | -0.4 scores on a scale | Standard Deviation 2.66 |
| Placebo | Mean Change From Baseline in Test-Day Global Pain Intensity at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (n=11,11) | 0.0 scores on a scale | Standard Deviation 2.94 |
Comparison: Week 3 (Visits 3 and 6)p-value: 0.175395% CI: [-2.6, 0.53]ANCOVA
Comparison: Week 4 (Visits 4 and 7)p-value: 0.019895% CI: [-2.75, -0.27]ANCOVA
Secondary
Mean Change From Baseline in Weekly Pain Score From the Daily Diary at Visits 3 and 6 and Visits 4 and 7
Daily pain diary: participant-rated pain during the past 24 hours rated on an 11 point NRS scale where 0=no pain and 10=worst possible pain. For a given week, the pain response was the average of the 7 daily entries for that week, or average of the available data for that week if fewer than 7 entries were recorded (\>=1 daily pain score for any given week required). The endpoint for each week consisted of the change from baseline in average pain score (follow-up value minus baseline).
Time frame: Week 3 (Visits 3 and 6) and Week 4 (Visits 4 and 7) of each period
Population: FAS. n=number of participants contributing to the mean. Missing weeks within a period were imputed using last observation carried forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Mean Change From Baseline in Weekly Pain Score From the Daily Diary at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (n=19,18) | -1.456 scores on a scale | Standard Deviation 1.8287 |
| Pregabalin | Mean Change From Baseline in Weekly Pain Score From the Daily Diary at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (n=18,18) | -1.397 scores on a scale | Standard Deviation 1.4823 |
| Placebo | Mean Change From Baseline in Weekly Pain Score From the Daily Diary at Visits 3 and 6 and Visits 4 and 7 | Week 3 (Visits 3 and 6) (n=19,18) | -0.484 scores on a scale | Standard Deviation 2.0721 |
| Placebo | Mean Change From Baseline in Weekly Pain Score From the Daily Diary at Visits 3 and 6 and Visits 4 and 7 | Week 4 (Visits 4 and 7) (n=18,18) | -0.769 scores on a scale | Standard Deviation 1.4778 |
Comparison: Week 3 (Visits 3 and 6)p-value: 0.013295% CI: [-2.73, -0.34]ANCOVA
Comparison: Week 4 (Visits 4 and 7)p-value: 0.040395% CI: [-1.95, -0.05]ANCOVA