Spinal Cord Injuries
Conditions
Keywords
Clinical Trial Methodology study Neuropathic pain in Spinal cord injury patients Pain endpoints Crossover design
Brief summary
The study is designed to assess if spinal cord injury patients have reduced pain after taking either pregabalin or placebo in a cross over design. Patients had either pain at the level of their injury or below the level of their injury.
Detailed description
This methodology study was terminated on October 13, 2008 based on interim results for an exploratory, novel endpoint. The results of the primary analysis at the interim for N=12 patients showed results that generally favored pregabalin but were not statistically significant compared to placebo. Based on the estimated conditional power, this result is unlikely to change with full recruitment of N=24 patients and therefore the data monitoring committee recommended termination of the trial. The decision to terminate the trial was not based on any safety concerns.
Interventions
DRUGPregabalin
Pregabalin 150mg capsules BID for 7.5 days
Placebo capsules BID for 7.5 days
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* subjects who are outpatients or inpatients * written informed consent obtained (signed by the subject or the subject's legally acceptable representative) * traumatic spinal cord injury of at least 1 year duration with a nonprogressive, i.e., chronic, stage of at least 6 months duration * At-level neuropathic pain: spontaneous or evoked pain with neuropathic features (sharp, shooting, electric or burning pain sensation) in the region of sensory disturbance in a segmental pattern and located within two dermatomes above or below the level of spinal cord injury * Below-level neuropathic pain: spontaneous or evoked pain with neuropathic features (sharp, shooting, electric or burning pain sensation) in the region of sensory disturbance located at least three dermatomes below the level of spinal cord injury
Exclusion criteria
* spinal cord injury (subjects with central pain and musculoskeletal pain must be able to make a distinction between the two) * subjects who have previously not responded to 300 mg/day pregabalin: a non-responder is defined as a subject who has a reduction in pain score of less than 30% from baseline
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Present Pain Intensity Score | Day 1: 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours (post-dose); Day 8: 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours (post-dose) | Present pain intensity score: 0-10 numeric rating scale (NRS), 0 (no pain) to 10 (worst possible pain). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dynamic Allodynia Area | Screening, Days 1 & 8: 0 (pre-dose) & 4 hours post-dose, | Area of dynamic allodynia was assessed using a brush (SENSElab Brush 05; velocity approximately 20 millimeters per second \[mm/s\]) by stimulating along a pattern of 8 radial spokes. Stimulation was started from the non-painful perimetry. Subjects were asked to report change in sensation from non-painful to painful and the spot was marked onto the skin. The area of dynamic allodynia was determined from these 8 distances by calculating the area of an octagon (in centimeter squared \[cm2\]). |
| Dynamic Allodynia Pain Score | Screening, Days 1 & 8: 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, and 6 hours post-dose | Five strokes (each approx. 6 centimeters \[cm\] long) were applied with a standardized brush (SENSELab Brush 05) across the painful site (and a control site) at a constant velocity (20 millimeters per second \[mm/sec\]). Pain in response to brush stimulation of the allodynic area was recorded using an 11-point numeric rating scale from 0 (no pain) to 10 (worst possible pain). Patients were asked to give a pain rating after each brush stroke. A painful sensation was considered as representing brush allodynia. |
| Punctate Allodynia Area | Screening, Days 1 & 8: 0 (pre-dose) and 4 hours post-dose | Area of punctate allodynia was determined using a von Frey filament (OptiHair2). Stimulation was started from the non-painful perimetry and repeated along a pattern of 8 radial spokes. With a movement along each spoke at steps of 5 millimeters (mm), the subjects reported sensation changes from non-painful to painful and the spot was marked on the skin. The area of punctate allodynia was determined from these 8 distances by calculating the area of an octagon (in square centimeter(s)\[cm2\]). |
| Daily Pain Score | Predose: Daily from 7 days before Visit 2 (start of Intervention 1) until the morning of Visit 5 (end of Intervention 2) | Daily Pain Score: Day 1 pain intensity over past 24 hours recorded on waking every morning. 0-10 numeric rating scale (NRS): 0 (no pain) to 10 (worst possible pain). |
| Neuropathic Pain Symptom Inventory (NPSI) | Prior to morning dosing on Day 1 and prior to discharge on Day 8 for each period. | NPSI: subject rated questionnaire to evaluate 5 dimensions of neuropathic pain (dimensions: burning \[superficial\] spontaneous pain, pressing \[deep\] spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dyesthesia). Includes 10 descriptors ranging from 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 relevant dimension. Total score is calculated as the sum of scores of the 10 descriptors, range: 0-100. Higher score indicates greater intensity of pain. |
| Pharmacokinetic Evaluations of Pregabalin | Day 1: 0 (pre-dose), 0.5, 1, 2, and 6 hours post-dose; Day 8: 0 (pre-dose), 1, 4, & 6 hours post-dose | Pharmacokinetic (PK) results are not presented in this report due to early termination of the trial. Pregabalin PK was not measured as there was incomplete data to conduct pharmacokinetic/pharmacodynamic analyses. |
| Mechanical Pain Sensitivity Stimulus-Response Function | Screening, Days 1 & 8: 0 (pre-dose), & 2, 4, and 6 hours post-dose | Mechanical pain sensitivity stimulus response function was assessed at the control and painful sites using calibrated von Frey monofilaments and the SENSElab brush. Seven different von Frey monofilaments (8 -512 milliNewtons \[mN\], force increases by a factor of two from filament to filament) and the brush were applied in a predetermined pseudo-random order. Pain rating for each stimulus: 11-point numeric rating scale (NRS) ranging from 0 (no pain) to 10 (worst possible pain). |
Countries
Australia
Participant flow
Recruitment details
Subjects were enrolled at 4 study centers and participated in the study between 13 February 2007 and 01 October 2008.
Pre-assignment details
Subjects completed a 1-2 week screening period to determine eligibility criteria prior to enrollment. Of 24 subjects screened, 15 subjects were enrolled into the study and randomized.
Participants by arm
| Arm | Count |
|---|---|
| All Subjects Pregabalin: Days 1-7: 150 mg twice a day (BID); Day 8: 150 mg in the morning; and Placebo: Days 1-7: twice a day (BID); Day 8: 1 dose in the morning. | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Washout Period of 2 Weeks | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | All Subjects |
|---|---|
| Age, Customized 18-44 years | 5 participants |
| Age, Customized 45-64 years | 7 participants |
| Age, Customized >= 65 years | 3 participants |
| Sex/Gender, Customized Female | 2 gender |
| Sex/Gender, Customized Male | 13 gender |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 12 / 15 | 9 / 14 |
| serious Total, serious adverse events | 0 / 15 | 1 / 14 |
Outcome results
Primary
Present Pain Intensity Score
Present pain intensity score: 0-10 numeric rating scale (NRS), 0 (no pain) to 10 (worst possible pain).
Time frame: Day 1: 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours (post-dose); Day 8: 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, and 48 hours (post-dose)
Population: Full analysis set (FAS): those subjects who completed both periods of the study. Combined results for At-level and Below-level neuropathic pain; At-level: located within 2 dermatomes above or below the level of spinal cord injury; Below-level: located at least 3 dermatomes below the level of spinal cord injury.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Present Pain Intensity Score | Day 1: 1 hours post-dose (n=15, 14) | 4.6 scores on scale | Standard Deviation 2.82 |
| Pregabalin | Present Pain Intensity Score | Day 8: 1 hour post-dose (n=13, 14) | 4.0 scores on scale | Standard Deviation 2.71 |
| Pregabalin | Present Pain Intensity Score | Day 1: 6 hours post-dose (n=15, 14) | 3.9 scores on scale | Standard Deviation 2.89 |
| Pregabalin | Present Pain Intensity Score | Day 8: 2 hours post-dose (n=13, 14) | 4.6 scores on scale | Standard Deviation 2.5 |
| Pregabalin | Present Pain Intensity Score | Day 1: 3 hours post-dose (n=15, 14) | 4.3 scores on scale | Standard Deviation 2.82 |
| Pregabalin | Present Pain Intensity Score | Day 8: 3 hours post-dose (n=15, 14) | 4.9 scores on scale | Standard Deviation 2.22 |
| Pregabalin | Present Pain Intensity Score | Day 1: 8 hours post-dose (n=15, 14) | 4.3 scores on scale | Standard Deviation 2.91 |
| Pregabalin | Present Pain Intensity Score | Day 8: 4 hours post-dose (n=15, 14) | 4.9 scores on scale | Standard Deviation 2.28 |
| Pregabalin | Present Pain Intensity Score | Day 1: 0.5 hours post-dose (n=15, 14) | 5.1 scores on scale | Standard Deviation 2.46 |
| Pregabalin | Present Pain Intensity Score | Day 8: 5 hours post-dose (n=15, 14) | 4.8 scores on scale | Standard Deviation 2.4 |
| Pregabalin | Present Pain Intensity Score | Day 1: 10 hours post-dose (n=14, 14) | 4.1 scores on scale | Standard Deviation 3.03 |
| Pregabalin | Present Pain Intensity Score | Day 8: 6 hours post-dose (n=15, 14) | 4.4 scores on scale | Standard Deviation 2.38 |
| Pregabalin | Present Pain Intensity Score | Day 1: 4 hours post-dose (n=15, 14) | 4.1 scores on scale | Standard Deviation 2.79 |
| Pregabalin | Present Pain Intensity Score | Day 8: 8 hours post-dose (n=15, 13) | 4.7 scores on scale | Standard Deviation 2.63 |
| Pregabalin | Present Pain Intensity Score | Day 1: 12 hours post-dose (n=14, 14) | 4.1 scores on scale | Standard Deviation 3.17 |
| Pregabalin | Present Pain Intensity Score | Day 8: 10 hours post-dose (n=15, 13) | 4.9 scores on scale | Standard Deviation 2.37 |
| Pregabalin | Present Pain Intensity Score | Day 1: 2 hours post-dose (n=15, 14) | 4.3 scores on scale | Standard Deviation 2.64 |
| Pregabalin | Present Pain Intensity Score | Day 8: 12 hours post-dose (n=15, 13) | 4.7 scores on scale | Standard Deviation 2.16 |
| Pregabalin | Present Pain Intensity Score | Day 8: pre-dose (n=13, 14) | 4.7 scores on scale | Standard Deviation 2.53 |
| Pregabalin | Present Pain Intensity Score | Day 8: 24 hours post-dose (n=15, 14) | 5.0 scores on scale | Standard Deviation 2.36 |
| Pregabalin | Present Pain Intensity Score | Day 1: 5 hours post-dose (n=15, 14) | 3.9 scores on scale | Standard Deviation 3.01 |
| Pregabalin | Present Pain Intensity Score | Day 8: 36 hours post-dose (n=15, 13) | 6.1 scores on scale | Standard Deviation 2.74 |
| Pregabalin | Present Pain Intensity Score | Day 8: 0.5 hours post-dose (n=13, 14) | 4.5 scores on scale | Standard Deviation 2.33 |
| Pregabalin | Present Pain Intensity Score | Day 8: 48 hours post-dose (n=15, 14) | 6.1 scores on scale | Standard Deviation 2.31 |
| Pregabalin | Present Pain Intensity Score | Day 1: pre-dose (n=15, 14) | 5.3 scores on scale | Standard Deviation 2.76 |
| Placebo | Present Pain Intensity Score | Day 8: 48 hours post-dose (n=15, 14) | 5.8 scores on scale | Standard Deviation 2.81 |
| Placebo | Present Pain Intensity Score | Day 1: pre-dose (n=15, 14) | 4.9 scores on scale | Standard Deviation 2.91 |
| Placebo | Present Pain Intensity Score | Day 1: 0.5 hours post-dose (n=15, 14) | 4.6 scores on scale | Standard Deviation 3.03 |
| Placebo | Present Pain Intensity Score | Day 1: 1 hours post-dose (n=15, 14) | 4.7 scores on scale | Standard Deviation 2.55 |
| Placebo | Present Pain Intensity Score | Day 1: 2 hours post-dose (n=15, 14) | 4.7 scores on scale | Standard Deviation 2.64 |
| Placebo | Present Pain Intensity Score | Day 1: 3 hours post-dose (n=15, 14) | 4.7 scores on scale | Standard Deviation 2.73 |
| Placebo | Present Pain Intensity Score | Day 1: 4 hours post-dose (n=15, 14) | 4.6 scores on scale | Standard Deviation 2.98 |
| Placebo | Present Pain Intensity Score | Day 1: 5 hours post-dose (n=15, 14) | 4.9 scores on scale | Standard Deviation 3.02 |
| Placebo | Present Pain Intensity Score | Day 1: 6 hours post-dose (n=15, 14) | 5.1 scores on scale | Standard Deviation 2.91 |
| Placebo | Present Pain Intensity Score | Day 1: 8 hours post-dose (n=15, 14) | 5.1 scores on scale | Standard Deviation 2.57 |
| Placebo | Present Pain Intensity Score | Day 1: 10 hours post-dose (n=14, 14) | 5.3 scores on scale | Standard Deviation 2.81 |
| Placebo | Present Pain Intensity Score | Day 1: 12 hours post-dose (n=14, 14) | 5.4 scores on scale | Standard Deviation 2.68 |
| Placebo | Present Pain Intensity Score | Day 8: pre-dose (n=13, 14) | 5.4 scores on scale | Standard Deviation 2.62 |
| Placebo | Present Pain Intensity Score | Day 8: 0.5 hours post-dose (n=13, 14) | 5.0 scores on scale | Standard Deviation 2.57 |
| Placebo | Present Pain Intensity Score | Day 8: 1 hour post-dose (n=13, 14) | 4.9 scores on scale | Standard Deviation 2.6 |
| Placebo | Present Pain Intensity Score | Day 8: 2 hours post-dose (n=13, 14) | 4.6 scores on scale | Standard Deviation 2.38 |
| Placebo | Present Pain Intensity Score | Day 8: 3 hours post-dose (n=15, 14) | 4.7 scores on scale | Standard Deviation 2.52 |
| Placebo | Present Pain Intensity Score | Day 8: 4 hours post-dose (n=15, 14) | 4.9 scores on scale | Standard Deviation 2.53 |
| Placebo | Present Pain Intensity Score | Day 8: 5 hours post-dose (n=15, 14) | 4.9 scores on scale | Standard Deviation 2.63 |
| Placebo | Present Pain Intensity Score | Day 8: 6 hours post-dose (n=15, 14) | 5.2 scores on scale | Standard Deviation 2.72 |
| Placebo | Present Pain Intensity Score | Day 8: 8 hours post-dose (n=15, 13) | 5.3 scores on scale | Standard Deviation 2.9 |
| Placebo | Present Pain Intensity Score | Day 8: 10 hours post-dose (n=15, 13) | 5.2 scores on scale | Standard Deviation 2.85 |
| Placebo | Present Pain Intensity Score | Day 8: 12 hours post-dose (n=15, 13) | 5.2 scores on scale | Standard Deviation 2.65 |
| Placebo | Present Pain Intensity Score | Day 8: 24 hours post-dose (n=15, 14) | 5.4 scores on scale | Standard Deviation 2.71 |
| Placebo | Present Pain Intensity Score | Day 8: 36 hours post-dose (n=15, 13) | 5.7 scores on scale | Standard Deviation 2.56 |
Comparison: Difference from placebo (including Baseline), Day 1: 0.5 hours post-dose.p-value: 0.679795% CI: [-0.83, 1.22]ANOVA
Comparison: Difference from placebo (including Baseline), Day 1: 1 hour post-dose.p-value: 0.481195% CI: [-1.54, 0.77]ANOVA
Comparison: Difference from placebo (including Baseline), Day 1: 2 hours post-dose.p-value: 0.169395% CI: [-1.67, 0.33]ANOVA
Comparison: Difference from placebo (including Baseline) , Day 1: 3 hours post-dose.p-value: 0.403495% CI: [-1.78, 0.87]ANOVA
Comparison: Difference from placebo (including Baseline), Day 1: 4 hours post-dose.p-value: 0.193595% CI: [-2.36, 0.5]ANOVA
Comparison: Difference from placebo (including Baseline), Day 1: 5 hours post-dose.p-value: 0.069495% CI: [-2.83, 0.12]ANOVA
Comparison: Difference from placebo (including Baseline), Day 1: 6 hours post-dose.p-value: 0.039695% CI: [-3.02, -0.08]ANOVA
Comparison: Difference from placebo (including Baseline), Day 1: 8 hours post-dose.p-value: 0.153195% CI: [-1.25, 0.24]ANOVA
Comparison: Difference from placebo (including Baseline), Day 1: 10 hours post-dose.p-value: 0.095195% CI: [-2.79, 0.29]ANOVA
Comparison: Difference from placebo (including Baseline), Day 1: 12 hours post-dose.p-value: 0.061495% CI: [-2.84, 0.09]ANOVA
Comparison: Difference from placebo (including Baseline), Day 8: pre-dose.p-value: 0.194695% CI: [-2.29, 0.54]ANOVA
Comparison: Difference from placebo (including Baseline), Day 8: 0.5 hours post-dose.p-value: 0.284395% CI: [-2.2, 0.84]ANOVA
Comparison: Difference from placebo (including Baseline), Day 8: 1 hour post-dose.p-value: 0.21595% CI: [-2.75, 0.65]ANOVA
Comparison: Difference from placebo (including Baseline), Day 8: 2 hours post-dose.p-value: 0.960195% CI: [-0.44, 0.42]ANOVA
Comparison: Difference from placebo (including baseline), Day 8: 3 hours post-dose.p-value: 0.86795% CI: [-0.64, 0.74]ANOVA
Comparison: Difference from placebo (including baseline), Day 8: 4 hours post-dose.p-value: 0.902495% CI: [-0.94, 0.84]ANOVA
Comparison: Difference from placebo (including Baseline), Day 8: 5 hours post-dose.p-value: 0.970895% CI: [-0.67, 0.65]ANOVA
Comparison: Difference from placebo (including Baseline), Day 8: 6 hours post-dose.p-value: 0.107895% CI: [-1.62, 0.19]ANOVA
Comparison: Difference from placebo (including Baseline), Day 8: 8 hours post-dose.p-value: 0.44695% CI: [-1.28, 0.61]ANOVA
Comparison: Difference from placebo (including Baseline), Day 8: 10 hours post-dose.p-value: 0.526695% CI: [-1.13, 0.62]ANOVA
Comparison: Difference from placebo (including Baseline), Day 8: 12 hours post-dose.p-value: 0.02995% CI: [-1.29, -0.08]ANOVA
Comparison: Difference from placebo (including Baseline), Day 8: 24 hours post-dose.p-value: 0.18395% CI: [-2.01, 0.45]ANOVA
Comparison: Difference from placebo (including Baseline), Day 8: 36 hours post-dose.p-value: 0.988495% CI: [-0.9, 0.91]ANOVA
Comparison: Difference from placebo (including Baseline), Day 8: 48 hours post-dose.p-value: 0.808295% CI: [-0.87, 0.69]ANOVA
Secondary
Daily Pain Score
Daily Pain Score: Day 1 pain intensity over past 24 hours recorded on waking every morning. 0-10 numeric rating scale (NRS): 0 (no pain) to 10 (worst possible pain).
Time frame: Predose: Daily from 7 days before Visit 2 (start of Intervention 1) until the morning of Visit 5 (end of Intervention 2)
Population: FAS; Combined results for At-level and Below-level of spinal cord injury.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Daily Pain Score | Day 1 (n=15, 13) | 6.2 scores on scale | Standard Deviation 1.78 |
| Pregabalin | Daily Pain Score | Day 5 (n= 15, 14) | 4.5 scores on scale | Standard Deviation 2.67 |
| Pregabalin | Daily Pain Score | Day 3 (n=15, 14) | 4.1 scores on scale | Standard Deviation 2.49 |
| Pregabalin | Daily Pain Score | Day 6 (n=15, 14) | 3.7 scores on scale | Standard Deviation 2.6 |
| Pregabalin | Daily Pain Score | Day 7 (n=15, 14) | 4.0 scores on scale | Standard Deviation 2.7 |
| Pregabalin | Daily Pain Score | Day 2 (n=15, 14) | 4.4 scores on scale | Standard Deviation 2.67 |
| Pregabalin | Daily Pain Score | Day 8 (n=14, 14) | 4.0 scores on scale | Standard Deviation 2.35 |
| Pregabalin | Daily Pain Score | Day 4 (n=15, 14) | 4.2 scores on scale | Standard Deviation 2.51 |
| Placebo | Daily Pain Score | Day 8 (n=14, 14) | 5.6 scores on scale | Standard Deviation 2.47 |
| Placebo | Daily Pain Score | Day 1 (n=15, 13) | 6.3 scores on scale | Standard Deviation 2.06 |
| Placebo | Daily Pain Score | Day 2 (n=15, 14) | 5.4 scores on scale | Standard Deviation 2.47 |
| Placebo | Daily Pain Score | Day 3 (n=15, 14) | 5.1 scores on scale | Standard Deviation 2.35 |
| Placebo | Daily Pain Score | Day 4 (n=15, 14) | 5.0 scores on scale | Standard Deviation 2.35 |
| Placebo | Daily Pain Score | Day 5 (n= 15, 14) | 5.1 scores on scale | Standard Deviation 2.37 |
| Placebo | Daily Pain Score | Day 7 (n=15, 14) | 4.9 scores on scale | Standard Deviation 2.54 |
| Placebo | Daily Pain Score | Day 6 (n=15, 14) | 4.9 scores on scale | Standard Deviation 2.3 |
Comparison: Difference from placebo (including baseline); Day 2. Combined analysis: values for the two patient groups were analyzed together using ANOVA and/or mixed models.p-value: 0.210195% CI: [-2.39, 0.55]ANOVA
Comparison: Difference from placebo (including baseline); Day 3.p-value: 0.106595% CI: [-2.33, 0.24]ANOVA
Comparison: Difference from placebo (including baseline); Day 4.p-value: 0.069795% CI: [-1.11, 0.05]ANOVA
Comparison: Difference from placebo; Day 5.p-value: 0.458995% CI: [-1.83, 0.85]ANOVA
Comparison: Difference from placebo; Day 6.p-value: 0.132695% CI: [-2.69, 0.38]ANOVA
Comparison: Difference from placebo (including baseline); Day 7.p-value: 0.28295% CI: [-2.45, 0.9]ANOVA
Comparison: Difference from placebo (including baseline); Day 8.p-value: 0.010895% CI: [-2.21, -0.44]ANOVA
Secondary
Dynamic Allodynia Area
Area of dynamic allodynia was assessed using a brush (SENSElab Brush 05; velocity approximately 20 millimeters per second \[mm/s\]) by stimulating along a pattern of 8 radial spokes. Stimulation was started from the non-painful perimetry. Subjects were asked to report change in sensation from non-painful to painful and the spot was marked onto the skin. The area of dynamic allodynia was determined from these 8 distances by calculating the area of an octagon (in centimeter squared \[cm2\]).
Time frame: Screening, Days 1 & 8: 0 (pre-dose) & 4 hours post-dose,
Population: FAS; Combined results for At-level and Below-level of spinal cord injury.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Dynamic Allodynia Area | Day 1: pre-dose (n=14, 14) | 95.8 cm2 | Standard Deviation 108.1 |
| Pregabalin | Dynamic Allodynia Area | Day 1: 4 hours post-dose (n=15, 13) | 63.0 cm2 | Standard Deviation 78.54 |
| Pregabalin | Dynamic Allodynia Area | Day 8: pre-dose (n=12, 14) | 48.4 cm2 | Standard Deviation 92.07 |
| Pregabalin | Dynamic Allodynia Area | Day 8: 4 hours post-dose (n=15, 13) | 50.5 cm2 | Standard Deviation 83.72 |
| Placebo | Dynamic Allodynia Area | Day 8: 4 hours post-dose (n=15, 13) | 68.0 cm2 | Standard Deviation 91.41 |
| Placebo | Dynamic Allodynia Area | Day 1: pre-dose (n=14, 14) | 81.6 cm2 | Standard Deviation 111.2 |
| Placebo | Dynamic Allodynia Area | Day 8: pre-dose (n=12, 14) | 68.4 cm2 | Standard Deviation 83.53 |
| Placebo | Dynamic Allodynia Area | Day 1: 4 hours post-dose (n=15, 13) | 50.9 cm2 | Standard Deviation 78.64 |
Comparison: Difference from placebo; Day 1: 4 hours post-dose (including Baseline).p-value: 0.906895% CI: [-41.78, 37.27]ANOVA
Comparison: Difference from placebo; Day 8: pre-dose (including Baseline).p-value: 0.780795% CI: [-30.53, 39.57]ANOVA
Comparison: Difference from placebo; Day 8: 4 hours post-dose (including Baseline).p-value: 0.229395% CI: [-61.79, 16.78]ANOVA
Secondary
Dynamic Allodynia Pain Score
Five strokes (each approx. 6 centimeters \[cm\] long) were applied with a standardized brush (SENSELab Brush 05) across the painful site (and a control site) at a constant velocity (20 millimeters per second \[mm/sec\]). Pain in response to brush stimulation of the allodynic area was recorded using an 11-point numeric rating scale from 0 (no pain) to 10 (worst possible pain). Patients were asked to give a pain rating after each brush stroke. A painful sensation was considered as representing brush allodynia.
Time frame: Screening, Days 1 & 8: 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, and 6 hours post-dose
Population: FAS; Combined results for At-level and Below-level of spinal cord injury.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Dynamic Allodynia Pain Score | Day 1: pre-dose (n=14, 13) | 2.2 scores on scale | Standard Deviation 2.99 |
| Pregabalin | Dynamic Allodynia Pain Score | Day 1: 0.5 hours post-dose (n=10, 8) | 2.8 scores on scale | Standard Deviation 3.14 |
| Pregabalin | Dynamic Allodynia Pain Score | Day 1: 1 hour post-dose (n=10, 8) | 2.3 scores on scale | Standard Deviation 2.83 |
| Pregabalin | Dynamic Allodynia Pain Score | Day 1: 2 hours post-dose (n=10, 8) | 2.5 scores on scale | Standard Deviation 3.09 |
| Pregabalin | Dynamic Allodynia Pain Score | Day 1: 3 hours post-dose (n=10, 8) | 2.3 scores on scale | Standard Deviation 2.94 |
| Pregabalin | Dynamic Allodynia Pain Score | Day 1: 4 hours post-dose (n=15, 13) | 1.5 scores on scale | Standard Deviation 2.63 |
| Pregabalin | Dynamic Allodynia Pain Score | Day 1: 5 hours post-dose (n=10, 8) | 2.2 scores on scale | Standard Deviation 2.95 |
| Pregabalin | Dynamic Allodynia Pain Score | Day 1: 6 hours post-dose (n=10, 8) | 2.1 scores on scale | Standard Deviation 2.8 |
| Pregabalin | Dynamic Allodynia Pain Score | Day 8: pre-dose (n=11, 12) | 1.9 scores on scale | Standard Deviation 2.93 |
| Pregabalin | Dynamic Allodynia Pain Score | Day 8: 0.5 hours post-dose (n=7, 8) | 1.7 scores on scale | Standard Deviation 2.74 |
| Pregabalin | Dynamic Allodynia Pain Score | Day 8: 1 hour post-dose (n=7, 8) | 1.6 scores on scale | Standard Deviation 2.66 |
| Pregabalin | Dynamic Allodynia Pain Score | Day 8: 2 hours post-dose (n=7, 8) | 1.9 scores on scale | Standard Deviation 2.93 |
| Pregabalin | Dynamic Allodynia Pain Score | Day 8: 3 hours post-dose (n=9, 8) | 1.7 scores on scale | Standard Deviation 2.45 |
| Pregabalin | Dynamic Allodynia Pain Score | Day 8: 4 hours post-dose (n=14, 13) | 1.0 scores on scale | Standard Deviation 1.99 |
| Pregabalin | Dynamic Allodynia Pain Score | Day 8: 5 hours post-dose (n=9, 8) | 1.9 scores on scale | Standard Deviation 2.83 |
| Pregabalin | Dynamic Allodynia Pain Score | Day 8: 6 hours post-dose (n=9, 8) | 1.9 scores on scale | Standard Deviation 3.05 |
| Placebo | Dynamic Allodynia Pain Score | Day 8: 6 hours post-dose (n=9, 8) | 1.5 scores on scale | Standard Deviation 2.57 |
| Placebo | Dynamic Allodynia Pain Score | Day 1: pre-dose (n=14, 13) | 2.1 scores on scale | Standard Deviation 3.33 |
| Placebo | Dynamic Allodynia Pain Score | Day 8: pre-dose (n=11, 12) | 2.0 scores on scale | Standard Deviation 2.97 |
| Placebo | Dynamic Allodynia Pain Score | Day 1: 0.5 hours post-dose (n=10, 8) | 1.9 scores on scale | Standard Deviation 3.35 |
| Placebo | Dynamic Allodynia Pain Score | Day 8: 3 hours post-dose (n=9, 8) | 1.6 scores on scale | Standard Deviation 2.51 |
| Placebo | Dynamic Allodynia Pain Score | Day 1: 1 hour post-dose (n=10, 8) | 1.8 scores on scale | Standard Deviation 3.15 |
| Placebo | Dynamic Allodynia Pain Score | Day 8: 0.5 hours post-dose (n=7, 8) | 1.7 scores on scale | Standard Deviation 2.66 |
| Placebo | Dynamic Allodynia Pain Score | Day 1: 2 hours post-dose (n=10, 8) | 1.7 scores on scale | Standard Deviation 2.67 |
| Placebo | Dynamic Allodynia Pain Score | Day 8: 5 hours post-dose (n=9, 8) | 1.5 scores on scale | Standard Deviation 2.4 |
| Placebo | Dynamic Allodynia Pain Score | Day 1: 3 hours post-dose (n=10, 8) | 2.3 scores on scale | Standard Deviation 2.98 |
| Placebo | Dynamic Allodynia Pain Score | Day 8: 1 hour post-dose (n=7, 8) | 1.4 scores on scale | Standard Deviation 2.58 |
| Placebo | Dynamic Allodynia Pain Score | Day 1: 4 hours post-dose (n=15, 13) | 1.2 scores on scale | Standard Deviation 2.28 |
| Placebo | Dynamic Allodynia Pain Score | Day 8: 4 hours post-dose (n=14, 13) | 0.9 scores on scale | Standard Deviation 1.99 |
| Placebo | Dynamic Allodynia Pain Score | Day 1: 5 hours post-dose (n=10, 8) | 1.9 scores on scale | Standard Deviation 2.7 |
| Placebo | Dynamic Allodynia Pain Score | Day 8: 2 hours post-dose (n=7, 8) | 1.5 scores on scale | Standard Deviation 2.43 |
| Placebo | Dynamic Allodynia Pain Score | Day 1: 6 hours post-dose (n=10, 8) | 1.9 scores on scale | Standard Deviation 2.75 |
Comparison: Difference from placebo (including Baseline); Day 1: 0.5 hours post-dose.p-value: 0.377495% CI: [-0.54, 1.27]ANOVA
Comparison: Difference from placebo (including Baseline); Day 1: 1 hour post-dose.p-value: 0.415395% CI: [-0.33, 0.7]ANOVA
Comparison: Difference from placebo (including Baseline); Day 1: 2 hours post-dose.p-value: 0.14795% CI: [-0.23, 1.2]ANOVA
Comparison: Difference from placebo (including Baseline); Day 1: 3 hours post-dose.p-value: 0.186295% CI: [-1.18, 0.29]ANOVA
Comparison: Difference from placebo (including Baseline); Day 1: 4 hours post-dose.p-value: 0.832195% CI: [-0.45, 0.55]ANOVA
Comparison: Difference from placebo (including Baseline); Day 1: 5 hours post-dose.p-value: 0.425195% CI: [-0.42, 0.88]ANOVA
Comparison: Difference from placebo (including Baseline); Day 1: 6 hours post-dose.p-value: 0.639495% CI: [-0.53, 0.8]ANOVA
Comparison: Difference from placebo (including Baseline); Day 8: pre-dose.p-value: 0.996495% CI: [-0.68, 0.68]ANOVA
Comparison: Difference from placebo (including Baseline); Day 8: 0.5 hours post-dose.p-value: 0.363895% CI: [-0.47, 1.11]ANOVA
Comparison: Difference from placebo (including Baseline); Day 8: 1 hour post-dose.p-value: 0.120295% CI: [-0.15, 0.99]ANOVA
Comparison: Difference from placebo (including Baseline); Day 8: 2 hours post-dose.p-value: 0.120495% CI: [-0.19, 1.39]ANOVA
Comparison: Difference from placebo (including Baseline); Day 8: 3 hours post-dose.p-value: 0.421395% CI: [-0.44, 0.93]ANOVA
Comparison: Difference from placebo (including Baseline); Day 8: 4 hours post-dose.p-value: 0.602895% CI: [-0.34, 0.56]ANOVA
Comparison: Difference from placebo (including Baseline); Day 8: 5 hours post-dose.p-value: 0.362495% CI: [-0.68, 1.64]ANOVA
Comparison: Difference from placebo (including Baseline); Day 8: 6 hours post-dose.p-value: 0.316395% CI: [-0.52, 1.49]ANOVA
Secondary
Mechanical Pain Sensitivity Stimulus-Response Function
Mechanical pain sensitivity stimulus response function was assessed at the control and painful sites using calibrated von Frey monofilaments and the SENSElab brush. Seven different von Frey monofilaments (8 -512 milliNewtons \[mN\], force increases by a factor of two from filament to filament) and the brush were applied in a predetermined pseudo-random order. Pain rating for each stimulus: 11-point numeric rating scale (NRS) ranging from 0 (no pain) to 10 (worst possible pain).
Time frame: Screening, Days 1 & 8: 0 (pre-dose), & 2, 4, and 6 hours post-dose
Population: FAS; combined results for At-level and Below-level of spinal cord injury.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Mechanical Pain Sensitivity Stimulus-Response Function | Day 1: pre-dose (n=14, 14) | 0.8 scores on scale | Standard Deviation 0.78 |
| Pregabalin | Mechanical Pain Sensitivity Stimulus-Response Function | Day 1: 2 hours post-dose (n=14, 14) | 0.7 scores on scale | Standard Deviation 0.58 |
| Pregabalin | Mechanical Pain Sensitivity Stimulus-Response Function | Day 1: 4 hours post-dose (n=14, 14) | 0.7 scores on scale | Standard Deviation 0.64 |
| Pregabalin | Mechanical Pain Sensitivity Stimulus-Response Function | Day 1: 6 hours post-dose (n=14, 14) | 0.8 scores on scale | Standard Deviation 0.61 |
| Pregabalin | Mechanical Pain Sensitivity Stimulus-Response Function | Day 8: pre-dose (n=13, 14) | 0.7 scores on scale | Standard Deviation 0.61 |
| Pregabalin | Mechanical Pain Sensitivity Stimulus-Response Function | Day 8: 2 hours post-dose (=13, 14) | 0.7 scores on scale | Standard Deviation 0.5 |
| Pregabalin | Mechanical Pain Sensitivity Stimulus-Response Function | Day 8: 4 hours post-dose (n=15, 13) | 0.7 scores on scale | Standard Deviation 0.65 |
| Pregabalin | Mechanical Pain Sensitivity Stimulus-Response Function | Day 8: 6 hours post-dose (n=15, 13) | 0.8 scores on scale | Standard Deviation 0.67 |
| Placebo | Mechanical Pain Sensitivity Stimulus-Response Function | Day 8: 6 hours post-dose (n=15, 13) | 0.7 scores on scale | Standard Deviation 0.59 |
| Placebo | Mechanical Pain Sensitivity Stimulus-Response Function | Day 1: pre-dose (n=14, 14) | 0.9 scores on scale | Standard Deviation 0.73 |
| Placebo | Mechanical Pain Sensitivity Stimulus-Response Function | Day 8: pre-dose (n=13, 14) | 0.8 scores on scale | Standard Deviation 0.64 |
| Placebo | Mechanical Pain Sensitivity Stimulus-Response Function | Day 1: 2 hours post-dose (n=14, 14) | 0.8 scores on scale | Standard Deviation 0.65 |
| Placebo | Mechanical Pain Sensitivity Stimulus-Response Function | Day 8: 4 hours post-dose (n=15, 13) | 0.7 scores on scale | Standard Deviation 0.62 |
| Placebo | Mechanical Pain Sensitivity Stimulus-Response Function | Day 1: 4 hours post-dose (n=14, 14) | 0.8 scores on scale | Standard Deviation 0.65 |
| Placebo | Mechanical Pain Sensitivity Stimulus-Response Function | Day 8: 2 hours post-dose (=13, 14) | 0.8 scores on scale | Standard Deviation 0.66 |
| Placebo | Mechanical Pain Sensitivity Stimulus-Response Function | Day 1: 6 hours post-dose (n=14, 14) | 0.9 scores on scale | Standard Deviation 0.68 |
Comparison: Difference from placebo (including Baseline); Day 1: 2 hours post-dose.p-value: 0.756995% CI: [-0.14, 0.1]ANOVA
Comparison: Difference from placebo (including Baseline); Day 1: 4 hours post-dose.p-value: 0.481495% CI: [-0.26, 0.13]ANOVA
Comparison: Difference from placebo (including Baseline); Day 1: 6 hours post-dose.p-value: 0.622295% CI: [-0.37, 0.23]ANOVA
Comparison: Difference from placebo (including Baseline); Day 8: pre-dose.p-value: 0.303595% CI: [-0.35, 0.12]ANOVA
Comparison: Difference from placebo (including Baseline); Day 8: 2 hours post-dose.p-value: 0.188195% CI: [-0.42, 0.09]ANOVA
Comparison: Difference from placebo (including Baseline); Day 8: 4 hours post-dose.p-value: 0.315995% CI: [-0.09, 0.24]ANOVA
Comparison: Difference from placebo (including Baseline); Day 8: 6 hours post-dose.p-value: 0.820395% CI: [-0.22, 0.27]ANOVA
Secondary
Neuropathic Pain Symptom Inventory (NPSI)
NPSI: subject rated questionnaire to evaluate 5 dimensions of neuropathic pain (dimensions: burning \[superficial\] spontaneous pain, pressing \[deep\] spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dyesthesia). Includes 10 descriptors ranging from 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 relevant dimension. Total score is calculated as the sum of scores of the 10 descriptors, range: 0-100. Higher score indicates greater intensity of pain.
Time frame: Prior to morning dosing on Day 1 and prior to discharge on Day 8 for each period.
Population: FAS; Combined results for At-level and Below-level of spinal cord injury.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Pregabalin | Neuropathic Pain Symptom Inventory (NPSI) | Category 1 Day 1 (n=15, 14) | 6.0 scores on scale |
| Pregabalin | Neuropathic Pain Symptom Inventory (NPSI) | Category 1: Day 8 (n=12, 11) | 5.5 scores on scale |
| Pregabalin | Neuropathic Pain Symptom Inventory (NPSI) | Category 2: Day 1 (n=15, 14) | 3.0 scores on scale |
| Pregabalin | Neuropathic Pain Symptom Inventory (NPSI) | Category 2: Day 8 (n=12, 11) | 2.5 scores on scale |
| Pregabalin | Neuropathic Pain Symptom Inventory (NPSI) | Category 3: Day 1 (n=15, 14) | 1.5 scores on scale |
| Pregabalin | Neuropathic Pain Symptom Inventory (NPSI) | Category 3: Day 8 (n=12, 11) | 1.8 scores on scale |
| Pregabalin | Neuropathic Pain Symptom Inventory (NPSI) | Category 4: Day 1 (n=15, 14) | 1.7 scores on scale |
| Pregabalin | Neuropathic Pain Symptom Inventory (NPSI) | Category 4: Day 8 (n=12, 11) | 2.7 scores on scale |
| Pregabalin | Neuropathic Pain Symptom Inventory (NPSI) | Category 5: Day 1 (n=15, 14) | 5.0 scores on scale |
| Pregabalin | Neuropathic Pain Symptom Inventory (NPSI) | Category 5: Day 8 (n=12, 11) | 3.5 scores on scale |
| Pregabalin | Neuropathic Pain Symptom Inventory (NPSI) | Total: Day 1 (n=15, 14) | 32 scores on scale |
| Pregabalin | Neuropathic Pain Symptom Inventory (NPSI) | Total: Day 8 (n=12, 11) | 22 scores on scale |
| Placebo | Neuropathic Pain Symptom Inventory (NPSI) | Total: Day 1 (n=15, 14) | 27 scores on scale |
| Placebo | Neuropathic Pain Symptom Inventory (NPSI) | Category 1 Day 1 (n=15, 14) | 6.0 scores on scale |
| Placebo | Neuropathic Pain Symptom Inventory (NPSI) | Category 4: Day 1 (n=15, 14) | 0.3 scores on scale |
| Placebo | Neuropathic Pain Symptom Inventory (NPSI) | Category 1: Day 8 (n=12, 11) | 6.0 scores on scale |
| Placebo | Neuropathic Pain Symptom Inventory (NPSI) | Category 5: Day 8 (n=12, 11) | 5.0 scores on scale |
| Placebo | Neuropathic Pain Symptom Inventory (NPSI) | Category 2: Day 1 (n=15, 14) | 2.5 scores on scale |
| Placebo | Neuropathic Pain Symptom Inventory (NPSI) | Category 4: Day 8 (n=12, 11) | 0.0 scores on scale |
| Placebo | Neuropathic Pain Symptom Inventory (NPSI) | Category 2: Day 8 (n=12, 11) | 3.0 scores on scale |
| Placebo | Neuropathic Pain Symptom Inventory (NPSI) | Total: Day 8 (n=12, 11) | 24 scores on scale |
| Placebo | Neuropathic Pain Symptom Inventory (NPSI) | Category 3: Day 1 (n=15, 14) | 3.3 scores on scale |
| Placebo | Neuropathic Pain Symptom Inventory (NPSI) | Category 5: Day 1 (n=15, 14) | 5.0 scores on scale |
| Placebo | Neuropathic Pain Symptom Inventory (NPSI) | Category 3: Day 8 (n=12, 11) | 2.0 scores on scale |
Secondary
Pharmacokinetic Evaluations of Pregabalin
Pharmacokinetic (PK) results are not presented in this report due to early termination of the trial. Pregabalin PK was not measured as there was incomplete data to conduct pharmacokinetic/pharmacodynamic analyses.
Time frame: Day 1: 0 (pre-dose), 0.5, 1, 2, and 6 hours post-dose; Day 8: 0 (pre-dose), 1, 4, & 6 hours post-dose
Secondary
Punctate Allodynia Area
Area of punctate allodynia was determined using a von Frey filament (OptiHair2). Stimulation was started from the non-painful perimetry and repeated along a pattern of 8 radial spokes. With a movement along each spoke at steps of 5 millimeters (mm), the subjects reported sensation changes from non-painful to painful and the spot was marked on the skin. The area of punctate allodynia was determined from these 8 distances by calculating the area of an octagon (in square centimeter(s)\[cm2\]).
Time frame: Screening, Days 1 & 8: 0 (pre-dose) and 4 hours post-dose
Population: FAS; combined results for At-level and Below-level spinal cord injury.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin | Punctate Allodynia Area | Day 1: pre-dose (n=15, 14) | 75.6 cm2 | Standard Deviation 113.3 |
| Pregabalin | Punctate Allodynia Area | Day 1: 4 hours post-dose (n=15, 13) | 68.7 cm2 | Standard Deviation 112.6 |
| Pregabalin | Punctate Allodynia Area | Day 8: pre-dose (n=13, 14) | 53.1 cm2 | Standard Deviation 102.2 |
| Pregabalin | Punctate Allodynia Area | Day 8: 4 hours post-dose (n=15, 13) | 70.8 cm2 | Standard Deviation 106.3 |
| Placebo | Punctate Allodynia Area | Day 8: 4 hours post-dose (n=15, 13) | 46.7 cm2 | Standard Deviation 80.73 |
| Placebo | Punctate Allodynia Area | Day 1: pre-dose (n=15, 14) | 65.1 cm2 | Standard Deviation 104.8 |
| Placebo | Punctate Allodynia Area | Day 8: pre-dose (n=13, 14) | 45.9 cm2 | Standard Deviation 74.32 |
| Placebo | Punctate Allodynia Area | Day 1: 4 hours post-dose (n=15, 13) | 54.1 cm2 | Standard Deviation 91.21 |
Comparison: Difference from placebo (including Baseline); Day 1.p-value: 0.591995% CI: [-16.26, 27.04]ANOVA
Comparison: Difference from placebo (including Baseline); Day 8: pre-dose.p-value: 0.398195% CI: [-17.7, 42.87]ANOVA
Comparison: Difference from placebo (including Baseline); Day 8: 4 hours post-dose.p-value: 0.831495% CI: [-24, 29.28]ANOVA