Nerve Pain
Conditions
Brief summary
The purpose of this study is to assess whether a cross-over type study design in post-traumatic neuropathic patients can be used to assess the activity of potential analgesic agents
Detailed description
Methodology study to evaluate a cross-over study design in post-traumatic neuropathic pain patients.
Interventions
Oral, 75mg or 150mg capsules, BID
DRUGPlacebo
Oral, matched capsules, BID
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 80 Years
Healthy volunteers
No
Inclusion criteria
* Patients require a diagnosis of post-traumatic peripheral neuropathic pain (NeP), including post-surgical NeP and NeP due to peripheral nerve injury, which has lasted at least 3 months following the traumatic event. * Patients during the screening week must have completed ≥ 4 daily pain scores and have an average daily pain score ≥ 4. * Female patients of childbearing potential must have a negative urine pregnancy test at Screening and be practicing an acceptable form of contraception.
Exclusion criteria
* Patients with neuropathic pain (NeP) that is not due to trauma; e.g. patients with trigeminal neuralgia, central pain, complex region pain syndrome type I, phantom limb pain, radiculopathy, painful diabetic neuropathy or post-herpetic neuralgia or patients with any other co-existing pain which cannot be differentiate from NeP of peripheral origin. * Patients who have previously failed to respond to pregabalin at a total daily dose of equal to or greater than 300 mg or are intolerant to those doses. * Patients who have previously failed to respond to gabapentin at a total daily dose of equal to or greater than 1800 mg. * Patients with any type or history of malignancy, except either where there has been no ongoing treatment for at least 6 months or all basal cell carcinomas; all patients with a history of brain or spinal tumors will be excluded. * Patients who currently have ongoing litigation related to any injury affecting their pain symptomatology.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Treatment Week 2 in Daily Pain Rating Scale | Week 0 to Week 2, Week 4 to Week 6 (Baseline to Week 2 [End of Treatment] for each treatment period) | Daily Pain Rating Scale by treatment and sequence using an 11-point Likert scale: range 0 (no pain) to 10 (worst possible pain) over the past 24 hours. Self-assessment was performed daily on rising from bed (for the final time in the case of interrupted sleep). Average daily pain score: mean of the previous 7 days daily pain scores. Baseline was defined as the mean of the last 7 pre-treatment pain scores for each period. End of treatment was defined as the mean of the last 7 on treatment pain scores for each period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neuropathic Pain Symptom Inventory (NPSI) | Week 0 to Week 2, Week 4 to Week 6 (Baseline to End of Treatment in Treatment Periods 1 and 2) | NPSI at end of treatment: 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. |
| Subject Activity as Captured by the Actiwatch Score Device: Total Activity Score at End of Treatment | Week 0 to Week 2, Week 4 to Week 6 (Baseline to End of Treatment in Treatment Periods 1 and 2) | Total activity score: Day (8 am to 8 pm) at end of treatment. Accelerometer measured physical activity by monitoring degree and intensity of body motion. Data is reported as activity counts. Subject activity was collected hourly for the variables: peak, average, and total activity. Higher score indicates greater activity (no activity = 0; total possible score was not defined). |
Countries
Canada, Sweden
Participant flow
Recruitment details
Subjects participated in the study between 05 May 2008 and 10 February 2009.
Pre-assignment details
Subjects meeting entry criteria entered into a 1-week screening period to monitor daily pain scores and activity levels. If pain severity met inclusion criteria subjects could enter the double-blind part of the study and were randomized to 1 of 2 treatment sequence crossovers (pregabalin/placebo or placebo/pregabalin).
Participants by arm
| Arm | Count |
|---|---|
| Pregabalin Then Placebo Pregabalin: Day 1: 75 mg in the evening, Days 2 & 3: 150 mg/day, Day 4: 225 mg/day, Days 5 to 14: 300 mg/day, Day 15: 150 mg in the morning. BID dosing Days 2-14. Placebo: Day 1 in the evening, Days 2 to 14 BID, Day 15 in the morning. | 13 |
| Placebo Then Pregabalin Placebo: Day 1 in the evening, Days 2 to 14 BID, Day 15 in the morning. Pregabalin: Day 1: 75 mg in the evening, Days 2 & 3: 150 mg/day, Day 4: 225 mg/day, Days 5 to 14: 300 mg/day, Day 15: 150 mg in the morning. BID dosing Days 2-14. | 12 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 | Adverse Event | 0 | 1 |
| Period 1 | Intolerable Pain Level | 1 | 0 |
Baseline characteristics
| Characteristic | Pregabalin Then Placebo | Placebo Then Pregabalin | Total |
|---|---|---|---|
| Age, Customized 18 - 44 years | 4 years 0 | 3 years 0 | 7 years 0 |
| Age, Customized 45 - 64 years | 5 years 16.7 | 8 years 11.8 | 13 years |
| Age, Customized >=65 years | 4 years 0 | 1 years 0 | 5 years 0 |
| Sex: Female, Male Female | 7 Participants | 7 Participants | 14 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 24 | 10 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 |
Outcome results
Primary
Change From Baseline to Treatment Week 2 in Daily Pain Rating Scale
Daily Pain Rating Scale by treatment and sequence using an 11-point Likert scale: range 0 (no pain) to 10 (worst possible pain) over the past 24 hours. Self-assessment was performed daily on rising from bed (for the final time in the case of interrupted sleep). Average daily pain score: mean of the previous 7 days daily pain scores. Baseline was defined as the mean of the last 7 pre-treatment pain scores for each period. End of treatment was defined as the mean of the last 7 on treatment pain scores for each period.
Time frame: Week 0 to Week 2, Week 4 to Week 6 (Baseline to Week 2 [End of Treatment] for each treatment period)
Population: Full Analysis Set: (FAS): all subjects randomized who received at least one dose of study drug, regardless of whether they had efficacy data. Baseline is Week 0 and Week 4 for Periods 1 and 2, respectively. Treatment Week 2 is End of Treatment (Week 2 and Week 6) for Periods 1 and 2, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Period 1: Pregabalin | Change From Baseline to Treatment Week 2 in Daily Pain Rating Scale | Change from Baseline | -0.63 scores on scale | Standard Deviation 1.01 |
| Period 1: Pregabalin | Change From Baseline to Treatment Week 2 in Daily Pain Rating Scale | Baseline | 6.03 scores on scale | Standard Deviation 1.29 |
| Period 1: Pregabalin | Change From Baseline to Treatment Week 2 in Daily Pain Rating Scale | Treatment Week 2 | 5.40 scores on scale | Standard Deviation 1.34 |
| Period 1: Placebo | Change From Baseline to Treatment Week 2 in Daily Pain Rating Scale | Baseline | 5.24 scores on scale | Standard Deviation 2.03 |
| Period 1: Placebo | Change From Baseline to Treatment Week 2 in Daily Pain Rating Scale | Change from Baseline | -0.16 scores on scale | Standard Deviation 0.97 |
| Period 1: Placebo | Change From Baseline to Treatment Week 2 in Daily Pain Rating Scale | Treatment Week 2 | 5.08 scores on scale | Standard Deviation 2.05 |
| Period 2: Placebo | Change From Baseline to Treatment Week 2 in Daily Pain Rating Scale | Treatment Week 2 | 6.11 scores on scale | Standard Deviation 1.2 |
| Period 2: Placebo | Change From Baseline to Treatment Week 2 in Daily Pain Rating Scale | Baseline | 5.96 scores on scale | Standard Deviation 0.88 |
| Period 2: Placebo | Change From Baseline to Treatment Week 2 in Daily Pain Rating Scale | Change from Baseline | 0.16 scores on scale | Standard Deviation 1.07 |
| Period 2: Pregabalin | Change From Baseline to Treatment Week 2 in Daily Pain Rating Scale | Baseline | 5.31 scores on scale | Standard Deviation 1.82 |
| Period 2: Pregabalin | Change From Baseline to Treatment Week 2 in Daily Pain Rating Scale | Change from Baseline | -0.93 scores on scale | Standard Deviation 1.24 |
| Period 2: Pregabalin | Change From Baseline to Treatment Week 2 in Daily Pain Rating Scale | Treatment Week 2 | 4.38 scores on scale | Standard Deviation 2.02 |
Comparison: Treatment comparison of pregabalin - placebo: mixed effects analysis of covariance model fitted on the full analysis set population, accounting for period and treatment effects. Subject was fitted as a random effect, and baseline was fitted as two covariates.80% CI: [-1.21, -0.41]ANCOVA
Secondary
Neuropathic Pain Symptom Inventory (NPSI)
NPSI at end of treatment: 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 0 to Week 2, Week 4 to Week 6 (Baseline to End of Treatment in Treatment Periods 1 and 2)
Population: FAS. Weeks 0 and 4 are baseline for Periods 1 and 2, respectively. Weeks 2 and 6 are End of Treatment for Periods 1 and 2, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Period 1: Pregabalin | Neuropathic Pain Symptom Inventory (NPSI) | Week 0 (Baseline: Treatment Period 1) | 5.31 scores on scale | Standard Deviation 3.5 |
| Period 1: Pregabalin | Neuropathic Pain Symptom Inventory (NPSI) | Week 2 (End of Treatment: Treatment Period 1) | 5.31 scores on scale | Standard Deviation 3.3 |
| Period 1: Pregabalin | Neuropathic Pain Symptom Inventory (NPSI) | Week 4 (Baseline: Treatment Period 2) | 4.33 scores on scale | Standard Deviation 3.14 |
| Period 1: Pregabalin | Neuropathic Pain Symptom Inventory (NPSI) | Week 6 (End of Treatment: Treatment Period 2) | 4.75 scores on scale | Standard Deviation 3.39 |
| Period 1: Placebo | Neuropathic Pain Symptom Inventory (NPSI) | Week 6 (End of Treatment: Treatment Period 2) | 3.00 scores on scale | Standard Deviation 2.24 |
| Period 1: Placebo | Neuropathic Pain Symptom Inventory (NPSI) | Week 0 (Baseline: Treatment Period 1) | 5.25 scores on scale | Standard Deviation 2.38 |
| Period 1: Placebo | Neuropathic Pain Symptom Inventory (NPSI) | Week 4 (Baseline: Treatment Period 2) | 5.27 scores on scale | Standard Deviation 2.45 |
| Period 1: Placebo | Neuropathic Pain Symptom Inventory (NPSI) | Week 2 (End of Treatment: Treatment Period 1) | 4.91 scores on scale | Standard Deviation 2.3 |
Comparison: Neuropathic Pain Symptom Inventory treatment comparison: Pregabalin - Placebo. Total score was analyzed using a mixed effect analysis of covariance model based on the full analysis set (FAS), accounting for period and treatment effects. Subject was fitted as a random effect and baseline was fitted as two covariates.80% CI: [-3.82, 2.78]ANCOVA
Secondary
Subject Activity as Captured by the Actiwatch Score Device: Total Activity Score at End of Treatment
Total activity score: Day (8 am to 8 pm) at end of treatment. Accelerometer measured physical activity by monitoring degree and intensity of body motion. Data is reported as activity counts. Subject activity was collected hourly for the variables: peak, average, and total activity. Higher score indicates greater activity (no activity = 0; total possible score was not defined).
Time frame: Week 0 to Week 2, Week 4 to Week 6 (Baseline to End of Treatment in Treatment Periods 1 and 2)
Population: FAS; End of Treatment is treatment week 2 (Week 2 and Week 6) for Periods 1 and 2.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Period 1: Pregabalin | Subject Activity as Captured by the Actiwatch Score Device: Total Activity Score at End of Treatment | 300000 scores on scale | Standard Error 12000 |
| Period 1: Placebo | Subject Activity as Captured by the Actiwatch Score Device: Total Activity Score at End of Treatment | 270000 scores on scale | Standard Error 12000 |
Comparison: Difference in least squares means Pregabalin-Placebo. Model of day (8 am to 8 pm) total activity score at end of treatment. Mixed effects analysis of covariance model was fitted on the full analysis set population, accounting for period and treatment effects. Subject was fitted as a random effect and baseline was fitted as two covariates.80% CI: [6100, 51000]ANCOVA