Neuralgia
Conditions
Keywords
neuralgia, postherpetic
Brief summary
The purpose of this trial is to determine whether a novel analgesic is effective in treating of neuropathic pain caused by herpetic infection, surgery, or trauma.
Detailed description
This trial evaluates the effectiveness of a novel analgesic in peripheral neuropathic pain in a mixed patient population. Participants were treated for one week and randomly assigned to the novel analgesic, pregabalin, or placebo. Pain will be characterized before and at the end of this period. This trial required the participants to stay at the investigational site for 14 consecutive days. The enrollment visit took place Day -28 to Day -16. Participants tapered down their existing medication from Visit 2 (Day -17 to Day -5) to Visit 3 and were given rescue medication (paracetamol/acetaminophen). At Visit 3 participants were hospitalized (Day -4). The baseline evaluation period took place from Day -3 to Day -1. Randomization to one of the three treatment arms was possible after the last assessment on Day - 1 alternatively randomization took place on Day 1. This was followed by the double-blind treatment period (Day 1 to Day 7). The participants were follow-up thereafter up to day 36 (Day 34 to 38). Participants were permitted to resume their previous medication.
Interventions
DRUGGRT6010
Oral solution given once daily.
DRUGPregabalin
Over-encapsulated pregabalin capsules 75mg twice daily on Days 1 to 3, and 150mg twice daily on Days 4 to 7.
DRUGMatching Placebo
Matching Placebo capsules to the over-encapsulated Pregabalin capsules and Matching Placebo oral solution to the GRT6010 solution. Capsules twice daily on Days 1 to 7. Solution once daily.
Sponsors
Grünenthal GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age 18 years to 75 years * Presence of persistent neuropathic pain for at least 6 months at the time of the Enrollment Visit. Allowed reasons for neuropathic pain are: modified radical mastectomy, breast conserving surgery, or cosmetic breast surgery. \[Germany: subjects after cosmetic breast surgery may not be enrolled.\] * Presence of probable or definite neuropathic pain. * Presence of dynamic mechanical allodynia on the affected side, or alternatively, the mechanical pain sensitivity for any of the pinprick stimuli is higher on the affected compared to the contralateral side. * At either Visit 5 or Visit 6: Presence of an average evoked pain intensity score of \>20 on the 0 100 point numeric rating scale (NRS) for at least 1 of the 3 clinical sub-tests for dynamic mechanical allodynia (i.e., standardized brush, cotton wool tip or cotton wisp). The average will be calculated as the arithmetic mean of all measurements per sub test. Alternatively, the arithmetic mean of the 5 test replicates for any of the pinprick stimuli for mechanical pain sensitivity is at least 3 times higher for the affected side compared to the contralateral side. * Presence of an average ongoing pain intensity score of \>4 to \<9 on the 0-10 point numerical rating scale (NRS) without the use of rescue medication within the 3 day Baseline pain intensity evaluation Period with at least 7 of 9 assessments being present. * Dissatisfaction with the current treatment (i.e., lack of efficacy or intolerable side effects) if taking an opioid or non opioid analgesic medication for the painful neuropathy before enrollment.
Exclusion criteria
* Any kind of hepatic impairment at Visit 1 or at Visit 3. * Either active hepatitis within the past 3 months or presence of chronic hepatitis irrespective of its activity status. * Estimated creatinine clearance of less than 60 mL/minute x 1.73 m2 at either Visit 1 or at Visit 3. * Clinically relevant cardiac disease (e.g., unstable angina pectoris, angina pectoris Canadian Cardiovascular Society \[CCS\] Grade III to IV, acute myocardial infarction within the last 3 months, cardiac insufficiency New York Heart Association \[NYHA\] Class III to IV). * Electrocardiogram (ECG) with clinically relevant findings at either Visit 1 or at Visit 3, including but not limited to repeated prolongation of QTc \> 450 ms (Fridericia correction), or a history of additional risk factors for torsade de pointes (e.g., family history of Long QT Syndrome). * Clinically relevant pulmonary disease (e.g., Medical Research Council breathlessness scale of 2 or above). * Specific antitumor therapy within the last 6 months, e.g., adjuvant radiotherapy or chemotherapy, biologics, or angiogenesis inhibitors. * CYP2D6 poor metabolizer phenotype as predicted by CYP2D6 genotyping. * Presence of confounding pain conditions (e.g., ulnar nerve entrapment, radial nerve injury associated with major soft-tissue or bone damage, cervico-thoracic radiculopathy, carpal tunnel syndrome, chemotherapy-induced peripheral neuropathy, or complex regional pain syndrome type I or type II). * Phantom breast or phantom limb pain. * Presence of exclusively negative symptoms of neuropathic pain (e.g., hypoesthesia or total anesthesia) in the affected area.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference Between Baseline and End-of-double-blind Treatment Ongoing Pain Intensity Scores | Baseline; Day 7 (end of double blind treatment) | The baseline pain intensity score was calculated as a mean of pain intensity scores during the Baseline Period (from Day -3 to Day -1). The ongoing pain intensity data from Day-3 to Day 7 was used. For the analysis, only pain scores on days where participants received study drug were considered. The primary efficacy analysis of the ongoing pain intensity score were analyzed in a Bayesian framework, via a mono exponential decay model, with the baseline Numeric Rating Score (NRS) as intercept. Considering the inclusion criteria of baseline pain intensity being in the range from 4 to 9, the range in ongoing pain intensity difference between baseline and end-of-double-blind treatment can be from 6 (worst possible value) to -9 (best possible value). A negative value indicates improvement whilst on the treatment. |
| The Difference Between Baseline and End-of-double-blind Treatment Brush-evoked Pain Intensity Scores | Baseline and day 7 (end of double blind treatment) | The difference between baseline and end-of-double-blind treatment brush-evoked pain intensity scores compared to placebo on a 0-100 point NRS (measured as part of the dynamic mechanical allodynia assessments). Each participant rated each brush-evoked pain intensity on a 0 to 100 point Numerical Pain Rating Scale, with 0 indicating 'No Pain' and 100 indicating 'most intense pain imaginable'. Lower values compared to an individual subject's baseline are an improvement in symptoms. The baseline brush-evoked pain intensity score was defined as the average of the geometric mean of all of the values obtained on Day -2 and Day -1, and compared with the scores obtained on day 6 and 7. For the analysis, only pain scores on days where participants received study drug were considered. A negative change indicates a decrease in brush-evoked pain intensity from baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Onset of Ongoing Pain Relief | Day 1 to Day 7 (end of double blind treatment) | Onset of ongoing pain relief defined as the first time-point at which the participant reports a decrease of more than 1-point reduction in ongoing pain relative to baseline (day -3 to day -1), after start of treatment with study drug on Day 1. Study drug intake started on Day 1. Due to the early termination of the trial this analysis was not performed. |
| Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1) | Day -1; Day 7 (end of double blind treatment) | The Neuropathic Pain Symptom Inventory (NPSI) Score is an assessment of neuropathic pain symptoms. A participant answered 10 questions on an 11-point scale 0 (no pain) to 10 (most intense pain imaginable). The total NPSI score is the sum of all ten responses and ranges between 0 and 100. The baseline score and the mean NPSI change is reported over the double-blind treatment period. A negative mean change in score on Day 7 indicates an improvement on this 0 to 100 point scale from baseline for the total score. For pain descriptions burning, pressing, paroxysmal (pain like electric shocks or stabbing), evoked (due to touch) and paresthesia (sensation that is not unpleasant) or dysesthesia (unpleasant) subscores a negative mean change indicate an improvement on the 11 point scale. A participant will score 10 to indicates the worst imaginable symptom, e.g. worst burning imaginable. A participant will score 0 if there is no burning, i.e. the symptom is absent. |
| Difference in Patient's Global Impression of Change | Day 7 (end of double blind treatment) | In the Patient Global Impression of Change (PGIC) the participant indicates the perceived change over the 7 day treatment period. The participant is requested to choose one of seven categories. Scores range from very much improved to very much worse. |
| The Difference Between Baseline and End-of-double-blind Treatment Scores for Dynamic Mechanical Allodynia and Mechanical Pain Sensitivity Compared to Placebo | Day 7 (end of double blind treatment) | Allodynia is pain due to a stimulus that does not normally provoke pain. Dynamic mechanical allodynia was assessed using a set of 3 light tactile stimulators as moving innocuous stimuli. Each participant gave numerical pain ratings for each of 15 stimuli at the affected side. Mechanical pain sensitivity was assessed using a set of 7 weighted pinprick stimuli to obtain the stimulus-response function for pinprick-evoked pain. The participant gave a numerical pain ratings for each of 35 pinprick stimuli at the affected site. Dynamic mechanical allodynia and mechanical pain sensitivity was calculated as the geometric mean of all numerical ratings. The values obtained on Day -2 and -1 were taken as the baseline and values on Day 6 and 7 were taken as the end of treatment. A negative change indicates an improvement on the 0 (no pain) to 100 point scale, where 100 indicates the worst imaginable pain. |
| Assessment of Responder Rates | Day 7 (end of double blind treatment) | The assessment was performed on Day 7. The percentage of change from baseline (Day -3 to Day -1, i.e. the 3 days in the days prior to first dose) in the daily ongoing pain intensity was calculated at Day 7. The percentage of change from baseline in the daily ongoing pain intensity was calculated at Day 7 as follows: % change = (Baseline Pain Intensity - Daily pain intensity at treatment visit) / Baseline Pain Intensity × 100 The threshold values represent an improvement in ongoing pain intensity greater than 20, 30, 40, 50, 60, 70, 80 or 90% as per calculation. Participants who showed a worsening in their daily pain intensity or who prematurely discontinued the trial were regarded as non-responders in terms of the respective treatment. |
| Difference in Leeds Sleep Evaluation Questionnaire After 7 Days of Treatment | Day 7 | On the last day of the double-blind treatment period sleep was evaluated using the Leeds sleep evaluation questionnaire. This questionnaire has 10 self-rating 100 mm line analogue questions concerning sleep and early morning behavior. The higher the score, i.e. the closer the value is to 100 the worse the rating by the participant. The 10 responses are grouped into 4 subscores: * The ease of getting to sleep. * The perceived quality of sleep. * The ease of awakening from sleep. * The integrity of behavior following wakefulness. |
| Change in painDETECT Grading From Baseline (Day -1) to End of Double-blind Treatment (Day 7) | Day 7 (end of double blind treatment) | The painDETECT questionnaire was used to determine the possibility of the presence of a neuropathic pain component. It is a participant completed questionnaire. A total score is calculated between 0 and 38 for each participant. Participants with a score between 0 and 12 are graded as negative and having no neuropathic pain component. Scores between 19 and 38 result in a positive grading, in other words having presence of neuropathic component. Values from 13 to 18 result in participants being graded as having an unclear neuropathic component to their pain. The painDETECT questionnaire was first administered on Day-1 (baseline). The data reported is for before treatment start (Day -1) and the change from baseline on Day 7 (end of the double-blind period). |
| Daily Current Pain Intensity | Baseline; Day 10 | Participants recorded their current pain intensity score 3 times a day, using a 0 -10 (11 point) Numeric Rating Scale where a rating of 0 corresponded to No Pain and a rating of 10 to Pain as bad as you can imagine. The daily current pain intensity reported was derived as the mean of the 3 current pain intensity assessments taken on the day from all participants in the treatment group. The lower the value on the 11 point scale the less pain was reported on a treatment. |
| Change in Area of Static Allodynia and Dynamic Allodynia From Baseline | Baseline; Day 7 (end of double blind treatment) | Allodynia is pain due to a stimulus that does not normally provoke pain. To measure the areas of dynamic and static allodynia, a point lying in the center of the area of maximum pain was marked at baseline (Day -2 and -1). From the baseline point, 8 radii were drawn. The area of dynamic allodynia was determined by gently stroking the skin with a standardized brush along the lines. The participant was asked to report when the sensation became unpleasant. The area of static allodynia was determined by a 128 mN (millinewton) pinprick stimulus along the lines of the 8 radii while asking the subject to report when the sensation became unpleasant. The area was calculated from the summing of the 8 triangles that are generated from the points along each of the 8 radii at which unpleasantness was reported. The larger the area in square centimeters the more allodynia. A reduction in the area of allodynia indicates improvement. |
| Onset of Current Pain Relief | Day 1 to Day 7 (end of double blind treatment) | Onset of current pain relief defined as the first time-point at which the participant reports a decrease of a 1-point reduction in current pain relative to baseline (day -3 to day -1), after start of treatment with study drug on Day 1. Due to the early termination of the trial this analysis was not performed. |
Countries
Germany, Hungary, Poland, United Kingdom
Participant flow
Recruitment details
The first participant was enrolled on the 23 Feb 2012 and the last participant completed the trial on the 18 Jan 2013. A decision to terminate the trial was taken on 18 Dec 2012 after the results of an interim analysis.
Pre-assignment details
114 participants signed informed consent to participate in the trial. 59 participants of the planned 90 were randomized and 57 received study drug (investigational medicinal product).
Participants by arm
| Arm | Count |
|---|---|
| Matching Placebo Oral administration. Pain not sufficiently controlled may be treated with acetaminophen.
Matching Placebo to the over-encapsulated pregabalin tablets and Matching Placebo oral solution to the GRT6010 solution.
Capsules twice daily on Days 1 to 7. Solution once daily. | 19 |
| GRT6010 Oral administration. Pain not sufficiently controlled may be treated with acetaminophen.
GRT6010: Oral solution given once daily. | 19 |
| Pregabalin Oral administration. Pain not sufficiently controlled may be treated with acetaminophen.
Pregabalin: Over-encapsulated Pregabalin tablets 75mg twice daily on Days 1 to 3, and 150mg twice daily on Days 4 to 7. | 19 |
| Total | 57 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Matching Placebo | GRT6010 | Pregabalin | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 3 Participants | 4 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants | 16 Participants | 15 Participants | 49 Participants |
| Age, Continuous | 46.53 years STANDARD_DEVIATION 14.83 | 54.00 years STANDARD_DEVIATION 9.93 | 50.53 years STANDARD_DEVIATION 14.55 | 50.35 years STANDARD_DEVIATION 13.41 |
| Body mass index | 27.56 kg/m2 STANDARD_DEVIATION 3.8 | 27.37 kg/m2 STANDARD_DEVIATION 3.03 | 27.27 kg/m2 STANDARD_DEVIATION 3.32 | 27.40 kg/m2 STANDARD_DEVIATION 3.34 |
| Region of Enrollment Germany | 1 participants | 1 participants | 1 participants | 3 participants |
| Region of Enrollment Hungary | 3 participants | 2 participants | 2 participants | 7 participants |
| Region of Enrollment Poland | 0 participants | 1 participants | 0 participants | 1 participants |
| Region of Enrollment United Kingdom | 15 participants | 15 participants | 16 participants | 46 participants |
| Sex: Female, Male Female | 12 Participants | 11 Participants | 12 Participants | 35 Participants |
| Sex: Female, Male Male | 7 Participants | 8 Participants | 7 Participants | 22 Participants |
| Time since diagnosis of neuropathic pain | 32.95 months STANDARD_DEVIATION 27.84 | 83.26 months STANDARD_DEVIATION 49.86 | 63.32 months STANDARD_DEVIATION 54.79 | 59.84 months STANDARD_DEVIATION 49.49 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 16 / 19 | 16 / 19 | 17 / 19 |
| serious Total, serious adverse events | 0 / 19 | 0 / 19 | 0 / 19 |
Outcome results
Primary
Difference Between Baseline and End-of-double-blind Treatment Ongoing Pain Intensity Scores
The baseline pain intensity score was calculated as a mean of pain intensity scores during the Baseline Period (from Day -3 to Day -1). The ongoing pain intensity data from Day-3 to Day 7 was used. For the analysis, only pain scores on days where participants received study drug were considered. The primary efficacy analysis of the ongoing pain intensity score were analyzed in a Bayesian framework, via a mono exponential decay model, with the baseline Numeric Rating Score (NRS) as intercept. Considering the inclusion criteria of baseline pain intensity being in the range from 4 to 9, the range in ongoing pain intensity difference between baseline and end-of-double-blind treatment can be from 6 (worst possible value) to -9 (best possible value). A negative value indicates improvement whilst on the treatment.
Time frame: Baseline; Day 7 (end of double blind treatment)
Population: Intention-to-treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Matching Placebo | Difference Between Baseline and End-of-double-blind Treatment Ongoing Pain Intensity Scores | -2.55 units on a scale | Standard Deviation 2.15 |
| GRT6010 | Difference Between Baseline and End-of-double-blind Treatment Ongoing Pain Intensity Scores | -2.30 units on a scale | Standard Deviation 1.73 |
| Pregabalin | Difference Between Baseline and End-of-double-blind Treatment Ongoing Pain Intensity Scores | -2.33 units on a scale | Standard Deviation 1.58 |
Primary
The Difference Between Baseline and End-of-double-blind Treatment Brush-evoked Pain Intensity Scores
The difference between baseline and end-of-double-blind treatment brush-evoked pain intensity scores compared to placebo on a 0-100 point NRS (measured as part of the dynamic mechanical allodynia assessments). Each participant rated each brush-evoked pain intensity on a 0 to 100 point Numerical Pain Rating Scale, with 0 indicating 'No Pain' and 100 indicating 'most intense pain imaginable'. Lower values compared to an individual subject's baseline are an improvement in symptoms. The baseline brush-evoked pain intensity score was defined as the average of the geometric mean of all of the values obtained on Day -2 and Day -1, and compared with the scores obtained on day 6 and 7. For the analysis, only pain scores on days where participants received study drug were considered. A negative change indicates a decrease in brush-evoked pain intensity from baseline.
Time frame: Baseline and day 7 (end of double blind treatment)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Matching Placebo | The Difference Between Baseline and End-of-double-blind Treatment Brush-evoked Pain Intensity Scores | -11.17 units on a scale | Standard Deviation 15.88 |
| GRT6010 | The Difference Between Baseline and End-of-double-blind Treatment Brush-evoked Pain Intensity Scores | -14.31 units on a scale | Standard Deviation 20.9 |
| Pregabalin | The Difference Between Baseline and End-of-double-blind Treatment Brush-evoked Pain Intensity Scores | -9.79 units on a scale | Standard Deviation 13.69 |
Secondary
Assessment of Responder Rates
The assessment was performed on Day 7. The percentage of change from baseline (Day -3 to Day -1, i.e. the 3 days in the days prior to first dose) in the daily ongoing pain intensity was calculated at Day 7. The percentage of change from baseline in the daily ongoing pain intensity was calculated at Day 7 as follows: % change = (Baseline Pain Intensity - Daily pain intensity at treatment visit) / Baseline Pain Intensity × 100 The threshold values represent an improvement in ongoing pain intensity greater than 20, 30, 40, 50, 60, 70, 80 or 90% as per calculation. Participants who showed a worsening in their daily pain intensity or who prematurely discontinued the trial were regarded as non-responders in terms of the respective treatment.
Time frame: Day 7 (end of double blind treatment)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Matching Placebo | Assessment of Responder Rates | 20% Threshold | 12 participants |
| Matching Placebo | Assessment of Responder Rates | 30% Threshold | 11 participants |
| Matching Placebo | Assessment of Responder Rates | 40% Threshold | 8 participants |
| Matching Placebo | Assessment of Responder Rates | 50% Threshold | 5 participants |
| Matching Placebo | Assessment of Responder Rates | 60% Threshold | 4 participants |
| Matching Placebo | Assessment of Responder Rates | 70% Threshold | 4 participants |
| Matching Placebo | Assessment of Responder Rates | 80% Threshold | 3 participants |
| Matching Placebo | Assessment of Responder Rates | 90% Threshold | 1 participants |
| GRT6010 | Assessment of Responder Rates | 40% Threshold | 9 participants |
| GRT6010 | Assessment of Responder Rates | 80% Threshold | 0 participants |
| GRT6010 | Assessment of Responder Rates | 50% Threshold | 7 participants |
| GRT6010 | Assessment of Responder Rates | 60% Threshold | 4 participants |
| GRT6010 | Assessment of Responder Rates | 70% Threshold | 1 participants |
| GRT6010 | Assessment of Responder Rates | 20% Threshold | 14 participants |
| GRT6010 | Assessment of Responder Rates | 30% Threshold | 10 participants |
| GRT6010 | Assessment of Responder Rates | 90% Threshold | 0 participants |
| Pregabalin | Assessment of Responder Rates | 40% Threshold | 6 participants |
| Pregabalin | Assessment of Responder Rates | 30% Threshold | 8 participants |
| Pregabalin | Assessment of Responder Rates | 20% Threshold | 13 participants |
| Pregabalin | Assessment of Responder Rates | 50% Threshold | 4 participants |
| Pregabalin | Assessment of Responder Rates | 80% Threshold | 2 participants |
| Pregabalin | Assessment of Responder Rates | 70% Threshold | 2 participants |
| Pregabalin | Assessment of Responder Rates | 60% Threshold | 4 participants |
| Pregabalin | Assessment of Responder Rates | 90% Threshold | 2 participants |
Secondary
Change in Area of Static Allodynia and Dynamic Allodynia From Baseline
Allodynia is pain due to a stimulus that does not normally provoke pain. To measure the areas of dynamic and static allodynia, a point lying in the center of the area of maximum pain was marked at baseline (Day -2 and -1). From the baseline point, 8 radii were drawn. The area of dynamic allodynia was determined by gently stroking the skin with a standardized brush along the lines. The participant was asked to report when the sensation became unpleasant. The area of static allodynia was determined by a 128 mN (millinewton) pinprick stimulus along the lines of the 8 radii while asking the subject to report when the sensation became unpleasant. The area was calculated from the summing of the 8 triangles that are generated from the points along each of the 8 radii at which unpleasantness was reported. The larger the area in square centimeters the more allodynia. A reduction in the area of allodynia indicates improvement.
Time frame: Baseline; Day 7 (end of double blind treatment)
Population: Intent-to-treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Matching Placebo | Change in Area of Static Allodynia and Dynamic Allodynia From Baseline | Dynamic allodynia area at baseline | 154.79 square centimeters | Standard Deviation 190.33 |
| Matching Placebo | Change in Area of Static Allodynia and Dynamic Allodynia From Baseline | Change in area of dynamic allodynia | 11.36 square centimeters | Standard Deviation 153.96 |
| Matching Placebo | Change in Area of Static Allodynia and Dynamic Allodynia From Baseline | Static allodynia area at baseline | 352.97 square centimeters | Standard Deviation 443.83 |
| Matching Placebo | Change in Area of Static Allodynia and Dynamic Allodynia From Baseline | Change in area of static allodynia | -58.01 square centimeters | Standard Deviation 415.29 |
| GRT6010 | Change in Area of Static Allodynia and Dynamic Allodynia From Baseline | Change in area of static allodynia | -137.47 square centimeters | Standard Deviation 234.46 |
| GRT6010 | Change in Area of Static Allodynia and Dynamic Allodynia From Baseline | Dynamic allodynia area at baseline | 152.11 square centimeters | Standard Deviation 178.43 |
| GRT6010 | Change in Area of Static Allodynia and Dynamic Allodynia From Baseline | Static allodynia area at baseline | 286.21 square centimeters | Standard Deviation 264.05 |
| GRT6010 | Change in Area of Static Allodynia and Dynamic Allodynia From Baseline | Change in area of dynamic allodynia | -73.98 square centimeters | Standard Deviation 149.54 |
| Pregabalin | Change in Area of Static Allodynia and Dynamic Allodynia From Baseline | Change in area of static allodynia | -95.16 square centimeters | Standard Deviation 108.04 |
| Pregabalin | Change in Area of Static Allodynia and Dynamic Allodynia From Baseline | Change in area of dynamic allodynia | -32.78 square centimeters | Standard Deviation 75.96 |
| Pregabalin | Change in Area of Static Allodynia and Dynamic Allodynia From Baseline | Static allodynia area at baseline | 244.75 square centimeters | Standard Deviation 250.03 |
| Pregabalin | Change in Area of Static Allodynia and Dynamic Allodynia From Baseline | Dynamic allodynia area at baseline | 98.4 square centimeters | Standard Deviation 99.2 |
Secondary
Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1)
The Neuropathic Pain Symptom Inventory (NPSI) Score is an assessment of neuropathic pain symptoms. A participant answered 10 questions on an 11-point scale 0 (no pain) to 10 (most intense pain imaginable). The total NPSI score is the sum of all ten responses and ranges between 0 and 100. The baseline score and the mean NPSI change is reported over the double-blind treatment period. A negative mean change in score on Day 7 indicates an improvement on this 0 to 100 point scale from baseline for the total score. For pain descriptions burning, pressing, paroxysmal (pain like electric shocks or stabbing), evoked (due to touch) and paresthesia (sensation that is not unpleasant) or dysesthesia (unpleasant) subscores a negative mean change indicate an improvement on the 11 point scale. A participant will score 10 to indicates the worst imaginable symptom, e.g. worst burning imaginable. A participant will score 0 if there is no burning, i.e. the symptom is absent.
Time frame: Day -1; Day 7 (end of double blind treatment)
Population: intent-to-treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Matching Placebo | Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1) | Day -1 Baseline NPSI total score | 59.11 units on a scale | Standard Deviation 16.47 |
| Matching Placebo | Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1) | Day 7 Change in NPSI total score | -23.89 units on a scale | Standard Deviation 18.81 |
| Matching Placebo | Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1) | Day -1 Baseline Burning spontaneous pain | 5.79 units on a scale | Standard Deviation 1.87 |
| Matching Placebo | Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1) | Day 7 Change in burning spontaneous pain | -2.53 units on a scale | Standard Deviation 2.34 |
| Matching Placebo | Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1) | Day -1 Baseline pressing spontaneous pain | 4.47 units on a scale | Standard Deviation 2.54 |
| Matching Placebo | Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1) | Day 7 Change in pressing spontaneous pain | -1.74 units on a scale | Standard Deviation 2.31 |
| Matching Placebo | Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1) | Day -1 Baseline paroxysmal pain | 6.39 units on a scale | Standard Deviation 2.07 |
| Matching Placebo | Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1) | Day 7 Change in paroxysmal pain | -2.92 units on a scale | Standard Deviation 2.21 |
| Matching Placebo | Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1) | Day -1 Baseline evoked pain | 6.02 units on a scale | Standard Deviation 2.06 |
| Matching Placebo | Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1) | Day 7 Change in evoked pain | -2.16 units on a scale | Standard Deviation 2.3 |
| Matching Placebo | Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1) | Day -1 Baseline paresthesia or dysesthesia | 6.76 units on a scale | Standard Deviation 2.12 |
| Matching Placebo | Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1) | Day 7 Change in paresthesia or dysesthesia | -2.79 units on a scale | Standard Deviation 2.28 |
| GRT6010 | Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1) | Day 7 Change in paresthesia or dysesthesia | -2.13 units on a scale | Standard Deviation 1.94 |
| GRT6010 | Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1) | Day -1 Baseline NPSI total score | 58.05 units on a scale | Standard Deviation 16.75 |
| GRT6010 | Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1) | Day -1 Baseline paroxysmal pain | 6.03 units on a scale | Standard Deviation 2.2 |
| GRT6010 | Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1) | Day -1 Baseline evoked pain | 5.83 units on a scale | Standard Deviation 1.94 |
| GRT6010 | Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1) | Day 7 Change in NPSI total score | -18.95 units on a scale | Standard Deviation 19.56 |
| GRT6010 | Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1) | Day 7 Change in pressing spontaneous pain | -1.68 units on a scale | Standard Deviation 1.88 |
| GRT6010 | Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1) | Day -1 Baseline paresthesia or dysesthesia | 6.45 units on a scale | Standard Deviation 1.79 |
| GRT6010 | Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1) | Day -1 Baseline Burning spontaneous pain | 5.68 units on a scale | Standard Deviation 2.36 |
| GRT6010 | Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1) | Day 7 Change in paroxysmal pain | -1.82 units on a scale | Standard Deviation 2.7 |
| GRT6010 | Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1) | Day -1 Baseline pressing spontaneous pain | 4.97 units on a scale | Standard Deviation 3.07 |
| GRT6010 | Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1) | Day 7 Change in burning spontaneous pain | -1.58 units on a scale | Standard Deviation 2.32 |
| GRT6010 | Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1) | Day 7 Change in evoked pain | -2.03 units on a scale | Standard Deviation 2.22 |
| Pregabalin | Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1) | Day 7 Change in burning spontaneous pain | -2.0 units on a scale | Standard Deviation 2.03 |
| Pregabalin | Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1) | Day -1 Baseline pressing spontaneous pain | 4.45 units on a scale | Standard Deviation 2.91 |
| Pregabalin | Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1) | Day 7 Change in evoked pain | -2.05 units on a scale | Standard Deviation 2.89 |
| Pregabalin | Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1) | Day 7 Change in pressing spontaneous pain | -0.58 units on a scale | Standard Deviation 2.58 |
| Pregabalin | Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1) | Day -1 Baseline paroxysmal pain | 6.76 units on a scale | Standard Deviation 2.39 |
| Pregabalin | Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1) | Day 7 Change in paroxysmal pain | -2.26 units on a scale | Standard Deviation 2.84 |
| Pregabalin | Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1) | Day -1 Baseline paresthesia or dysesthesia | 5.39 units on a scale | Standard Deviation 3.18 |
| Pregabalin | Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1) | Day -1 Baseline NPSI total score | 55.84 units on a scale | Standard Deviation 22.97 |
| Pregabalin | Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1) | Day 7 Change in NPSI total score | -16.79 units on a scale | Standard Deviation 25.31 |
| Pregabalin | Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1) | Day -1 Baseline evoked pain | 5.67 units on a scale | Standard Deviation 2.31 |
| Pregabalin | Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1) | Day -1 Baseline Burning spontaneous pain | 5.63 units on a scale | Standard Deviation 3.06 |
| Pregabalin | Change in Neuropathic Pain Symptom Inventory Scores on Day 7 From Baseline (Day -1) | Day 7 Change in paresthesia or dysesthesia | -1.47 units on a scale | Standard Deviation 3.25 |
Secondary
Change in painDETECT Grading From Baseline (Day -1) to End of Double-blind Treatment (Day 7)
The painDETECT questionnaire was used to determine the possibility of the presence of a neuropathic pain component. It is a participant completed questionnaire. A total score is calculated between 0 and 38 for each participant. Participants with a score between 0 and 12 are graded as negative and having no neuropathic pain component. Scores between 19 and 38 result in a positive grading, in other words having presence of neuropathic component. Values from 13 to 18 result in participants being graded as having an unclear neuropathic component to their pain. The painDETECT questionnaire was first administered on Day-1 (baseline). The data reported is for before treatment start (Day -1) and the change from baseline on Day 7 (end of the double-blind period).
Time frame: Day 7 (end of double blind treatment)
Population: Intent-to-treat. 5 participants did not complete the painDETECT questionnaire on Day 7. Two participants in both the placebo and pregabalin treatment arm and 1 in the GRT6010 treatment arm.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Matching Placebo | Change in painDETECT Grading From Baseline (Day -1) to End of Double-blind Treatment (Day 7) | Day -1 Presence of neuropathic component | 17 participants |
| Matching Placebo | Change in painDETECT Grading From Baseline (Day -1) to End of Double-blind Treatment (Day 7) | Day -1 Unclear neuropathic component | 2 participants |
| Matching Placebo | Change in painDETECT Grading From Baseline (Day -1) to End of Double-blind Treatment (Day 7) | Day 7 Unclear neuropathic component | 4 participants |
| Matching Placebo | Change in painDETECT Grading From Baseline (Day -1) to End of Double-blind Treatment (Day 7) | Day 7 Presence of neuropathic component | 12 participants |
| Matching Placebo | Change in painDETECT Grading From Baseline (Day -1) to End of Double-blind Treatment (Day 7) | Day 7 no neuropathic pain component | 1 participants |
| Matching Placebo | Change in painDETECT Grading From Baseline (Day -1) to End of Double-blind Treatment (Day 7) | Day -1 no neuropathic pain component | 0 participants |
| GRT6010 | Change in painDETECT Grading From Baseline (Day -1) to End of Double-blind Treatment (Day 7) | Day -1 no neuropathic pain component | 0 participants |
| GRT6010 | Change in painDETECT Grading From Baseline (Day -1) to End of Double-blind Treatment (Day 7) | Day -1 Unclear neuropathic component | 1 participants |
| GRT6010 | Change in painDETECT Grading From Baseline (Day -1) to End of Double-blind Treatment (Day 7) | Day 7 no neuropathic pain component | 2 participants |
| GRT6010 | Change in painDETECT Grading From Baseline (Day -1) to End of Double-blind Treatment (Day 7) | Day 7 Unclear neuropathic component | 4 participants |
| GRT6010 | Change in painDETECT Grading From Baseline (Day -1) to End of Double-blind Treatment (Day 7) | Day -1 Presence of neuropathic component | 18 participants |
| GRT6010 | Change in painDETECT Grading From Baseline (Day -1) to End of Double-blind Treatment (Day 7) | Day 7 Presence of neuropathic component | 12 participants |
| Pregabalin | Change in painDETECT Grading From Baseline (Day -1) to End of Double-blind Treatment (Day 7) | Day 7 no neuropathic pain component | 2 participants |
| Pregabalin | Change in painDETECT Grading From Baseline (Day -1) to End of Double-blind Treatment (Day 7) | Day 7 Presence of neuropathic component | 12 participants |
| Pregabalin | Change in painDETECT Grading From Baseline (Day -1) to End of Double-blind Treatment (Day 7) | Day -1 Presence of neuropathic component | 14 participants |
| Pregabalin | Change in painDETECT Grading From Baseline (Day -1) to End of Double-blind Treatment (Day 7) | Day -1 Unclear neuropathic component | 5 participants |
| Pregabalin | Change in painDETECT Grading From Baseline (Day -1) to End of Double-blind Treatment (Day 7) | Day -1 no neuropathic pain component | 0 participants |
| Pregabalin | Change in painDETECT Grading From Baseline (Day -1) to End of Double-blind Treatment (Day 7) | Day 7 Unclear neuropathic component | 3 participants |
Secondary
Daily Current Pain Intensity
Participants recorded their current pain intensity score 3 times a day, using a 0 -10 (11 point) Numeric Rating Scale where a rating of 0 corresponded to No Pain and a rating of 10 to Pain as bad as you can imagine. The daily current pain intensity reported was derived as the mean of the 3 current pain intensity assessments taken on the day from all participants in the treatment group. The lower the value on the 11 point scale the less pain was reported on a treatment.
Time frame: Baseline; Day 10
Population: Intent-to-Treat.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Matching Placebo | Daily Current Pain Intensity | Day 7 | 3.64 units on a scale | Standard Deviation 2.41 |
| Matching Placebo | Daily Current Pain Intensity | Day 4 | 4.09 units on a scale | Standard Deviation 2.5 |
| Matching Placebo | Daily Current Pain Intensity | Day 9 | 4.21 units on a scale | Standard Deviation 2.3 |
| Matching Placebo | Daily Current Pain Intensity | Day 6 | 4.13 units on a scale | Standard Deviation 2.43 |
| Matching Placebo | Daily Current Pain Intensity | Day 5 | 3.82 units on a scale | Standard Deviation 2.36 |
| Matching Placebo | Daily Current Pain Intensity | Baseline | 6.32 units on a scale | Standard Deviation 1.72 |
| Matching Placebo | Daily Current Pain Intensity | Day 2 | 4.49 units on a scale | Standard Deviation 2.34 |
| Matching Placebo | Daily Current Pain Intensity | Day 1 | 4.82 units on a scale | Standard Deviation 2.17 |
| Matching Placebo | Daily Current Pain Intensity | Day 8 | 3.68 units on a scale | Standard Deviation 2.09 |
| Matching Placebo | Daily Current Pain Intensity | Day 3 | 4.46 units on a scale | Standard Deviation 2.19 |
| Matching Placebo | Daily Current Pain Intensity | Day 10 | 4.06 units on a scale | Standard Deviation 2.35 |
| GRT6010 | Daily Current Pain Intensity | Day 5 | 4.61 units on a scale | Standard Deviation 2.04 |
| GRT6010 | Daily Current Pain Intensity | Baseline | 6.52 units on a scale | Standard Deviation 0.98 |
| GRT6010 | Daily Current Pain Intensity | Day 1 | 5.74 units on a scale | Standard Deviation 1.47 |
| GRT6010 | Daily Current Pain Intensity | Day 2 | 5.19 units on a scale | Standard Deviation 2.02 |
| GRT6010 | Daily Current Pain Intensity | Day 3 | 4.68 units on a scale | Standard Deviation 1.77 |
| GRT6010 | Daily Current Pain Intensity | Day 4 | 4.75 units on a scale | Standard Deviation 1.92 |
| GRT6010 | Daily Current Pain Intensity | Day 6 | 4.16 units on a scale | Standard Deviation 1.81 |
| GRT6010 | Daily Current Pain Intensity | Day 7 | 3.84 units on a scale | Standard Deviation 1.82 |
| GRT6010 | Daily Current Pain Intensity | Day 8 | 3.76 units on a scale | Standard Deviation 1.81 |
| GRT6010 | Daily Current Pain Intensity | Day 9 | 4.28 units on a scale | Standard Deviation 1.88 |
| GRT6010 | Daily Current Pain Intensity | Day 10 | 4.35 units on a scale | Standard Deviation 1.88 |
| Pregabalin | Daily Current Pain Intensity | Day 9 | 4.05 units on a scale | Standard Deviation 2.32 |
| Pregabalin | Daily Current Pain Intensity | Day 7 | 3.63 units on a scale | Standard Deviation 2.06 |
| Pregabalin | Daily Current Pain Intensity | Day 2 | 4.58 units on a scale | Standard Deviation 1.97 |
| Pregabalin | Daily Current Pain Intensity | Baseline | 6.13 units on a scale | Standard Deviation 1.49 |
| Pregabalin | Daily Current Pain Intensity | Day 8 | 3.85 units on a scale | Standard Deviation 2.14 |
| Pregabalin | Daily Current Pain Intensity | Day 1 | 5.37 units on a scale | Standard Deviation 1.86 |
| Pregabalin | Daily Current Pain Intensity | Day 5 | 3.95 units on a scale | Standard Deviation 1.78 |
| Pregabalin | Daily Current Pain Intensity | Day 4 | 4.47 units on a scale | Standard Deviation 1.93 |
| Pregabalin | Daily Current Pain Intensity | Day 10 | 4.15 units on a scale | Standard Deviation 2.47 |
| Pregabalin | Daily Current Pain Intensity | Day 6 | 4.08 units on a scale | Standard Deviation 1.85 |
| Pregabalin | Daily Current Pain Intensity | Day 3 | 4.61 units on a scale | Standard Deviation 1.93 |
Secondary
Difference in Leeds Sleep Evaluation Questionnaire After 7 Days of Treatment
On the last day of the double-blind treatment period sleep was evaluated using the Leeds sleep evaluation questionnaire. This questionnaire has 10 self-rating 100 mm line analogue questions concerning sleep and early morning behavior. The higher the score, i.e. the closer the value is to 100 the worse the rating by the participant. The 10 responses are grouped into 4 subscores: * The ease of getting to sleep. * The perceived quality of sleep. * The ease of awakening from sleep. * The integrity of behavior following wakefulness.
Time frame: Day 7
Population: Intention-to-treat. No responses were obtained from 2 participants, one in the placebo and one in the pregabalin treatment arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Matching Placebo | Difference in Leeds Sleep Evaluation Questionnaire After 7 Days of Treatment | Day 7 ease of getting to sleep | 36.37 units on a scale | Standard Deviation 14.77 |
| Matching Placebo | Difference in Leeds Sleep Evaluation Questionnaire After 7 Days of Treatment | Day 7 perceived quality of sleep | 42.69 units on a scale | Standard Deviation 19.73 |
| Matching Placebo | Difference in Leeds Sleep Evaluation Questionnaire After 7 Days of Treatment | Day 7 ease of awakening from sleep | 44.94 units on a scale | Standard Deviation 21.04 |
| Matching Placebo | Difference in Leeds Sleep Evaluation Questionnaire After 7 Days of Treatment | Day 7 integrity of behavior following wakefulness | 46.91 units on a scale | Standard Deviation 22.55 |
| GRT6010 | Difference in Leeds Sleep Evaluation Questionnaire After 7 Days of Treatment | Day 7 integrity of behavior following wakefulness | 44.88 units on a scale | Standard Deviation 23.97 |
| GRT6010 | Difference in Leeds Sleep Evaluation Questionnaire After 7 Days of Treatment | Day 7 ease of getting to sleep | 41.25 units on a scale | Standard Deviation 14.77 |
| GRT6010 | Difference in Leeds Sleep Evaluation Questionnaire After 7 Days of Treatment | Day 7 ease of awakening from sleep | 48.29 units on a scale | Standard Deviation 17.51 |
| GRT6010 | Difference in Leeds Sleep Evaluation Questionnaire After 7 Days of Treatment | Day 7 perceived quality of sleep | 42.33 units on a scale | Standard Deviation 23.01 |
| Pregabalin | Difference in Leeds Sleep Evaluation Questionnaire After 7 Days of Treatment | Day 7 integrity of behavior following wakefulness | 44.35 units on a scale | Standard Deviation 17.35 |
| Pregabalin | Difference in Leeds Sleep Evaluation Questionnaire After 7 Days of Treatment | Day 7 perceived quality of sleep | 37.06 units on a scale | Standard Deviation 24.86 |
| Pregabalin | Difference in Leeds Sleep Evaluation Questionnaire After 7 Days of Treatment | Day 7 ease of awakening from sleep | 46.56 units on a scale | Standard Deviation 21.29 |
| Pregabalin | Difference in Leeds Sleep Evaluation Questionnaire After 7 Days of Treatment | Day 7 ease of getting to sleep | 32.57 units on a scale | Standard Deviation 22.81 |
Secondary
Difference in Patient's Global Impression of Change
In the Patient Global Impression of Change (PGIC) the participant indicates the perceived change over the 7 day treatment period. The participant is requested to choose one of seven categories. Scores range from very much improved to very much worse.
Time frame: Day 7 (end of double blind treatment)
Population: Intention-to-treat
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Matching Placebo | Difference in Patient's Global Impression of Change | Much improved | 4 participants |
| Matching Placebo | Difference in Patient's Global Impression of Change | Minimally worse | 0 participants |
| Matching Placebo | Difference in Patient's Global Impression of Change | No change | 5 participants |
| Matching Placebo | Difference in Patient's Global Impression of Change | Very much improved | 5 participants |
| Matching Placebo | Difference in Patient's Global Impression of Change | Very much worse | 0 participants |
| Matching Placebo | Difference in Patient's Global Impression of Change | Much worse | 0 participants |
| Matching Placebo | Difference in Patient's Global Impression of Change | Minimally improved | 5 participants |
| GRT6010 | Difference in Patient's Global Impression of Change | No change | 2 participants |
| GRT6010 | Difference in Patient's Global Impression of Change | Very much improved | 2 participants |
| GRT6010 | Difference in Patient's Global Impression of Change | Much improved | 6 participants |
| GRT6010 | Difference in Patient's Global Impression of Change | Minimally improved | 8 participants |
| GRT6010 | Difference in Patient's Global Impression of Change | Minimally worse | 1 participants |
| GRT6010 | Difference in Patient's Global Impression of Change | Much worse | 0 participants |
| GRT6010 | Difference in Patient's Global Impression of Change | Very much worse | 0 participants |
| Pregabalin | Difference in Patient's Global Impression of Change | Minimally worse | 0 participants |
| Pregabalin | Difference in Patient's Global Impression of Change | Much improved | 4 participants |
| Pregabalin | Difference in Patient's Global Impression of Change | Very much worse | 0 participants |
| Pregabalin | Difference in Patient's Global Impression of Change | Much worse | 1 participants |
| Pregabalin | Difference in Patient's Global Impression of Change | No change | 1 participants |
| Pregabalin | Difference in Patient's Global Impression of Change | Minimally improved | 8 participants |
| Pregabalin | Difference in Patient's Global Impression of Change | Very much improved | 5 participants |
Secondary
Onset of Current Pain Relief
Onset of current pain relief defined as the first time-point at which the participant reports a decrease of a 1-point reduction in current pain relative to baseline (day -3 to day -1), after start of treatment with study drug on Day 1. Due to the early termination of the trial this analysis was not performed.
Time frame: Day 1 to Day 7 (end of double blind treatment)
Population: Due to the early termination of the trial this analysis was not performed.
Secondary
Onset of Ongoing Pain Relief
Onset of ongoing pain relief defined as the first time-point at which the participant reports a decrease of more than 1-point reduction in ongoing pain relative to baseline (day -3 to day -1), after start of treatment with study drug on Day 1. Study drug intake started on Day 1. Due to the early termination of the trial this analysis was not performed.
Time frame: Day 1 to Day 7 (end of double blind treatment)
Population: Due to the early termination of the trial this analysis was not performed.
Secondary
The Difference Between Baseline and End-of-double-blind Treatment Scores for Dynamic Mechanical Allodynia and Mechanical Pain Sensitivity Compared to Placebo
Allodynia is pain due to a stimulus that does not normally provoke pain. Dynamic mechanical allodynia was assessed using a set of 3 light tactile stimulators as moving innocuous stimuli. Each participant gave numerical pain ratings for each of 15 stimuli at the affected side. Mechanical pain sensitivity was assessed using a set of 7 weighted pinprick stimuli to obtain the stimulus-response function for pinprick-evoked pain. The participant gave a numerical pain ratings for each of 35 pinprick stimuli at the affected site. Dynamic mechanical allodynia and mechanical pain sensitivity was calculated as the geometric mean of all numerical ratings. The values obtained on Day -2 and -1 were taken as the baseline and values on Day 6 and 7 were taken as the end of treatment. A negative change indicates an improvement on the 0 (no pain) to 100 point scale, where 100 indicates the worst imaginable pain.
Time frame: Day 7 (end of double blind treatment)
Population: Intention-to-treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Matching Placebo | The Difference Between Baseline and End-of-double-blind Treatment Scores for Dynamic Mechanical Allodynia and Mechanical Pain Sensitivity Compared to Placebo | Mechanical pain sensitivity (Affected side) | -12.26 units on a scale | Standard Deviation 23.28 |
| Matching Placebo | The Difference Between Baseline and End-of-double-blind Treatment Scores for Dynamic Mechanical Allodynia and Mechanical Pain Sensitivity Compared to Placebo | Dynamic mechanical allodynia (Affected side) | -11.12 units on a scale | Standard Deviation 17.49 |
| GRT6010 | The Difference Between Baseline and End-of-double-blind Treatment Scores for Dynamic Mechanical Allodynia and Mechanical Pain Sensitivity Compared to Placebo | Mechanical pain sensitivity (Affected side) | -14.60 units on a scale | Standard Deviation 17.79 |
| GRT6010 | The Difference Between Baseline and End-of-double-blind Treatment Scores for Dynamic Mechanical Allodynia and Mechanical Pain Sensitivity Compared to Placebo | Dynamic mechanical allodynia (Affected side) | -13.81 units on a scale | Standard Deviation 19.81 |
| Pregabalin | The Difference Between Baseline and End-of-double-blind Treatment Scores for Dynamic Mechanical Allodynia and Mechanical Pain Sensitivity Compared to Placebo | Mechanical pain sensitivity (Affected side) | -13.86 units on a scale | Standard Deviation 15.32 |
| Pregabalin | The Difference Between Baseline and End-of-double-blind Treatment Scores for Dynamic Mechanical Allodynia and Mechanical Pain Sensitivity Compared to Placebo | Dynamic mechanical allodynia (Affected side) | -9.63 units on a scale | Standard Deviation 13 |