Trial Outcomes & Findings for A Study to Assess the Safety and Efficacy of 7 Days Treatment With a Novel Analgesic in Subjects With Peripheral Neuropathic Pain (NCT NCT01485094)

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.

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).

A Study to Assess the Safety and Efficacy of 7 Days Treatment With a Novel Analgesic in Subjects With Peripheral Neuropathic Pain

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 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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.