Study of Mirogabalin for Central Neuropathic Pain

The pain scores on a scale of 0-10, where 0 = no pain and 10 = the worst possible pain. Negative changes in ADPS indicated an improvement in pain scores. The weekly ADPS is based on participants daily pain scores.

Responder rate (%) = 100 × (observed weekly ADPS - baseline weekly ADPS) / baseline weekly ADPS, where the baseline weekly ADPS was defined as the average of up to 7 available pain scores in the last 7 days at or before the randomization visit (Visit 2).

Participants rated their present pain intensity on a scale of 0 (no pain) to 5 (most intense pain). Negative changes in present pain intensity indicated an improvement in pain intensity.

At the end-of-treatment (Visit 7)/early termination visit, participants provided a self-assessment of their condition compared to the randomization visit (Visit 2) using the 7-point scale in the Patient Global Impression of Change (PGIC), where 1 = very much improved to 7 = very much worse. Here, the PGIC responder rates were categorized and defined as the percentage of participants who satisfied the following PGIC score criteria: Minimally improved or better (ie, score ≤3); Much improved or better (ie, score ≤2). Patient Global Impression of Change scores are used to determine categorical responder rates.

The daily sleep interference diary consisted of an 11-point numerical rating scale (NRS) which was used to assess how pain had interfered with the participant's sleep during the past 24 hours. Participants recorded a sleep interference score in the patient diary once daily from the day after the screening visit (Visit 1) through the end-of-treatment (Visit 7)/early termination visit. Every morning upon awakening, prior to taking the study drug, each participant selected the number that best described his/her sleep interference experience during the past 24 hours on a scale of 0 = pain did not interfere with sleep to 10 = pain completely interfered with sleep. Negative values indicate an improvement in sleep interference. The weekly average daily sleep interference score (ADSIS) was based on the sleep interference scores from the patient diaries.

The MOS sleep scale was based on questions about sleep quality during the past 4 weeks and consisted of 3 parts. Average time required to fall asleep, average hours of sleep per night, and ten questions based on sleep disturbance that were given a score of 1 (all the time) to 5 (none of the time). Based on the 12 questions, the following scales were calculated: sleep disturbance, snoring, awakening due to shortness of breath or headache, sleep adequacy, sleep somnolence, 9-item sleep item index, sleep quantity, and optimal sleep (not reported since it is a yes/no response). Each scale was given a score ranging from 1 (all the time) to 5 (none of the time), except for the 9-item sleep item index. Individual item scores of the 9-item sleep index were averaged and the total score ranged from 1 to 5. For all items reported, higher scores indicate an improvement in sleep disturbance.

The Hospital Anxiety and Depression (HADS) scale consisted of 7 items to score depression (4-point scale: 0 to 3; where a score of 3 indicates highest depression levels [worse outcome]) and 7 items to score anxiety (4-point scale: 0 to 3; where score of 3 indicates highest anxiety levels [worse outcome]). The depression and anxiety subscales were calculated by summing the corresponding scores for 7 items. Negative scores indicate an improvement in depression and anxiety.

The Neuropathic Pain Symptom Inventory assessment was comprised of 4 distinct dimensions of neuropathic pain: spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dysesthesia. Each dimension was scored on an 11-point scale from 0 (no pain) to 10 (the most intense pain imaginable) for reporting the mean intensity of each item of the dimension during the last 24 hours. The total score is the sum of each of the 4 dimensions of neuropathic pain and total score ranged from 0 to 40. Higher scores indicated worse outcome; negative values indicate an improvement.

The EuroQoL 5 Dimensions 5 Levels (EuroQoL-5D-5L) questionnaire yielded a 5-scale profile of the participant's self-assessed quality of life in each of the following dimensions: mobility (5-point scale), self-care (5-point scale), usual activities (5-point scale), pain/discomfort (5-point scale), and anxiety/depression (5-point scale). These profiles were combined into an overall health utilities index, and a visual analog scale (VAS) that measured the participants' perceptions of overall health. EQ-5D-5L index scores range from -0.59 (worst health state) to 1 (best possible health state). EQ VAS scores range from 0 (worse imaginable health or worst outcome) to 100 (best imaginable health or best outcome). Higher scores for index value and VAS indicate better outcome.

The Spinal Cord Independence Measure (SCIM) score assessed the participants' activities of daily living (ADL). The SCIM instrument yielded a profile of the participant's ADL in the following categories: total SCIM score (0 to 100), self-care (scored 0 to 20; with higher scores indicating better self care), respiration and sphincter management (0 to 40; with higher scores indicating better management), and mobility (0 to 40; with higher scores indicating better mobility). Overall higher scores indicated better outcomes.

Study investigators performed the test for allodynia (at level, below level) using a scale assessing the presence (at level) or absence (below level) of allodynia. Testing usually requires an external stimulation of non-painful quality.

Participants rated their present pain intensity on a visual analog scale of 0 (no pain) to 5 (most intense pain). Higher scores indicate worse outcome; negative changes in present pain intensity indicated an improvement in pain intensity.