Central Neuropathic Pain
Conditions
Keywords
Central neuropathic pain, Developmental phase III
Brief summary
Investigate the efficacy and safety of mirogabalin in participants with central neuropathic pain in comparison to placebo
Detailed description
\[Double Blind Phase\] The primary objective is to compare change in the Average Daily Pain Score (ADPS) from baseline to Week 14 in Asian participants with central neuropathic pain (central neuropathic pain after spinal cord injury) receiving mirogabalin versus placebo. \[Open Extension Phase\] The objective is to assess the long-term safety and efficacy of mirogabalin in participants with central neuropathic pain (central neuropathic pain after spinal cord injury, central post stroke pain, and central neuropathic pain in Parkinson's disease).
Interventions
DRUGPlacebo
Matching placebo tablets for oral administration
DRUGMirogabalin
Mirogabalin tablets for oral administration
Sponsors
Daiichi Sankyo Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
During the Double-blind Phase, masking will be triple (as shown above). During the Open Extension Phase, there will be no masking - the allocation is not applicable.
Intervention model description
During the Double-blind Phase, participants will be randomized into parallel treatment arms. During the Open Extension Phase, all participants will be assigned to a single group.
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Spinal cord injury (SCI) due to trauma * American Spinal Injury Association impairment scale A, B, C, or D
Exclusion criteria
* Other severe pain at screening or randomization, unrelated to central neuropathic pain after SCI, that may confound the assessment of central neuropathic pain after SCI * Neurologic disorders at screening or randomization, unrelated to central neuropathic pain after SCI, that may confound the assessment of central neuropathic pain after SCI * Major psychiatric disorders within 1 year prior to screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Weekly Average Daily Pain Score (ADPS) at Week 14 Following Administration With Mirogabalin or Placebo | Baseline to Week 14 postdose | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Present Pain Intensity on the Short Form-McGill Pain Questionnaire at Week 14 Following Administration With Mirogabalin or Placebo | Baseline to Week 14 postdose | 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. |
| Patient Global Impression of Change at Week 14 Following Administration With Mirogabalin or Placebo | at Week 14 postdose | 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. |
| Change From Baseline in the Weekly Average Daily Sleep Interference Score (ADSIS) Following Administration With Mirogabalin or Placebo | Baseline to Week 14 postdose | 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. |
| Change From Baseline in the Medical Outcomes Study Sleep Scale Scores Following Administration With Mirogabalin or Placebo | Baseline to Week 14 postdose | 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. |
| Change From Baseline in the Hospital Anxiety & Depression Scale Following Administration With Mirogabalin or Placebo | Baseline to Week 14 postdose | 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. |
| Number of Participants With ≥30% Reduction and ≥50% Reductions From Baseline in Average Daily Pain Score (ADPS) | Baseline to Week 14 postdose | 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). |
| Change From Baseline in the EuroQoL 5 Dimensions 5 Levels Following Administration With Mirogabalin or Placebo | Baseline to Week 14 postdose | 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. |
| Change From Baseline in the Spinal Cord Independence Measure Scores Following Administration With Mirogabalin or Placebo | Baseline to Week 14 postdose | 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. |
| Number of Participants Who Performed At Level or Below Level for Allodynia Following Administration With Mirogabalin or Placebo | Baseline to Week 14 postdose | 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. |
| Change From Baseline in Present Pain Intensity on the Short Form-McGill Pain Questionnaire at Week 52 Following Administration With Mirogabalin During the Long-term Extension (LTE) | Baseline to Week 52 postdose | 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. |
| Change From Baseline in the Neuropathic Pain Symptom Inventory Score Following Administration With Mirogabalin or Placebo | Baseline to Week 14 postdose | 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. |
Countries
Japan, South Korea, Taiwan
Participant flow
Recruitment details
A total of 300 participants who met all inclusion and no exclusion criteria were randomized to treatment at 118 study sites in Japan, South Korea, and Taiwan.
Pre-assignment details
Participants being treated underwent a washout period ≥28 days. Mirogabalin starting dose and titration schedule were based on creatinine clearance per the Japanese drug insert. All mirogabalin patients who received any dose were assessed as 1 group for efficacy/safety as prespecified in the protocol.
Participants by arm
| Arm | Count |
|---|---|
| Mirogabalin Patients with creatinine clearance (CLcr) ≥ 60 mL/min were randomized to receive mirogabalin 20 mg or 30 mg by oral administration with a 2-weeks titration period and 12-weeks maintenance period.
Patients with creatinine clearance (CLcr) 30 to \< 60 mL/min were randomized to receive mirogabalin 10 mg or 15 mg by oral administration with a 2-weeks titration period and 12-weeks maintenance period. | 150 |
| Placebo Patients who received placebo for 14 weeks by oral administration. | 149 |
| Total | 299 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-blind Phase | Adverse Event | 6 | 4 |
| Double-blind Phase | Death | 1 | 0 |
| Double-blind Phase | Lack of Efficacy | 0 | 1 |
| Double-blind Phase | Protocol Violation | 0 | 1 |
| Double-blind Phase | Withdrawal by Subject | 10 | 8 |
| Open-label Extension Phase | Adverse Event | 24 | 0 |
| Open-label Extension Phase | Lack of Efficacy | 1 | 0 |
| Open-label Extension Phase | Other | 1 | 0 |
| Open-label Extension Phase | Withdrawal by Subject | 14 | 0 |
Baseline characteristics
| Characteristic | Mirogabalin | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 57 Participants | 60 Participants | 117 Participants |
| Age, Categorical Between 18 and 65 years | 93 Participants | 89 Participants | 182 Participants |
| Age, Continuous | 57.3 years STANDARD_DEVIATION 14.3 | 59.6 years STANDARD_DEVIATION 14 | 58.5 years STANDARD_DEVIATION 14.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 150 Participants | 149 Participants | 299 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Japan | 121 participants | 121 participants | 242 participants |
| Region of Enrollment South Korea | 19 participants | 16 participants | 35 participants |
| Region of Enrollment Taiwan | 10 participants | 12 participants | 22 participants |
| Sex: Female, Male Female | 19 Participants | 24 Participants | 43 Participants |
| Sex: Female, Male Male | 131 Participants | 125 Participants | 256 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 151 | 0 / 148 | 0 / 210 |
| other Total, other adverse events | 112 / 151 | 34 / 148 | 178 / 210 |
| serious Total, serious adverse events | 9 / 151 | 7 / 148 | 28 / 210 |
Outcome results
Primary
Change From Baseline in the Weekly Average Daily Pain Score (ADPS) at Week 14 Following Administration With Mirogabalin or Placebo
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.
Time frame: Baseline to Week 14 postdose
Population: Data were assessed in the mITT population. Mirogabalin starting dose and titration schedule were based on creatinine clearance per the Japanese drug insert. All mirogabalin patients who received any dose were assessed as 1 group for efficacy/safety as prespecified in the protocol.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Mirogabalin | Change From Baseline in the Weekly Average Daily Pain Score (ADPS) at Week 14 Following Administration With Mirogabalin or Placebo | -1.23 units on a scale | Standard Error 0.132 |
| Placebo | Change From Baseline in the Weekly Average Daily Pain Score (ADPS) at Week 14 Following Administration With Mirogabalin or Placebo | -0.52 units on a scale | Standard Error 0.132 |
p-value: 0.000195% CI: [-1.08, -0.34]ANCOVA
Secondary
Change From Baseline in Present Pain Intensity on the Short Form-McGill Pain Questionnaire at Week 14 Following Administration With Mirogabalin or Placebo
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.
Time frame: Baseline to Week 14 postdose
Population: Data were assessed in the mITT population. Mirogabalin starting dose and titration schedule were based on creatinine clearance per the Japanese drug insert. All mirogabalin patients who received any dose were assessed as 1 group for efficacy/safety as prespecified in the protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mirogabalin | Change From Baseline in Present Pain Intensity on the Short Form-McGill Pain Questionnaire at Week 14 Following Administration With Mirogabalin or Placebo | -0.6 units on a scale | Standard Deviation 0.92 |
| Placebo | Change From Baseline in Present Pain Intensity on the Short Form-McGill Pain Questionnaire at Week 14 Following Administration With Mirogabalin or Placebo | -0.3 units on a scale | Standard Deviation 0.95 |
Secondary
Change From Baseline in Present Pain Intensity on the Short Form-McGill Pain Questionnaire at Week 52 Following Administration With Mirogabalin During the Long-term Extension (LTE)
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.
Time frame: Baseline to Week 52 postdose
Population: Data were assessed in the mITT population in the LTE phase. Mirogabalin starting dose and titration schedule were based on creatinine clearance per the Japanese drug insert. All mirogabalin patients who received any dose were assessed as 1 group for efficacy/safety as prespecified in the protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mirogabalin | Change From Baseline in Present Pain Intensity on the Short Form-McGill Pain Questionnaire at Week 52 Following Administration With Mirogabalin During the Long-term Extension (LTE) | -9.6 units on a scale | Standard Deviation 24.7 |
Secondary
Change From Baseline in the EuroQoL 5 Dimensions 5 Levels Following Administration With Mirogabalin or Placebo
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.
Time frame: Baseline to Week 14 postdose
Population: Data were assessed in the mITT population. Mirogabalin starting dose and titration schedule were based on creatinine clearance per the Japanese drug insert. All mirogabalin patients who received any dose were assessed as 1 group for efficacy/safety as prespecified in the protocol.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mirogabalin | Change From Baseline in the EuroQoL 5 Dimensions 5 Levels Following Administration With Mirogabalin or Placebo | Visual analog scale | 4.9 score on a scale | Standard Deviation 21.76 |
| Mirogabalin | Change From Baseline in the EuroQoL 5 Dimensions 5 Levels Following Administration With Mirogabalin or Placebo | Index value | 0.0395 score on a scale | Standard Deviation 0.136 |
| Placebo | Change From Baseline in the EuroQoL 5 Dimensions 5 Levels Following Administration With Mirogabalin or Placebo | Index value | 0.0153 score on a scale | Standard Deviation 0.134 |
| Placebo | Change From Baseline in the EuroQoL 5 Dimensions 5 Levels Following Administration With Mirogabalin or Placebo | Visual analog scale | -1.8 score on a scale | Standard Deviation 21.28 |
Secondary
Change From Baseline in the Hospital Anxiety & Depression Scale Following Administration With Mirogabalin or Placebo
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.
Time frame: Baseline to Week 14 postdose
Population: Data were assessed in the mITT population. Mirogabalin starting dose and titration schedule were based on creatinine clearance per the Japanese drug insert. All mirogabalin patients who received any dose were assessed as 1 group for efficacy/safety as prespecified in the protocol.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mirogabalin | Change From Baseline in the Hospital Anxiety & Depression Scale Following Administration With Mirogabalin or Placebo | Depression | -0.8 score on a scale | Standard Deviation 3.18 |
| Mirogabalin | Change From Baseline in the Hospital Anxiety & Depression Scale Following Administration With Mirogabalin or Placebo | Anxiety | -1.0 score on a scale | Standard Deviation 3.2 |
| Placebo | Change From Baseline in the Hospital Anxiety & Depression Scale Following Administration With Mirogabalin or Placebo | Anxiety | -0.8 score on a scale | Standard Deviation 2.85 |
| Placebo | Change From Baseline in the Hospital Anxiety & Depression Scale Following Administration With Mirogabalin or Placebo | Depression | -0.7 score on a scale | Standard Deviation 2.85 |
Secondary
Change From Baseline in the Medical Outcomes Study Sleep Scale Scores Following Administration With Mirogabalin or Placebo
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.
Time frame: Baseline to Week 14 postdose
Population: Data were assessed in the mITT population. Mirogabalin starting dose and titration schedule were based on creatinine clearance per the Japanese drug insert. All mirogabalin patients who received any dose were assessed as 1 group for efficacy/safety as prespecified in the protocol.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mirogabalin | Change From Baseline in the Medical Outcomes Study Sleep Scale Scores Following Administration With Mirogabalin or Placebo | Sleep somnolence | -1.18 score on a scale | Standard Deviation 10.04 |
| Mirogabalin | Change From Baseline in the Medical Outcomes Study Sleep Scale Scores Following Administration With Mirogabalin or Placebo | Sleep quantity | 0.3 score on a scale | Standard Deviation 1.46 |
| Mirogabalin | Change From Baseline in the Medical Outcomes Study Sleep Scale Scores Following Administration With Mirogabalin or Placebo | Sleep disturbance | 4.23 score on a scale | Standard Deviation 8.39 |
| Mirogabalin | Change From Baseline in the Medical Outcomes Study Sleep Scale Scores Following Administration With Mirogabalin or Placebo | Sleep adequacy | 1.94 score on a scale | Standard Deviation 9.87 |
| Mirogabalin | Change From Baseline in the Medical Outcomes Study Sleep Scale Scores Following Administration With Mirogabalin or Placebo | Awakening due to shortness of breath or headache | 2.04 score on a scale | Standard Deviation 12.64 |
| Mirogabalin | Change From Baseline in the Medical Outcomes Study Sleep Scale Scores Following Administration With Mirogabalin or Placebo | 9-item sleep problems index | 2.70 score on a scale | Standard Deviation 7.74 |
| Mirogabalin | Change From Baseline in the Medical Outcomes Study Sleep Scale Scores Following Administration With Mirogabalin or Placebo | Snoring | -1.12 score on a scale | Standard Deviation 7.89 |
| Placebo | Change From Baseline in the Medical Outcomes Study Sleep Scale Scores Following Administration With Mirogabalin or Placebo | Sleep quantity | 0.1 score on a scale | Standard Deviation 0.93 |
| Placebo | Change From Baseline in the Medical Outcomes Study Sleep Scale Scores Following Administration With Mirogabalin or Placebo | Snoring | 0.61 score on a scale | Standard Deviation 7.73 |
| Placebo | Change From Baseline in the Medical Outcomes Study Sleep Scale Scores Following Administration With Mirogabalin or Placebo | Awakening due to shortness of breath or headache | 0.71 score on a scale | Standard Deviation 9.9 |
| Placebo | Change From Baseline in the Medical Outcomes Study Sleep Scale Scores Following Administration With Mirogabalin or Placebo | Sleep somnolence | -0.05 score on a scale | Standard Deviation 7.85 |
| Placebo | Change From Baseline in the Medical Outcomes Study Sleep Scale Scores Following Administration With Mirogabalin or Placebo | 9-item sleep problems index | 1.29 score on a scale | Standard Deviation 6.15 |
| Placebo | Change From Baseline in the Medical Outcomes Study Sleep Scale Scores Following Administration With Mirogabalin or Placebo | Sleep disturbance | 1.27 score on a scale | Standard Deviation 7.15 |
| Placebo | Change From Baseline in the Medical Outcomes Study Sleep Scale Scores Following Administration With Mirogabalin or Placebo | Sleep adequacy | 0.81 score on a scale | Standard Deviation 8.44 |
Secondary
Change From Baseline in the Neuropathic Pain Symptom Inventory Score Following Administration With Mirogabalin or Placebo
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.
Time frame: Baseline to Week 14 postdose
Population: Data were assessed in the mITT population. Mirogabalin starting dose and titration schedule were based on creatinine clearance per the Japanese drug insert. All mirogabalin patients who received any dose were assessed as 1 group for efficacy/safety as prespecified in the protocol.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mirogabalin | Change From Baseline in the Neuropathic Pain Symptom Inventory Score Following Administration With Mirogabalin or Placebo | Evoked pain | -2.6 score on a scale | Standard Deviation 5.8 |
| Mirogabalin | Change From Baseline in the Neuropathic Pain Symptom Inventory Score Following Administration With Mirogabalin or Placebo | Paroxysmal pain | -2.5 score on a scale | Standard Deviation 4.4 |
| Mirogabalin | Change From Baseline in the Neuropathic Pain Symptom Inventory Score Following Administration With Mirogabalin or Placebo | Total score | -12.0 score on a scale | Standard Deviation 15.47 |
| Mirogabalin | Change From Baseline in the Neuropathic Pain Symptom Inventory Score Following Administration With Mirogabalin or Placebo | Paresthesia/dysesthesia | -2.7 score on a scale | Standard Deviation 4.29 |
| Mirogabalin | Change From Baseline in the Neuropathic Pain Symptom Inventory Score Following Administration With Mirogabalin or Placebo | Spontaneous pain | -4.2 score on a scale | Standard Deviation 5.66 |
| Placebo | Change From Baseline in the Neuropathic Pain Symptom Inventory Score Following Administration With Mirogabalin or Placebo | Total score | -4.5 score on a scale | Standard Deviation 15.9 |
| Placebo | Change From Baseline in the Neuropathic Pain Symptom Inventory Score Following Administration With Mirogabalin or Placebo | Paroxysmal pain | -0.9 score on a scale | Standard Deviation 4.78 |
| Placebo | Change From Baseline in the Neuropathic Pain Symptom Inventory Score Following Administration With Mirogabalin or Placebo | Paresthesia/dysesthesia | -1.2 score on a scale | Standard Deviation 3.67 |
| Placebo | Change From Baseline in the Neuropathic Pain Symptom Inventory Score Following Administration With Mirogabalin or Placebo | Spontaneous pain | -1.5 score on a scale | Standard Deviation 6.17 |
| Placebo | Change From Baseline in the Neuropathic Pain Symptom Inventory Score Following Administration With Mirogabalin or Placebo | Evoked pain | -1.0 score on a scale | Standard Deviation 6.52 |
Secondary
Change From Baseline in the Spinal Cord Independence Measure Scores Following Administration With Mirogabalin or Placebo
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.
Time frame: Baseline to Week 14 postdose
Population: Participants with available data were assessed in mITT population. Mirogabalin starting dose and titration schedule were based on creatinine clearance per the Japanese drug insert. All mirogabalin patients who received any dose were assessed as 1 group for efficacy/safety as prespecified in the protocol.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mirogabalin | Change From Baseline in the Spinal Cord Independence Measure Scores Following Administration With Mirogabalin or Placebo | Total score | 1.0 score on a scale | Standard Deviation 4.71 |
| Mirogabalin | Change From Baseline in the Spinal Cord Independence Measure Scores Following Administration With Mirogabalin or Placebo | Mobility | 0 score on a scale | Standard Deviation 2.45 |
| Mirogabalin | Change From Baseline in the Spinal Cord Independence Measure Scores Following Administration With Mirogabalin or Placebo | Self care | 0.3 score on a scale | Standard Deviation 1.61 |
| Mirogabalin | Change From Baseline in the Spinal Cord Independence Measure Scores Following Administration With Mirogabalin or Placebo | Respiration and sphincter management | 0.7 score on a scale | Standard Deviation 2.9 |
| Placebo | Change From Baseline in the Spinal Cord Independence Measure Scores Following Administration With Mirogabalin or Placebo | Respiration and sphincter management | 0 score on a scale | Standard Deviation 3.21 |
| Placebo | Change From Baseline in the Spinal Cord Independence Measure Scores Following Administration With Mirogabalin or Placebo | Self care | 0 score on a scale | Standard Deviation 1.59 |
| Placebo | Change From Baseline in the Spinal Cord Independence Measure Scores Following Administration With Mirogabalin or Placebo | Mobility | 0 score on a scale | Standard Deviation 1.68 |
| Placebo | Change From Baseline in the Spinal Cord Independence Measure Scores Following Administration With Mirogabalin or Placebo | Total score | 0 score on a scale | Standard Deviation 4.7 |
Secondary
Change From Baseline in the Weekly Average Daily Sleep Interference Score (ADSIS) Following Administration With Mirogabalin or Placebo
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.
Time frame: Baseline to Week 14 postdose
Population: Data were assessed in the mITT population. Mirogabalin starting dose and titration schedule were based on creatinine clearance per the Japanese drug insert. All mirogabalin patients who received any dose were assessed as 1 group for efficacy/safety as prespecified in the protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mirogabalin | Change From Baseline in the Weekly Average Daily Sleep Interference Score (ADSIS) Following Administration With Mirogabalin or Placebo | -1.14 units on a scale | Standard Deviation 1.705 |
| Placebo | Change From Baseline in the Weekly Average Daily Sleep Interference Score (ADSIS) Following Administration With Mirogabalin or Placebo | -0.35 units on a scale | Standard Deviation 1.306 |
Secondary
Number of Participants Who Performed At Level or Below Level for Allodynia Following Administration With Mirogabalin or Placebo
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.
Time frame: Baseline to Week 14 postdose
Population: Participants with available data in mITT population were assessed. Mirogabalin starting dose and titration schedule were based on creatinine clearance per the Japanese drug insert. All mirogabalin patients who received any dose were assessed as 1 group for efficacy/safety as prespecified in the protocol.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mirogabalin | Number of Participants Who Performed At Level or Below Level for Allodynia Following Administration With Mirogabalin or Placebo | Below Level | 10 Participants |
| Mirogabalin | Number of Participants Who Performed At Level or Below Level for Allodynia Following Administration With Mirogabalin or Placebo | At Level | 5 Participants |
| Placebo | Number of Participants Who Performed At Level or Below Level for Allodynia Following Administration With Mirogabalin or Placebo | Below Level | 13 Participants |
| Placebo | Number of Participants Who Performed At Level or Below Level for Allodynia Following Administration With Mirogabalin or Placebo | At Level | 6 Participants |
Secondary
Number of Participants With ≥30% Reduction and ≥50% Reductions From Baseline in Average Daily Pain Score (ADPS)
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).
Time frame: Baseline to Week 14 postdose
Population: Data were assessed in the mITT population. Mirogabalin starting dose and titration schedule were based on creatinine clearance per the Japanese drug insert. All mirogabalin patients who received any dose were assessed as 1 group for efficacy/safety as prespecified in the protocol.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mirogabalin | Number of Participants With ≥30% Reduction and ≥50% Reductions From Baseline in Average Daily Pain Score (ADPS) | ≥30% reduction from baseline at Week 14 | 46 Participants |
| Mirogabalin | Number of Participants With ≥30% Reduction and ≥50% Reductions From Baseline in Average Daily Pain Score (ADPS) | ≥50% reduction from baseline at Week 14 | 21 Participants |
| Placebo | Number of Participants With ≥30% Reduction and ≥50% Reductions From Baseline in Average Daily Pain Score (ADPS) | ≥30% reduction from baseline at Week 14 | 28 Participants |
| Placebo | Number of Participants With ≥30% Reduction and ≥50% Reductions From Baseline in Average Daily Pain Score (ADPS) | ≥50% reduction from baseline at Week 14 | 9 Participants |
Secondary
Patient Global Impression of Change at Week 14 Following Administration With Mirogabalin or Placebo
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.
Time frame: at Week 14 postdose
Population: Data were assessed in the mITT population. Mirogabalin starting dose and titration schedule were based on creatinine clearance per the Japanese drug insert. All mirogabalin patients who received any dose were assessed as 1 group for efficacy/safety as prespecified in the protocol.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mirogabalin | Patient Global Impression of Change at Week 14 Following Administration With Mirogabalin or Placebo | Much improved or better (≤2) | 26 Participants |
| Mirogabalin | Patient Global Impression of Change at Week 14 Following Administration With Mirogabalin or Placebo | Minimally improved or better (≤3) | 80 Participants |
| Placebo | Patient Global Impression of Change at Week 14 Following Administration With Mirogabalin or Placebo | Much improved or better (≤2) | 11 Participants |
| Placebo | Patient Global Impression of Change at Week 14 Following Administration With Mirogabalin or Placebo | Minimally improved or better (≤3) | 53 Participants |