Trial Outcomes & Findings for Study of Mirogabalin for Central Neuropathic Pain (NCT NCT03901352)

Last Updated: 2024-10-21

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

300 participants

Primary outcome timeframe

Baseline to Week 14 postdose

Results posted on

2024-10-21

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	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.	Placebo Patients who received placebo for 14 weeks by oral administration.
Double-blind Phase STARTED	150	150
Double-blind Phase COMPLETED	133	136
Double-blind Phase NOT COMPLETED	17	14
Open-label Extension Phase STARTED	210	0
Open-label Extension Phase COMPLETED	170	0
Open-label Extension Phase NOT COMPLETED	40	0

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	Placebo Patients who received placebo for 14 weeks by oral administration.
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 Withdrawal by Subject	14	0
Open-label Extension Phase Other	1	0

Baseline Characteristics

Study of Mirogabalin for Central Neuropathic Pain

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Mirogabalin n=150 Participants 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.	Placebo n=149 Participants Patients who received placebo for 14 weeks by oral administration.	Total n=299 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	93 Participants n=5 Participants	89 Participants n=7 Participants	182 Participants n=5 Participants
Age, Categorical >=65 years	57 Participants n=5 Participants	60 Participants n=7 Participants	117 Participants n=5 Participants
Age, Continuous	57.3 years STANDARD_DEVIATION 14.3 • n=5 Participants	59.6 years STANDARD_DEVIATION 14.0 • n=7 Participants	58.5 years STANDARD_DEVIATION 14.2 • n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	24 Participants n=7 Participants	43 Participants n=5 Participants
Sex: Female, Male Male	131 Participants n=5 Participants	125 Participants n=7 Participants	256 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	150 Participants n=5 Participants	149 Participants n=7 Participants	299 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment South Korea	19 participants n=5 Participants	16 participants n=7 Participants	35 participants n=5 Participants
Region of Enrollment Japan	121 participants n=5 Participants	121 participants n=7 Participants	242 participants n=5 Participants
Region of Enrollment Taiwan	10 participants n=5 Participants	12 participants n=7 Participants	22 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Mirogabalin n=150 Participants 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.	Placebo n=149 Participants Patients who received placebo for 14 weeks by oral administration.
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	-0.52 units on a scale Standard Error 0.132

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Mirogabalin n=150 Participants 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.	Placebo n=149 Participants Patients who received placebo for 14 weeks by oral administration.
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	28 Participants
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	9 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Mirogabalin n=150 Participants 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.	Placebo n=149 Participants Patients who received placebo for 14 weeks by oral administration.
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	-0.3 units on a scale Standard Deviation 0.95

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Mirogabalin n=150 Participants 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.	Placebo n=149 Participants Patients who received placebo for 14 weeks by oral administration.
Patient Global Impression of Change at Week 14 Following Administration With Mirogabalin or Placebo Much improved or better (≤2)	26 Participants	11 Participants
Patient Global Impression of Change at Week 14 Following Administration With Mirogabalin or Placebo Minimally improved or better (≤3)	80 Participants	53 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Mirogabalin n=150 Participants 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.	Placebo n=149 Participants Patients who received placebo for 14 weeks by oral administration.
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	-0.35 units on a scale Standard Deviation 1.306

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Mirogabalin n=150 Participants 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.	Placebo n=149 Participants Patients who received placebo for 14 weeks by oral administration.
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	0.61 score on a scale Standard Deviation 7.73
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	1.27 score on a scale Standard Deviation 7.15
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	0.71 score on a scale Standard Deviation 9.90
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	0.81 score on a scale Standard Deviation 8.44
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	-0.05 score on a scale Standard Deviation 7.85
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	1.29 score on a scale Standard Deviation 6.15
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	0.1 score on a scale Standard Deviation 0.93

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Mirogabalin n=150 Participants 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.	Placebo n=149 Participants Patients who received placebo for 14 weeks by oral administration.
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	-0.7 score on a scale Standard Deviation 2.85
Change From Baseline in the Hospital Anxiety & Depression Scale Following Administration With Mirogabalin or Placebo Anxiety	-1.0 score on a scale Standard Deviation 3.20	-0.8 score on a scale Standard Deviation 2.85

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Mirogabalin n=150 Participants 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.	Placebo n=149 Participants Patients who received placebo for 14 weeks by oral administration.
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	-1.5 score on a scale Standard Deviation 6.17
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 4.40	-0.9 score on a scale Standard Deviation 4.78
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 5.80	-1.0 score on a scale Standard Deviation 6.52
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	-1.2 score on a scale Standard Deviation 3.67
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	-4.5 score on a scale Standard Deviation 15.90

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Mirogabalin n=150 Participants 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.	Placebo n=149 Participants Patients who received placebo for 14 weeks by oral administration.
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	0.0153 score on a scale Standard Deviation 0.134
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	-1.8 score on a scale Standard Deviation 21.28

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Mirogabalin n=149 Participants 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.	Placebo n=149 Participants Patients who received placebo for 14 weeks by oral administration.
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	0 score on a scale Standard Deviation 1.59
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 2.90	0 score on a scale Standard Deviation 3.21
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	0 score on a scale Standard Deviation 1.68
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	0 score on a scale Standard Deviation 4.70

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Mirogabalin n=49 Participants 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.	Placebo n=50 Participants Patients who received placebo for 14 weeks by oral administration.
Number of Participants Who Performed At Level or Below Level for Allodynia Following Administration With Mirogabalin or Placebo Below Level	10 Participants	13 Participants
Number of Participants Who Performed At Level or Below Level for Allodynia Following Administration With Mirogabalin or Placebo At Level	5 Participants	6 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Mirogabalin n=210 Participants 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.	Placebo Patients who received placebo for 14 weeks by oral administration.
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 24.70	—

Adverse Events

Mirogabalin

Serious events: 9 serious events

Other events: 112 other events

Deaths: 1 deaths

Placebo

Serious events: 7 serious events

Other events: 34 other events

Deaths: 0 deaths

Mirogabalin Open-Label Extension

Serious events: 28 serious events

Other events: 178 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Mirogabalin n=151 participants at risk 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.	Placebo n=148 participants at risk Patients who received placebo for 14 weeks by oral administration.	Mirogabalin Open-Label Extension n=210 participants at risk Participants with creatinine clearance (CLcr) ≥60 mL/min who received 5 mg twice daily (BID) of mirogabalin in the first 2 weeks, followed by 10 mg BID in the second 2 weeks. From the fifth week on, if no safety concerns were raised, the dosage was increased to 15 mg BID. For the following weeks, the dosage could be either 10 mg BID or 15 mg BID, depending on the safety findings at each visit. During the last week of the treatment period, participants underwent tapering, receiving half of the daily dose received just before tapering. Participants with CLcr 30 to \<60 mL/min received half of the dose of mirogabalin as participants with CLcr ≥60 mL/min during the treatment period.
Infections and infestations Nasopharyngitis	7.9% 12/151 • Adverse events were collected from baseline up to 52 weeks postdose. 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.	5.4% 8/148 • Adverse events were collected from baseline up to 52 weeks postdose. 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.	11.0% 23/210 • Adverse events were collected from baseline up to 52 weeks postdose. 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.
Nervous system disorders Somnolence	29.8% 45/151 • Adverse events were collected from baseline up to 52 weeks postdose. 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.	5.4% 8/148 • Adverse events were collected from baseline up to 52 weeks postdose. 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.	16.7% 35/210 • Adverse events were collected from baseline up to 52 weeks postdose. 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.
Nervous system disorders Dizziness	8.6% 13/151 • Adverse events were collected from baseline up to 52 weeks postdose. 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.	3.4% 5/148 • Adverse events were collected from baseline up to 52 weeks postdose. 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.	7.6% 16/210 • Adverse events were collected from baseline up to 52 weeks postdose. 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.
Gastrointestinal disorders Constipation	6.0% 9/151 • Adverse events were collected from baseline up to 52 weeks postdose. 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.	1.4% 2/148 • Adverse events were collected from baseline up to 52 weeks postdose. 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.	6.2% 13/210 • Adverse events were collected from baseline up to 52 weeks postdose. 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.
General disorders Oedema peripheral	6.0% 9/151 • Adverse events were collected from baseline up to 52 weeks postdose. 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.	1.4% 2/148 • Adverse events were collected from baseline up to 52 weeks postdose. 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.	12.4% 26/210 • Adverse events were collected from baseline up to 52 weeks postdose. 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.
Investigations Weight increased	7.3% 11/151 • Adverse events were collected from baseline up to 52 weeks postdose. 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.	0.68% 1/148 • Adverse events were collected from baseline up to 52 weeks postdose. 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.	7.1% 15/210 • Adverse events were collected from baseline up to 52 weeks postdose. 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.
Infections and infestations Urinary tract infection	3.3% 5/151 • Adverse events were collected from baseline up to 52 weeks postdose. 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.	3.4% 5/148 • Adverse events were collected from baseline up to 52 weeks postdose. 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.	5.7% 12/210 • Adverse events were collected from baseline up to 52 weeks postdose. 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.
Musculoskeletal and connective tissue disorders Back pain	2.0% 3/151 • Adverse events were collected from baseline up to 52 weeks postdose. 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.	2.0% 3/148 • Adverse events were collected from baseline up to 52 weeks postdose. 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.	5.2% 11/210 • Adverse events were collected from baseline up to 52 weeks postdose. 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.
General disorders Oedema	3.3% 5/151 • Adverse events were collected from baseline up to 52 weeks postdose. 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.	0.00% 0/148 • Adverse events were collected from baseline up to 52 weeks postdose. 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.	11.4% 24/210 • Adverse events were collected from baseline up to 52 weeks postdose. 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.
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/151 • Adverse events were collected from baseline up to 52 weeks postdose. 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.	0.00% 0/148 • Adverse events were collected from baseline up to 52 weeks postdose. 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.	5.2% 11/210 • Adverse events were collected from baseline up to 52 weeks postdose. 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.

Additional Information

Contact of Clinical Trial Information

Daiichi Sankyo

Phone: 908-992-6400

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place