Study of Mirogabalin for Central Neuropathic Pain

An Asian, Multicenter, Randomized, Double-blind, Placebo-controlled, 14-week Study of Mirogabalin in Participants With Central Neuropathic Pain Followed by a 52-week, Open-label Extension

Investigate the efficacy and safety of mirogabalin in participants with central neuropathic pain in comparison to placebo

Study Overview

• Status: Completed
• Conditions: Central Neuropathic Pain
• Intervention / Treatment: Drug: Placebo; Drug: Mirogabalin

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).

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Aichi, Japan, 455-8530
    • Chubu-Rosai Hospital
  • Aichi, Japan, 457-8511
    • Social Medical Corporation Daido Clinic
  • Aichi, Japan, 460-0008
    • Honmachi Clinic
  • Aichi, Japan, 462-8508
    • Nagoya City West Medical Center
  • Aichi, Japan, 470-0396
    • Toyota Kosei Hospital
  • Aichi, Japan, 487-0016
    • Nagoya Tokushukai General Hospital
  • Aichi, Japan, 498-8502
    • Kainan Hospital
  • Aomori, Japan, 031-8555
    • Hachinohe City Hospital
  • Aomori, Japan, 036-8563
    • Hirosaki University Hospital
  • Chiba, Japan, 260-8677
    • Chiba University Hospital
  • Chiba, Japan, 266-0005
    • Chiba Rehabilitation Center
  • Chiba, Japan, 273-8588
    • Funabashi Municipal Medical Center
  • Chiba, Japan, 292-8535
    • Kimitsu Chuo Hospital
  • Ehime, Japan, 790-0024
    • Ehime Prefectural Central Hospital
  • Fukui, Japan, 918-8503
    • Fukui-ken Saiseikai Hospital
  • Fukui, Japan, 910-1193
    • University of Fukui Hospital
  • Fukuoka, Japan, 800-0057
    • Shin Komonji Hospital
  • Fukuoka, Japan, 800-0296
    • Kyushu Rosai Hospital
  • Fukuoka, Japan, 805-8508
    • Steel Memorial Yawata Hospital
  • Fukuoka, Japan, 811-1244
    • Go Neurosurgical Clinic
  • Fukuoka, Japan, 820-8508
    • Japan Organization of Occupational Health and Safety SPINAL INJURIES CENTER
  • Fukuoka, Japan, 824-0026
    • Shin Yukuhashi Hospital
  • Fukushima, Japan, 960-1295
    • Fukushima Medical University Hospital
  • Fukushima, Japan, 963-8052
    • Southern TOHOKU Medical Clinic
  • Gunma, Japan, 371-0811
    • Japanese Red Cross Maebashi Hospital
  • Hiroshima, Japan, 720-0052
    • Goodlife Hospital
  • Hiroshima, Japan, 730-0053
    • Medical Corporation Suiseikai Suiseikai Kajikawa Hospital
  • Hiroshima, Japan, 731-0293
    • Hiroshima City Asa Citizens Hospital
  • Hiroshima, Japan, 734-8530
    • Hiroshima Prefectural Hospital
  • Hokkaido, Japan, 006-8555
    • Teine Keijinkai Hospital
  • Hokkaido, Japan, 041-8680
    • Hakodate Municipal Hospital
  • Hokkaido, Japan, 060-8543
    • Sapporo Medical University Hospital
  • Hokkaido, Japan, 060-8570
    • Nakamura Memorial Hospital
  • Hokkaido, Japan, 060-8604
    • Sapporo City General Hospital
  • Hokkaido, Japan, 070-8530
    • Japanese Red Cross Asahikawa Hospital
  • Hokkaido, Japan, 072-0015
    • Hokkaido Spinal Cord Injury Center
  • Hyōgo, Japan, 650-0047
    • Kobe City Medical Center General Hospital
  • Hyōgo, Japan, 651-0073
    • Japanese Red Cross Kobe Hospital
  • Hyōgo, Japan, 651-2181
    • Hyogo Social Welfare Corporation Hyogo Rehabilitation Center Central Hospital
  • Hyōgo, Japan, 670-8540
    • Japanese Red Cross Society Himeji Hospital
  • Ibaraki, Japan, 305-8576
    • University of Tsukuba Hospital
  • Ibaraki, Japan, 306-0433
    • Ibaraki Seinan Medical Center Hospital
  • Ishikawa, Japan, 920-8530
    • Ishikawa Prefectural Central Hospital
  • Iwate, Japan, 020-0503
    • Iwate Rehabilitation Center
  • Kagawa, Japan, 760-8557
    • Kagawa Prefectural Central Hospital
  • Kagawa, Japan, 765-8597
    • Shikoku Medical Center for Children and Adults
  • Kanagawa, Japan, 222-0036
    • Japan Organization of Occupational Health and Safety(JOHAS), Yokohama Rosai Hospital
  • Kanagawa, Japan, 231-8682
    • Yokohama City Minato Red Cross Hospital
  • Kanagawa, Japan, 236-0004
    • Yokohama City University Hospital
  • Kanagawa, Japan, 243-0121
    • Kanagawa Rehabilitation Hospital
  • Kanagawa, Japan, 252-5188
    • Sagamihara Kyodo Hospital
  • Kumamoto, Japan, 860-8518
    • Kumamoto Kinoh Hospital
  • Kumamoto, Japan, 860-0008
    • National Hospital Organaization Kumamoto Medical Center
  • Kumamoto, Japan, 862-0924
    • Kumamoto Takumadai Rehabilitation Hospital
  • Kumamoto, Japan, 869-1106
    • Kumamoto Rehabilitation Hospital
  • Kyoto, Japan, 611-0041
    • Uji-Tokushukai Medical Center
  • Mie, Japan, 514-8507
    • Mie University Hospital
  • Miyagi, Japan, 981-8563
    • Tohoku Rosai Hospital
  • Miyagi, Japan, 983-8520
    • National Hospital Organization Sendai Medical Center
  • Miyagi, Japan, 989-0231
    • Katta General Hospital
  • Miyazaki, Japan, 880-2112
    • Junwakai Memorial Hospital
  • Miyazaki, Japan, 889-1692
    • University of Miyazaki Hospital
  • Nagano, Japan, 399-8292
    • Japan Red Cross Society Azumino Hospital
  • Nagasaki, Japan, 852-8501
    • Nagasaki University Hospital
  • Nagasaki, Japan, 857-0134
    • Nagasaki Rosai Hospital
  • Nara, Japan, 636-0345
    • Nara Prefecture General Rehabilitation Center
  • Niigata, Japan, 951-8520
    • Niigata University Medical & Dental Hospital
  • Niigata, Japan, 940-2485
    • Japanese Red Cross Society Nagaoka Red Cross Hospital
  • Niigata, Japan, 940-8653
    • Nagaoka Chuo General Hospital
  • Niigata, Japan, 950-1197
    • Niigata City General Hospital
  • Okayama, Japan, 700-8557
    • Okayama City General Medical Center Okayama City Hospital
  • Okayama, Japan, 716-1241
    • Kibikogen Rehabilitation Center For Employment Injuries
  • Okinawa, Japan, 904-2173
    • Medical Corporation Tapic Okinawa Rehabilitation Center Hospital
  • Osaka, Japan, 565-0871
    • Osaka University Hospital
  • Osaka, Japan, 558-8558
    • Osaka General Medical Center
  • Osaka, Japan, 569-1116
    • Aijinkai Rehabilitation Hospital
  • Osaka, Japan, 591-8025
    • Osaka Rosai Hospital
  • Saga, Japan, 840-8571
    • Saga-Ken Medical Centre Koseikan
  • Saitama, Japan, 348-8505
    • Hanyu General Hospital
  • Shiga, Japan, 520-0804
    • Otsu City Hospital
  • Shiga, Japan, 520-3046
    • Saiseikai Shiga Hospital
  • Shimane, Japan, 693-8501
    • Shimane University Hospital
  • Shizuoka, Japan, 424-8636
    • Shizuoka City Shimizu Hospital
  • Shizuoka, Japan, 426-8677
    • Fujieda Municipal General Hospital
  • Shizuoka, Japan, 431-3192
    • Hamamatsu University Hospital
  • Shizuoka, Japan, 434-8533
    • Japanese Red Cross Hamamatsu Hospital
  • Shizuoka, Japan, 439-0022
    • Kikugawa General Hospital
  • Tochigi, Japan, 329-0498
    • Jichi Medical University Hospital
  • Tochigi, Japan, 321-0293
    • Dokkyo Medical University Hospital
  • Tokushima, Japan, 770-8503
    • Tokushima University Hospital
  • Tokyo, Japan, 143-8505
    • Makita General Hospital
  • Tokyo, Japan, 173-8610
    • Nihon University Itabashi Hospital
  • Tokyo, Japan, 208-0011
    • National Hospital Organaization Murayama Medical Center
  • Tottori, Japan, 683-8504
    • Tottori University Hospital
  • Toyama, Japan, 930-0194
    • Toyama University Hospital Hospital
  • Wakayama, Japan, 641-8510
    • Wakayama Medical University Hospital
  • Yamagata, Japan, 992-0057
    • Sanyudo Rehabilitation Center
  • Yamaguchi, Japan, 755-8505
    • Yamaguchi University Hospital
  • Yamaguchi, Japan, 756-0095
    • Yamaguchi Rosai Hospital
  • Yamanashi, Japan, 400-8506
    • Yamanashi Prefectural Central Hospital
  • Ōita, Japan, 874-0937
    • Medical Corporation Keiaikai Nakamura Hospital
• Korea, Republic of
  • Daegu, Korea, Republic of, 41199
    • Daegu Fatima Hospital
  • Daejeon, Korea, Republic of, 35015
    • Chungnam National University Hospital
  • Gyeonggi-do, Korea, Republic of, 13620
    • Seoul National University Bundang Hospital
  • Gyeonggi-do, Korea, Republic of, 13496
    • Cha Bundang Medical Center
  • Gyeonggi-do, Korea, Republic of, 16247
    • The Catholic University of Korea St. Vincent's Hospital
  • Gyeonggi-do, Korea, Republic of, 16499
    • Ajou University Hospital
  • Gyeonggi-do, Korea, Republic of, 21431
    • The Catholic University of Korea Incheon St. Mary's Hospital
  • Jeollabuk-do, Korea, Republic of, 54907
    • Chonbuk National University Hospital
  • Pusan, Korea, Republic of, 49241
    • Pusan National University Hospital
  • Pusan, Korea, Republic of, 50612
    • Pusan National University Yangsan Hospital
  • Seoul, Korea, Republic of, 6351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 06591
    • The Catholic University of Korea Seoul St. Mary'S Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul Universtiy Hospital
• Taiwan
  • Hualien, Taiwan, 97002
    • Hualien Tzu Chi Hospital
  • Taipei city, Taiwan, 11217
    • Taipei Veterans General Hospital
  • Taipei city, Taiwan, 10002
    • National Taiwan University Hospital
  • Taoyuan, Taiwan, 33305
    • Chang Gung Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mirogabalin; The patients with creatinine clearance (CLcr) ≥ 60 mL/min: Mirogabalin 20 mg or 30 mg, oral administration, Treatment period; 2-weeks titration and 12-weeks maintenance dose. The patients with creatinine clearance (CLcr) 30 to < 60 mL/min: Mirogabalin 10 mg or 15 mg, oral administration, Treatment period; 2-weeks titration and 12-weeks maintenance dose	Drug: Mirogabalin; Mirogabalin tablets for oral administration; Other Names: DS-5565
Placebo Comparator: Placebo; Placebo (14-weeks)	Drug: Placebo; Matching placebo tablets for oral administration; Other Names: Matching Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline to Week 14 postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Baseline to Week 14 postdose
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.	Baseline to Week 14 postdose
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.	at Week 14 postdose
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.	Baseline to Week 14 postdose
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.	Baseline to Week 14 postdose
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.	Baseline to Week 14 postdose
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.	Baseline to Week 14 postdose
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.	Baseline to Week 14 postdose
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.	Baseline to Week 14 postdose
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.	Baseline to Week 14 postdose
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.	Baseline to Week 52 postdose

Collaborators and Investigators

• Sponsor: Daiichi Sankyo Co., Ltd.
• Investigators: Study Director: Clinical Study Leader, Daiichi Sankyo

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2019
• Primary Completion (Actual): December 28, 2020
• Study Completion (Actual): December 28, 2020

Study Registration Dates

• First Submitted: April 1, 2019
• First Submitted That Met QC Criteria: April 1, 2019
• First Posted (Actual): April 3, 2019

Study Record Updates

• Last Update Posted (Actual): October 21, 2024
• Last Update Submitted That Met QC Criteria: October 8, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Central neuropathic pain; Developmental phase III
• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Neuromuscular Diseases; Peripheral Nervous System Diseases; Neuralgia
• Other Study ID Numbers: DS5565-A-J314; 194653 (Registry Identifier: JAPIC CTI)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No