臨床研究等提出・公開システム

An Asian, multicenter, randomized, double-blind, placebo-controlled 14 week study of mirogabalin in patients with central neuropathic pain followed by a 52 week open-label extension

Mirogabalin phase 3 study for central neuropathic pain

300

In the mITT analysis set, no notable differences were found in demographic or other baseline characteristics between the treatment groups. The median age was 60.0 (range, 20 to 82) years, and the percentage of subjects >=65 years old was 39.1%. Overall, 85.6% of subjects were male. The mean body weight was 65.80 kg. The mean CLcr was 108.6 mL/min. The median duration of CNePSCI was 57.0 (range, 3 to 499) months. The mean baseline weekly ADPS was 6.06. The mean SF-MPQ VAS score at baseline (randomization visit) was 63.6 mm. Most subjects (80.9%) were enrolled in Japan.

300 were randomized to mirogabalin or placebo in a ratio of 1:1 (150 subjects each). The study was completed by overall 269 subjects (89.7%): 133 (88.7%) in the mirogabalin group and 136 (90.7%) in the placebo group. The mITT analysis set included 299 randomized subjects: 150 in the mirogabalin group and 149 in the placebo group.

Treatment-emergent AEs (TEAEs) were reported in 118 subjects (78.1%) in the mirogabalin group and 82 subjects (55.4%) in the placebo group. Adverse drug reactions (ADRs) were reported in 62 subjects (41.1%) in the mirogabalin group and 19 subjects (12.8%) in the placebo group. The incidences of TEAEs and ADRs were higher in the mirogabalin group than in the placebo group. The most common TEAEs in the mirogabalin group (reported in >=5% of subjects receiving mirogabalin) were somnolence (29.8% in the mirogabalin group and 5.4% in the placebo group; the same order hereinafter), dizziness (8.6% and 3.4%), nasopharyngitis (7.9% and 5.4%), weight increased (7.3% and 0.7%), constipation (6.0% and 1.4%), and oedema peripheral (6.0% and 1.4%).

<mITT analysis> For the mirogabalin group, the least squares (LS) mean weekly ADPS decreased from Week 1 and then remained at a lower level compared with placebo throughout the entire treatment period. The decrease in the weekly ADPS remained almost unchanged from Week 4 onwards in the mirogabalin group. From the baseline weekly ADPS (mean 6.04 in the mirogabalin group and 6.09 in the placebo group), the LS mean changes (SE) in the imputed weekly ADPS at Week 14 were -1.23 (0.132) in the mirogabalin group and -0.52 (0.132) in the placebo group. The improvement in the imputed weekly ADPS was statistically greater in the mirogabalin group than that in the placebo group.

At Week 14, the percentage of subjects with a >=30% reduction in the weekly ADPS from baseline was greater in the mirogabalin group (30.7%) than in the placebo group (18.8%). The percentage of subjects with a >=50% reduction in the weekly ADPS from baseline was greater in the mirogabalin group (14.0%) than in the placebo group (6.0%). These differences versus placebo were statistically significant. Mirogabalin resulted in numerically greater improvements from baseline to Week 14/last observation carried forward (LOCF) in all SF-MPQ subscales than placebo. The LS mean differences versus placebo were statistically significant.

In subjects with CNePSCI receiving flexible-dose mirogabalin (up to 30 mg/day for subjects with CLcr >=60 mL/min and 15 mg/day for subjects with CLcr 30 to <60 mL/min) for 14 weeks, including a 2-week titration period, mirogabalin resulted in a statistically significant improvement in weekly ADPS compared with placebo. The results of secondary endpoints were generally supportive of the results of primary endpoint. Mirogabalin was generally well-torelated without any significant specific safety concern.

Yes

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/ Supporting Documents: - Study Protocol - Statistical Analysis Plan - Clinical Study Report 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. 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. URL: https://vivli.org/ourmember/daiichi-sankyo/

https://www.clinicaltrials.jp/file/ohzJIMpgd

DAIICHI SANKYO Co.,Ltd.

dsclinicaltrial@daiichisankyo.co.jp

DAIICHI SANKYO Co.,Ltd.

dsclinicaltrial@daiichisankyo.co.jp

completed

Mar. 12, 2019

Interventional

A double-blind study followed by open-label extension

treatment purpose

3

- Spinal cord injury due to trauma
- American Spinal Injury Association (ASIA) impairment scale A, B, C, or D

- Other severe pain at screening or randomization, unrelated to central neuropathic pain after spinal cord injury, that may confound the assessment of central neuropathic pain after spinal cord injury
- Neurologic disorders at screening or randomization, unrelated to central neuropathic pain after spinal cord injury, that may confound the assessment of central neuropathic pain after spinal cord injury

Both

central neuropathic pain

investigational material(s)
Generic name etc : DS-5565
INN of investigational material : mirogabalin
Therapeutic category code : 119 Other agents affecting central nervous system
Dosage and Administration for Investigational material : Oral administration

control material(s)
Generic name etc : Placebo
INN of investigational material : -
Therapeutic category code : --- Other
Dosage and Administration for Investigational material : Oral administration

efficacy
Average daily pain score

safety
efficacy
- Short-Form McGill Pain Questionnaire
- Average Daily Sleep Interference Score

Feb. 28, 2019