臨床研究等提出・公開システム

An Asian, phase 3, multicenter, randomized, double-blind, placebo-controlled 14-week study of DS-5565 in patients with post-herpetic neuralgia followed by a 52-week open-label extension

DS-5565 phase 3 study for post-herpetic neuralgia

765

In the randomized analysis set (765 subjects), the mean (SD) age at informed consent was 66.5 (9.94) years. Overall, 60.3% (461/765) of subjects were male and 39.7% (304/765) were female. The mean (SD) body weight was 62.26 (10.384) kg, and mean (SD) BMI was 23.87 (3.051) kg/m2. The median (min, max) duration of PHN was 18.0 (0, 437) months. The mean (SD) baseline ADPS was 5.71 (1.068). The mean (SD) VAS in SF-MPQ was 58.6 (11.48) mm at the screening visit (Visit 1), and 59.1 (10.50) mm at the randomization visit (Visit 2). Overall 80.0% of subjects were enrolled in Japan, and the subjects were randomized approximately equally among the treatment groups.

765 subjects were randomized to one of the treatment groups (304 subjects in the placebo group, 153 subjects in the 15-mg QD group, 153 subjects in the 10-mg BID group, and 155 subjects in the 15-mg BID group). A total of 671 subjects (87.7%) completed the study: 266 subjects (87.5%) in the placebo group, 137 subjects (89.5%) in the 15-mg QD group, 128 subjects (83.7%) in the 10-mg BID group, and 140 subjects (90.3%) in the 15-mg BID group.

The incidence of TEAEs was 51.8% (157/303) in the placebo group, 60.5% (92/152) in the 15-mg QD group, 66.7% (102/153) in the 10-mg BID group, and 72.9% (113/155) in the 15-mg BID group. The incidence of TEAEs was higher in all DS-5565 groups than in the placebo group. The incidence of TEAEs was higher as the daily dose of DS-5565 was increased. The most common TEAEs (reported for >= 5% of subjects in any treatment group) were somnolence (3.6% in the placebo group, 13.2% in the 15-mg QD group, 17.0% in the 10-mg BID group, and 23.9% in the 15-mg BID group; hereinafter, the same order), nasopharyngitis (8.6%, 8.6%, 10.5%, and 12.9%), dizziness (3.3%, 6.6%, 9.8%, and 15.5%), weight increased (0.3%, 4.6%, 5.2%, and 5.2%), and oedema (0.7%, 1.3%, 3.9%, and 7.1%). Of the most common TEAEs above, the incidence of TEAEs of somnolence, dizziness, and oedema was higher as the daily dose of DS-5565 was increased. Most of these TEAEs of somnolence, dizziness, weight increased, and oedema were resolved without any treatment.

The time course of LS mean ADPS showed a gradual decrease through Week 14 in all groups, with greater decreases seen in all DS-5565 groups than in the placebo group starting from Week 1. The decrease was greatest in the 15-mg BID group, showing the lowest score in most weeks compared with other groups. The LS mean ADPS in the 10-mg BID group showed lower score in most weeks than in the 15-mg QD group. The LS mean (SE) changes from baseline in imputed ADPS at Week 14 were -1.20 (0.099) in the placebo group, -1.61 (0.138) in the 15-mg QD group, -1.68 (0.141) in the 10-mg BID group, and -1.97 (0.137) in the 15-mg BID group. The LS mean ADPS at Week 14 decreased from baseline in all groups. The LS mean changes from baseline were greater as the daily dose of DS-5565 was increased. The LS mean (95% CI, P-value) differences versus placebo in change from baseline in the imputed ADPS at Week 14 were statistically significant in all DS-5565 groups after taking into account for multiplicity: -0.41 (-0.74 to -0.07, P = 0.0170) in the 15-mg QD group, -0.47 (-0.81 to -0.14, P = 0.0058) in the 10-mg BID group, and -0.77 (-1.10 to -0.44, P <0.0001) in the 15-mg BID group.

The changes from baseline in SF-MPQ at Week 14/LOCF showed greater improvement in all DS-5565 groups than in the placebo group. For all SF-MPQ subscales (sensory score, affective score, total score, VAS, and present pain intensity), the LS mean differences versus placebo in change from baseline at Week 14/LOCF were significantly greater in all DS-5565 groups.

In this study, DS-5565 was administered at doses of 15 mg QD, 10 mg BID, or 15 mg BID for 14 weeks, including the titration period, to evaluate the efficacy and safety of DS-5565 in Asian patients with PHN. The mean changes from baseline in ADPS at Week 14 were greater as the daily dose of DS-5565 was increased, and the differences versus placebo were statistically significant in all DS-5565 treatment group. DS-5565 at a dose of 15 mg BID or below is considered safe and well tolerated.

May. 01, 2019

https://journals.lww.com/pain/Fulltext/2019/05000/Mirogabalin_for_the_management_of_postherpetic.19.aspx

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/

DAIICHI SANKYO Co.,Ltd.

dsclinicaltrial@daiichisankyo.co.jp

DAIICHISANKYO Co.,Ltd.

dsclinicaltrial@daiichisankyo.co.jp

completed

Jan. 23, 2015

Interventional

A double-blind study followed by open-label extension

treatment purpose

3

- Post-herpetic neuralgia defined as pain present for more than 3 months after herpes zoster skin rash
- Average daily pain score >= 4

- Previous use of neurolytic block (eg, chemical neurolytic block using phenol or ethyl alcohol, radiofrequency thermocoagulation) or neurosurgical therapy for current post-herpetic neuralgia
- Other severe pain at screening or randomization, unrelated to post-herpetic neuralgia, that may confound the assessment of post-herpetic neuralgia
- Neurologic disorders at screening or randomization, unrelated to post-herpetic neuralgia, that may confound the assessment of post-herpetic neuralgia

Both

Post-herpetic neuralgia

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 (15mg/day, 20mg/day, 30mg/day)

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

efficacy
confirmatory
Average daily pain score

safety
efficacy
pharmacokinetics
- Short-Form McGill Pain Questionnaire
- Safety

-

Nov. 20, 2014