臨床研究等提出・公開システム

An Asian, phase 2, multicenter, randomized, double-blind, placebo- and pregabalin-controlled, dose-finding study of DS-5565 in patients with pain associated with diabetic peripheral neuropathy

DS-5565 phase 2 study

450

Of 446 FAS subjects, no notable differences were found in demographic and other baseline characteristics between treatment groups. The mean age was 59.8 years. The percentage of male subjects was 64.6%, and the percentage was higher for male subjects than that for female subjects (35.4%). The mean body weight was 67.7 kg. The mean creatinine clearance was 91.3 mL/min. The percentage of subjects with type 2 diabetes mellitus was 97.1% and the median duration of diabetes was 11.0 years. The median duration of DPN was 46.0 months and that of painful DPN was 36.0 months.

450 subjects were randomized to one of the treatment groups (89 subjects in the placebo group, 87 subjects in the pregabalin group, 90 subjects in the 5-mg BID group, 94 subjects in the 10-mg BID group, and 90 subjects in the 15-mg BID group). The study was completed by 84 subjects in the placebo group, 75 subjects in the pregabalin group, 86 subjects in the 5-mg BID group, 75 subjects in the 10-mg BID group, and 77 subjects in the 15-mg BID group.

The incidence of TEAEs was 53.4% (47/88) in the placebo group, 48.9% (44/90) in the 5-mg BID group, 63.4% (59/93) in the 10-mg BID group, 73.3% (66/90) in the 15-mg BID group, and 58.1% (50/86) in the pregabalin group. The most common TEAEs in the DS-5565 groups were somnolence (14.7% [40/273]), dizziness (11.0% [30/273]), and nasopharyngitis (8.4% [23/273]). The incidence of somnolence was 8.9% (8/90) in the 5-mg BID group, 14.0% (13/93) in the 10-mg BID group, and 21.1% (19/90) in the 15-mg BID group. The incidence of dizziness was 5.6% (5/90) in the 5-mg BID group, 10.8% (10/93) in the 10-mg BID group, and 16.7% (15/90) in the 15-mg BID group. The incidence of nasopharyngitis was 7.8% (7/90) in the 5-mg BID group, 14.0% (13/93) in the 10-mg BID group, and 3.3% (3/90) in the 15-mg BID group. As the dose of DS-5565 increased, the incidence of somnolence and dizziness numerically increased. In addition to these common TEAEs, the incidence of oedema peripheral in the 15-mg BID group (7.8% [7/90]), that of gait disturbance in the 10-mg BID group (7.5% [7/93]), and that of weight increased in the 15-mg BID group (5.6% [5/90]) were of note.

The LS mean changes (standard error [SE]) in ADPS from baseline to Week 7/LOCF were -1.45 (0.172) in the placebo group, -1.87 (0.170) in the 5-mg BID group, -1.81 (0.167) in the 10-mg BID group, -1.74 (0.170) in the 15-mg BID group, and -1.41 (0.175) in the pregabalin group. The LS mean change in ADPS was numerically lower in each DS-5565 group than that in the placebo group, showing a numerically greater improvement in each DS-5565 group. No notable difference in the LS mean change in ADPS was found among the 3 DS-5565 groups. The LS mean difference (95% confidence interval [CI]) versus placebo in change from baseline to Week 7/LOCF in ADPS was -0.42 (-0.99 to 0.15) in the 5-mg BID group, -0.37 (-0.93 to 0.20) in the 10-mg BID group, -0.30 (-0.87 to 0.27) in the 15-mg BID group, and 0.03 (-0.45 to 0.52) in the pregabalin group. These differences versus placebo were not statistically significant in any groups.

DS-5565 showed a numerically greater improvement in the SF-MPQ VAS score, and the LS mean difference versus placebo was statistically significant in the 15-mg BID group.

In subjects with pain associated with DPN receiving DS-5565 at a dose of 5 mg BID, 10 mg BID, or 15 mg BID for 7 weeks including 1-week titration, DS-5565 showed a numerically greater improvement in ADPS than placebo, although these differences versus placebo were not statistically significant for any treatment groups. DS-5565 was tolerated in this population at doses of 5 mg BID, 10 mg BID, and 15 mg BID.

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

DAIICHI SANKYO Co.,Ltd.

dsclinicaltrial@daiichisankyo.co.jp

completed

Jan. 27, 2012

Interventional

A double-blind study

treatment purpose

2

- Type 1 or type 2 diabetes mellitus
- Painful distal symmetric polyneuropathy
- Average daily pain score >=4

HbA1c (National Glycohemoglobin Standardization
Program) > 9.0%

Both

Pain associated with diabetic peripheral neuropathy

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 (10mg/day, 20mg/day, 30mg/day)

control material(s)
Generic name etc : placebo, pregabalin
INN of investigational material : Pregabalin, Placebo
Therapeutic category code : 119 Other agents affecting central nervous system
Dosage and Administration for Investigational material : oral administration (pregabalin: 300mg/day)

efficacy
exploratory
Average daily pain score

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

-

Nov. 25, 2011