臨床研究等提出・公開システム

A Japanese, phase 3, open-label, 14-week study of DS-5565 in patients with pain associated with diabetic peripheral neuropathy (DPNP) with renal impairment or post-herpetic neuralgia (PHN) with renal impairment

DS-5565 phase 3 study for renal impairment

35

In all eligible subjects (35 subjects), the mean (SD) age at informed consent was 73.4 (7.31) years. The majority of subjects were male (80.0% [28/35] male subjects and 20.0% [7/35] female subjects). The mean (SD) body weight was 59.85 (9.730) kg. The mean (SD) BMI was 23.01 (3.112) kg/m2. The mean (SD) CLcr at baseline was 51.8 (9.55) mL/min in subjects with moderate renal impairment (RI) and 22.0 (6.16) mL/min in subjects with severe RI. The mean (SD) ADPS at baseline was 5.70 (1.069). The mean (SD) VAS in SF-MPQ was 58.2 (9.36) mm at the screening visit (Visit 1), and 59.6 (9.63) mm at initiation of the study treatment (Visit 2). For primary disease, 82.9% (29/35) of subjects had a DPNP and 17.1% (6/35) of subjects had a PHN. The median (min, max) duration of painful DPN was 51.0 (9, 156) months. The mean (SD) duration of PHN was 14.5 (10, 87) months.

35 subjects (30 subjects with moderate RI and 5 subjects with severe RI) were enrolled into the study. The study was completed by 30 subjects (26 subjects with moderate RI and 4 subjects with severe RI).

The incidence of TEAEs was 83.3% (25/30) in subjects with moderate RI and 80.0% (4/5) in subjects with severe RI. All TEAEs were mild or moderate, except for 1 severe TEAE reported in 1 subject with moderate RI. The most common TEAEs were nasopharyngitis (22.9% [8/35]), somnolence (11.4% [4/35]), and oedema peripheral (8.6% [3/35]).

The incidence of TEAEs was 83.3% in subjects with moderate renal impairment and 80.0% in subjects with severe renal impairment. The most common TEAEs were nasopharyngitis (22.9%), somnolence (11.4%), and oedema peripheral (8.6%). Most TEAEs were mild or moderate, and resolved. No deaths were reported.

The mean baseline ADPS was 5.65 in subjects with moderate RI and 5.97 in subjects with severe RI. The LS mean changes (95% CI) from baseline in imputed ADPS at Week 14 were -1.79 (-2.45 to -1.14) in subjects with moderate RI and -2.07 (-3.77 to -0.36) in subjects with severe RI. DS-5565 significantly decreased the ADPS from baseline at Week 14 both in subjects with moderate RI and with severe RI.

DS-5565 was safe and well tolerated in subjects with DPNP or PHN when used for 14 weeks, including 2-weeks' titration period, at a fixed dose of 7.5 mg BID for subjects with moderate RI and at a fixed dose of 7.5 mg QD for subjects with severe RI. DS-5565 reduced pain from baseline to Week 14 in subjects with DPNP or PHN and with moderate or severe RI.

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. 21, 2016

Interventional

Multicenter, single-arm, open-label study

treatment purpose

3

Patients with DPNP and patients with PHN:
-Average daily pain score >= 4
-Creatinine clearance (using Cockcroft-Gault equation): 15-59 mL/min at screening

Patients with DPNP only:
-Type 1 or Type 2 diabetes mellitus
-Painful distal symmetric polyneuropathy

Patients with PHN only:
-Post-herpetic neuralgia defined as pain present for more than 3 months after herpes zoster skin rash

For patients with DPNP only:
-HbA1c > 10.0%
-Uncontrolled blood glucose at screening at initiation of study treatment that may require changes in diabetes treatment (non-insulin drug therapy, exercise therapy, diet therapy) during the study
-Other severe pain at screening or initiation of study treatment, unrelated to diabetic peripheral neuropathy (DPN), that may confound the assessment of DPNP
-Neurologic disorders at screening or initiation of study treatment, unrelated to DPN, that may confound the assessment of DPNP

For patients with PHN only:
-Previous use of neurolytic block (eg, chemical neurolytic block using phenol or ethyl alcohol, radiofrequency thermocoagulation) or neurosurgical therapy for current PHN
-Other severe pain at screening or initiation of study treatment, unrelated to PHN, that may confound the assessment of PHN
-Neurologic disorders at screening or initiation of study treatment, unrelated to PHN, that may confound the assessment of PHN

Both

Diabetic peripheral neuropathic pain, 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

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

safety
safety and tolerability

efficacy
pharmacokinetics
Average Daily Pain Score

-

Dec. 03, 2015