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DS-5565 Clinical Pharmacology Study An Open-Label, Single-Dose Study to Assess the Pharmacokinetics and Safety of DS-5565 in Japanese Subjects with varying degrees of renal function

DS-5565 Clinical Pharmacology Study in Japanese Subjects with varying degrees of renal function

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No notable differences were found in age, sex, or body weight among the renal classifications studied. The mean estimated CLcr was 100.3 mL/min/1.73 m2 for the subjects with normal renal function, 69.8 mL/min/1.73 m2 for the subjects with mild renal impairment, 40.9 mL/min/1.73 m2 for the subjects with moderate renal impairment, 23.4 mL/min/1.73 m2 for the subjects with severe renal impairment, and 9.7 mL/min/1.73 m2 for the subjects with ESRD.

A total of 30 Japanese subjects with varying degrees of renal function (6 subjects for each renal function category) were enrolled in the study as planned. All of the subjects received the study drug and completed the study.

No deaths and no severe TEAEs, serious TEAEs, or TEAEs that led to study discontinuation were reported. TEAEs were reported in 2 of 6 subjects with normal renal function and 4 of 6 subjects with ESRD. No TEAEs were reported in subjects with mild, moderate, or severe renal impairment. The most frequently reported TEAEs were dizziness (ESRD, n = 3), somnolence (ESRD, n = 2), and vomiting (ESRD, n = 2) in subjects with ESRD. Moderate dizziness and vomiting were reported in 1 subject with ESRD, the other TEAEs were mild. There were no notable changes in laboratory parameters or physical evaluations.

In subjects with severe renal impairment and ESRD, Cmax values were approximately 50% and approximately 30% higher, respectively, than those of subjects with normal renal function. Cmax was not notably different in the other categories compared with subjects with normal renal function. Tmax was 1.3 hours for subjects with normal renal function compared with 2.0, 1.7, 2.0, and 4.0 hours for subjects with mild, moderate, and severe impairment and ESRD, respectively. AUClast increased with severity of renal impairment. Compared with subjects with normal renal function, the ratio of AUClast were 1.3, 1.9, and 3.6 for patients with mild, moderate, and severe impairment, respectively. In patients with ESRD who undertook 4-hour hemodialysis 24 hours after drug administration, the ratio of AUClast compared with subjects with normal renal function was 5.3. CL/F, CLr, and the cumulative percentage of mirogabalin dose excreted into urine were all found to decrease as severity of renal impairment increase, in accordance with the increase in AUClast. In the subjects with ESRD, the t1/2 was substantially increased in patients with ESRD compared with subjects with normal renal function and those with mild, moderate, or severe renal impairment.

NA

The AUClast increased with severity of renal impairment. It was notably greater for the subjects with ESRD than that for normal renal function. The CL/F and CLR decreased with severity of renal impairment. A single 5-mg oral dose of DS-5565 was considered to be well tolerated in subjects with normal renal function, mild renal impairment, moderate renal impairment, or severe renal impairment. In subjects with ESRD, it was also considered to be tolerated, but with a relatively high incidence of TEAEs.

June. 13, 2017

https://www.ncbi.nlm.nih.gov/pubmed/28834546

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

July. 24, 2013

Interventional

Multicenter open-label study

treatment purpose

1

-Japanese with renal function impairment (Estimated CLcr [mL/min/1.73 m2] by Cockcroft-Gault Formula within the categories as follows; Normal renal function [CLcr > 80], Mild renal impairment [50 =< CLcr =< 80], Moderate renal impairment [30 =< CLcr =< 50], Severe renal impairment [CLcr < 30], End-stage renal disease [patients undergoing hemodialysis regardless of CLcr])
-between the age of 20 or more
-between the BMI of 18.5 and 30.0

-A history of serious diseases caused by disorders of the central nervous system, circulatory system, respiratory system, blood/hematopoietic system, gastrointestinal system, hepatic and renal function, thyroid function, pituitary gland function, adrenal function, etc., and the judgment of the investigator or subinvestigator that participation in the clinical study could pose a risk to the subject's safety
-Presence or history of drug allergies or idiosyncratic drug response (such as to penicillin)
-History of drug or alcohol abuse
-Inappropriateness for inclusion into the study as judged by the investigator or subinvestigator (for example, subjects who may have difficulty in visiting the study center or ensuring compliance)

Both

Japanese Subjects with varying degrees of renal function

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 : A oral single dose (one 5-mg tablet)

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

pharmacokinetics
Pharmacokinetic and Safety
To evaluate pharmacokinetic endpoints according to the free form of DS-5565 in plasma.
To evaluate safety endpoints according to the adverse events, vital signs, 12-lead ECGs and laboratory values.

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July. 11, 2013