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CS-747S clinical pharmacology study

CS-747S clinical pharmacology study

133

The baseline characteristics were similar between groups A and B.

133 subjects (66 subjects in Group A and 67 subjects in Group B) were randomized and received the study treatment. 4 subjects (2 subjects in each groups) who did not receive study treatment for five consecutive days including the final day of study treatment in either period 1 or period 2 were excluded from the per protocol set (PPS). Of the total 129 subjects in PPS (64 subjects in Group A and 65 subjects in Group B), 30 subjects (16 subjects in Group A and 14 subjects in Group B) who did not have available pharmacokinetic data were excluded from the pharmacokinetic analysis set. 129 subjects same as PPS were included in the pharmacodynamic analysis set (no subjects were excluded from the pharmacodynamic analysis set).

Hemorrhagic AEs were reported in 6.8% (9/133) of subjects: 3.0% (4/132) of subjects during treatment with CS-747S 2.5 mg/day, and 3.8% (5/133) of subjects during treatment with CS-747S 3.75 mg/day. Most of these AEs were mild, and none necessitated permanent discontinuation of the study drug.

The PRU (arithmetic mean +- SD) during the 2 weeks pretreatment period, when patients received clopidogrel treatment, was 198.2 +- 86.7. After 4 week treatment with CS-747S 2.5 and 3.75 mg/day (combining the results of groups A and B), PRU was 200.9 +- 74.0 and 147.1 +- 71.6, respectively; a reduction in PRU was noted after treatment with CS-747S 3.75 mg/day, as compared with the pre-dose value (after treatment with clopidogrel) , whereas no significant difference was observed after treatment with CS-747S 2.5 mg/day. In the subsequent analysis of PRU by CYP2C19 phenotypes, after treatment with CS-747S 3.75 mg/day, reduction in PRU was noted in extensive metabolizers (EMs), intermediate metabolizers (IMs) and poor metabolizers (PMs) compared with the pre-dose value (after treatment with clopidogrel)at 4 weeks. After treatment with CS-747S (2.5 mg/day), increase in PRU was found in EMs and in IMs, and a decrease was found in PMs at 4 weeks.

Plasma active metabolite concentrations (R-138727) with treatment of CS-747S 2.5 mg and 3.75 mg did not differ significantly depending on the CYP2C19 phenotype. On the other hand, the plasma active metabolite concentration with treatment of clopidogrel tended to be lower in PM than in EM and IM of CYP2C19.

In patients with non-cardioembolic stroke, who switched from treatment with clopidogrel 75 mg, 4 week CS-747S treatment provided equivalent antiplatelet effects at 2.5 mg and greater effects at 3.75 mg. By CYP2C19 phenotypes, the antiplatelet effects of CS-747S were greater at 3.75 mg in IMs and PMs, and at 2.5 mg in PMs compared with clopidogrel 75 mg. CYP2C19 polymorphisms did not affect the plasma concentration of the active metabolite of CS-747S or its antiplatelet effects, compared to clopidogrel.

Aug. 03, 2018

https://doi.org/10.1007/s11239-018-1714-2

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

Mar. 04, 2010

Interventional

Multi-center, Randomized, Double-blind, 2-way crossover

treatment purpose

2

Inclusion criteria
At the time of informed consent signature,
-The most recent ischemic stroke: 4 weeks or more
-Age: Between 20 and 74 years old
-Body weight: > 50kg (screening period)
-Patients on clopidogrel (75mg/day) for 2 weeks or more
(exclude patients with concomitant use of aspirin)

-Modified Rankin Scale grade 5 or more
-Cardiac cerebral embolism, or cardiovascular disease cause of cardiac cerebral embolism (atrial fibrillation, patent foramen ovale, etc.)
-Concomitant administration of clopidogrel and aspirin for secondary prevention of ACS etc.
-Have active or prior history of intracranial hemorrhage
-Have bleeding disorder or bleeding diathesis

Both

Ischemic Stroke (exclude cardiac cerebral embolism)

investigational material(s)
Generic name etc : CS-747S (Prasugrel)
INN of investigational material : prasugrel
Therapeutic category code : 339 Other agents relating to blood and body fluides
Dosage and Administration for Investigational material : once daily orally

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

pharmacodynamics
-PRI value (VASP)
-PRU value and % Inhibition (VerifyNow System)

safety
pharmacokinetics
pharmacogenomics
-Plasma concentration of active metabolite
-Adverse event, Bleeding event

-

Jan. 20, 2010