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CS-747S PhaseIII trial -Double-blind study of CS-747S versus clopidogrel bisulfate in elderly and/or low body weight patients with ischemic cerebrovascular accident-

CS-747S PhaseIII trial (CVA: elderly and/or low body weight)

654

There was no apparent imbalance in background factors between the treatment groups.

654 subjects were randomized; including 216 in the CS-747S 3.75 mg group, 215 in the CS-747S 2.5 mg group, and 223 in the clopidogrel group. All 654 randomized subjects received study drug and were included in the Full Analysis Set (FAS) and safety analysis set. 98 patients (27 in the CS-747S 3.75 mg group, 34 in the CS-747S 2.5 mg group, 37 in the clopidogrel group) discontinued from the study.

The incidence rate of adverse events was 83.3% (180/216 subjects) in the CS-747S 3.75 mg group, 83.7% (180/215 subjects) in the CS-747S 2.5 mg group, and 85.2% (190/223 subjects) in the clopidogrel sulfate group. The incidence rate of adverse events considered related to the study drug was 30.6% (66/216 subjects) in the CS-747S 3.75 mg group, 22.3% (48/215 subjects) in the CS-747S 2.5 mg group, and 24.7% (55/223 subjects) in the clopidogrel sulfate group. One subject in the CS-747S 2.5 mg group died that considered not related to the study drug. The incidence rate of nonfatal serious adverse events was 16.2% (35/216 subjects) in the CS-747S 3.75 mg group, 16.7% (36/215 subjects) in the CS-747S 2.5 mg group, and 16.1% (36/223 subjects) in the clopidogrel sulfate group.

The incidence rate of life-threatening bleeding, major bleeding, and clinically relevant bleeding found during the period from the initiation of study treatment to 14 days after completion/discontinuation of study treatment was 4.2% (9/216 subjects) in the CS-747S 3.75 mg group, 1.9% (4/215 subjects) in the CS-747S 2.5 mg group, and 3.6% (8/223 subjects) in the clopidogrel sulfate group. The hazard ratio (95% CI) of the CS-747S 3.75 mg group and 2.5 mg group relative to the clopidogrel sulfate group was 1.128 (0.435 to 2.925) and 0.510 (0.154 to 1.694), respectively. The bleeding events were life-threatening bleeding in 3 subjects and clinically relevant bleeding in 6 subjects in the CS-747S 3.75 mg group; life-threatening bleeding in 1 subject, major bleeding in 1 subject, and clinically relevant bleeding in 2 subjects in the CS-747S 2.5 mg group; and clinically relevant bleeding in 8 subjects in the clopidogrel sulfate group.

- The incidence rate of cerebro-cardiovascular events (ischemic stroke, myocardial infarction, and other vascular death) found during the period from the initiation of study treatment to 1 day after completion /discontinuation of study treatment was 3.3% (7/215 subjects) in the CS-747S 2.5 mg group, 3.6% (8/223 subjects) in the clopidogrel sulfate group, and 0% (0/216 subjects) in the CS-747S 3.75 mg group. These events were ischemic stroke reported in 7 subjects in the CS-747S 2.5 mg group and ischemic stroke and myocardial infarction reported in 6 and 2 subjects, respectively, in the clopidogrel sulfate group. The hazard ratio (95% CI) of the CS-747S 2.5 mg group relative to the clopidogrel sulfate group was 0.895 (0.324 to 2.467). - The incidence rate of ischemic cerebrovascular events (ischemic stroke and TIA) was 3.7% (8/215 subjects) in the CS-747S 2.5 mg group, 2.7% (6/223 subjects) in the clopidogrel sulfate group, and 0% (0/216 subjects) in the CS-747S 3.75 mg group. - The incidence rate of stroke was 0.5% (1/216 subjects) in the CS-747S 3.75 mg group, 3.3% (7/215 subjects) in the CS-747S 2.5 mg group, and 2.7% (6/223 subjects) in the clopidogrel sulfate group.

In elderly and/or low body weight patients with non-cardioembolic stroke, the incidence of bleeding events, the primary endpoint, was nearly equivalent in the CS-747S 3.75 mg and lower in the CS-747S 2.5 mg compared with the clopidogrel sulfate 50 mg. CS-747S 3.75 or 2.5 mg is considered almost same safety profile compare to clopidogrel sulfate 50 mg. These results also suggested that CS-747S 2.5 mg is as effective as clopidogrel sulfate 50 mg and CS-747S 3.75 mg was experienced no efficacy event.

Mar. 26, 2020

https://doi.org/10.1159/000506825

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

Sept. 16, 2012

Interventional

Multi-center, randomized, double-blind, double-dummy, parallel group study

treatment purpose

3

-Patients with cerebral infarction that was suggested as the cause of the last attack.
-The last attack: more than 4 weeks prior to informed consent.
-Age >= 75 years old and/or body weight =< 50 kg

-Patients who need the dual antiplatelet therapy.
-History of intracerebral hemorrhage.
-Bleeding disorder or bleeding diathesis.
-Patients with poorly-controlled blood pressure.
-Severe hepatic disorder or kidney disturbance.
-Body weight : less than 40kg

Both

Ischemic cerebrovascular accident (except cardiogenic cerebral embolism and asymptomatic cerebral infarction)

investigational material(s)
Generic name etc : prasugrel hydrochloride
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 : clopidogrel bisulfate
INN of investigational material : clopidogrel
Therapeutic category code : 339 Other agents relating to blood and body fluides
Dosage and Administration for Investigational material : Once daily orally

safety
Frequency of clinically relevant bleeding events.
The frequency and 95% confidence intervals of clinically relevant bleeding events which observed from the beginning of the administration of the study drug to the 14 days after the completion or discontinuation of study drug, are to be calculated by each group.

safety
efficacy
pharmacokinetics
pharmacodynamics
pharmacogenomics
Rate of efficacy endpoints, etc.
The rate of efficacy endpoints in each group and their 95% confidence intervals are to be calculated.

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Aug. 24, 2012