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CS-747S PhaseIII trial - A Double-blind Study of CS-747S Versus Clopidogrel Sulfate in Patients with Thrombotic Stroke Having Risk Factors for Stroke Recurrence -

PRASTRO-III

235

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

235 subjects were randomized; only 1 subject in clopidogrel sulfate group did not receive the study drug. 234 subjects who received study drug (120 subjects in the CS-747S group and 114 subjects in the clopidogrel sulfate group) were included in the safety analysis set. Of those 230 subjects were included in the full analysis set [4 subjects meet major violation of inclusion criteria were excluded (2 subjects in the CS-747S group and 2 subjects in the clopidogrel sulfate group)]. Of the 235 subjects who were randomized, 44 subjects discontinued from the study (21 subjects in the CS-747S group and 23 subjects in the clopidogrel sulfate group).

The incidence of adverse events was 76.7% (92/120 subjects) in the CS-747S group and 82.5% (94/114 subjects) in the clopidogrel sulfate group. The incidence of adverse events considered related to the study drug (hereinafter, drug-related adverse events) was 11.7% (14/120 subjects) in the CS-747S group and 14.9% (17/114 subjects) in the clopidogrel sulfate group. The incidence of serious adverse events was 18.3% (22/120 subjects) in the CS-747S group and 16.7% (19/114 subjects) in the clopidogrel sulfate group. No drug-related serious adverse events were found in the CS-747S group, and their incidence in the clopidogrel sulfate group was 3.5% (4/114 subjects).

The incidence of ischemic cerebrovascular and cardiovascular events (a composite of ischemic stroke, myocardial infarction, and death from other vascular cause) observed in the FAS from the start of study treatment to the day after completion or discontinuation of study treatment was 6.8% (8/118 subjects) in the CS-747S group and 7.1% (8/112 subjects) in the clopidogrel sulfate group. The risk ratio (95% CI) for the CS-747S group relative to the clopidogrel sulfate group was 0.949 (0.369 to 2.443), which was below 1. There was no marked difference between the CS-747S group and clopidogrel sulfate group in the time course of cumulative incidence of ischemic cerebrovascular and cardiovascular events.

- The incidence of "ischemic stroke" observed in the FAS from the start of study treatment to the day after completion or discontinuation of study treatment was 5.9% (7/118 subjects) in the CS-747S group and 7.1% (8/112 subjects) in the clopidogrel sulfate group, and the incidence of "myocardial infarction" was 0.8% (1/118 subjects) in the CS-747S group and 0.0% (0/112 subjects) in the clopidogrel sulfate group, and "death from other vascular cause" was not found in either treatment group. The incidence of "ischemic cerebrovascular events (ischemic stroke and TIA)" was 5.9% (7/118) in the CS-747S group and 8.9% (10/112) in the clopidogrel sulfate group, and the risk ratio (95% CI) for the CS-747S group relative to the clopidogrel sulfate group was 0.664 (0.262 to 1.685). - The incidence of bleeding events (a composite of life-threatening bleeding, major bleeding, and clinically relevant bleeding) was 5.0% (6/120 subjects) in the CS-747S group and 3.5% (4/114 subjects) in the clopidogrel sulfate group. "Life-threatening bleeding" was not found in either group. For "major bleeding," retinal tear was found in 1 subject in the CS-747S group. "Clinically relevant bleeding" was found in 5 subjects in the CS-747S group and 4 subjects in the clopidogrel sulfate group. - The incidence of "all bleeding events (life-threatening bleeding, major bleeding, clinically relevant bleeding, and other bleeding)" was 19.2% (23/120 subjects) in the CS-747S group and 24.6% (28/114 subjects) in the clopidogrel sulfate group, and thus the incidence was lower in the CS-747S group than in the clopidogrel sulfate group. - The arithmetic mean values of PRU in the CS-747S group and clopidogrel sulfate group were 193.4 and 203.1 before the start of administration, 111.2 and 168.6 in the 4th week of treatment, and 111.6 and 166.6 in the 24th week of treatment, respectively. The PRU in the CS-747S group was lower than in the clopidogrel sulfate group, and the 95% CI of the difference in arithmetic mean did not contain 0 from Week 4 of the treatment period. The percentage inhibition values in the CS-747S group were higher than in the clopidogrel sulfate group, and the 95% CI of the difference in arithmetic mean did not contain 0 from Week 4 of the treatment period.

When 3.75 mg of CS-747S or 75/50 mg of clopidogrel sulfate was administered for 24 to 48 weeks, in patients with thrombotic stroke having risk factors for stroke recurrence, the risk ratio of the CS-747S relative to the clopidogrel sulfate group for the primary efficacy endpoint, the incidence of ischemic cardiovascular and cerebrovascular events (a composite of ischemic stroke, myocardial infarction, and death from other vascular cause) was below 1. There were no new safety concerns.

May. 21, 2022

https://doi.org/10.5551/jat.63473

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/

https://www.clinicaltrials.jp/file/qgJBVNUed

DAIICHI SANKYO Co.,Ltd.

dsclinicaltrial@daiichisankyo.co.jp

DAIICHI SANKYO Co.,Ltd.

dsclinicaltrial@daiichisankyo.co.jp

completed

Oct. 25, 2018

Interventional

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

prevention purpose

3

-Patients with evidence of infarct lesion(s) that may have caused the last episode of attack on head imaging
-Patients whose subtype of stroke is either large-artery atherosclerosis or small-artery occlusion
-Patients with at least one of the following risk factors i. to vi.
i. Hypertension: Systolic and diastolic blood pressure of >=140 mmHg and >=90 mmHg.
ii. Diabetes mellitus: HbA1c >=6.5%.
iii. Chronic kidney disease: Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or urine protein rated as >=1+.
iv. Dyslipidemia: LDL cholesterol >=120 mg/dL, HDL cholesterol <40 mg/dL, and triglyceride >=150 mg/dL.
v. If none of the above numerical criteria i. to iv. are met in the presence of pharmacotherapy etc., patients having at least two risk factors from among hypertension, diabetes mellitus, chronic kidney disease, and dyslipidemia are eligible for the study.
vi. History of stroke before the last episode of attack
-Patients who are able to start treatment with the study drug during the period from 7 days to 26 weeks after onset of the last episode of ischemic attack

-Patients with symptomatic non-traumatic intracerebral hemorrhage or a known history thereof
-Patients with bleeding or a high risk of bleeding
-Patients scheduled to undergo cerebral revascularization for the latest ischemic attack
-Patients with a severe hepatic disorder
-Patients with severe renal disorder requiring dialysis therapy
-Patients who have received clopidogrel sulfate for at least 22 days during the period from the last episode of ischemic attack to the start of treatment with the study drug

Both

Thrombotic Stroke

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

efficacy
Rate of ischemic cerebrovascular and cardiovascular events (stroke, myocardial infarction, and death from other vascular cause)
The rate of ischemic cerebrovascular and cardiovascular events, and their 95% confidence intervals of each groups, which observed from the beginning of the administration of the studying drug to the day after the completion or discontinuation of administration, are to be calculated. Then risk ratio and their 95% confidence intervals of CS-747S group against clopidogrel bisulfate group are to be calculated.

safety
efficacy
pharmacodynamics
Rate of bleeding event, etc.
The rate of bleeding events and their 95% confidence intervals are to be calculated.

+81-95-819-7200

Sept. 20, 2018