Safety and Efficacy of Two Doses of SP-8203 in Patients With Ischemic Stroke Requiring rtPA "SP-8203-2001"

Active, not recruiting

Phase 2 Results N/A

Trial Description

The current study aims to evaluate the safety of SP-8203, designing in two stages (stage-1, stage-2) to evaluate the safety and efficacy of the combination therapy of SP-8203 and rtPA for the occurrence of cerebral hemorrhage in patients with acute ischemic stroke receiving rtPA standard of care.

Detailed Description

As the standard procedure of rtPA therapy, rtPA will be injected intravenously using a device like infusion pump. When reperfusion is not achieved in spite of rtPA therapy, endovascular therapy can be performed according to the judgment of a site investigator.
Stage 1-The trial will be conducted with 11 subjects participating in an open label design manner. Subjects with neurologic deficit of ≥4 point and ≤10 points on NIHSS score will be given SP-8203, 80mg/dose, a total of 6 times at intervals of 12 hours. For the first administration of SP-8203, it should be administered within 30 minutes from the initiation of rtPA administration via a vein route different from one via which rtPA is injected.
Thereafter, the subject will be transferred to MRI scanning room to have brain MRI and MRA performed, and brain CT will be performed to check the occurrence of intracranial hemorrhage at 24 hours after complete administration of the first dose of SP-8203. The subject will be closely monitored by research staff daily from the day of first administration of SP-8203 (Day 0) to Day 5. Brain MRI and MRA will be followed up after the last administration of SP-8203 on Day 5. The subject will make a visit on Day 14 to have his/her neurologic symptoms checked, after which subject's participation in the trial will be completed.
*The DSMB (Date Safety Monitoring Board) meeting will be held, to decide whether to proceed with Stage 2 or not, based on the results of Stage 1.
Stage 2- A total of 69 subjects will be enrolled in double-blind, randomized and parallel design with 23 subjects assigned to low-dose (40mg/dose, 80mg/ day) SP-8203 group, high-dose (80mg/dose, 160mg/day) SP-8203 group or placebo group, respectively.
If a subject, who is able to be enrolled in Stage 2, has neurological deficit of ≥4 point on NIHSS score and give patient's consent to participate in the trial, randomization will be performed and each treatment arm (one of three) will be assigned. The subject will receive the Investigational products a total of 6 times, with 12 hours intervals. Blood sample will be taken after the sixth administration of the Investigational product for pharmacokinetic and pharmacodynamics analysis. For pharmacokinetic analysis , blood sample will be taken at 0, 30, and 120 minutes after the complete sixth administration of the investigational products. For pharmacodynamics analysis, blood sample will be taken at between 24 to 48 hours after the first administration, at 0 minute after the sixth administration and at 4th week visit.
As with Stage 1, the subject will have brain MRI and MRA performed after the administration of investigational product, and brain CT will be performed at 24 hours after completion of the first administration of investigational products.
Brain MRI and MRA will be followed-up on Day 5, similarly to Stage 1. However, in Stage 2, the subject will make a visit for close monitoring for patient's neurological condition at 4th week and 12th week. Thereafter, all the procedures of the clinical trial will be completed.

Conditions

Interventions

  • Placebo Drug
    Intervention Desc: Same dosage of SP8203. Placebo will be intravenously administered twice daily (intervals of 12 hours)
    ARM 1: Kind: Experimental
    Label: Placebo group
    Description: Placebo group: Same dosage of SP8203 (twice a day)
  • SP-8203 Drug
    Other Names: SP-8203 is produced by Shin Poong Pharmaceutical company
    Intervention Desc: Low dose group: SP-8203 80mg will be intravenously administered as 40mg/dose twice daily (intervals of 12 hours). High-dose group: 160mg will be intravenously administered as 80mg/dose twice daily (intervals of 12 hours).
    ARM 1: Kind: Experimental
    Label: SP-8203 High-dose group
    Description: High-dose group: SP-8203 160mg (80mg/dose twice a day)
    ARM 2: Kind: Experimental
    Label: SP-8203 Low dose group
    Description: Low-dose group: SP-8203 80mg (40mg/dose twice a day)
  • SP-8203 High dose Drug
    Other Names: SP-8203 is produced by Shin Poong Pharmaceutical company
    Intervention Desc: High-dose group: 160mg will be intravenously administered as 80mg/dose twice daily (intervals of 12 hours).
    ARM 1: Kind: Experimental
    Label: SP-8203 High-dose group
    Description: High-dose group: SP-8203 160mg (80mg/dose twice a day)
    ARM 2: Kind: Experimental
    Label: SP-8203 High dose group
    Description: SP-8203 160mg (80mg/dose twice a day for three days)
  • SP-8203 Low dose Drug
    Other Names: SP-8203 is produced by Shin Poong Pharmaceutical company
    Intervention Desc: Low dose group: 80mg will be intravenously administered as 40mg/dose twice daily (intervals of 12 hours).
    ARM 1: Kind: Experimental
    Label: SP-8203 Low dose group
    Description: Low-dose group: SP-8203 80mg (40mg/dose twice a day)

Trial Design

  • Allocation: Randomized
  • Masking: Double Blind (Subject, Caregiver, Investigator)
  • Purpose: Treatment
  • Endpoint: Safety Study
  • Intervention: Parallel Assignment

Outcomes

Type Measure Time Frame Safety Issue
Primary The ratio of the incidence of parenchymal hematoma observed on brain CT follow up period is the adverse event to be resolved. Monitoring of adverse events and safety will last for 30 days after the last visit. Yes
Secondary Incidence rate of serious adverse events Follow up period is 30 days after the last visit. Yes
Secondary Neurologic outcomes evaluated by modified Rankin Scale (mRS) Follow up period is 30 days after the last visit. Yes
Secondary Incidence rate symptomatic intracranial hemorrhage (sICH) occuring within 5 dyas. Follow up period is 30 days after the last visit. Yes
Secondary Neurologic outcomes evaluated by NIHSS Follow up period is 30 days after the last visit. Yes
Secondary Neurologic outcomes evaluated by Barthel Index Follow up period is 30 days after the last visit. Yes
Secondary The rate of death due to any cause Follow up period is 30 days after the last visit. Yes
Secondary Incidence rate of adverse events and adverse drug reactions Follow up period is 30 days after the last visit. Yes
Secondary Incidence rate of major systemic bleeding according to the International Society on Thrombosis and Hemostasis (ISTH Follow up period is 30 days after the last visit. Yes
Secondary Incidence rate symptomatic intracranial hemorrhage (sICH) occuring within 5 days Day 1 Brain CT, Day 5 Brain MRI

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