NBP in Adult Patients With Acute Ischemic Stroke (AIS)

A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Add-On to Standard Of-Care Study of n Butylphthalide (NBP) Softgel Capsules for Treatment of Mild to Moderate Acute Ischemic Stroke (AIS) in Adult Subjects

Sponsors

Lead Sponsor: CSPC-NBP Pharmaceutical Co., Ltd.

Source CSPC-NBP Pharmaceutical Co., Ltd.
Brief Summary

This is a Phase 2 multicenter, randomized, double-blind, placebo-controlled, add-on to standard of care study of NBP softgel capsules for the treatment of mild to moderate AIS in adults.

Detailed Description

This is a randomized, double-blind, placebo-controlled, add-on to standard-of-care study with a primary objective to assess the safety of NBP treatment in patients with mild to moderate acute ischemic stroke. The secondary objectives include determination of pharmacokinetic (PK) profile and exploratory evaluation for the efficacy of NBP treatment in stroke patients.

All randomized subjects will also receive standard supportive medical care for treatment of AIS throughout the study. The overall duration of the study will be approximately 90 days, including 30 days of treatment and an additional 60 days for follow up assessments. Subjects will be hospitalized long enough to receive the first four doses of study drug. After discharge from the hospital, subjects will continue to take study treatment daily through Day 30 and have scheduled assessments completed.

To maintain the blind, all subjects will take 4 softgel capsules BID, which will contain either 100 mg NBP or matching placebo. The first dose must be taken within 12 hours of the onset of the AIS defined as the last known normal.

Overall Status Recruiting
Start Date February 28, 2018
Completion Date January 2021
Primary Completion Date January 2021
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Incidence rate of treatment-emergent adverse events (TEAEs) 90 days
Secondary Outcome
Measure Time Frame
PK profile of NBP treatment in subjects with AIS 1 day
Exploratory efficacy outcome: mRS 90 days
Exploratory efficacy outcome: Barthel Index (BI) Assessment 90 days
Exploratory efficacy outcome: NIHSS 90 days
Exploratory efficacy outcome: Stroke Impact Scale (SIS) Assessment 90 days
Enrollment 400
Condition
Intervention

Intervention Type: Drug

Intervention Name: NBP Softgel Capsules

Description: Take 4 capsules BID on an empty stomach at least 1 hour before food intake, and remain fasting at least 1 hour after dosing.

Arm Group Label: 800 mg of NBP daily

Other Name: NBP

Intervention Type: Drug

Intervention Name: Placebo

Description: Take 4 capsules BID on an empty stomach at least 1 hour before food intake, and remain fasting at least 1 hour after dosing

Arm Group Label: Placebo

Other Name: NBP Placebo Softgel Capsules

Eligibility

Criteria:

Inclusion Criteria

1. Males or females aged ≥ 18 and ≤ 85 years.

2. Women of childbearing potential (WOCBP) must have a negative urine HCG pregnancy test at Screening and be practicing a medically acceptable method of contraception with an annual failure rate of less than 1% until the completion of the trial or 60 days after discontinuation of study treatment. Women are considered not childbearing if they are > 1 year postmenopausal or surgically sterile (ie, hysterectomy, bilateral oophorectomy, or bilateral salpingectomy tubal ligation). If serum bHCG is the standard of care, then this value can be used to determine eligibility.

3. A clinical diagnosis of mild to moderate cortical or subcortical AIS.

4. Able to swallow the softgel capsules as defined by the investigator.

5. Completes screening procedures such that study treatment is first administered within 24 hours of stroke onset. The stroke onset time will be defined as the last known normal.

6. If tPA is given as part of standard of care, the first dose of NBP must be administered no sooner than 4 hours after the end of the tPA infusion.

7. A standard NIHSS score of 4 to 17, inclusive. If patients receive tPA and/or endovascular treatment (EVT), the NIHSS score must be obtained after the infusion and/or procedure is completed. If sedation is used for EVT, then the NIHSS score must be obtained after sedation no longer confounds the assessment. All subjects must meet a NIHSS consciousness score of 0-1 in order to meet eligibility.

8. Functionally independent, as defined by a Modified Rankin Scale (mRS) score of 0 to 1 before their present illness as determined by the subject or provided by a representative if the subject is unable to participate at the time of study entry (determined by retrospective assessment by the Investigator).

9. Capable of understanding the purpose and risk of the study and has signed, in writing, the ICF. If the subject is not capable of this at the time of enrollment, a legally authorized representative (LAR) will provide written informed consent in accordance with all regulations.

10. Ability to comply with study requirements.

Exclusion Criteria:

1. Female subjects who are pregnant, lactating/breast-feeding, or plan to become pregnant within the next 3 months.

2. Suspected diagnosis of stroke isolated to brainstem or brain areas other than cortical or subcortical AIS that may have caused the present symptoms, based on the opinion of the Investigator.

3. Rapidly improving or resolving symptoms, suggesting a possible transient ischemic attack (TIA) rather than a qualifying stroke.

4. Signs of acute intracranial hemorrhage or symptomatic hemorrhagic transformation of AIS defined by a 4-point worsening in NIHSS from presentation, or other cause of acute stroke symptoms (other than early ischemic findings) on cranial imaging at Screening.

5. History of intracranial hemorrhage.

6. Seizure at onset of stroke.

7. A previous clinical diagnosis of stroke within 6 months of current AIS. A previously undiagnosed stroke evidenced on screening CT or MRI may be enrolled provided it does not affect neurological and functional assessments based on the opinion of the Investigator.

8. Uncontrolled severe hypertension defined as a systolic blood pressure (SBP) ≥ 220 mm Hg or diastolic blood pressure (DBP) ≥ 110 mm Hg.

9. Treatment with intensive antihypertensive therapy within 4 hours of randomization.

10. SBP < 100 mm Hg, temperature > 38.0º C, or heart rate < 40 beats/minute or > 120 beats/minute at Screening or prior to randomization.

11. A glucose level of < 50 mg/dL at Screening.

12. An international normalized ratio (INR) ≥ 1.5 if not being treated with anticoagulant therapy, or an INR ≥ 3.5 if being treated with an acceptable anticoagulant therapy.

13. A serum ALT or AST level > 1.5 × ULN, or bilirubin > 1.5 ULN (except in setting of known Gilbert's disease) at Screening.

14. Clinically significant renal dysfunction (including serum creatinine level > 2.0 mg/dL or 177 µmol/L) at Screening.

15. A hemoglobin level < 10 g/dL at Screening.

16. Current or within the last 6 months prior to Screening, New York Heart Association Class III/IV heart failure, severe uncorrected valve disease, known or suspected infective/vegetative endocarditis, ventricular tachycardia, or torsade de pointes.

17. Corrected QTcF (Fridericia) > 450 ms for male subjects or > 470 ms for female subjects (average of 3 ECG tracings) prior to randomization.

18. Current diagnosis of cancer or is being treated or has received any treatments for cancer within the last 5 years except basal cell carcinoma or curatively resected squamous cell carcinoma.

19. Known life expectancy < 6 months (for any reason).

20. Known allergy or hypersensitivity to celery or soybeans.

21. Received treatment with any other investigational drug within 30 days before Baseline, was previously treated with NBP, is currently taking celery seed extract, or is currently participating in another clinical study.

22. Known or suspected history of alcohol or drug dependence within the past 6 months, or is known to have abused alcohol (eg, been intoxicated) within the last 24 hours.

23. Known history of hepatitis B, hepatitis C, HIV, or TB.

24. Any other reasons that, in the opinion of the investigator, make the subject unsuitable for enrollment.

Gender: All

Minimum Age: 18 Years

Maximum Age: 85 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Wayne Clarke, MD Principal Investigator Oregon Health and Science University
Overall Contact

Last Name: Lisa Arvay, RN, MBA

Phone: 609-356-0210

Email: [email protected]

Location
Facility: Status:
Investigative Site | Tucson, Arizona, 85721, United States Withdrawn
Investigative Site | Irvine, California, 92868, United States Withdrawn
Investigative Site | Los Angeles, California, 90027, United States Active, not recruiting
Investigative Site | Los Angeles, California, 90095, United States Active, not recruiting
Investigative Site | Jacksonville, Florida, 32207, United States Withdrawn
Investigative Site | Jacksonville, Florida, 32209, United States Active, not recruiting
Investigative Site | Fort Wayne, Indiana, 46804, United States Active, not recruiting
Investigative Site | Des Moines, Iowa, 50314, United States Terminated
Investigative Site | Louisville, Kentucky, 40202, United States Active, not recruiting
Investigative Site | Boston, Massachusetts, 02111, United States Active, not recruiting
Investigative Site | Golden Valley, Minnesota, 55422, United States Active, not recruiting
Investigative Site | Saint Louis, Missouri, 63110, United States Active, not recruiting
Investigative Site | Columbia Falls, Montana, 65201, United States Active, not recruiting
Investigative Site | Omaha, Nebraska, 68123, United States Active, not recruiting
Investigative Site | Buffalo, New York, 14202, United States Active, not recruiting
Investigative Site | Asheville, North Carolina, 28801, United States Terminated
Investigative Site | Columbus, Ohio, 43210, United States Active, not recruiting
Investigative Site | Dayton, Ohio, 45324, United States Active, not recruiting
Investigative Site | Hillsboro, Oregon, 97123, United States Active, not recruiting
Investigative Site | Portland, Oregon, 97213, United States Recruiting Biggya Sapkota, MD
Investigative Site | Portland, Oregon, 97225, United States Recruiting Theodore Lowenkopf, MD
Investigative Site | Portland, Oregon, 97239, United States Recruiting Wayne Clark, MD
Investigative Site | Philadelphia, Pennsylvania, 19104, United States Active, not recruiting
Investigative Site | Charleston, South Carolina, 29425, United States Active, not recruiting
Investigative Site | Columbia, South Carolina, 29203, United States Active, not recruiting
Investigative Site | Chattanooga, Tennessee, 37403, United States Active, not recruiting
Investigative Site | Burlington, Vermont, 05401, United States Terminated
Investigative Site | Richmond, Virginia, 23298, United States Withdrawn
Investigative Site | Morgantown, West Virginia, 26506, United States Withdrawn
Investigative Site | Milwaukee, Wisconsin, 53215, United States Withdrawn
Location Countries

United States

Verification Date

November 2019

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Number Of Arms 2
Arm Group

Label: Placebo

Type: Placebo Comparator

Description: Interventions: Placebo (NBP placebo softgel capsules, 0 mg NBP, BID)

Label: 800 mg of NBP daily

Type: Active Comparator

Description: Interventions: 800 mg NBP softgel capsules daily (400 mg BID)

Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Triple (Participant, Care Provider, Investigator)

Source: ClinicalTrials.gov