NBP in Adult Patients With Acute Ischemic Stroke (AIS)

Phase 2

Completed

• Conditions: AIS
• Interventions: Drug: Placebo; Drug: NBP Softgel Capsules

• Registration Number: NCT02905565
• Lead Sponsor: 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.

Study Timeline

• Study First Submitted: 2016-08-23
• Study First Submitted QC: 2016-09-14
• Study First Posted: 2016-09-19
• Study Start: 2018-02-28
• Status Verified: 2019-11
• Primary Completion: 2020-08-07
• Study Completion: 2020-08-07
• Last Update Submitted: 2020-09-16
• Last Update Posted: 2020-09-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 177

Inclusion Criteria

Not provided

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 alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level > 1.5 × Upper Limits of Normal (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 tuberculous (TB).
24. Any other reasons that, in the opinion of the investigator, make the subject unsuitable for enrollment.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Interventions: Placebo (NBP placebo softgel capsules, 0 mg NBP, BID)
800 mg of NBP daily	NBP Softgel Capsules	Interventions: 800 mg NBP softgel capsules daily (400 mg BID)

Primary Outcome Measures

Name	Time	Method
Incidence rate of treatment-emergent adverse events (TEAEs)	90 days	Safety will be evaluated through the collection of TEAEs, serious adverse events (SAEs), clinical laboratory assessments, vital sign measurements, 12-lead ECGs, and physical and neurologic examinations. Suicidality will be evaluated at each clinical visit using the Columbia-Suicide Severity Rating Scale (C-SSRS).

Secondary Outcome Measures

Name	Time	Method
PK profile of NBP treatment in subjects with AIS	1 day	Peak and trough levels of NBP and metabolites
Exploratory efficacy outcome: mRS	90 days	Improvement of disability as measured by the mRS at Day 30 and Day 90
Exploratory efficacy outcome: Barthel Index (BI) Assessment	90 days	Stroke recovery as measured by the BI Assessment at Day 30 and Day 90
Exploratory efficacy outcome: NIHSS	90 days	Stroke recovery as measured by the NIHSS at Day 30 and Day 90
Exploratory efficacy outcome: Stroke Impact Scale (SIS) Assessment	90 days	SIS-16 on study Day 30 and 90

Trial Locations

Locations (1)

Investigative Site; 🇺🇸 Burlington, Vermont, United States