NCT05995405进行中（未招募）3 期
Safety and Tolerability of GTX-104 (Nimodipine Injection for IV Infusion) Compared With Oral Nimodipine in Patients Hospitalized for Aneurysmal Subarachnoid Hemorrhage (aSAH): a Prospective, Randomized Trial
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 100
- 试验地点
- 22
- 主要终点
- Incidence (% or proportion) of subjects with at least one episode of clinically significant hypotension with a reasonable possibility that GTX-104/oral nimodipine caused the event, according to the Endpoint Adjudication Committee.
研究概览
简要总结
The purpose of this study is to deliver nimodipine via IV directly into the bloodstream and to determine if this is as safe and tolerable as oral nimodipine capsules.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female ≥18 years of age.
- •Diagnosis of aneurysmal subarachnoid hemorrhage (aSAH) based on CT scan and angiography (computed tomography angiography [CTA], magnetic resonance angiography [MRA], or digital subtraction angiography [DSA]).
- •Hunt and Hess score from I to V just prior to randomization.
- •Subject or the subject's legal representative has signed informed consent (either in person or by fax, scan, or email) before any study-specific procedures are performed.
- •Able to start IP within 96 hours from the onset of aSAH. Note 1: The onset of aSAH is defined as the time when the subject experienced the first symptom of aSAH (e.g., severe headache or loss of consciousness reported either by the subject or by a witness).
- •Note 2: If found unconscious or the time of first symptoms is unknown, the onset of aSAH will be defined as the last time the subject was seen at baseline neurological state.
- •If a woman of childbearing potential (WOCBP), must have a negative pregnancy test during the pre-randomization phase (screening). A woman is not of childbearing potential if she has undergone surgical sterilization (total hysterectomy, or bilateral tubal ligation, or bilateral oophorectomy at least 6 weeks before taking IP) or if she is abstinent (see below) or postmenopausal and has had no menstrual bleeding of any kind including menstrual period, irregular bleeding, spotting, etc., for at least 12 months, with an appropriate clinical profile, and there is no other cause of amenorrhea (e.g., hormonal therapy, prior chemotherapy).
- •WOCBP and males whose sexual partners are WOCBP must agree to use barrier contraception and a second form of contraception while receiving IP and for 30 days following their last dose of IP. Alternatively, total abstinence is also considered a highly effective contraception method when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
- •Sexually active males must use a condom during intercourse while taking IP and for 30 days after the last dose of IP and should not father a child during this period. A condom is required to be used also by vasectomized men as well as during intercourse with a male partner to prevent delivery of the IP via seminal fluid.
排除标准
- •Is at imminent risk of death and/or has Do Not Resuscitate (DNR) orders.
- •Required cardiopulmonary resuscitation within 4 days prior to randomization.
- •Has second- or third-degree atrio-ventricular block or bradycardia (heart rate ≤50 bpm) prior to randomization.
- •Has history of cirrhosis (Child-Pugh class B and C) prior to randomization.
- •Has alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) more than 2.5 times the upper limit of normal (ULN).
- •Has history of malabsorption syndrome, recent ileus (in the last 3 months), or other gastrointestinal (GI) conditions that would interfere with absorption of nimodipine, in the opinion of the Investigator.
- •Has a severe or unstable concomitant condition or disease other than what may be attributed to the SAH that, in the opinion of the Investigator, may increase the risk associated with study participation or nimodipine administration, or may interfere with the interpretation of study results.
- •Has a history of recurrent syncope or hypotension that may interfere with the safety assessments of nimodipine.
- •Has a known hypersensitivity to nimodipine or capsule constituents or to GTX-
- •Is pregnant/has a positive serum or urine pregnancy test.
- •Has received more than 12 doses (or 720 mg) of oral nimodipine (as a solution [e.g., Nymalize] or capsules) as part of the standard of care (SOC) for the ruptured aneurysm prior to randomization.
- •Is receiving strong inhibitors of CYP3A4 such as some macrolide antibiotics (e.g., clarithromycin, telithromycin), some anti-HIV protease inhibitors (e.g., delavirdine, indinavir, nelfinavir, ritonavir, saquinavir), some azole antimycotics (e.g., ketoconazole, itraconazole, voriconazole), and some antidepressants (e.g., nefazadone). See Appendix
- •Is receiving or has received any other investigational agent(s)/device(s) in the last 30 days.
研究组 & 干预措施
GTX-104
Experimental
GTX-104 is a sterile concentrate of 10 mg nimodipine/5 mL (2 mg/mL), to be diluted in normal saline to obtain a dosing solution composed of dispersed micelles containing nimodipine for IV infusion. It will be administered as a continuous IV infusion of 0.15 mg/hour and a 30-minute IV bolus of 4 mg every 4 hours for up to 21 days
干预措施: GTX-104 (Drug)
Oral nimodipine
Active Comparator
Oral nimodipine is a soft gelatin capsule. The dose is 60 mg (two 30 mg capsules) every 4 hours for up to 21 consecutive days.
干预措施: Nimotop 30 MG Oral Capsule (Drug)
结局指标
主要结局
Incidence (% or proportion) of subjects with at least one episode of clinically significant hypotension with a reasonable possibility that GTX-104/oral nimodipine caused the event, according to the Endpoint Adjudication Committee.
时间窗: 90 days
Hypotension events requiring medical treatment
次要结局
- Incidence of delayed cerebral ischemia (DCI)(Day 1 - Day 21)
- Suicidal ideation using the Columbia-Suicide Severity Rating Scale (C-SSRS) score of ≥ 4(Day 1 - Day 90)
- Total number of episodes of clinically significant hypotension(Day 1 - Day 90)
- Duration of episodes of clinically significant hypotension(Day 1 - Day 90)
- Incidence and severity of Adverse Events (AEs) based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, Version 5.0).(Day 1 - Day 90)
- Use of rescue therapy for DCI(Day 1 - Day 21)
研究者
研究点 (22)
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相关资讯
Phase 3 Trial Success: GTx-104 Shows Promise in Treating Brain Hemorrhage with Reduced Hypotension Risk- Grace Therapeutics' Phase 3 STRIVE-ON trial of GTx-104, an injectable nimodipine formulation, met its primary endpoint with 19% reduction in clinically significant hypotension compared to oral nimodipine in aSAH patients.
- The novel IV formulation demonstrated superior drug delivery, with 54% of GTx-104 patients achieving ≥95% relative dose intensity compared to only 8% with oral nimodipine, alongside reduced ICU stays and ventilator days.
- Grace Therapeutics plans to submit New Drug Application (NDA) in first half of 2025, potentially offering the first major innovation in aSAH treatment in nearly 40 years.last yearAcasti Completes Enrollment in Phase 3 STRIVE-ON Trial of GTX-104 for aSAH- Acasti Pharma has completed patient enrollment in its Phase 3 STRIVE-ON trial evaluating GTX-104 for aneurysmal subarachnoid hemorrhage (aSAH).
- The STRIVE-ON trial is comparing intravenous GTX-104 to oral nimodipine in 100 patients hospitalized with aSAH across 25 U.S. hospitals.
- GTX-104, an injectable formulation of nimodipine, aims to address challenges associated with oral administration and improve patient outcomes.
- Acasti anticipates STRIVE-ON data readout in early 2025 and plans to submit an NDA to the FDA in the first half of 2025.last year