Safety and Tolerability of GTX-104 Compared with Oral Nimodipine in Patients with ASAH

NCT ID: NCT05995405

Last Updated: 2024-10-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-10-20

Study Completion Date

2024-12-31

Brief Summary

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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.

Detailed Description

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Conditions

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Aneurysmal Subarachnoid Hemorrhage (aSAH)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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GTX-104

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

Group Type EXPERIMENTAL

GTX-104

Intervention Type DRUG

Nimodipine IV infusion

Oral nimodipine

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.

Group Type ACTIVE_COMPARATOR

Nimotop 30 MG Oral Capsule

Intervention Type DRUG

Oral nimodipine capsules

Interventions

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GTX-104

Nimodipine IV infusion

Intervention Type DRUG

Nimotop 30 MG Oral Capsule

Oral nimodipine capsules

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Male or female ≥18 years of age.
2. Diagnosis of aneurysmal subarachnoid hemorrhage (aSAH) based on CT scan and angiography (computed tomography angiography \[CTA\], magnetic resonance angiography \[MRA\], or digital subtraction angiography \[DSA\]).
3. Hunt and Hess score from I to V just prior to randomization.
4. 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.
5. 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.
6. 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.
7. 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.

Exclusion Criteria

1. Is at imminent risk of death and/or has Do Not Resuscitate (DNR) orders.
2. Required cardiopulmonary resuscitation within 4 days prior to randomization.
3. Has second- or third-degree atrio-ventricular block or bradycardia (heart rate ≤50 bpm) prior to randomization.
4. Has history of cirrhosis (Child-Pugh class B and C) prior to randomization.
5. Has alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) more than 2.5 times the upper limit of normal (ULN).
6. 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.
7. 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.
8. Has a history of recurrent syncope or hypotension that may interfere with the safety assessments of nimodipine.
9. Has a known hypersensitivity to nimodipine or capsule constituents or to GTX-104.
10. Is pregnant/has a positive serum or urine pregnancy test.
11. 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.
12. 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 5.
13. Is receiving or has received any other investigational agent(s)/device(s) in the last 30 days.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Grace Therapeutics Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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R. Loch Macdonald, MD

Role: STUDY_DIRECTOR

Grace Therapeutics Inc.

Locations

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The University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Brain and Spine Neurological Institute

Phoenix, Arizona, United States

Site Status

Community Regional Medical Center

Fresno, California, United States

Site Status

Mayo Clinic Florida

Jacksonville, Florida, United States

Site Status

Emory University School of Medicine Emergency Neurosciences

Atlanta, Georgia, United States

Site Status

Northwestern Feinberg Pavillion Neuro and Spine ICU

Chicago, Illinois, United States

Site Status

Indiana University Health Methodist Hospital

Indianapolis, Indiana, United States

Site Status

University of Kentucky Hospital

Lexington, Kentucky, United States

Site Status

University of Maryland Medical Center

Baltimore, Maryland, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Washington University

St Louis, Missouri, United States

Site Status

The Mount Sinai Hospital

New York, New York, United States

Site Status

University of North Carolina

Chapel Hill, North Carolina, United States

Site Status

Duke University

Durham, North Carolina, United States

Site Status

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

Site Status

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Site Status

The Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Site Status

Oregon Health and Science University

Portland, Oregon, United States

Site Status

Methodist University Hospital

Memphis, Tennessee, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

University of Texas Health Science Center at Houston

Houston, Texas, United States

Site Status

Virginia Commonwealth University

Richmond, Virginia, United States

Site Status

Countries

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United States

References

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Choi AH, Chou SY, Ducruet AF, Kimberly WT, Loch Macdonald R, Rabinstein AA. Description of STRIVE-ON Study Protocol: 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, Phase III Trial (STRIVE-ON). Neurocrit Care. 2025 Jun;42(3):1107-1117. doi: 10.1007/s12028-024-02207-8. Epub 2025 Jan 28.

Reference Type DERIVED
PMID: 39875683 (View on PubMed)

Other Identifiers

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GTX-104-003

Identifier Type: -

Identifier Source: org_study_id

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