xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT05995405</url>
    </required_header>
    <id_info>
      <org_study_id>GTX-104-003</org_study_id>
      <nct_id>NCT05995405</nct_id>
    </id_info>
    <brief_title>Safety and Tolerability of GTX-104 Compared With Oral Nimodipine in Patients With aSAH</brief_title>
    <acronym>STRIVE-ON</acronym>
    <official_title>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</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Acasti Pharma Inc.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Acasti Pharma Inc.</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The purpose of this study is to deliver nimodipine via IV directly into the bloodstream and&#xD;
        to determine if this is as safe and tolerable as oral nimodipine capsules.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">November 2023</start_date>
    <completion_date type="Anticipated">November 2024</completion_date>
    <primary_completion_date type="Anticipated">November 2024</primary_completion_date>
    <phase>Phase 3</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>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.</measure>
      <time_frame>90 days</time_frame>
      <description>Hypotension events requiring medical treatment</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Total number of episodes of clinically significant hypotension</measure>
      <time_frame>Day 1 - Day 90</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of episodes of clinically significant hypotension</measure>
      <time_frame>Day 1 - Day 90</time_frame>
      <description>Calendar days</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence and severity of Adverse Events (AEs) based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, Version 5.0).</measure>
      <time_frame>Day 1 - Day 90</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of delayed cerebral ischemia (DCI)</measure>
      <time_frame>Day 1 - Day 21</time_frame>
      <description>Delayed cerebral ischemia will be evaluated and defined by the following:&#xD;
  For subjects in whom changes in the mGCS and Abbreviated National Institutes of Health Stroke Scale (aNIHSS) are assessable: a decrease of at least 2 points on the mGCS or an increase of at least 2 points on the aNIHSS, lasting for at least 2 hours, where other medical or surgical causes are excluded. The deterioration is measured relative to the best score attained after aneurysm repair.&#xD;
  For subjects in whom the neurologic scales are not assessable: radiological evidence and clinical judgement.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Use of rescue therapy for DCI</measure>
      <time_frame>Day 1 - Day 21</time_frame>
      <description>Rescue therapy is defined as induced hypertension, selective intraarterial infusion of vasodilator drugs or balloon angioplasty.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Suicidal ideation using the Columbia-Suicide Severity Rating Scale (C-SSRS) score of ≥ 4</measure>
      <time_frame>Day 1 - Day 90</time_frame>
    </secondary_outcome>
    <other_outcome>
      <measure>Number of intensive care unit (ICU) stays</measure>
      <time_frame>Day 1 - Day 90</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Duration of intensive care unit (ICU) stays</measure>
      <time_frame>Day 1 - Day 90</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Duration (calendar days) of mechanical ventilation</measure>
      <time_frame>Day 1 - Day 90</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Therapeutic Intensity Scale (TIS)</measure>
      <time_frame>Day 1 - Day 14</time_frame>
      <description>Assessed on a daily basis until Day 14 post-aSAH for the occurrence or use of mechanical ventilation, ICP monitoring, a central venous or arterial line, an external ventricular drain, deep sedation, pharmacological paralysis, and whether or not the patient is comatose for a period of at least 8 hours on that day.</description>
    </other_outcome>
    <other_outcome>
      <measure>Number of hospital stays</measure>
      <time_frame>Day 1 - Day 90</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Duration of hospital stays</measure>
      <time_frame>Day 1 - Day 90</time_frame>
      <description>Calendar days</description>
    </other_outcome>
    <other_outcome>
      <measure>Hospital discharge disposition</measure>
      <time_frame>Day 1 - Day 90</time_frame>
      <description>Discharge to: (e.g., home, rehabilitation, long-term care)</description>
    </other_outcome>
    <other_outcome>
      <measure>Quality of Life as measured by EQ-5D-3L</measure>
      <time_frame>Day 30 and Day 90</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Modified Rankin Scale (mRS)</measure>
      <time_frame>Day 30 and Day 90</time_frame>
      <description>0 - No symptoms&#xD;
  - No significant disability despite symptoms; able to carry out all usual duties and activities&#xD;
  - Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance&#xD;
  - Moderate disability; requiring some help, but able to walk without assistance&#xD;
  - Moderately severe disability; unable to walk and attend to bodily needs without assistance&#xD;
  - Severe disability; bedridden, incontinent and requiring constant nursing care and attention&#xD;
  - Dead</description>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">100</enrollment>
    <condition>Aneurysmal Subarachnoid Hemorrhage (aSAH)</condition>
    <arm_group>
      <arm_group_label>GTX-104</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>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</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Oral nimodipine</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>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.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>GTX-104</intervention_name>
      <description>Nimodipine IV infusion</description>
      <arm_group_label>GTX-104</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Nimotop 30 MG Oral Capsule</intervention_name>
      <description>Oral nimodipine capsules</description>
      <arm_group_label>Oral nimodipine</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Male or female ≥18 years of age.&#xD;
  &#xD;
            2. Diagnosis of aneurysmal subarachnoid hemorrhage (aSAH) based on CT scan and&#xD;
               angiography (computed tomography angiography [CTA], magnetic resonance angiography&#xD;
               [MRA], or digital subtraction angiography [DSA]).&#xD;
  &#xD;
            3. Hunt and Hess score from I to V just prior to randomization.&#xD;
  &#xD;
            4. Subject or the subject's legal representative has signed informed consent (either in&#xD;
               person or by fax, scan, or email) before any study-specific procedures are performed.&#xD;
  &#xD;
            5. Able to start IP within 96 hours from the onset of aSAH. Note 1: The onset of aSAH is&#xD;
               defined as the time when the subject experienced the first symptom of aSAH (e.g.,&#xD;
               severe headache or loss of consciousness reported either by the subject or by a&#xD;
               witness).&#xD;
  &#xD;
               Note 2: If found unconscious or the time of first symptoms is unknown, the onset of&#xD;
               aSAH will be defined as the last time the subject was seen at baseline neurological&#xD;
               state.&#xD;
  &#xD;
            6. If a woman of childbearing potential (WOCBP), must have a negative pregnancy test&#xD;
               during the pre-randomization phase (screening). A woman is not of childbearing&#xD;
               potential if she has undergone surgical sterilization (total hysterectomy, or&#xD;
               bilateral tubal ligation, or bilateral oophorectomy at least 6 weeks before taking IP)&#xD;
               or if she is abstinent (see below) or postmenopausal and has had no menstrual bleeding&#xD;
               of any kind including menstrual period, irregular bleeding, spotting, etc., for at&#xD;
               least 12 months, with an appropriate clinical profile, and there is no other cause of&#xD;
               amenorrhea (e.g., hormonal therapy, prior chemotherapy).&#xD;
  &#xD;
               WOCBP and males whose sexual partners are WOCBP must agree to use barrier&#xD;
               contraception and a second form of contraception while receiving IP and for 30 days&#xD;
               following their last dose of IP. Alternatively, total abstinence is also considered a&#xD;
               highly effective contraception method when this is in line with the preferred and&#xD;
               usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation,&#xD;
               symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of&#xD;
               contraception.&#xD;
  &#xD;
            7. Sexually active males must use a condom during intercourse while taking IP and for 30&#xD;
               days after the last dose of IP and should not father a child during this period. A&#xD;
               condom is required to be used also by vasectomized men as well as during intercourse&#xD;
               with a male partner to prevent delivery of the IP via seminal fluid.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Is at imminent risk of death and/or has Do Not Resuscitate (DNR) orders.&#xD;
  &#xD;
            2. Required cardiopulmonary resuscitation within 4 days prior to randomization.&#xD;
  &#xD;
            3. Has second- or third-degree atrio-ventricular block or bradycardia (heart rate ≤50&#xD;
               bpm) prior to randomization.&#xD;
  &#xD;
            4. Has history of cirrhosis (Child-Pugh class B and C) prior to randomization.&#xD;
  &#xD;
            5. Has alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) more than&#xD;
               2.5 times the upper limit of normal (ULN).&#xD;
  &#xD;
            6. Has history of malabsorption syndrome, recent ileus (in the last 3 months), or other&#xD;
               gastrointestinal (GI) conditions that would interfere with absorption of nimodipine,&#xD;
               in the opinion of the Investigator.&#xD;
  &#xD;
            7. Has a severe or unstable concomitant condition or disease other than what may be&#xD;
               attributed to the SAH that, in the opinion of the Investigator, may increase the risk&#xD;
               associated with study participation or nimodipine administration, or may interfere&#xD;
               with the interpretation of study results.&#xD;
  &#xD;
            8. Has a history of recurrent syncope or hypotension that may interfere with the safety&#xD;
               assessments of nimodipine.&#xD;
  &#xD;
            9. Has a known hypersensitivity to nimodipine or capsule constituents or to GTX-104.&#xD;
  &#xD;
           10. Is pregnant/has a positive serum or urine pregnancy test.&#xD;
  &#xD;
           11. Has received more than 5 doses of oral nimodipine (as a solution [e.g., Nymalize] or&#xD;
               capsules) as part of the standard of care (SOC) for the ruptured aneurysm prior to&#xD;
               randomization.&#xD;
  &#xD;
           12. Is receiving strong inhibitors of CYP3A4 such as some macrolide antibiotics (e.g.,&#xD;
               clarithromycin, telithromycin), some anti-HIV protease inhibitors (e.g., delavirdine,&#xD;
               indinavir, nelfinavir, ritonavir, saquinavir), some azole antimycotics (e.g.,&#xD;
               ketoconazole, itraconazole, voriconazole), and some antidepressants (e.g.,&#xD;
               nefazadone). See Appendix 5.&#xD;
  &#xD;
           13. Is receiving or has received any other investigational agent(s)/device(s) in the last&#xD;
               30 days.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>R. Loch Macdonald, MD</last_name>
      <role>Study Director</role>
      <affiliation>Acasti Pharma Inc.</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Carrie DAndrea, MS</last_name>
      <phone>908-514-3969</phone>
      <email>c.dandrea@acasti.com</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 31, 2023</study_first_submitted>
    <study_first_submitted_qc>August 8, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 16, 2023</study_first_posted>
    <last_update_submitted>August 8, 2023</last_update_submitted>
    <last_update_submitted_qc>August 8, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 16, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Subarachnoid Hemorrhage</mesh_term>
      <mesh_term>Hemorrhage</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Nimodipine</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT05995405
  org study id: GTX-104-003
  nct id: NCT05995405
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  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.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: 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.
  time frame: 90 days
  description: Hypotension events requiring medical treatment
  measure: Total number of episodes of clinically significant hypotension
  time frame: Day 1 - Day 90
  measure: Duration of episodes of clinically significant hypotension
  time frame: Day 1 - Day 90
  description: Calendar days
  measure: Incidence and severity of Adverse Events (AEs) based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, Version 5.0).
  time frame: Day 1 - Day 90
  measure: Incidence of delayed cerebral ischemia (DCI)
  time frame: Day 1 - Day 21
  description: Delayed cerebral ischemia will be evaluated and defined by the following:
  For subjects in whom changes in the mGCS and Abbreviated National Institutes of Health Stroke Scale (aNIHSS) are assessable: a decrease of at least 2 points on the mGCS or an increase of at least 2 points on the aNIHSS, lasting for at least 2 hours, where other medical or surgical causes are excluded. The deterioration is measured relative to the best score attained after aneurysm repair.
  For subjects in whom the neurologic scales are not assessable: radiological evidence and clinical judgement.
  measure: Use of rescue therapy for DCI
  time frame: Day 1 - Day 21
  description: Rescue therapy is defined as induced hypertension, selective intraarterial infusion of vasodilator drugs or balloon angioplasty.
  measure: Suicidal ideation using the Columbia-Suicide Severity Rating Scale (C-SSRS) score of ≥ 4
  time frame: Day 1 - Day 90
  measure: Number of intensive care unit (ICU) stays
  time frame: Day 1 - Day 90
  measure: Duration of intensive care unit (ICU) stays
  time frame: Day 1 - Day 90
  measure: Duration (calendar days) of mechanical ventilation
  time frame: Day 1 - Day 90
  measure: Therapeutic Intensity Scale (TIS)
  time frame: Day 1 - Day 14
  description: Assessed on a daily basis until Day 14 post-aSAH for the occurrence or use of mechanical ventilation, ICP monitoring, a central venous or arterial line, an external ventricular drain, deep sedation, pharmacological paralysis, and whether or not the patient is comatose for a period of at least 8 hours on that day.
  measure: Number of hospital stays
  time frame: Day 1 - Day 90
  measure: Duration of hospital stays
  time frame: Day 1 - Day 90
  description: Calendar days
  measure: Hospital discharge disposition
  time frame: Day 1 - Day 90
  description: Discharge to: (e.g., home, rehabilitation, long-term care)
  measure: Quality of Life as measured by EQ-5D-3L
  time frame: Day 30 and Day 90
  measure: Modified Rankin Scale (mRS)
  time frame: Day 30 and Day 90
  description: 0 - No symptoms
  - No significant disability despite symptoms; able to carry out all usual duties and activities
  - Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance
  - Moderate disability; requiring some help, but able to walk without assistance
  - Moderately severe disability; unable to walk and attend to bodily needs without assistance
  - Severe disability; bedridden, incontinent and requiring constant nursing care and attention
  - Dead
  arm group label: GTX-104
  arm group type: Experimental
  description: 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
  arm group label: Oral nimodipine
  arm group type: Active Comparator
  description: 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.
  intervention type: Drug
  intervention name: GTX-104
  description: Nimodipine IV infusion
  arm group label: GTX-104
  intervention type: Drug
  intervention name: Nimotop 30 MG Oral Capsule
  description: Oral nimodipine capsules
  arm group label: Oral nimodipine
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: R. Loch Macdonald, MD
  role: Study Director
  affiliation: Acasti Pharma Inc.
  last name: Carrie DAndrea, MS
  phone: 908-514-3969
  email: c.dandrea@acasti.com
  responsible party type: Sponsor
  mesh term: Subarachnoid Hemorrhage
  mesh term: Hemorrhage
  mesh term: Nimodipine
  sharing ipd: No