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出境医 / 临床实验 / Trial for Treatment Refractory Trigeminal Neuralgia

Trial for Treatment Refractory Trigeminal Neuralgia

Study Description
Brief Summary:
The purpose of this study is to evaluate the efficacy of BHV3000 compared to placebo for subjects with treatment refractory Trigeminal Neuralgia as measured by a 2-point or greater reduction in the average Numeric Pain Rating Scale between the two-week treatment phases.

Condition or disease Intervention/treatment Phase
Trigeminal Neuralgia Drug: Rimegepant Drug: Placebo Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: BHV3000-202: Phase 2: A Double-Blind, Placebo Controlled, Crossover Trial of BHV-3000 (Rimegepant) for Treatment Refractory Trigeminal Neuraligia
Actual Study Start Date : June 25, 2019
Estimated Primary Completion Date : December 15, 2021
Estimated Study Completion Date : December 15, 2021
Arms and Interventions
Arm Intervention/treatment
Active Comparator: BHV3000 Drug: Rimegepant
BHV3000 (rimegepant) 75mg tablet

Placebo Comparator: Placebo Drug: Placebo
Placebo

Outcome Measures
Primary Outcome Measures :
  1. Efficacy of BHV-3000 compared to placebo in providing symptomatic pain relief in patients with refractory Trigeminal Neuralgia, as measured by a 2-point or greater reduction in the average Numeric Pain Rating Scale. [ Time Frame: From Baseline to End of Randomization Phase, up to 5 weeks. ]
    Change in mean NPRS between the treatment phase. Pain will be measured on a 4 point Likert scale (0=none, 1=mild, 2=moderate, 3=severe)


Secondary Outcome Measures :
  1. Safety and tolerability (Incidence of treatment emergent adverse events) of BHV-3000 relative to placebo in patients with Trigeminal Neuralgia [ Time Frame: From Baseline to End of Randomization Phase up to 5 weeks. ]
    Safety and tolerability will be measured by the frequency and severity of adverse events and discontinuations due to adverse events.

  2. Efficacy of BHV-3000 vs placebo for improving physical function in Trigeminal Neuralgia patients as measured by the Penn Facial Pain Scale-Revised [ Time Frame: From Baseline to End of Randomization Phase ]
    12 questions in which the higher the score the more pain and disability

  3. Efficacy of BHV-3000 vs placebo for improving functional disability in Trigeminal Neuralgia patients as measured by the Pain Disability Index [ Time Frame: From Baseline to End of Randomization Phase, up to 5 weeks. ]
    7 question's that are Scored 0-10, ten being more disabled.

  4. Efficacy of BHV-3000 vs placebo on global functioning as measured by the Patient Global Impression of Change Scale. [ Time Frame: From Baseline to End of Randomization Phase, up to 5 weeks. ]
    Measured by a likert scale from No change to a great deal better.

  5. Efficacy of BHV-3000 vs placebo in providing symptomic pain relief as captured by daily rating of worst pain episode as measured by the 11 point numeric rating scale. [ Time Frame: From Baseline to End of Randomization Phase, up to 5 weeks. ]
    11 point numeric rating scale.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subjects with a clinical diagnosis of typical or atypical classical trigeminal neuralgia based on the International Classification of Headache Disorders, 3rd edition, beta version.
  2. Trigeminal neuralgia symptoms for a minimum of 8 weeks prior to randomization visit.
  3. Neuroimaging to exclude another cause for the neuralgia, other than neurovascular compression.

Exclusion Criteria:

  1. Subject has a structural lesion on neuroimaging, other than vascular compression of the trigeminal nerve or nerve root that would explain the neuralgia
  2. Subject has a clinically evident neurologic deficit on neurologic exam of the cranial nerves
  3. Subjects with a history of HIV disease
  4. Subject history with current evidence of uncontrolled, unstable or recently diagnosed cardiovascular disease, such as ischemic heart disease, coronary artery vasospasm, and cerebral ischemia. Subjects with Myocardial Infarction (MI), Acute Coronary Syndrome (ACS), Percutaneous Coronary Intervention (PCI), cardiac surgery, stroke or transient ischemic attack (TIA) during the 6 months prior to screening
  5. Uncontrolled hypertension (high blood pressure) at screening
  6. Subject has a current diagnosis of major depression, other pain syndromes, psychiatric conditions (e.g., schizophrenia), dementia, or significant neurological disorders (other than migraine) that, in the Investigator's opinion, might interfere with study assessments
  7. Subject has a history of gastric, or small intestinal surgery (including Gastric Bypass, Gastric Banding, Gastric Sleeve, Gastric Balloon, etc.), or has a disease that causes malabsorption
  8. Subject has a history or diagnosis of Gilbert's Syndrome or any other active hepatic or biliary disorder
  9. The subject has a history or current evidence of any significant and/or unstable medical conditions (e.g., history of congenital heart disease or arrhythmia, known suspected infection, hepatitis B or C, or cancer) that, in the investigator's opinion, would expose them to undue risk of a significant adverse event (AE) or interfere with assessments of safety or efficacy during the course of the trial
  10. History of, treatment for, or evidence of, alcohol or drug abuse within the past 12 months or subjects who have met DSM-V criteria for any significant substance use disorder within the past 12 months from the date of the screening visit
  11. Hematologic or solid malignancy diagnosis within 5 years prior to screening. Subjects with a history of localized basal cell or squamous cell skin cancer are eligible for the study if they are cancer-free prior to the screening visit in this study.
  12. Hematologic or solid malignancy diagnosis within 5 years prior to screening. Subjects with a history of localized basal cell or squamous cell skin cancer are eligible for the study if they are cancer-free prior to the screening visit in this study.
  13. Body mass index >33kg/m²
  14. History of gallstones or cholecystectomy
Contacts and Locations

Contacts
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Contact: Elyse Stock, MD 203-404-0410 clinicaltrials@biohavenpharma.com

Locations
Layout table for location information
United States, California
Center for Neurohealth: Kaizen Brain Center Recruiting
La Jolla, California, United States, 92037
Contact: Nancy Tomka    858-294-0161    research@kaizenbraincenter.com   
Stanford University Recruiting
Stanford, California, United States, 94305
Contact: Anthony Bet    650-683-5823    abet0915@stanford.edu   
United States, Florida
SouthCoast Research Center Recruiting
Miami, Florida, United States, 33136
Contact: Lourdes Martinez    786-343-6937    sc2@southresearch.org   
United States, Louisiana
Ochsner Baptist Medical Center Recruiting
New Orleans, Louisiana, United States, 70115
Contact: Colleen Dionne    504-894-2864    colleen.dionne@ochsner.org   
United States, Maryland
Johns Hopkins University Recruiting
Baltimore, Maryland, United States, 21287
Contact: Whitney Isennock    410-955-7008    wwebb10@jhmi.edu   
United States, Missouri
Clinical Research Professionals Recruiting
Chesterfield, Missouri, United States, 63005
Contact: Malana Kanallakan    636-220-1200    recruitment@clinicalresearchprofessionals.net   
United States, New York
Dent Neurological Institute Recruiting
Amherst, New York, United States, 14226
Contact: Rebecca Hogan    716-558-5670    rhogan@dentinstitute.com   
North Suffolk Neurology Recruiting
Port Jefferson Station, New York, United States, 11776
Contact: Matthew Kluko    631-629-8810    mkluko@nsneuro.net   
United States, Ohio
Neurology Diagnostics Inc. Recruiting
Dayton, Ohio, United States, 45459
Contact: Taylor Rhodes    937-224-8200    taylor.rhodes@neurologydiagnostics.com   
Sponsors and Collaborators
Biohaven Pharmaceuticals, Inc.
Tracking Information
First Submitted Date  ICMJE April 29, 2019
First Posted Date  ICMJE May 8, 2019
Last Update Posted Date June 2, 2021
Actual Study Start Date  ICMJE June 25, 2019
Estimated Primary Completion Date December 15, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 7, 2019)
Efficacy of BHV-3000 compared to placebo in providing symptomatic pain relief in patients with refractory Trigeminal Neuralgia, as measured by a 2-point or greater reduction in the average Numeric Pain Rating Scale. [ Time Frame: From Baseline to End of Randomization Phase, up to 5 weeks. ]
Change in mean NPRS between the treatment phase. Pain will be measured on a 4 point Likert scale (0=none, 1=mild, 2=moderate, 3=severe)
Original Primary Outcome Measures  ICMJE
 (submitted: May 6, 2019)
Efficacy of BHV-3000 compared to placebo in providing symptomatic pain relief in patients with refractory Trigeminal Neuralgia, as measured by a 2-point or greater reduction in the average Numeric Pain Rating Scale. [ Time Frame: From Baseline to End of Randomization Phase, up to 5 weeks. ]
Change in mean NPRS between the treatment phase.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 13, 2020)
  • Safety and tolerability (Incidence of treatment emergent adverse events) of BHV-3000 relative to placebo in patients with Trigeminal Neuralgia [ Time Frame: From Baseline to End of Randomization Phase up to 5 weeks. ]
    Safety and tolerability will be measured by the frequency and severity of adverse events and discontinuations due to adverse events.
  • Efficacy of BHV-3000 vs placebo for improving physical function in Trigeminal Neuralgia patients as measured by the Penn Facial Pain Scale-Revised [ Time Frame: From Baseline to End of Randomization Phase ]
    12 questions in which the higher the score the more pain and disability
  • Efficacy of BHV-3000 vs placebo for improving functional disability in Trigeminal Neuralgia patients as measured by the Pain Disability Index [ Time Frame: From Baseline to End of Randomization Phase, up to 5 weeks. ]
    7 question's that are Scored 0-10, ten being more disabled.
  • Efficacy of BHV-3000 vs placebo on global functioning as measured by the Patient Global Impression of Change Scale. [ Time Frame: From Baseline to End of Randomization Phase, up to 5 weeks. ]
    Measured by a likert scale from No change to a great deal better.
  • Efficacy of BHV-3000 vs placebo in providing symptomic pain relief as captured by daily rating of worst pain episode as measured by the 11 point numeric rating scale. [ Time Frame: From Baseline to End of Randomization Phase, up to 5 weeks. ]
    11 point numeric rating scale.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 6, 2019)
  • Safety and tolerability of BHV-3000 relative to placebo in patients with Trigeminal Neuralgia [ Time Frame: From Baseline to End of Randomization Phaseup to 5 weeks. ]
    Safety and tolerability will be measured by the frequency and severity of adverse events and discontinuations due to adverse events
  • Efficacy of BHV-3000 vs placebo for improving physical function in Trigeminal Neuralgia patients as measured by the Penn Facial Pain Scale-Revised [ Time Frame: From Baseline to End of Randomization Phase ]
  • Efficacy of BHV-3000 vs placebo for improving functional disability in Trigeminal Neuralgia patients as measured by the Pain Disability Index [ Time Frame: From Baseline to End of Randomization Phase, up to 5 weeks. ]
  • Efficacy of BHV-3000 vs placebo on global functioning as measured by the Patient Global Impression of Change Scale. [ Time Frame: From Baseline to End of Randomization Phase, up to 5 weeks. ]
  • Efficacy of BHV-3000 vs placebo in improving emotional functioning as measured by the Hospital Anxiety and Depression Scale (HADS) [ Time Frame: From Randomization to end of treatment period, up to 5 weeks. ]
  • Efficacy of BHV-3000 vs placebo in providing pain relief as captured by daily rating of worst pain episode as measured by the 11 point numeric rating scale. [ Time Frame: From Baseline to End of Randomization Phase, up to 5 weeks. ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Trial for Treatment Refractory Trigeminal Neuralgia
Official Title  ICMJE BHV3000-202: Phase 2: A Double-Blind, Placebo Controlled, Crossover Trial of BHV-3000 (Rimegepant) for Treatment Refractory Trigeminal Neuraligia
Brief Summary The purpose of this study is to evaluate the efficacy of BHV3000 compared to placebo for subjects with treatment refractory Trigeminal Neuralgia as measured by a 2-point or greater reduction in the average Numeric Pain Rating Scale between the two-week treatment phases.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Trigeminal Neuralgia
Intervention  ICMJE
  • Drug: Rimegepant
    BHV3000 (rimegepant) 75mg tablet
  • Drug: Placebo
    Placebo
Study Arms  ICMJE
  • Active Comparator: BHV3000
    Intervention: Drug: Rimegepant
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 6, 2019)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 15, 2021
Estimated Primary Completion Date December 15, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Subjects with a clinical diagnosis of typical or atypical classical trigeminal neuralgia based on the International Classification of Headache Disorders, 3rd edition, beta version.
  2. Trigeminal neuralgia symptoms for a minimum of 8 weeks prior to randomization visit.
  3. Neuroimaging to exclude another cause for the neuralgia, other than neurovascular compression.

Exclusion Criteria:

  1. Subject has a structural lesion on neuroimaging, other than vascular compression of the trigeminal nerve or nerve root that would explain the neuralgia
  2. Subject has a clinically evident neurologic deficit on neurologic exam of the cranial nerves
  3. Subjects with a history of HIV disease
  4. Subject history with current evidence of uncontrolled, unstable or recently diagnosed cardiovascular disease, such as ischemic heart disease, coronary artery vasospasm, and cerebral ischemia. Subjects with Myocardial Infarction (MI), Acute Coronary Syndrome (ACS), Percutaneous Coronary Intervention (PCI), cardiac surgery, stroke or transient ischemic attack (TIA) during the 6 months prior to screening
  5. Uncontrolled hypertension (high blood pressure) at screening
  6. Subject has a current diagnosis of major depression, other pain syndromes, psychiatric conditions (e.g., schizophrenia), dementia, or significant neurological disorders (other than migraine) that, in the Investigator's opinion, might interfere with study assessments
  7. Subject has a history of gastric, or small intestinal surgery (including Gastric Bypass, Gastric Banding, Gastric Sleeve, Gastric Balloon, etc.), or has a disease that causes malabsorption
  8. Subject has a history or diagnosis of Gilbert's Syndrome or any other active hepatic or biliary disorder
  9. The subject has a history or current evidence of any significant and/or unstable medical conditions (e.g., history of congenital heart disease or arrhythmia, known suspected infection, hepatitis B or C, or cancer) that, in the investigator's opinion, would expose them to undue risk of a significant adverse event (AE) or interfere with assessments of safety or efficacy during the course of the trial
  10. History of, treatment for, or evidence of, alcohol or drug abuse within the past 12 months or subjects who have met DSM-V criteria for any significant substance use disorder within the past 12 months from the date of the screening visit
  11. Hematologic or solid malignancy diagnosis within 5 years prior to screening. Subjects with a history of localized basal cell or squamous cell skin cancer are eligible for the study if they are cancer-free prior to the screening visit in this study.
  12. Hematologic or solid malignancy diagnosis within 5 years prior to screening. Subjects with a history of localized basal cell or squamous cell skin cancer are eligible for the study if they are cancer-free prior to the screening visit in this study.
  13. Body mass index >33kg/m²
  14. History of gallstones or cholecystectomy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Elyse Stock, MD 203-404-0410 clinicaltrials@biohavenpharma.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03941834
Other Study ID Numbers  ICMJE BHV3000-202
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Biohaven Pharmaceuticals, Inc.
Study Sponsor  ICMJE Biohaven Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Biohaven Pharmaceuticals, Inc.
Verification Date June 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP