Trial for Treatment Refractory Trigeminal Neuralgia

BHV3000-202: Phase 2: A Double-Blind, Placebo Controlled, Crossover Trial of BHV-3000 (Rimegepant) for Treatment Refractory Trigeminal Neuralgia

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.

Study Overview

• Status: Terminated
• Conditions: Trigeminal Neuralgia
• Intervention / Treatment: Drug: Placebo; Drug: Rimegepant

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Gilbert, Arizona, United States, 85297
      • Gilbert Neurology Partners, PLLC/CCT Research
  • California
    • La Jolla, California, United States, 92037
      • Center for Neurohealth DBA Kaizen Brain Center
    • Palo Alto, California, United States, 94304
      • Stanford Neuroscience Health Center
    • Palo Alto, California, United States, 94304
      • Imaging Clinic at Stanford Neuroscience Health Center
    • Palo Alto, California, United States, 94304
      • Stanford Hoover Pavilion
    • Palo Alto, California, United States, 94304
      • Stanford Neuroscience Health Center- SNHC Pharmacy
    • Stanford, California, United States, 94305
      • Stanford University- CAM Building
  • Florida
    • Miami, Florida, United States, 33136
      • SouthCoast Research Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70115
      • Ochsner Baptist Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Clinical Outpatient Center
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins ICTR Clinical Research Unit (CRU)
  • Missouri
    • Chesterfield, Missouri, United States, 63005
      • Clinical Research Professionals
  • New York
    • Amherst, New York, United States, 14226
      • Dent Neurosciences Research Center
    • Lake Success, New York, United States, 11042
      • Neurological Surgery Practice of Long Island PLCC
    • Lake Success, New York, United States, 11042
      • Neurological Surgery
    • Lake Success, New York, United States, 11042
      • Premier Cardiolog Consultants
    • New Hyde Park, New York, United States, 11042
      • Premier Cardiology Consultants
    • New Hyde Park, New York, United States, 11042
      • Premier Cardiolog Consultants
    • Port Jefferson Station, New York, United States, 11776
      • North Suffolk Neurology, PC
  • Ohio
    • Dayton, Ohio, United States, 45459
      • Neurology Diagnostics Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo
Active Comparator: BHV3000	Drug: Rimegepant; BHV3000 (rimegepant) 75mg tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Average Daily Pain Score on Numeric Pain Rating Scale (NPRS) at 2 Week Treatment Phase: DBT Phase	NPRS is an 11-point scale ranging from 0 (no pain) to 10 (worst pain imaginable), higher scores represent worse pain. Participants daily recorded their average pain level over a 24-hour period on NPRS. Pain score was the average of the daily 11-point NPRS recorded within each period. Average of pain score on NPRS according to treatment received in first or second treatment period of DBT phase are used for evaluation of the outcome measure.	DBT Phase: Baseline (before dose on Day 1), 2 Weeks Treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With All-Causality Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Study Drug Discontinuation and Treatment Related AEs: DBT Phase	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. SAE: Any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect other important medical events. A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. Relatedness to drug was assessed by investigator.	DBT Phase: Day 1 of dosing up to last day of dosing (up to 5 weeks)
Number of Participants With Any Change From Baseline in Sheehan Suicidality Tracking Scale (S-STS) Scores: DBT Phase	S-STS is a scale that assesses the seriousness of suicidality phenomena on a 5-point Likert-type scale (0 to 4) ranging from "not at all" (0) to "extremely" (4), where higher scores signify suicidal tendency. In this outcome measure, number of participants who had any change in S-STS score from baseline to end of treatment are reported according to the treatment received in first or second treatment period of DBT phase.	DBT Phase: Baseline, 2 Weeks Treatment
Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities: DBT Phase	ECG abnormalities included were a Corrected QT interval exceeding 470 milliseconds (QTc calculated using the Frederica method), left bundle branch block, right bundle branch block with a QRS duration of 150 milliseconds or more, and intraventricular conduction defect with a QRS duration equal to or greater than 150 milliseconds. Clinical significance in ECG abnormalities was judged by investigator.	DBT Phase: Day 1 of dosing up to last day of dosing (up to 5 weeks)
Number of Participants With Clinically Significant Laboratory Abnormalities: DBT Phase	Laboratory abnormalities included 1)Hematology: hemoglobin, hematocrit, platelets, complete blood count with differential and absolute neutrophil count; 2)Serum chemistry: sodium, potassium, chloride, calcium, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase, gamma-glutamyl transferase, phosphorus, bicarbonate, creatine phosphokinase, total protein, albumin, total bilirubin, glucose, creatinine, blood urea nitrogen, uric acid, total cholesterol, low-density lipoprotein, high-density lipoprotein, triglycerides, folate, hemoglobin A1C, pancreatic amylase or lipase, thyroid-stimulating Hormone, thyroxine; 3)Urinalysis: macroscopic examination, pH, specific gravity, ketones, nitrites, urobilinogen, leukocyte esterase, protein, glucose, occult blood; 4)Liver function tests: alanine aminotransferase, aspartate aminotransferase, total bilirubin, alkaline phosphatase. Clinical significance in laboratory abnormalities was judged by investigator.	DBT Phase: Day 1 of dosing up to last day of dosing (up to 5 weeks)
Change From Baseline in Penn Facial Pain Scale-Revised (Penn-FPS-R) Total Score at 2 Week Treatment Phase: DBT Phase	Penn-FPS-R: a 12-item scale, utilized to evaluate the impact of TN pain on health-related quality of life and daily activities. Each 12 items ranged from 0 (does not interfere) to 10 (completely interferes). Penn-FPS-R total score was calculated by adding scores of all items and had a score range of (does not interfere) 0 to 120 (completely interferes).Higher Penn-FPS-R total scores signifies worse condition. Participants were asked to complete the Penn-FPS-R at the beginning and end of each treatment period. Average of total Penn-FPS-score according to treatment received in first or second treatment period of DBT phase are used in evaluation of the outcome measure.	DBT Phase: Baseline, 2 Weeks Treatment
Change From Baseline in Pain Disability Index Total Score at 2 Week Treatment Phase: DBT Phase	Pain disability index measures the extent of disruption in a participant's daily life caused by pain, utilizing a 7-item scale scored on an 11-point Likert Scale, where "0" denotes "no disability," and "10" indicates "worst disability". Higher scores signify worse outcome. Pain disability index total score was calculated by adding scores of all the 7 items and had a score range of 0 to 70. Higher pain disability index total scores signifies worse condition. Participants were instructed to complete the pain disability index at the beginning and end of each treatment period. Average of pain disability index total scores according to treatment received in first or second treatment period of DBT phase are used for evaluation of the outcome measure.	DBT Phase: Baseline, 2 Weeks Treatment
Patient Global Impression of Change Scale (PGI-C) Score at 2 Week Treatment Phase: DBT Phase	PGI-C is a participant-reported scale utilized to evaluate the improvement or deterioration of the participant's current illness status compared to the baseline visit. Participants were asked to rate a change in their overall disease condition on a 7-point scale, ranging from 1 (no change) to 7 (a great deal better). Higher PGI-C scores signify better outcome. PGI-C assessments were conducted at the beginning and end of each treatment phase. Average of PGI-C score according to treatment received in first or second treatment period of DBT phase are used in evaluation of the outcome measure.	DBT Phase: Baseline, 2 Weeks Treatment
Change From Baseline in Average Worst Pain Score on NPRS at 2 Week Treatment Phase: DBT Phase	NPRS is an 11-point scale ranging from 0 (no pain) to 10 (worst pain imaginable), higher scores represent worse pain. Participants daily recorded their worst pain rating over a 24-hour period on NPRS. Average of worst pain NPRS score according to treatment received in first or second treatment period of DBT phase are used in evaluation of the outcome measure.	DBT Phase: Baseline, 2 Weeks Treatment
Percentage of Participants With >= 2 Point Reduction From Baseline in Average Daily Pain Score on NPRS at 2 Week Treatment Phase: DBT Phase	NPRS is an 11-point scale ranging from 0 (no pain) to 10 (worst pain imaginable), higher scores represent worse pain. Participants daily recorded their average pain level over a 24-hour period. Pain score was the average of the daily 11-point NPRS recorded within each period. Average of pain score on NPRS according to treatment received in first or second treatment period of DBT Phase are used in evaluation of the outcome measure.	DBT Phase: Baseline, 2 Weeks Treatment

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): June 25, 2019
• Primary Completion (Actual): May 11, 2023
• Study Completion (Actual): May 11, 2023

Study Registration Dates

• First Submitted: April 29, 2019
• First Submitted That Met QC Criteria: May 6, 2019
• First Posted (Actual): May 8, 2019

Study Record Updates

• Last Update Posted (Actual): June 10, 2024
• Last Update Submitted That Met QC Criteria: June 7, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Trigeminal Neuralgia, Pain
• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Neuromuscular Diseases; Stomatognathic Diseases; Mouth Diseases; Peripheral Nervous System Diseases; Cranial Nerve Diseases; Facial Nerve Diseases; Trigeminal Nerve Diseases; Facial Neuralgia; Neuralgia; Trigeminal Neuralgia
• Other Study ID Numbers: BHV3000-202; C4951014 (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No