Safety and Efficacy of BHV-3000 (Rimegepant) Orally Disintegrating Tablet for Acute Treatment of Temporomandibular Disorders

A Phase 2/3, Double-Blind, Randomized, Placebo-Controlled, Safety and Efficacy Trial of BHV-3000 (Rimegepant) Orally Disintegrating Tablet (ODT) for the Acute Treatment of Temporomandibular Disorders (TMD)

The purpose of this study is to compare the efficacy and safety of rimegepant versus placebo in the acute treatment of Temporomandibular Disorders (TMD), which are medical conditions involving the temporomandibular joint (the joint connecting the jawbone to the skull) and surrounding muscles and tissues.

Study Overview

• Status: Terminated
• Conditions: Temporomandibular Disorders (TMD)
• Intervention / Treatment: Drug: Placebo; Drug: Rimegepant

• Study Type: Interventional
• Enrollment (Actual): 126
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85053
      • Arizona Research Center
    • Phoenix, Arizona, United States, 85020
      • Bruce Nelson, DDS
  • Florida
    • Hollywood, Florida, United States, 33021
      • The Medici Medical Research, LLC
    • Hollywood, Florida, United States, 33021
      • The Medici Medical Research
    • Miami, Florida, United States, 33136
      • SouthCoast Research Center
    • Miami, Florida, United States, 33144
      • Oceane7 Medical & Research Center, Inc.
    • Miami, Florida, United States, 33136
      • SouthCoast Research Center, Inc
    • Tampa, Florida, United States, 33613
      • Forcare Clinical Research
    • Tampa, Florida, United States, 33607
      • Florida Craniofacial Institute
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University School of Dentistry
    • Indianapolis, Indiana, United States, 46202
      • Campus Health, Indiana University-Purdue University Indianapolis
    • Indianapolis, Indiana, United States, 46202
      • IDS-IU Simon Cancer Center (IUSCC)
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky, College of Dentistry
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • TMD, Orofacial Pain and Dental Sleep Medicine Clinic, School of Dentistry, University of Minnesota
  • Missouri
    • Springfield, Missouri, United States, 65810
      • Clinvest Research
    • Springfield, Missouri, United States, 65807
      • Clinvest Research, LLC
  • New York
    • Commack, New York, United States, 11725
      • North Suffolk Neurology
    • Rochester, New York, United States, 14618
      • University of Rochester
  • North Carolina
    • Raleigh, North Carolina, United States, 27617
      • Duke University
  • Ohio
    • Dayton, Ohio, United States, 45432
      • META Medical Research Institute,LLC.
    • Dayton, Ohio, United States, 45432
      • Meta Medical Research
    • Springboro, Ohio, United States, 45066
      • Kulkarni Orthodonties
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Perelman Center for Advanced Medicine
    • Pittsburgh, Pennsylvania, United States, 15201
      • University of Pittsburgh
  • Texas
    • Lake Jackson, Texas, United States, 77566
      • Red Star Research, LLC
    • Lake Jackson, Texas, United States, 77566
      • Red Star Research
    • Lampasas, Texas, United States, 76550
      • FMC Science
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • JBR Clinical Research
    • Salt Lake City, Utah, United States, 84107
      • JBR
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center
    • Seattle, Washington, United States, 98121
      • Snoring and Sleep Apnea Center (DC/TMD Exam - Dr. Christian)

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

* Subject has a minimum 3-month to a maximum 5-year history of temporomandibular disorder diagnosed by a healthcare provider.

• At least one instance of pain ≥ 6 on a Numeric Rating Scale (NRS) (0-10) in the jaw and/or temple area on either side in the past 30 days prior to the Screening Visit.
• Subject agrees to study-required restrictions of new pain medication, injection therapy, oral devices, occlusal splint therapy or any other pain management techniques during the course of the study.
• Subject agrees to study-required birth control methods during the course of the study and female subjects must not be breastfeeding.
• No clinically significant abnormality identified on the medical or laboratory evaluation.

Exclusion Criteria:

* Subject has an exclusionary headache, joint, pain, connective tissue, or developmental disorder.

• Subject has an exclusionary history of trauma, surgery, or radiation treatment to the head and neck.
• Body Mass Index ≥ 33kg/m2.
• Subject history of exclusionary medical conditions such as HIV disease, cardiovascular conditions, uncontrolled hypertension or diabetes, psychiatric conditions, drug or alcohol abuse, malignancies, drug allergies, or any significant and/or unstable medical conditions.
• Subjects taking/using excluded therapies.
• Participation in clinical trial with non-biological investigational agents or investigational interventional treatments.
• Subjects who have previously participated in any BHV-3000/ BMS-927711/ rimegepant study.
• Planned participation in any other investigational clinical trial while participating in this clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BHV3000 (rimegepant); One dose of rimegepant 75 mg ODT	Drug: Rimegepant; 75 mg ODT; Other Names: BHV3000
Placebo Comparator: Matching Placebo; One dose of matching placebo	Drug: Placebo; matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sum of Pain Intensity Difference (SPID) From Baseline to 2-Hours Post-dose (SPID-2)	The SPID-2 was calculated by multiplying the pain intensity difference (PID) score at each post-dose timepoint by the duration (in hours) since the preceding timepoint, then summing the values over the 2 hours. Participants indicated pain using e-diary at each timepoint (0, 15, 30, 45-, 60-, 90- and 120-minutes post-dose) on an NRS score ranging from 0 (no pain) to 10 (worst imaginable pain). PID: calculated by finding the difference between the NRS score at each timepoint from the baseline NRS score (PID range is -6 [best] to 4 [worst]). Assuming a baseline pain intensity score of 6, possible score range of SPID-2 was: -12 (best) to 8 (worst). Lower SPID-2 score = more improvement from pain. SPID-2 Best is 2 hours*-6 = -12 (assuming 0 pain intensity score [pain-free] for each timepoint) and 2) Worst is 2 hours*4 = 8 (assuming 10 pain intensity score [worst imaginable pain] for each timepoint).	Baseline (0 hours) to 2-hours post-dose
SPID From Baseline to 24-Hours Post-dose (SPID-24)	The SPID-24 was calculated by multiplying the PID score at each post-dose timepoint by the duration (in hours) since the preceding timepoint, then summing the values over the 24 hours. Participants indicated pain using e-diary at each timepoint (0, 15, 30, 45, 60, 90 and 120 minutes and 4-, 8-, and 24-hours post-dose) on an NRS score ranging from 0 (no pain) to 10 (worst imaginable pain). PID: calculated by finding the difference between the NRS score at each timepoint from the baseline NRS score (PID range is -6 [best] to 4 [worst]). Assuming a baseline pain intensity score of 6, possible score range of SPID-24 was: -144 (Best) to 96 (worst). Lower SPID-24 score = more improvement from pain. SPID-24 best and worst scores were calculated as: 1) Best is 24 hours* -6 = -144 (assuming 0 pain intensity score for each timepoint) and 2) Worst is 24 hours*4 = 96 (assuming 10 pain intensity score for each timepoint).	Baseline (0 hours) to 24-hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in NRS Score at 2-Hours Post-Dose	TMD pain was assessed using an NRS score ranging in integers from 0 to 10, with 0 being "no pain" and 10 being "worst imaginable pain."	Baseline (0 hours), 2-hours post-dose
Percentage of Participants Who Experienced Pain Freedom at 2-Hours Post-Dose	Pain freedom was defined as an NRS score of zero at 2 hours post-dose (yes or no). TMD pain was assessed using an NRS score ranging in integers from 0 to 10, with 0 being "no pain" and 10 being "worst imaginable pain."	Baseline (0 hour) to 2-hours post-dose
Time to Onset of Meaningful Pain Relief	Time to onset of meaningful pain relief post-dose is defined as the first nominal timepoint at which a 30% reduction of pain from baseline on NRS is achieved. TMD pain was assessed using an NRS score ranging in integers from 0 to 10, with 0 being "no pain" and 10 being "worst imaginable pain." Kaplan-Meier method was used for analysis.	Baseline (0 hours) up to 24 hours post-dose
Time to Onset of Initial Pain Relief	Time to onset of initial pain relief post-dose is defined as the first nominal timepoint at which a 1-point reduction of pain from baseline on NRS is achieved. TMD pain was assessed using an NRS score ranging in integers from 0 to 10, with 0 being "no pain" and 10 being "worst imaginable pain." Kaplan-Meier method was used for analysis.	Baseline (0 hour) to 24 hours post-dose
Percentage of Participants Using Rescue Medication Within 24 Hours Post-Dose	Rescue medications included any non-study medication recorded on the rescue medication case report form (CRF) with complete medication dates, and either (1) medication date/time is after the study drug start date/time if the medication time and study drug start time are both not missing, or (2) medication date is on or after study drug start date if the medication time or study drug start time is missing.	Through 24 hours post-dose

Collaborators and Investigators

• Sponsor: Pfizer
• Collaborators: Biohaven Pharmaceutical Holding Company Ltd.
• 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): May 5, 2022
• Primary Completion (Actual): May 18, 2023
• Study Completion (Actual): May 18, 2023

Study Registration Dates

• First Submitted: February 21, 2022
• First Submitted That Met QC Criteria: February 21, 2022
• First Posted (Actual): March 2, 2022

Study Record Updates

• Last Update Posted (Actual): May 16, 2024
• Last Update Submitted That Met QC Criteria: May 7, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: TMD; TMJ; Temporomandibular Disorders; Temporomandibular Joint
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Muscular Diseases; Stomatognathic Diseases; Jaw Diseases; Craniomandibular Disorders; Mandibular Diseases; Myofascial Pain Syndromes; Temporomandibular Joint Disorders; Temporomandibular Joint Dysfunction Syndrome
• Other Study ID Numbers: BHV3000-317; C4951016 (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