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

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).

Time frame: Baseline (0 hours) to 24-hours post-dose

Population: Treated analysis population included enrolled participants who took study therapy (rimegepant or placebo); i.e., non-missing study drug start date. Missing postbaseline NRS assessments were imputed as the last non-missing observation prior to the missing assessment. Missing baseline assessments were imputed as the mean of the non-missing baseline assessments across participants.

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).

Time frame: Baseline (0 hours) to 2-hours post-dose

Population: Treated analysis population included enrolled participants who took study therapy (rimegepant or placebo); i.e., non-missing study drug start date. Missing postbaseline NRS assessments were imputed as the last non-missing observation prior to the missing assessment. Missing baseline assessments were imputed as the mean of the non-missing baseline assessments across participants.

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.

Time frame: Baseline (0 hours), 2-hours post-dose

Population: Treated analysis population included enrolled participants who took study therapy (rimegepant or placebo); i.e., non-missing study drug start date.

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.

Time frame: Through 24 hours post-dose

Population: Treated analysis population included enrolled participants who took study therapy (rimegepant or placebo); i.e., non-missing study drug start date.

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.

Time frame: Baseline (0 hour) to 2-hours post-dose

Population: Treated analysis population included enrolled participants who took study therapy (rimegepant or placebo); i.e., non-missing study drug start date. Participants who (1) had missing data at 2-hours post-dose or (2) took rescue medication at or before 2-hours post-dose were imputed as failures.

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.

Time frame: Baseline (0 hour) to 24 hours post-dose

Population: Treated analysis population included enrolled participants who took study therapy (rimegepant or placebo); i.e., non-missing study drug start date.

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.

Time frame: Baseline (0 hours) up to 24 hours post-dose

Population: Treated analysis population included enrolled participants who took study therapy (rimegepant or placebo); i.e., non-missing study drug start date.