Trial Outcomes & Findings for Trial for Treatment Refractory Trigeminal Neuralgia (NCT NCT03941834)

Last Updated: 2024-06-10

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

65 participants

Primary outcome timeframe

DBT Phase: Baseline (before dose on Day 1), 2 Weeks Treatment

Results posted on

2024-06-10

Participant Flow

There were 2 phases in the study: double blind treatment (DBT) phase followed by open label extension (OLE) phase. Participants after completing DBT phase could enter OLE phase if the Principal Investigator (PI) believed open-label treatment offered an acceptable risk-benefit profile. A total of 65 participants with refractory trigeminal neuralgia (TN) were enrolled in the study.

Out of 65 participants, only 30 were randomized in DBT phase, and 35 participants were not randomized (screen failure \[28\], sponsor decision \[1\], medical monitor decision \[1\], physician decision \[1\], withdrawal of consent \[4\]).

Participant milestones

Participant milestones
Measure	DBT Phase: Placebo Then Rimegepant (BHV-3000) Participants included in this arm were randomized to first sequence. Participants in first treatment period received placebo (matched to rimegepant) orally once daily (QD) for 2 weeks and in second treatment period received rimegepant 75 milligram (mg) immediate release (IR) tablet orally QD for 2 weeks. Treatment periods were separated by a washout period of 7 days.	DBT Phase: Rimegepant Then Placebo Participants in first treatment period received rimegepant 75 mg IR tablet orally QD for 2 weeks and in second period received placebo (matched to rimegepant) QD for 2 weeks. Treatment periods were separated by a washout period of 7 days.	OLE Phase: Rimegepant Participants who completed DBT phase, were eligible per PI judgment and agreed to enter OLE phase, received rimegepant 75 mg Orally disintegrating tablet (ODT) QD for 12 weeks in OLE phase.
DBT Phase: 1st Treatment Period (2Weeks) STARTED	15	15	0
DBT Phase: 1st Treatment Period (2Weeks) Treated	15	14	0
DBT Phase: 1st Treatment Period (2Weeks) COMPLETED	14	14	0
DBT Phase: 1st Treatment Period (2Weeks) NOT COMPLETED	1	1	0
DBT Phase: Washout Period (7 Days) STARTED	14	14	0
DBT Phase: Washout Period (7 Days) COMPLETED	14	14	0
DBT Phase: Washout Period (7 Days) NOT COMPLETED	0	0	0
2nd Treatment Period (2Weeks) STARTED	14	14	0
2nd Treatment Period (2Weeks) COMPLETED	14	14	0
2nd Treatment Period (2Weeks) NOT COMPLETED	0	0	0
OLE Phase (12 Weeks) STARTED	0	0	13
OLE Phase (12 Weeks) COMPLETED	0	0	9
OLE Phase (12 Weeks) NOT COMPLETED	0	0	4

Reasons for withdrawal

Reasons for withdrawal
Measure	DBT Phase: Placebo Then Rimegepant (BHV-3000) Participants included in this arm were randomized to first sequence. Participants in first treatment period received placebo (matched to rimegepant) orally once daily (QD) for 2 weeks and in second treatment period received rimegepant 75 milligram (mg) immediate release (IR) tablet orally QD for 2 weeks. Treatment periods were separated by a washout period of 7 days.	DBT Phase: Rimegepant Then Placebo Participants in first treatment period received rimegepant 75 mg IR tablet orally QD for 2 weeks and in second period received placebo (matched to rimegepant) QD for 2 weeks. Treatment periods were separated by a washout period of 7 days.	OLE Phase: Rimegepant Participants who completed DBT phase, were eligible per PI judgment and agreed to enter OLE phase, received rimegepant 75 mg Orally disintegrating tablet (ODT) QD for 12 weeks in OLE phase.
DBT Phase: 1st Treatment Period (2Weeks) Randomized but not treated	0	1	0
DBT Phase: 1st Treatment Period (2Weeks) Non compliance	1	0	0
OLE Phase (12 Weeks) Study terminated by sponsor	0	0	1
OLE Phase (12 Weeks) Lack of Efficacy	0	0	1
OLE Phase (12 Weeks) Sponsor decision	0	0	1
OLE Phase (12 Weeks) Withdrawal by Subject	0	0	1

Baseline Characteristics

Number Analyzed for DBT Phase and OLE Phase = number of participants analyzed for reporting arms for respective phases. Participants in DBT and OLE phases are not exclusive.

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: DBT Phase: Baseline (before dose on Day 1), 2 Weeks Treatment

Population: Modified intent-to-treat (mITT) analysis set included randomized participants who received at least 1 dose of study therapy and provided a baseline and at least one post-baseline efficacy assessment in each sequence. Here, "Number of Participants Analyzed" signifies number of participants in mITT set, per treatment (pooled) received either in first or second treatment period of DBT phase.

Outcome measures

Outcome measures
Measure	DBT Phase: Pooled Rimegepant n=28 Participants Participants who received rimegepant 75 mg IR tablet in treatment period 1 or 2 of DBT phase.	DBT Phase: Pooled Placebo n=28 Participants Participants who received placebo matched to rimegepant in treatment period 1 or 2 of DBT phase.
Change From Baseline in the Average Daily Pain Score on Numeric Pain Rating Scale (NPRS) at 2 Week Treatment Phase: DBT Phase	-.5 Units on a scale Interval -1.1 to -0.1	-1.2 Units on a scale Interval -1.8 to -0.6

SECONDARY outcome

Timeframe: DBT Phase: Day 1 of dosing up to last day of dosing (up to 5 weeks)

Population: DBT treated set consisted of participants in the treated analysis set who took \>= 1 dose of DB study drug (rimegepant or placebo), i.e., non-missing study drug start date. Here, "Number of Participants Analyzed" signifies number of participants in DBT treated set, per treatment (pooled) received either in first or second treatment period of 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.

Outcome measures

Outcome measures
Measure	DBT Phase: Pooled Rimegepant n=28 Participants Participants who received rimegepant 75 mg IR tablet in treatment period 1 or 2 of DBT phase.	DBT Phase: Pooled Placebo n=29 Participants Participants who received placebo matched to rimegepant in treatment period 1 or 2 of DBT phase.
Number of Participants With All-Causality Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Study Drug Discontinuation and Treatment Related AEs: DBT Phase SAEs	0 Participants	0 Participants
Number of Participants With All-Causality Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Study Drug Discontinuation and Treatment Related AEs: DBT Phase AEs Leading to Study Drug Discontinuation	0 Participants	0 Participants
Number of Participants With All-Causality Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Study Drug Discontinuation and Treatment Related AEs: DBT Phase Treatment Related AEs	4 Participants	0 Participants

SECONDARY outcome

Timeframe: DBT Phase: Baseline, 2 Weeks Treatment

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.

Outcome measures

Outcome measures
Measure	DBT Phase: Pooled Rimegepant n=28 Participants Participants who received rimegepant 75 mg IR tablet in treatment period 1 or 2 of DBT phase.	DBT Phase: Pooled Placebo n=29 Participants Participants who received placebo matched to rimegepant in treatment period 1 or 2 of DBT phase.
Number of Participants With Any Change From Baseline in Sheehan Suicidality Tracking Scale (S-STS) Scores: DBT Phase	0 Participants	0 Participants

SECONDARY outcome

Timeframe: DBT Phase: Day 1 of dosing up to last day of dosing (up to 5 weeks)

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.

Outcome measures

Outcome measures
Measure	DBT Phase: Pooled Rimegepant n=28 Participants Participants who received rimegepant 75 mg IR tablet in treatment period 1 or 2 of DBT phase.	DBT Phase: Pooled Placebo n=29 Participants Participants who received placebo matched to rimegepant in treatment period 1 or 2 of DBT phase.
Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities: DBT Phase	0 Participants	0 Participants

SECONDARY outcome

Timeframe: DBT Phase: Day 1 of dosing up to last day of dosing (up to 5 weeks)

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.

Outcome measures

Outcome measures
Measure	DBT Phase: Pooled Rimegepant n=28 Participants Participants who received rimegepant 75 mg IR tablet in treatment period 1 or 2 of DBT phase.	DBT Phase: Pooled Placebo n=29 Participants Participants who received placebo matched to rimegepant in treatment period 1 or 2 of DBT phase.
Number of Participants With Clinically Significant Laboratory Abnormalities: DBT Phase	0 Participants	0 Participants

SECONDARY outcome

Timeframe: DBT Phase: Baseline, 2 Weeks Treatment

Population: mITT analysis set included randomized participants who received at least 1 dose of study therapy and provided a baseline and at least one post-baseline efficacy assessment in each sequence. Here, "Number of Participants Analyzed" signifies number of participants in mITT set, per treatment (pooled) received either in first or second treatment period of 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.

Outcome measures

Outcome measures
Measure	DBT Phase: Pooled Rimegepant n=28 Participants Participants who received rimegepant 75 mg IR tablet in treatment period 1 or 2 of DBT phase.	DBT Phase: Pooled Placebo n=28 Participants Participants who received placebo matched to rimegepant in treatment period 1 or 2 of DBT phase.
Change From Baseline in Penn Facial Pain Scale-Revised (Penn-FPS-R) Total Score at 2 Week Treatment Phase: DBT Phase	-14.2 Units on a scale Interval -22.2 to -6.2	-16.6 Units on a scale Interval -24.6 to -8.6

SECONDARY outcome

Timeframe: DBT Phase: Baseline, 2 Weeks Treatment

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.

Outcome measures

Outcome measures
Measure	DBT Phase: Pooled Rimegepant n=28 Participants Participants who received rimegepant 75 mg IR tablet in treatment period 1 or 2 of DBT phase.	DBT Phase: Pooled Placebo n=28 Participants Participants who received placebo matched to rimegepant in treatment period 1 or 2 of DBT phase.
Change From Baseline in Pain Disability Index Total Score at 2 Week Treatment Phase: DBT Phase	-7.8 Units on a scale Interval -12.6 to -2.9	-9.3 Units on a scale Interval -14.2 to -4.5

SECONDARY outcome

Timeframe: DBT Phase: Baseline, 2 Weeks Treatment

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.

Outcome measures

Outcome measures
Measure	DBT Phase: Pooled Rimegepant n=28 Participants Participants who received rimegepant 75 mg IR tablet in treatment period 1 or 2 of DBT phase.	DBT Phase: Pooled Placebo n=28 Participants Participants who received placebo matched to rimegepant in treatment period 1 or 2 of DBT phase.
Patient Global Impression of Change Scale (PGI-C) Score at 2 Week Treatment Phase: DBT Phase	3.0 Units on a scale Interval 2.3 to 3.8	3.1 Units on a scale Interval 2.4 to 3.8

SECONDARY outcome

Timeframe: DBT Phase: Baseline, 2 Weeks Treatment

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.

Outcome measures

Outcome measures
Measure	DBT Phase: Pooled Rimegepant n=28 Participants Participants who received rimegepant 75 mg IR tablet in treatment period 1 or 2 of DBT phase.	DBT Phase: Pooled Placebo n=28 Participants Participants who received placebo matched to rimegepant in treatment period 1 or 2 of DBT phase.
Change From Baseline in Average Worst Pain Score on NPRS at 2 Week Treatment Phase: DBT Phase	-0.6 Units on a scale Interval -1.3 to 0.1	-1.3 Units on a scale Interval -2.0 to -0.6

SECONDARY outcome

Timeframe: DBT Phase: Baseline, 2 Weeks Treatment

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.