Trigeminal Neuralgia
Conditions
Keywords
Trigeminal Neuralgia, Pain
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.
Interventions
DRUGRimegepant
BHV3000 (rimegepant) 75mg tablet
DRUGPlacebo
Placebo
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Average Daily Pain Score on Numeric Pain Rating Scale (NPRS) at 2 Week Treatment Phase: DBT Phase | DBT Phase: Baseline (before dose on Day 1), 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 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Any Change From Baseline in Sheehan Suicidality Tracking Scale (S-STS) Scores: DBT Phase | 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. |
| Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities: DBT Phase | 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. |
| Number of Participants With Clinically Significant Laboratory Abnormalities: DBT Phase | 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. |
| Change From Baseline in Penn Facial Pain Scale-Revised (Penn-FPS-R) Total Score at 2 Week Treatment Phase: DBT Phase | DBT Phase: Baseline, 2 Weeks Treatment | 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. |
| Number of Participants With All-Causality Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Study Drug Discontinuation and Treatment Related AEs: DBT Phase | DBT Phase: Day 1 of dosing up to last day of dosing (up to 5 weeks) | 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. |
| Patient Global Impression of Change Scale (PGI-C) Score at 2 Week Treatment Phase: DBT Phase | 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. |
| Change From Baseline in Average Worst Pain Score on NPRS at 2 Week Treatment Phase: DBT Phase | 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. |
| Percentage of Participants With >= 2 Point Reduction From Baseline in Average Daily Pain Score on NPRS at 2 Week Treatment Phase: DBT Phase | 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. |
| Change From Baseline in Pain Disability Index Total Score at 2 Week Treatment Phase: DBT Phase | 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. |
Countries
United States
Participant flow
Recruitment details
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.
Pre-assignment details
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 \[4\]).
Participants by arm
| Arm | Count |
|---|---|
| DBT: Placebo Then Rimegepant Participants in first treatment period received placebo (matched to rimegepant) QD for 2 weeks and in second treatment period received rimegepant 75 mg IR tablet orally QD for 2 weeks. | 15 |
| DBT Phase: Rimegepant Then Placebo Participants in first treatment period received rimegepant 75 mg IR tablet orally QD for 2 weeks and in second treatment period received placebo (matched to rimegepant) QD for 2 weeks. | 14 |
| OLE Phase: Rimegepant Participants received rimegepant 75 mg ODT QD for 12 weeks in OLE phase. | 13 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| DBT Phase: 1st Treatment Period (2Weeks) | Non compliance | 1 | 0 | 0 |
| DBT Phase: 1st Treatment Period (2Weeks) | Randomized but not treated | 0 | 1 | 0 |
| OLE Phase (12 Weeks) | Lack of Efficacy | 0 | 0 | 1 |
| OLE Phase (12 Weeks) | Sponsor decision | 0 | 0 | 1 |
| OLE Phase (12 Weeks) | Study terminated by sponsor | 0 | 0 | 1 |
| OLE Phase (12 Weeks) | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | DBT: Placebo Then Rimegepant | DBT Phase: Rimegepant Then Placebo | Total | OLE Phase: Rimegepant |
|---|---|---|---|---|
| Age, Continuous DBT Phase | 57.9 Years STANDARD_DEVIATION 13.05 | 66.2 Years STANDARD_DEVIATION 14.61 | 61.9 Years STANDARD_DEVIATION 14.21 | — |
| Age, Continuous OLE Phase | — | — | 61.8 Years STANDARD_DEVIATION 17.83 | 61.8 Years STANDARD_DEVIATION 17.83 |
| Ethnicity (NIH/OMB) DBT Phase Hispanic or Latino | 3 Participants | 4 Participants | 7 Participants | — |
| Ethnicity (NIH/OMB) DBT Phase Not Hispanic or Latino | 12 Participants | 10 Participants | 22 Participants | — |
| Ethnicity (NIH/OMB) DBT Phase Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | — |
| Ethnicity (NIH/OMB) OLE Phase Hispanic or Latino | — | — | 5 Participants | 5 Participants |
| Ethnicity (NIH/OMB) OLE Phase Not Hispanic or Latino | — | — | 8 Participants | 8 Participants |
| Ethnicity (NIH/OMB) OLE Phase Unknown or Not Reported | — | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) DBT Phase American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) DBT Phase Asian | 0 Participants | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) DBT Phase Black or African American | 3 Participants | 1 Participants | 4 Participants | — |
| Race (NIH/OMB) DBT Phase More than one race | 0 Participants | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) DBT Phase Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) DBT Phase Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | — |
| Race (NIH/OMB) DBT Phase White | 12 Participants | 12 Participants | 24 Participants | — |
| Race (NIH/OMB) OLE Phase American Indian or Alaska Native | — | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) OLE Phase Asian | — | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) OLE Phase Black or African American | — | — | 2 Participants | 2 Participants |
| Race (NIH/OMB) OLE Phase More than one race | — | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) OLE Phase Native Hawaiian or Other Pacific Islander | — | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) OLE Phase Unknown or Not Reported | — | — | 1 Participants | 1 Participants |
| Race (NIH/OMB) OLE Phase White | — | — | 10 Participants | 10 Participants |
| Sex: Female, Male DBT Phase Female | 11 Participants | 10 Participants | 21 Participants | — |
| Sex: Female, Male DBT Phase Male | 4 Participants | 4 Participants | 8 Participants | — |
| Sex: Female, Male OLE Phase Female | — | — | 10 Participants | 10 Participants |
| Sex: Female, Male OLE Phase Male | — | — | 3 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 14 | 0 / 14 | 0 / 14 | 0 / 28 | 0 / 29 | 0 / 13 |
| other Total, other adverse events | 1 / 15 | 3 / 14 | 3 / 14 | 0 / 14 | 6 / 28 | 1 / 29 | 4 / 13 |
| serious Total, serious adverse events | 0 / 15 | 0 / 14 | 0 / 14 | 0 / 14 | 0 / 28 | 0 / 29 | 0 / 13 |
Outcome results
Primary
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| DBT Phase: Pooled Rimegepant | 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 |
| DBT Phase: Pooled Placebo | Change From Baseline in the Average Daily Pain Score on Numeric Pain Rating Scale (NPRS) at 2 Week Treatment Phase: DBT Phase | -1.2 Units on a scale |
Comparison: Analysis were performed using a mixed model with fixed effects for treatment, period and sequence; baseline NPRS as a covariate; and participant as a random effect.95% CI: [0.1, 1.2]
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| DBT Phase: Pooled Rimegepant | Change From Baseline in Average Worst Pain Score on NPRS at 2 Week Treatment Phase: DBT Phase | -0.6 Units on a scale |
| DBT Phase: Pooled Placebo | Change From Baseline in Average Worst Pain Score on NPRS at 2 Week Treatment Phase: DBT Phase | -1.3 Units on a scale |
Comparison: Analysis was performed using a mixed model with fixed effects for treatment, period and sequence; baseline NPRS as a covariate; and participant as a random effect.95% CI: [0.1, 1.4]
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| DBT Phase: Pooled Rimegepant | Change From Baseline in Pain Disability Index Total Score at 2 Week Treatment Phase: DBT Phase | -7.8 Units on a scale |
| DBT Phase: Pooled Placebo | Change From Baseline in Pain Disability Index Total Score at 2 Week Treatment Phase: DBT Phase | -9.3 Units on a scale |
Comparison: Analysis was performed using a mixed model with fixed effects for treatment, period and sequence; baseline pain disability index as a covariate; and participant as a random effect.95% CI: [-3.8, 6.9]
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| DBT Phase: Pooled Rimegepant | 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 |
| DBT Phase: Pooled Placebo | Change From Baseline in Penn Facial Pain Scale-Revised (Penn-FPS-R) Total Score at 2 Week Treatment Phase: DBT Phase | -16.6 Units on a scale |
Comparison: Analysis was performed using a mixed model with fixed effects for treatment, period and sequence; baseline Penn-FPS-R as a covariate; and participant as a random effect.95% CI: [-6.8, 11.5]
Secondary
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DBT Phase: Pooled Rimegepant | 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 |
| DBT Phase: Pooled Rimegepant | 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 |
| DBT Phase: Pooled Rimegepant | 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 |
| DBT Phase: Pooled Placebo | 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 |
| DBT Phase: Pooled Placebo | 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 |
| DBT Phase: Pooled Placebo | 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 | 0 Participants |
Secondary
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.
Time frame: DBT Phase: Baseline, 2 Weeks Treatment
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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DBT Phase: Pooled Rimegepant | Number of Participants With Any Change From Baseline in Sheehan Suicidality Tracking Scale (S-STS) Scores: DBT Phase | 0 Participants |
| DBT Phase: Pooled Placebo | Number of Participants With Any Change From Baseline in Sheehan Suicidality Tracking Scale (S-STS) Scores: DBT Phase | 0 Participants |
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DBT Phase: Pooled Rimegepant | Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities: DBT Phase | 0 Participants |
| DBT Phase: Pooled Placebo | Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities: DBT Phase | 0 Participants |
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DBT Phase: Pooled Rimegepant | Number of Participants With Clinically Significant Laboratory Abnormalities: DBT Phase | 0 Participants |
| DBT Phase: Pooled Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities: DBT Phase | 0 Participants |
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| DBT Phase: Pooled Rimegepant | Patient Global Impression of Change Scale (PGI-C) Score at 2 Week Treatment Phase: DBT Phase | 3.0 Units on a scale |
| DBT Phase: Pooled Placebo | Patient Global Impression of Change Scale (PGI-C) Score at 2 Week Treatment Phase: DBT Phase | 3.1 Units on a scale |
Comparison: Analysis was performed using a mixed model with fixed effects for treatment, period and sequence; and participant as a random effect.95% CI: [-0.7, 0.5]
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DBT Phase: Pooled Rimegepant | Percentage of Participants With >= 2 Point Reduction From Baseline in Average Daily Pain Score on NPRS at 2 Week Treatment Phase: DBT Phase | 10.7 Percentage of participants |
| DBT Phase: Pooled Placebo | Percentage of Participants With >= 2 Point Reduction From Baseline in Average Daily Pain Score on NPRS at 2 Week Treatment Phase: DBT Phase | 35.7 Percentage of participants |
Comparison: Analysis was performed using a logistic regression model, including fixed effects for treatment, sequence, period and baseline NPRS score as a covariate.95% CI: [0.7, 229.6]