Chronic Rhinosinusitis (CRS) With and Without Nasal Polyps
Conditions
Keywords
Chronic Rhinosinusitis (CRS), Chronic Rhinosinusitis (CRS) with Nasal Polyps, Chronic Rhinosinusitis (CRS) without Nasal Polyps
Brief summary
The purpose of this study is to compare the efficacy and safety of rimegepant versus placebo in the acute treatment of chronic rhinosinusitis (CRS) with and without nasal polyps.
Interventions
One dose of rimegepant 75 mg ODT
DRUGMatching placebo
One dose of matching placebo
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* At least two episodes of facial pain/pressure/fullness of moderate or severe intensity on a 4-point rating scale (0 = None, 1 = Mild, 2 = Moderate, 3 = Severe) in the past 30 days prior to the Screening Visit. * Subject agrees to study-required medication restrictions and the restriction of not starting new medication to treat CRS symptoms 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 primary headache disorder. * Subject has history of nasal or facial surgery within the 6 months prior to screening. * Subject has ongoing rhinitis medicamentosa. * Subject has diagnosed or suspected invasive fungal rhinosinusitis. * Subject is currently receiving aspirin desensitization or maintenance therapy for Samter's Triad. * Subject has a history of recurrent acute sinusitis (four or more episodes per year of acute bacterial rhinosinusitis (ABRS) without signs or symptoms of rhinosinusitis between episodes). * Body Mass Index \> 35.0kg/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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Facial Pain/Pressure/Fullness on NRS at 2 Hours Post-Dose | Baseline, 2 hours post-dose | Facial pain/pressure/fullness was assessed using an NRS score ranging in integers from 0 to 10, with 0 being no facial pain/pressure/fullness and 10 being worst imaginable facial pain/pressure/fullness. Higher scores signified worse condition. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Total Nasal Symptom Score (TNSS) at 2 Hours Post-Dose | Baseline, 2 hours post-dose | TNSS was calculated as the sum of 3 symptom scores: facial pain/pressure/fullness, score ranged from 0 (no facial pain/pressure/fullness) to 10 (worst imaginable facial pain/pressure/fullness); nasal obstruction (congestion), score ranged from 0 (no nasal obstruction (congestion) to 10 (worst imaginable nasal obstruction (congestion); and nasal discharge, score ranged from 0 (no nasal discharge) to 10 (worst nasal discharge). TNSS overall score ranged from 0 (no nasal symptom) to 30 (worst nasal symptom); higher scores signified worse condition. |
| Change From Baseline in Nasal Obstruction (Congestion) at 2 Hours Post-Dose | Baseline, 2 hours post-dose | Nasal obstruction (congestion) severity was assessed using a NRS ranging in integers from 0 (no nasal obstruction \[congestion\]) to 10 (worst imaginable nasal obstruction \[congestion\]). Higher scores signified worse condition. |
| Change From Baseline in Nasal Discharge at 2 Hours Post-Dose | Baseline, 2 hours post-dose | Nasal discharge severity was assessed using a NRS ranging in integers from 0 (no nasal discharge) to 10 (worst imaginable nasal discharge). Higher scores signified worse condition. |
| Percentage of Participants With Headache Pain Relief at 2 Hours Post-Dose | 2 hours post-dose | Headache pain relief was defined as a headache pain level of none or mild at 2 hours post-dose on a 4-point Likert scale (0 = None; 1 = Mild; 2 = Moderate; 3 = Severe). |
| Percentage of Participants Who Used Rescue Medication Within 24 Hours Post-dose | Through 24 hours post-dose | Post 2 hours after dosing with study medication and after the 2-hour assessments were completed on the e-diary, participants were permitted to use the following rescue medications (non-study medications) such as: acetaminophen or aspirin, ibuprofen, naproxen (or any other type of nonsteroidal anti-inflammatory drug \[NSAID\]), oral antihistamines (non- sedating), oral decongestants, topical nasal decongestants, topical nasal anticholinergics. |
Countries
United States
Participant flow
Recruitment details
A total of 261 participants were enrolled and randomized in the study. Amongst which 99 received rimegepant and 105 received placebo.
Pre-assignment details
Participants were to administer one dose of study medication only when participant had a facial pain/pressure/fullness that reached intensity of greater than or equal to (\>=) 6 on the numeric rating scale (NRS, 0 to 10) and they had completed pre-dose assessments in electronic (e)-diary. Study medication was to be administered only within 45 days of randomization.
Participants by arm
| Arm | Count |
|---|---|
| Rimegepant 75 mg Participants were randomized for administration of rimegepant 75 mg, single dose, orally, as an ODT sublingually. | 131 |
| Placebo Participants were randomized for administration of placebo (matched to rimegepant), single dose, orally, as an ODT sublingually. | 130 |
| Total | 261 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Randomized but not treated | 32 | 25 |
Baseline characteristics
| Characteristic | Placebo | Total | Rimegepant 75 mg |
|---|---|---|---|
| Age, Continuous | 49.9 Years STANDARD_DEVIATION 15.83 | 49.3 Years STANDARD_DEVIATION 15.53 | 48.6 Years STANDARD_DEVIATION 15.27 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 36 Participants | 63 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 93 Participants | 195 Participants | 102 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 5 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 17 Participants | 36 Participants | 19 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) White | 105 Participants | 211 Participants | 106 Participants |
| Sex: Female, Male Female | 68 Participants | 145 Participants | 77 Participants |
| Sex: Female, Male Male | 62 Participants | 116 Participants | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 99 | 0 / 105 |
| other Total, other adverse events | 4 / 99 | 5 / 105 |
| serious Total, serious adverse events | 0 / 99 | 0 / 105 |
Outcome results
Primary
Change From Baseline in Facial Pain/Pressure/Fullness on NRS at 2 Hours Post-Dose
Facial pain/pressure/fullness was assessed using an NRS score ranging in integers from 0 to 10, with 0 being no facial pain/pressure/fullness and 10 being worst imaginable facial pain/pressure/fullness. Higher scores signified worse condition.
Time frame: Baseline, 2 hours post-dose
Population: Modified Intent to Treat (mITT) analysis set included randomized participants that received study therapy, had a facial pain/pressure/fullness which reached pain intensity of \>= 6 on the NRS (0-10) prior to administration of treatment and provided at least one post-baseline efficacy data point in the e-diary. All assessments after rescue medication administration were set to missing. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Rimegepant 75 mg | Change From Baseline in Facial Pain/Pressure/Fullness on NRS at 2 Hours Post-Dose | -2.70 Scores on a scale |
| Placebo | Change From Baseline in Facial Pain/Pressure/Fullness on NRS at 2 Hours Post-Dose | -2.61 Scores on a scale |
p-value: 0.778295% CI: [-0.71, 0.53]Linear model (LM)
Secondary
Change From Baseline in Nasal Discharge at 2 Hours Post-Dose
Nasal discharge severity was assessed using a NRS ranging in integers from 0 (no nasal discharge) to 10 (worst imaginable nasal discharge). Higher scores signified worse condition.
Time frame: Baseline, 2 hours post-dose
Population: mITT analysis set included randomized participants that received study therapy, had a facial pain/pressure/fullness which reached pain intensity of \>= 6 on the NRS (0-10) prior to administration of treatment and provide at least one post-baseline efficacy data point in the e-diary. All assessments after rescue medication administration were set to missing. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Rimegepant 75 mg | Change From Baseline in Nasal Discharge at 2 Hours Post-Dose | -1.81 Scores on a scale |
| Placebo | Change From Baseline in Nasal Discharge at 2 Hours Post-Dose | -1.85 Scores on a scale |
p-value: 0.88995% CI: [-0.51, 0.59]Linear model (LM)
Secondary
Change From Baseline in Nasal Obstruction (Congestion) at 2 Hours Post-Dose
Nasal obstruction (congestion) severity was assessed using a NRS ranging in integers from 0 (no nasal obstruction \[congestion\]) to 10 (worst imaginable nasal obstruction \[congestion\]). Higher scores signified worse condition.
Time frame: Baseline, 2 hours post-dose
Population: mITT analysis set included randomized participants that received study therapy, had a facial pain/pressure/fullness which reached pain intensity of \>=6 on the NRS (0-10) prior to administration of treatment and provide at least one post-baseline efficacy data point in the e-diary. All assessments after rescue medication administration were set to missing. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Rimegepant 75 mg | Change From Baseline in Nasal Obstruction (Congestion) at 2 Hours Post-Dose | -2.48 Scores on a scale |
| Placebo | Change From Baseline in Nasal Obstruction (Congestion) at 2 Hours Post-Dose | -2.25 Scores on a scale |
p-value: 0.439895% CI: [-0.81, 0.36]Linear model (LM)
Secondary
Change From Baseline in Total Nasal Symptom Score (TNSS) at 2 Hours Post-Dose
TNSS was calculated as the sum of 3 symptom scores: facial pain/pressure/fullness, score ranged from 0 (no facial pain/pressure/fullness) to 10 (worst imaginable facial pain/pressure/fullness); nasal obstruction (congestion), score ranged from 0 (no nasal obstruction (congestion) to 10 (worst imaginable nasal obstruction (congestion); and nasal discharge, score ranged from 0 (no nasal discharge) to 10 (worst nasal discharge). TNSS overall score ranged from 0 (no nasal symptom) to 30 (worst nasal symptom); higher scores signified worse condition.
Time frame: Baseline, 2 hours post-dose
Population: mITT analysis set included randomized participants that received study therapy, had a facial pain/pressure/fullness which reached pain intensity of \>= 6 on the NRS (0-10) prior to administration of treatment and provided at least one post-baseline efficacy data point in the e-diary. All assessments after rescue medication administration were set to missing. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Rimegepant 75 mg | Change From Baseline in Total Nasal Symptom Score (TNSS) at 2 Hours Post-Dose | -7.04 Scores on a scale |
| Placebo | Change From Baseline in Total Nasal Symptom Score (TNSS) at 2 Hours Post-Dose | -6.74 Scores on a scale |
p-value: 0.707995% CI: [-1.83, 1.24]Linear model (LM)
Secondary
Percentage of Participants Who Used Rescue Medication Within 24 Hours Post-dose
Post 2 hours after dosing with study medication and after the 2-hour assessments were completed on the e-diary, participants were permitted to use the following rescue medications (non-study medications) such as: acetaminophen or aspirin, ibuprofen, naproxen (or any other type of nonsteroidal anti-inflammatory drug \[NSAID\]), oral antihistamines (non- sedating), oral decongestants, topical nasal decongestants, topical nasal anticholinergics.
Time frame: Through 24 hours post-dose
Population: mITT analysis set included randomized participants that received study therapy, had a facial pain/pressure/fullness which reached pain intensity of greater than or equal to (\>=) 6 on the NRS (0-10) prior to administration of treatment and provided at least one post-baseline efficacy data point in the e-diary. Participants who recorded rescue medication use within 24 hours post-dose were considered failures, where failure was the event being analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rimegepant 75 mg | Percentage of Participants Who Used Rescue Medication Within 24 Hours Post-dose | 7.3 Percentage of Participants |
| Placebo | Percentage of Participants Who Used Rescue Medication Within 24 Hours Post-dose | 10.0 Percentage of Participants |
p-value: 0.500195% CI: [-10.6, 5.2]Mantel-Haenszel
Secondary
Percentage of Participants With Headache Pain Relief at 2 Hours Post-Dose
Headache pain relief was defined as a headache pain level of none or mild at 2 hours post-dose on a 4-point Likert scale (0 = None; 1 = Mild; 2 = Moderate; 3 = Severe).
Time frame: 2 hours post-dose
Population: mITT analysis set analyzed. Participants who reported a headache pain level of moderate or severe intensity at baseline were assessed. Participants who had missing data at 2 hours post-dose, or who took rescue medication at or before 2 hours post-dose were imputed as failures. Here, Overall Number of Participants Analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rimegepant 75 mg | Percentage of Participants With Headache Pain Relief at 2 Hours Post-Dose | 59.4 Percentage of Participants |
| Placebo | Percentage of Participants With Headache Pain Relief at 2 Hours Post-Dose | 55.6 Percentage of Participants |
p-value: 0.641295% CI: [-12.1, 19.7]Mantel-Haenszel