Migraine
Conditions
Keywords
Acute Migraine, phonophobia, photophobia, nausea
Brief summary
The purpose of the study is to evaluate the safety and efficacy of three different intranasal dose levels of zavegepant (BHV-3500), relative to placebo, in the acute treatment of moderate to severe migraine.
Interventions
DRUGZavegepant
A single dose of zavegepant
DRUGZavegepant matching placebo
A single dose of placebo matched to zavegepant
DEVICEIntranasal Aptar Pharma Unit Dose System
A single-dose intranasal device
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Double-blind to Sponsor, Investigator and Subject
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1\. Participants have at least 1-year history of migraines (with or without aura), consistent with a diagnosis according to the International Classification of Headache Disorder, 3rd Edition, including the following: 1. Migraine attacks present for more than 1 year with the age of onset prior to 50 years of age. 2. Migraine attacks, on average, lasting about 4-72 hours if untreated. 3. Not more than 8 attacks of moderate to severe intensity per month within the last 3 months. 4. At least 2 consistent migraine headache attacks of moderate or severe intensity in each of the 3 months prior to the Screening Visit and throughout the Screening Period. 5. Less than 15 days with headache (migraine or non-migraine) per month in each of the 3 months prior to the Screening Visit and throughout the Screening Period. 6. Participants on prophylactic migraine medication are permitted to remain on therapy provided they have been on a stable dose for at least 3 months prior to Screening Visit and the dose is not expected to change during the course of the study. 7. Participants with contraindications for use of triptans may be included provided they meet all other study entry criteria.
Exclusion criteria
Key
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Freedom From Pain at 2 Hours Post-dose | 2 hours post-dose | Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the electronic clinical outcome assessment (eCOA) handheld device. Pain freedom was defined as pain level of none post-dose. |
| Percentage of Participants With Freedom From Most Bothersome Symptom (MBS) at 2 Hours Post-dose | 2 hours post-dose | MBS was reported as nausea, photophobia, or phonophobia at migraine onset using the eCOA handheld device. Symptom status (absent, present) was assessed post-dose using the eCOA handheld device separately for nausea, photophobia, and phonophobia. Freedom from MBS was defined as MBS reported at on-study migraine attack onset that was absent post-dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Were Able to Function Normally at 2 Hours Post-dose | 2 hours post-dose | Functional disbaility level was assessed on a 4-point scale (normal function, mildly impaired, severely impaired, requires bedrest) using the eCOA handheld device. Normal function was defined as a functional disability level of normal post-dose in the subset of participants with functional disability (mildly impaired, severely impaired, requires bedrest) at on-study migraine attack onset. |
| Percentage of Participants With Pain Relapse From 2 to 48 Hours Post-dose | From 2 hours up to 48 hours post-dose | Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eCOA handheld device. Pain relapse was defined as pain level of mild, moderate, or severe after 2 hours up to 48 hours post-dose in the subset of participants with pain level of none at 2 hours post-dose. |
| Percentage of Participants With Rescue Medication Use Within 24 Hours Post-dose | Through 24 hours post-dose | Participants who did not experience relief of their migraine headache at the end of 2 hours after dosing with study medication (and after the 2-hour assessments had been completed on the eCOA handheld device) were permitted to use the following rescue medications: aspirin, ibuprofen, acetaminophen up to 1000 mg/day (this includes Excedrin® Migraine), naproxen (or any other type of nonsteroidal anti-inflammatory drug), antiemetics (for example, metoclopramide or promethazine), or baclofen. The participant's use of rescue medication was recorded by the site on a case report form. |
| Percentage of Participants With Freedom From Photophobia at 2 Hours Post-dose | 2 hours post-dose | Photophobia (sensitivity to light) status was measured as absent or present in the eCOA handheld device. Freedom from photophobia was defined as photophobia absent post-dose in the subset of participants with photophobia present at on-study migraine attack onset. |
| Percentage of Participants With Freedom From Phonophobia at 2 Hours Post-dose | 2 hours post-dose | Phonophobia (sensitivity to sound) status was measured as absent or present in the eCOA handheld device. Freedom from phonophobia was defined as phonophobia absent post-dose in the subset of participants with phonophobia present at on-study migraine attack onset. |
| Percentage of Participants With Pain Relief at 60 Minutes Post-dose | 60 minutes post-dose | Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eCOA handheld device. Pain relief was defined as pain level of none or mild. |
| Percentage of Participants With Freedom From Nausea at 2 Hours Post-dose | 2 hours post-dose | Nausea status was measured as absent or present in the eCOA handheld device. Freedom from nausea was defined as nausea absent post-odse in the subset of participants with nausea present at on-study migraine attack onset. |
| Percentage of Participants With Pain Relief at 30 Minutes Post-dose | 30 minutes post-dose | Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eCOA handheld device. Pain relief was defined as pain level of none or mild. |
| Percentage of Participants Who Were Able to Function Normally at 30 Minutes Post-dose | 30 minutes post-dose | Functional disbaility level was assessed on a 4-point scale (normal function, mildly impaired, severely impaired, requires bedrest) using the eCOA handheld device. Normal function was defined as a functional disability level of normal post-dose in the subset of participants with functional disability (mildly impaired, severely impaired, requires bedrest) at on-study migraine attack onset. |
| Percentage of Participants With Sustained Pain Relief From 2 to 24 Hours Post-dose | From 2 hours up to 24 hours post-dose | Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eCOA handheld device. Sustained pain relief was defined as pain level of none or mild at 2 hours up to 24 hours post-dose. |
| Percentage of Participants With Sustained Pain Freedom From 2 to 24 Hours Post-dose | From 2 hours up to 24 hours post-dose | Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eCOA handheld device. Sustained pain freedom was defined as pain level of none at 2 hours up to 24 hours post-dose. |
| Percentage of Participants With Sustained Pain Relief From 2 to 48 Hours Post-dose | From 2 hours up to 48 hours post-dose | Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eCOA handheld device. Sustained pain relief was defined as pain level of none or mild at 2 hours up to 48 hours post-dose. |
| Percentage of Participants With Sustained Pain Freedom From 2 to 48 Hours Post-dose | From 2 hours up to 48 hours post-dose | Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eCOA handheld device. Sustained pain freedom was defined as pain level of none at 2 hours up to 48 hours post-dose. |
| Percentage of Participants Who Were Able to Function Normally at 60 Minutes Post-dose | 60 minutes post-dose | Functional disbaility level was assessed on a 4-point scale (normal function, mildly impaired, severely impaired, requires bedrest) using the eCOA handheld device. Normal function was defined as a functional disability level of normal post-dose in the subset of participants with functional disability (mildly impaired, severely impaired, requires bedrest) at on-study migraine attack onset. |
| Percentage of Participants With Pain Relief at 2 Hours Post-dose | 2 hours post-dose | Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eCOA handheld device. Pain relief was defined as pain level of none or mild. |
Countries
United States
Participant flow
Recruitment details
The study was conducted at 82 sites in the United States.
Pre-assignment details
A total of 2154 participants were enrolled, of which 1673 participants were randomized in a 1:1:1:1 ratio across the 4 treatment groups into the zavegepant (5 mg, 10 mg, or 20 mg) or placebo treatment groups. The randomization was stratified by the use of prophylactic migraine medications (yes or no). 481 participants were not randomized due to lost to follow-up, screen failure, withdrawal by participants, or other reasons.
Participants by arm
| Arm | Count |
|---|---|
| Zavegepant 5 mg Participants administered a single intranasal dose of zavegepant 5 mg on occurrence of migraine that reached moderate or severe intensity within 45 days after randomization. The dose was administered using Aptar UDS liquid spray device. | 388 |
| Zavegepant 10 mg Participants administered a single intranasal dose of zavegepant 10 mg on occurrence of migraine that reached moderate or severe intensity within 45 days after randomization. The dose was administered using Aptar UDS liquid spray device. | 394 |
| Zavegepant 20 mg Participants administered a single intranasal dose of zavegepant 20 mg migraine that reached moderate or severe intensity within 45 days after randomization. The dose was administered using Aptar UDS liquid spray device. | 403 |
| Placebo Participants administered a single intranasal dose of zavegepant-matching placebo on occurrence of migraine that reached moderate or severe intensity within 45 days after randomization. The dose was administered using Aptar UDS liquid spray device. | 403 |
| Total | 1,588 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 8 | 7 | 4 | 4 |
| Overall Study | Never Treated Migraine | 19 | 17 | 13 | 12 |
| Overall Study | Other Than Specified | 1 | 0 | 0 | 0 |
| Overall Study | Pregnancy | 1 | 0 | 0 | 0 |
| Overall Study | Protocol Deviation | 2 | 0 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 2 | 0 |
Baseline characteristics
| Characteristic | Total | Placebo | Zavegepant 20 mg | Zavegepant 10 mg | Zavegepant 5 mg |
|---|---|---|---|---|---|
| Age, Continuous | 40.8 years STANDARD_DEVIATION 12.66 | 40.0 years STANDARD_DEVIATION 12.07 | 40.0 years STANDARD_DEVIATION 12.95 | 41.3 years STANDARD_DEVIATION 12.96 | 41.9 years STANDARD_DEVIATION 12.58 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 286 Participants | 81 Participants | 72 Participants | 69 Participants | 64 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1302 Participants | 322 Participants | 331 Participants | 325 Participants | 324 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Prophylactic migraine medication use at randomization No | 1372 Participants | 348 Participants | 346 Participants | 344 Participants | 334 Participants |
| Prophylactic migraine medication use at randomization Yes | 216 Participants | 55 Participants | 57 Participants | 50 Participants | 54 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 6 Participants | 1 Participants | 3 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 58 Participants | 13 Participants | 15 Participants | 13 Participants | 17 Participants |
| Race (NIH/OMB) Black or African American | 260 Participants | 59 Participants | 62 Participants | 74 Participants | 65 Participants |
| Race (NIH/OMB) More than one race | 22 Participants | 1 Participants | 7 Participants | 9 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1241 Participants | 329 Participants | 316 Participants | 297 Participants | 299 Participants |
| Sex: Female, Male Female | 1354 Participants | 338 Participants | 344 Participants | 335 Participants | 337 Participants |
| Sex: Female, Male Male | 234 Participants | 65 Participants | 59 Participants | 59 Participants | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 388 | 0 / 394 | 0 / 403 | 0 / 403 |
| other Total, other adverse events | 57 / 388 | 58 / 394 | 81 / 403 | 15 / 403 |
| serious Total, serious adverse events | 0 / 388 | 1 / 394 | 0 / 403 | 1 / 403 |
Outcome results
Primary
Percentage of Participants With Freedom From Most Bothersome Symptom (MBS) at 2 Hours Post-dose
MBS was reported as nausea, photophobia, or phonophobia at migraine onset using the eCOA handheld device. Symptom status (absent, present) was assessed post-dose using the eCOA handheld device separately for nausea, photophobia, and phonophobia. Freedom from MBS was defined as MBS reported at on-study migraine attack onset that was absent post-dose.
Time frame: 2 hours post-dose
Population: The mITT participants were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zavegepant 5 mg | Percentage of Participants With Freedom From Most Bothersome Symptom (MBS) at 2 Hours Post-dose | 39.0 percentage of participants |
| Zavegepant 10 mg | Percentage of Participants With Freedom From Most Bothersome Symptom (MBS) at 2 Hours Post-dose | 41.9 percentage of participants |
| Zavegepant 20 mg | Percentage of Participants With Freedom From Most Bothersome Symptom (MBS) at 2 Hours Post-dose | 42.5 percentage of participants |
| Placebo | Percentage of Participants With Freedom From Most Bothersome Symptom (MBS) at 2 Hours Post-dose | 33.7 percentage of participants |
p-value: 0.116298.3% CI: [-2.8, 13.6]Cochran-Mantel-Haenszel
p-value: 0.015598.3% CI: [0.1, 16.5]Cochran-Mantel-Haenszel
p-value: 0.009498.3% CI: [0.7, 17]Cochran-Mantel-Haenszel
Primary
Percentage of Participants With Freedom From Pain at 2 Hours Post-dose
Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the electronic clinical outcome assessment (eCOA) handheld device. Pain freedom was defined as pain level of none post-dose.
Time frame: 2 hours post-dose
Population: mITT participants included treated participants who were randomized only once, had moderate to severe pain at on-study migraine attack onset, and had non-missing, post-baseline efficacy data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zavegepant 5 mg | Percentage of Participants With Freedom From Pain at 2 Hours Post-dose | 19.6 percentage of participants |
| Zavegepant 10 mg | Percentage of Participants With Freedom From Pain at 2 Hours Post-dose | 22.5 percentage of participants |
| Zavegepant 20 mg | Percentage of Participants With Freedom From Pain at 2 Hours Post-dose | 23.1 percentage of participants |
| Placebo | Percentage of Participants With Freedom From Pain at 2 Hours Post-dose | 15.5 percentage of participants |
p-value: 0.121498.3% CI: [-2.3, 10.7]Cochran-Mantel-Haenszel
p-value: 0.011398.3% CI: [0.4, 13.7]Cochran-Mantel-Haenszel
p-value: 0.005598.3% CI: [1.1, 14.3]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Were Able to Function Normally at 2 Hours Post-dose
Functional disbaility level was assessed on a 4-point scale (normal function, mildly impaired, severely impaired, requires bedrest) using the eCOA handheld device. Normal function was defined as a functional disability level of normal post-dose in the subset of participants with functional disability (mildly impaired, severely impaired, requires bedrest) at on-study migraine attack onset.
Time frame: 2 hours post-dose
Population: The mITT participants with functional disability at on-study migraine attack onset were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zavegepant 5 mg | Percentage of Participants Who Were Able to Function Normally at 2 Hours Post-dose | 31.7 percentage of participants |
| Zavegepant 10 mg | Percentage of Participants Who Were Able to Function Normally at 2 Hours Post-dose | 34.5 percentage of participants |
| Zavegepant 20 mg | Percentage of Participants Who Were Able to Function Normally at 2 Hours Post-dose | 34.7 percentage of participants |
| Placebo | Percentage of Participants Who Were Able to Function Normally at 2 Hours Post-dose | 27.4 percentage of participants |
Secondary
Percentage of Participants Who Were Able to Function Normally at 30 Minutes Post-dose
Functional disbaility level was assessed on a 4-point scale (normal function, mildly impaired, severely impaired, requires bedrest) using the eCOA handheld device. Normal function was defined as a functional disability level of normal post-dose in the subset of participants with functional disability (mildly impaired, severely impaired, requires bedrest) at on-study migraine attack onset.
Time frame: 30 minutes post-dose
Population: The mITT participants with functional disability at on-study migraine attack onset were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zavegepant 5 mg | Percentage of Participants Who Were Able to Function Normally at 30 Minutes Post-dose | 8.8 percentage of participants |
| Zavegepant 10 mg | Percentage of Participants Who Were Able to Function Normally at 30 Minutes Post-dose | 7.6 percentage of participants |
| Zavegepant 20 mg | Percentage of Participants Who Were Able to Function Normally at 30 Minutes Post-dose | 9.9 percentage of participants |
| Placebo | Percentage of Participants Who Were Able to Function Normally at 30 Minutes Post-dose | 5.4 percentage of participants |
Secondary
Percentage of Participants Who Were Able to Function Normally at 60 Minutes Post-dose
Functional disbaility level was assessed on a 4-point scale (normal function, mildly impaired, severely impaired, requires bedrest) using the eCOA handheld device. Normal function was defined as a functional disability level of normal post-dose in the subset of participants with functional disability (mildly impaired, severely impaired, requires bedrest) at on-study migraine attack onset.
Time frame: 60 minutes post-dose
Population: The mITT participants with functional disability at on-study migraine attack onset were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zavegepant 5 mg | Percentage of Participants Who Were Able to Function Normally at 60 Minutes Post-dose | 22.6 percentage of participants |
| Zavegepant 10 mg | Percentage of Participants Who Were Able to Function Normally at 60 Minutes Post-dose | 18.9 percentage of participants |
| Zavegepant 20 mg | Percentage of Participants Who Were Able to Function Normally at 60 Minutes Post-dose | 18.8 percentage of participants |
| Placebo | Percentage of Participants Who Were Able to Function Normally at 60 Minutes Post-dose | 17.1 percentage of participants |
Secondary
Percentage of Participants With Freedom From Nausea at 2 Hours Post-dose
Nausea status was measured as absent or present in the eCOA handheld device. Freedom from nausea was defined as nausea absent post-odse in the subset of participants with nausea present at on-study migraine attack onset.
Time frame: 2 hours post-dose
Population: The mITT participants with symptom of nausea present at on-study migraine attack onset were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zavegepant 5 mg | Percentage of Participants With Freedom From Nausea at 2 Hours Post-dose | 53.2 percentage of participants |
| Zavegepant 10 mg | Percentage of Participants With Freedom From Nausea at 2 Hours Post-dose | 53.9 percentage of participants |
| Zavegepant 20 mg | Percentage of Participants With Freedom From Nausea at 2 Hours Post-dose | 54.7 percentage of participants |
| Placebo | Percentage of Participants With Freedom From Nausea at 2 Hours Post-dose | 51.0 percentage of participants |
Secondary
Percentage of Participants With Freedom From Phonophobia at 2 Hours Post-dose
Phonophobia (sensitivity to sound) status was measured as absent or present in the eCOA handheld device. Freedom from phonophobia was defined as phonophobia absent post-dose in the subset of participants with phonophobia present at on-study migraine attack onset.
Time frame: 2 hours post-dose
Population: The mITT participants with symptom of phonophobia present at on-study migraine attack onset were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zavegepant 5 mg | Percentage of Participants With Freedom From Phonophobia at 2 Hours Post-dose | 44.2 percentage of participants |
| Zavegepant 10 mg | Percentage of Participants With Freedom From Phonophobia at 2 Hours Post-dose | 44.8 percentage of participants |
| Zavegepant 20 mg | Percentage of Participants With Freedom From Phonophobia at 2 Hours Post-dose | 43.3 percentage of participants |
| Placebo | Percentage of Participants With Freedom From Phonophobia at 2 Hours Post-dose | 34.1 percentage of participants |
Secondary
Percentage of Participants With Freedom From Photophobia at 2 Hours Post-dose
Photophobia (sensitivity to light) status was measured as absent or present in the eCOA handheld device. Freedom from photophobia was defined as photophobia absent post-dose in the subset of participants with photophobia present at on-study migraine attack onset.
Time frame: 2 hours post-dose
Population: The mITT participants with symptom of photophobia present at on-study migraine attack onset were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zavegepant 5 mg | Percentage of Participants With Freedom From Photophobia at 2 Hours Post-dose | 35.0 percentage of participants |
| Zavegepant 10 mg | Percentage of Participants With Freedom From Photophobia at 2 Hours Post-dose | 35.6 percentage of participants |
| Zavegepant 20 mg | Percentage of Participants With Freedom From Photophobia at 2 Hours Post-dose | 37.9 percentage of participants |
| Placebo | Percentage of Participants With Freedom From Photophobia at 2 Hours Post-dose | 30.4 percentage of participants |
Secondary
Percentage of Participants With Pain Relapse From 2 to 48 Hours Post-dose
Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eCOA handheld device. Pain relapse was defined as pain level of mild, moderate, or severe after 2 hours up to 48 hours post-dose in the subset of participants with pain level of none at 2 hours post-dose.
Time frame: From 2 hours up to 48 hours post-dose
Population: The mITT participants with pain freedom at 2 hours post-dose were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zavegepant 5 mg | Percentage of Participants With Pain Relapse From 2 to 48 Hours Post-dose | 31.6 percentage of participants |
| Zavegepant 10 mg | Percentage of Participants With Pain Relapse From 2 to 48 Hours Post-dose | 33.0 percentage of participants |
| Zavegepant 20 mg | Percentage of Participants With Pain Relapse From 2 to 48 Hours Post-dose | 37.6 percentage of participants |
| Placebo | Percentage of Participants With Pain Relapse From 2 to 48 Hours Post-dose | 50.0 percentage of participants |
Secondary
Percentage of Participants With Pain Relief at 2 Hours Post-dose
Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eCOA handheld device. Pain relief was defined as pain level of none or mild.
Time frame: 2 hours post-dose
Population: The mITT participants were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zavegepant 5 mg | Percentage of Participants With Pain Relief at 2 Hours Post-dose | 57.9 percentage of participants |
| Zavegepant 10 mg | Percentage of Participants With Pain Relief at 2 Hours Post-dose | 60.6 percentage of participants |
| Zavegepant 20 mg | Percentage of Participants With Pain Relief at 2 Hours Post-dose | 61.2 percentage of participants |
| Placebo | Percentage of Participants With Pain Relief at 2 Hours Post-dose | 53.6 percentage of participants |
Comparison: If the coprimary endpoint tests were both significant for a zavegepant dose group versus placebo, the secondary endpoints were tested for that zavegepant dose group versus placebo using a hierarchical gate-keeping procedure in the order the endpoints are reported, with each test in the hierarchy conducted at alpha = 0.0167. If a test in the hierarchy was not significant, any further tests on endpoints in the sequence were not considered significant for any zavegepant dose group versus placebo.p-value: 0.043998.3% CI: [-1.3, 15.4]Cochran-Mantel-Haenszel
Comparison: If the coprimary endpoint tests were both significant for a zavegepant dose group versus placebo, the secondary endpoints were tested for that zavegepant dose group versus placebo using a hierarchical gate-keeping procedure in the order the endpoints are reported, with each test in the hierarchy conducted at alpha = 0.0167. If a test in the hierarchy was not significant, any further tests on endpoints in the sequence were not considered significant for any zavegepant dose group versus placebo.p-value: 0.030298.3% CI: [-0.8, 15.9]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Pain Relief at 30 Minutes Post-dose
Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eCOA handheld device. Pain relief was defined as pain level of none or mild.
Time frame: 30 minutes post-dose
Population: The mITT participants were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zavegepant 5 mg | Percentage of Participants With Pain Relief at 30 Minutes Post-dose | 26.6 percentage of participants |
| Zavegepant 10 mg | Percentage of Participants With Pain Relief at 30 Minutes Post-dose | 29.9 percentage of participants |
| Zavegepant 20 mg | Percentage of Participants With Pain Relief at 30 Minutes Post-dose | 26.6 percentage of participants |
| Placebo | Percentage of Participants With Pain Relief at 30 Minutes Post-dose | 24.7 percentage of participants |
Secondary
Percentage of Participants With Pain Relief at 60 Minutes Post-dose
Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eCOA handheld device. Pain relief was defined as pain level of none or mild.
Time frame: 60 minutes post-dose
Population: The mITT participants were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zavegepant 5 mg | Percentage of Participants With Pain Relief at 60 Minutes Post-dose | 47.0 percentage of participants |
| Zavegepant 10 mg | Percentage of Participants With Pain Relief at 60 Minutes Post-dose | 46.0 percentage of participants |
| Zavegepant 20 mg | Percentage of Participants With Pain Relief at 60 Minutes Post-dose | 49.8 percentage of participants |
| Placebo | Percentage of Participants With Pain Relief at 60 Minutes Post-dose | 41.9 percentage of participants |
Secondary
Percentage of Participants With Rescue Medication Use Within 24 Hours Post-dose
Participants who did not experience relief of their migraine headache at the end of 2 hours after dosing with study medication (and after the 2-hour assessments had been completed on the eCOA handheld device) were permitted to use the following rescue medications: aspirin, ibuprofen, acetaminophen up to 1000 mg/day (this includes Excedrin® Migraine), naproxen (or any other type of nonsteroidal anti-inflammatory drug), antiemetics (for example, metoclopramide or promethazine), or baclofen. The participant's use of rescue medication was recorded by the site on a case report form.
Time frame: Through 24 hours post-dose
Population: The mITT participants were analyzed. Participants with rescue medication start date less than or equal to (≤) study drug start date + 1 day and missing rescue medication start time were excluded.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zavegepant 5 mg | Percentage of Participants With Rescue Medication Use Within 24 Hours Post-dose | 24.9 percentage of participants |
| Zavegepant 10 mg | Percentage of Participants With Rescue Medication Use Within 24 Hours Post-dose | 26.0 percentage of participants |
| Zavegepant 20 mg | Percentage of Participants With Rescue Medication Use Within 24 Hours Post-dose | 20.2 percentage of participants |
| Placebo | Percentage of Participants With Rescue Medication Use Within 24 Hours Post-dose | 27.3 percentage of participants |
Secondary
Percentage of Participants With Sustained Pain Freedom From 2 to 24 Hours Post-dose
Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eCOA handheld device. Sustained pain freedom was defined as pain level of none at 2 hours up to 24 hours post-dose.
Time frame: From 2 hours up to 24 hours post-dose
Population: The mITT participants were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zavegepant 5 mg | Percentage of Participants With Sustained Pain Freedom From 2 to 24 Hours Post-dose | 14.2 percentage of participants |
| Zavegepant 10 mg | Percentage of Participants With Sustained Pain Freedom From 2 to 24 Hours Post-dose | 15.1 percentage of participants |
| Zavegepant 20 mg | Percentage of Participants With Sustained Pain Freedom From 2 to 24 Hours Post-dose | 15.7 percentage of participants |
| Placebo | Percentage of Participants With Sustained Pain Freedom From 2 to 24 Hours Post-dose | 9.0 percentage of participants |
Secondary
Percentage of Participants With Sustained Pain Freedom From 2 to 48 Hours Post-dose
Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eCOA handheld device. Sustained pain freedom was defined as pain level of none at 2 hours up to 48 hours post-dose.
Time frame: From 2 hours up to 48 hours post-dose
Population: The mITT participants were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zavegepant 5 mg | Percentage of Participants With Sustained Pain Freedom From 2 to 48 Hours Post-dose | 12.9 percentage of participants |
| Zavegepant 10 mg | Percentage of Participants With Sustained Pain Freedom From 2 to 48 Hours Post-dose | 13.8 percentage of participants |
| Zavegepant 20 mg | Percentage of Participants With Sustained Pain Freedom From 2 to 48 Hours Post-dose | 13.2 percentage of participants |
| Placebo | Percentage of Participants With Sustained Pain Freedom From 2 to 48 Hours Post-dose | 7.5 percentage of participants |
Secondary
Percentage of Participants With Sustained Pain Relief From 2 to 24 Hours Post-dose
Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eCOA handheld device. Sustained pain relief was defined as pain level of none or mild at 2 hours up to 24 hours post-dose.
Time frame: From 2 hours up to 24 hours post-dose
Population: The mITT participants were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zavegepant 5 mg | Percentage of Participants With Sustained Pain Relief From 2 to 24 Hours Post-dose | 43.7 percentage of participants |
| Zavegepant 10 mg | Percentage of Participants With Sustained Pain Relief From 2 to 24 Hours Post-dose | 42.5 percentage of participants |
| Zavegepant 20 mg | Percentage of Participants With Sustained Pain Relief From 2 to 24 Hours Post-dose | 44.5 percentage of participants |
| Placebo | Percentage of Participants With Sustained Pain Relief From 2 to 24 Hours Post-dose | 35.7 percentage of participants |
Secondary
Percentage of Participants With Sustained Pain Relief From 2 to 48 Hours Post-dose
Pain levels were assessed on a 4-point scale (none, mild, moderate, severe) using the eCOA handheld device. Sustained pain relief was defined as pain level of none or mild at 2 hours up to 48 hours post-dose.
Time frame: From 2 hours up to 48 hours post-dose
Population: The mITT participants were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zavegepant 5 mg | Percentage of Participants With Sustained Pain Relief From 2 to 48 Hours Post-dose | 40.1 percentage of participants |
| Zavegepant 10 mg | Percentage of Participants With Sustained Pain Relief From 2 to 48 Hours Post-dose | 39.6 percentage of participants |
| Zavegepant 20 mg | Percentage of Participants With Sustained Pain Relief From 2 to 48 Hours Post-dose | 38.8 percentage of participants |
| Placebo | Percentage of Participants With Sustained Pain Relief From 2 to 48 Hours Post-dose | 32.7 percentage of participants |