Trial Outcomes & Findings for Acute Treatment Trial in Adult Subjects With Migraines (NCT NCT03872453)
NCT ID: NCT03872453
Last Updated: 2023-09-25
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2/PHASE3
Target enrollment
2154 participants
Primary outcome timeframe
2 hours post-dose
Results posted on
2023-09-25
Participant Flow
The study was conducted at 82 sites in the United States.
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.
Participant milestones
| Measure |
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 Unidose System (UDS) liquid spray device.
|
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.
|
Zavegepant 20 mg
Participants administered a single intranasal dose of zavegepant 20 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.
|
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.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
418
|
417
|
418
|
420
|
|
Overall Study
Treated
|
388
|
394
|
403
|
403
|
|
Overall Study
Modified Intent-to-Treat (mITT) Participants
|
387
|
391
|
402
|
401
|
|
Overall Study
COMPLETED
|
386
|
391
|
399
|
402
|
|
Overall Study
NOT COMPLETED
|
32
|
26
|
19
|
18
|
Reasons for withdrawal
| Measure |
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 Unidose System (UDS) liquid spray device.
|
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.
|
Zavegepant 20 mg
Participants administered a single intranasal dose of zavegepant 20 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.
|
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.
|
|---|---|---|---|---|
|
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
Pregnancy
|
1
|
0
|
0
|
0
|
|
Overall Study
Protocol Deviation
|
2
|
0
|
0
|
2
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
2
|
0
|
|
Overall Study
Other Than Specified
|
1
|
0
|
0
|
0
|
Baseline Characteristics
Acute Treatment Trial in Adult Subjects With Migraines
Baseline characteristics by cohort
| Measure |
Zavegepant 5 mg
n=388 Participants
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.
|
Zavegepant 10 mg
n=394 Participants
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.
|
Zavegepant 20 mg
n=403 Participants
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.
|
Placebo
n=403 Participants
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.
|
Total
n=1588 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
41.9 years
STANDARD_DEVIATION 12.58 • n=99 Participants
|
41.3 years
STANDARD_DEVIATION 12.96 • n=107 Participants
|
40.0 years
STANDARD_DEVIATION 12.95 • n=206 Participants
|
40.0 years
STANDARD_DEVIATION 12.07 • n=7 Participants
|
40.8 years
STANDARD_DEVIATION 12.66 • n=31 Participants
|
|
Sex: Female, Male
Female
|
337 Participants
n=99 Participants
|
335 Participants
n=107 Participants
|
344 Participants
n=206 Participants
|
338 Participants
n=7 Participants
|
1354 Participants
n=31 Participants
|
|
Sex: Female, Male
Male
|
51 Participants
n=99 Participants
|
59 Participants
n=107 Participants
|
59 Participants
n=206 Participants
|
65 Participants
n=7 Participants
|
234 Participants
n=31 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
64 Participants
n=99 Participants
|
69 Participants
n=107 Participants
|
72 Participants
n=206 Participants
|
81 Participants
n=7 Participants
|
286 Participants
n=31 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
324 Participants
n=99 Participants
|
325 Participants
n=107 Participants
|
331 Participants
n=206 Participants
|
322 Participants
n=7 Participants
|
1302 Participants
n=31 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
2 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
6 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Asian
|
17 Participants
n=99 Participants
|
13 Participants
n=107 Participants
|
15 Participants
n=206 Participants
|
13 Participants
n=7 Participants
|
58 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Black or African American
|
65 Participants
n=99 Participants
|
74 Participants
n=107 Participants
|
62 Participants
n=206 Participants
|
59 Participants
n=7 Participants
|
260 Participants
n=31 Participants
|
|
Race (NIH/OMB)
White
|
299 Participants
n=99 Participants
|
297 Participants
n=107 Participants
|
316 Participants
n=206 Participants
|
329 Participants
n=7 Participants
|
1241 Participants
n=31 Participants
|
|
Race (NIH/OMB)
More than one race
|
5 Participants
n=99 Participants
|
9 Participants
n=107 Participants
|
7 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
22 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Prophylactic migraine medication use at randomization
Yes
|
54 Participants
n=99 Participants
|
50 Participants
n=107 Participants
|
57 Participants
n=206 Participants
|
55 Participants
n=7 Participants
|
216 Participants
n=31 Participants
|
|
Prophylactic migraine medication use at randomization
No
|
334 Participants
n=99 Participants
|
344 Participants
n=107 Participants
|
346 Participants
n=206 Participants
|
348 Participants
n=7 Participants
|
1372 Participants
n=31 Participants
|
PRIMARY outcome
Timeframe: 2 hours post-dosePopulation: 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.
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.
Outcome measures
| Measure |
Zavegepant 5 mg
n=387 Participants
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.
|
Zavegepant 10 mg
n=391 Participants
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.
|
Zavegepant 20 mg
n=402 Participants
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.
|
Placebo
n=401 Participants
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.
|
|---|---|---|---|---|
|
Percentage of Participants With Freedom From Pain at 2 Hours Post-dose
|
19.6 percentage of participants
Interval 14.8 to 24.5
|
22.5 percentage of participants
Interval 17.5 to 27.6
|
23.1 percentage of participants
Interval 18.1 to 28.2
|
15.5 percentage of participants
Interval 11.1 to 19.8
|
PRIMARY outcome
Timeframe: 2 hours post-dosePopulation: The mITT participants were analyzed.
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.
Outcome measures
| Measure |
Zavegepant 5 mg
n=387 Participants
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.
|
Zavegepant 10 mg
n=391 Participants
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.
|
Zavegepant 20 mg
n=402 Participants
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.
|
Placebo
n=401 Participants
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.
|
|---|---|---|---|---|
|
Percentage of Participants With Freedom From Most Bothersome Symptom (MBS) at 2 Hours Post-dose
|
39.0 percentage of participants
Interval 33.1 to 45.0
|
41.9 percentage of participants
Interval 36.0 to 47.9
|
42.5 percentage of participants
Interval 36.6 to 48.4
|
33.7 percentage of participants
Interval 28.0 to 39.3
|
SECONDARY outcome
Timeframe: 2 hours post-dosePopulation: The mITT participants were analyzed.
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.
Outcome measures
| Measure |
Zavegepant 5 mg
n=387 Participants
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.
|
Zavegepant 10 mg
n=391 Participants
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.
|
Zavegepant 20 mg
n=402 Participants
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.
|
Placebo
n=401 Participants
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.
|
|---|---|---|---|---|
|
Percentage of Participants With Pain Relief at 2 Hours Post-dose
|
57.9 percentage of participants
Interval 51.9 to 63.9
|
60.6 percentage of participants
Interval 54.7 to 66.5
|
61.2 percentage of participants
Interval 55.4 to 67.0
|
53.6 percentage of participants
Interval 47.7 to 59.6
|
SECONDARY outcome
Timeframe: 2 hours post-dosePopulation: The mITT participants with functional disability at on-study migraine attack onset were analyzed.
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.
Outcome measures
| Measure |
Zavegepant 5 mg
n=363 Participants
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.
|
Zavegepant 10 mg
n=354 Participants
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.
|
Zavegepant 20 mg
n=372 Participants
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.
|
Placebo
n=369 Participants
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.
|
|---|---|---|---|---|
|
Percentage of Participants Who Were Able to Function Normally at 2 Hours Post-dose
|
31.7 percentage of participants
Interval 25.8 to 37.5
|
34.5 percentage of participants
Interval 28.4 to 40.5
|
34.7 percentage of participants
Interval 28.8 to 40.6
|
27.4 percentage of participants
Interval 21.8 to 32.9
|
SECONDARY outcome
Timeframe: Through 24 hours post-dosePopulation: 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.
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.
Outcome measures
| Measure |
Zavegepant 5 mg
n=385 Participants
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.
|
Zavegepant 10 mg
n=388 Participants
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.
|
Zavegepant 20 mg
n=397 Participants
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.
|
Placebo
n=400 Participants
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.
|
|---|---|---|---|---|
|
Percentage of Participants With Rescue Medication Use Within 24 Hours Post-dose
|
24.9 percentage of participants
Interval 19.7 to 30.2
|
26.0 percentage of participants
Interval 20.7 to 31.4
|
20.2 percentage of participants
Interval 15.3 to 25.0
|
27.3 percentage of participants
Interval 21.9 to 32.6
|
SECONDARY outcome
Timeframe: 2 hours post-dosePopulation: The mITT participants with symptom of photophobia present at on-study migraine attack onset were analyzed.
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.
Outcome measures
| Measure |
Zavegepant 5 mg
n=337 Participants
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.
|
Zavegepant 10 mg
n=340 Participants
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.
|
Zavegepant 20 mg
n=354 Participants
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.
|
Placebo
n=358 Participants
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.
|
|---|---|---|---|---|
|
Percentage of Participants With Freedom From Photophobia at 2 Hours Post-dose
|
35.0 percentage of participants
Interval 28.8 to 41.2
|
35.6 percentage of participants
Interval 29.4 to 41.8
|
37.9 percentage of participants
Interval 31.7 to 44.0
|
30.4 percentage of participants
Interval 24.6 to 36.3
|
SECONDARY outcome
Timeframe: 2 hours post-dosePopulation: The mITT participants with symptom of phonophobia present at on-study migraine attack onset were analyzed.
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.
Outcome measures
| Measure |
Zavegepant 5 mg
n=260 Participants
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.
|
Zavegepant 10 mg
n=239 Participants
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.
|
Zavegepant 20 mg
n=263 Participants
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.
|
Placebo
n=276 Participants
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.
|
|---|---|---|---|---|
|
Percentage of Participants With Freedom From Phonophobia at 2 Hours Post-dose
|
44.2 percentage of participants
Interval 36.9 to 51.6
|
44.8 percentage of participants
Interval 37.1 to 52.5
|
43.3 percentage of participants
Interval 36.0 to 50.7
|
34.1 percentage of participants
Interval 27.2 to 40.9
|
SECONDARY outcome
Timeframe: 60 minutes post-dosePopulation: The mITT participants were analyzed.
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.
Outcome measures
| Measure |
Zavegepant 5 mg
n=387 Participants
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.
|
Zavegepant 10 mg
n=391 Participants
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.
|
Zavegepant 20 mg
n=402 Participants
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.
|
Placebo
n=401 Participants
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.
|
|---|---|---|---|---|
|
Percentage of Participants With Pain Relief at 60 Minutes Post-dose
|
47.0 percentage of participants
Interval 41.0 to 53.1
|
46.0 percentage of participants
Interval 40.0 to 52.1
|
49.8 percentage of participants
Interval 43.8 to 55.7
|
41.9 percentage of participants
Interval 36.0 to 47.8
|
SECONDARY outcome
Timeframe: 60 minutes post-dosePopulation: The mITT participants with functional disability at on-study migraine attack onset were analyzed.
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.
Outcome measures
| Measure |
Zavegepant 5 mg
n=363 Participants
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.
|
Zavegepant 10 mg
n=354 Participants
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.
|
Zavegepant 20 mg
n=372 Participants
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.
|
Placebo
n=369 Participants
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.
|
|---|---|---|---|---|
|
Percentage of Participants Who Were Able to Function Normally at 60 Minutes Post-dose
|
22.6 percentage of participants
Interval 17.3 to 27.8
|
18.9 percentage of participants
Interval 13.9 to 23.9
|
18.8 percentage of participants
Interval 14.0 to 23.7
|
17.1 percentage of participants
Interval 12.4 to 21.8
|
SECONDARY outcome
Timeframe: 30 minutes post-dosePopulation: The mITT participants were analyzed.
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.
Outcome measures
| Measure |
Zavegepant 5 mg
n=387 Participants
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.
|
Zavegepant 10 mg
n=391 Participants
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.
|
Zavegepant 20 mg
n=402 Participants
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.
|
Placebo
n=401 Participants
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.
|
|---|---|---|---|---|
|
Percentage of Participants With Pain Relief at 30 Minutes Post-dose
|
26.6 percentage of participants
Interval 21.2 to 32.0
|
29.9 percentage of participants
Interval 24.4 to 35.5
|
26.6 percentage of participants
Interval 21.3 to 31.9
|
24.7 percentage of participants
Interval 19.5 to 29.8
|
SECONDARY outcome
Timeframe: 30 minutes post-dosePopulation: The mITT participants with functional disability at on-study migraine attack onset were analyzed.
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.
Outcome measures
| Measure |
Zavegepant 5 mg
n=363 Participants
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.
|
Zavegepant 10 mg
n=354 Participants
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.
|
Zavegepant 20 mg
n=372 Participants
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.
|
Placebo
n=369 Participants
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.
|
|---|---|---|---|---|
|
Percentage of Participants Who Were Able to Function Normally at 30 Minutes Post-dose
|
8.8 percentage of participants
Interval 5.3 to 12.4
|
7.6 percentage of participants
Interval 4.2 to 11.0
|
9.9 percentage of participants
Interval 6.2 to 13.7
|
5.4 percentage of participants
Interval 2.6 to 8.2
|
SECONDARY outcome
Timeframe: From 2 hours up to 24 hours post-dosePopulation: The mITT participants were analyzed.
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.
Outcome measures
| Measure |
Zavegepant 5 mg
n=387 Participants
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.
|
Zavegepant 10 mg
n=391 Participants
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.
|
Zavegepant 20 mg
n=402 Participants
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.
|
Placebo
n=401 Participants
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.
|
|---|---|---|---|---|
|
Percentage of Participants With Sustained Pain Relief From 2 to 24 Hours Post-dose
|
43.7 percentage of participants
Interval 37.6 to 49.7
|
42.5 percentage of participants
Interval 36.5 to 48.4
|
44.5 percentage of participants
Interval 38.6 to 50.5
|
35.7 percentage of participants
Interval 29.9 to 41.4
|
SECONDARY outcome
Timeframe: From 2 hours up to 24 hours post-dosePopulation: The mITT participants were analyzed.
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.
Outcome measures
| Measure |
Zavegepant 5 mg
n=387 Participants
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.
|
Zavegepant 10 mg
n=391 Participants
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.
|
Zavegepant 20 mg
n=402 Participants
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.
|
Placebo
n=401 Participants
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.
|
|---|---|---|---|---|
|
Percentage of Participants With Sustained Pain Freedom From 2 to 24 Hours Post-dose
|
14.2 percentage of participants
Interval 10.0 to 18.5
|
15.1 percentage of participants
Interval 10.8 to 19.4
|
15.7 percentage of participants
Interval 11.3 to 20.0
|
9.0 percentage of participants
Interval 5.6 to 12.4
|
SECONDARY outcome
Timeframe: From 2 hours up to 48 hours post-dosePopulation: The mITT participants were analyzed.
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.
Outcome measures
| Measure |
Zavegepant 5 mg
n=387 Participants
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.
|
Zavegepant 10 mg
n=391 Participants
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.
|
Zavegepant 20 mg
n=402 Participants
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.
|
Placebo
n=401 Participants
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.
|
|---|---|---|---|---|
|
Percentage of Participants With Sustained Pain Relief From 2 to 48 Hours Post-dose
|
40.1 percentage of participants
Interval 34.1 to 46.0
|
39.6 percentage of participants
Interval 33.7 to 45.6
|
38.8 percentage of participants
Interval 33.0 to 44.6
|
32.7 percentage of participants
Interval 27.1 to 38.3
|
SECONDARY outcome
Timeframe: From 2 hours up to 48 hours post-dosePopulation: The mITT participants were analyzed.
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.
Outcome measures
| Measure |
Zavegepant 5 mg
n=387 Participants
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.
|
Zavegepant 10 mg
n=391 Participants
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.
|
Zavegepant 20 mg
n=402 Participants
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.
|
Placebo
n=401 Participants
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.
|
|---|---|---|---|---|
|
Percentage of Participants With Sustained Pain Freedom From 2 to 48 Hours Post-dose
|
12.9 percentage of participants
Interval 8.8 to 17.0
|
13.8 percentage of participants
Interval 9.6 to 18.0
|
13.2 percentage of participants
Interval 9.1 to 17.2
|
7.5 percentage of participants
Interval 4.3 to 10.6
|
SECONDARY outcome
Timeframe: 2 hours post-dosePopulation: The mITT participants with symptom of nausea present at on-study migraine attack onset were analyzed.
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.
Outcome measures
| Measure |
Zavegepant 5 mg
n=237 Participants
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.
|
Zavegepant 10 mg
n=243 Participants
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.
|
Zavegepant 20 mg
n=265 Participants
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.
|
Placebo
n=239 Participants
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.
|
|---|---|---|---|---|
|
Percentage of Participants With Freedom From Nausea at 2 Hours Post-dose
|
53.2 percentage of participants
Interval 45.4 to 60.9
|
53.9 percentage of participants
Interval 46.3 to 61.6
|
54.7 percentage of participants
Interval 47.4 to 62.0
|
51.0 percentage of participants
Interval 43.3 to 58.8
|
SECONDARY outcome
Timeframe: From 2 hours up to 48 hours post-dosePopulation: The mITT participants with pain freedom at 2 hours post-dose were analyzed.
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.
Outcome measures
| Measure |
Zavegepant 5 mg
n=76 Participants
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.
|
Zavegepant 10 mg
n=88 Participants
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.
|
Zavegepant 20 mg
n=93 Participants
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.
|
Placebo
n=62 Participants
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.
|
|---|---|---|---|---|
|
Percentage of Participants With Pain Relapse From 2 to 48 Hours Post-dose
|
31.6 percentage of participants
Interval 18.8 to 44.3
|
33.0 percentage of participants
Interval 21.0 to 45.0
|
37.6 percentage of participants
Interval 25.6 to 49.7
|
50.0 percentage of participants
Interval 34.8 to 65.2
|
Adverse Events
Zavegepant 5 mg
Serious events: 0 serious events
Other events: 57 other events
Deaths: 0 deaths
Zavegepant 10 mg
Serious events: 1 serious events
Other events: 58 other events
Deaths: 0 deaths
Zavegepant 20 mg
Serious events: 0 serious events
Other events: 81 other events
Deaths: 0 deaths
Placebo
Serious events: 1 serious events
Other events: 15 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Zavegepant 5 mg
n=388 participants at risk
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.
|
Zavegepant 10 mg
n=394 participants at risk
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.
|
Zavegepant 20 mg
n=403 participants at risk
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.
|
Placebo
n=403 participants at risk
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.
|
|---|---|---|---|---|
|
Nervous system disorders
Vestibular migraine
|
0.00%
0/388 • Adverse events were assessed from study drug dosing up to the end of the study (up to 52 days).
Treated Participants included enrolled participants who took study therapy (zavegepant or placebo).
|
0.00%
0/394 • Adverse events were assessed from study drug dosing up to the end of the study (up to 52 days).
Treated Participants included enrolled participants who took study therapy (zavegepant or placebo).
|
0.00%
0/403 • Adverse events were assessed from study drug dosing up to the end of the study (up to 52 days).
Treated Participants included enrolled participants who took study therapy (zavegepant or placebo).
|
0.25%
1/403 • Adverse events were assessed from study drug dosing up to the end of the study (up to 52 days).
Treated Participants included enrolled participants who took study therapy (zavegepant or placebo).
|
|
Vascular disorders
Thrombosis
|
0.00%
0/388 • Adverse events were assessed from study drug dosing up to the end of the study (up to 52 days).
Treated Participants included enrolled participants who took study therapy (zavegepant or placebo).
|
0.25%
1/394 • Adverse events were assessed from study drug dosing up to the end of the study (up to 52 days).
Treated Participants included enrolled participants who took study therapy (zavegepant or placebo).
|
0.00%
0/403 • Adverse events were assessed from study drug dosing up to the end of the study (up to 52 days).
Treated Participants included enrolled participants who took study therapy (zavegepant or placebo).
|
0.00%
0/403 • Adverse events were assessed from study drug dosing up to the end of the study (up to 52 days).
Treated Participants included enrolled participants who took study therapy (zavegepant or placebo).
|
Other adverse events
| Measure |
Zavegepant 5 mg
n=388 participants at risk
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.
|
Zavegepant 10 mg
n=394 participants at risk
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.
|
Zavegepant 20 mg
n=403 participants at risk
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.
|
Placebo
n=403 participants at risk
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.
|
|---|---|---|---|---|
|
Nervous system disorders
Dysgeusia
|
13.9%
54/388 • Adverse events were assessed from study drug dosing up to the end of the study (up to 52 days).
Treated Participants included enrolled participants who took study therapy (zavegepant or placebo).
|
13.5%
53/394 • Adverse events were assessed from study drug dosing up to the end of the study (up to 52 days).
Treated Participants included enrolled participants who took study therapy (zavegepant or placebo).
|
16.1%
65/403 • Adverse events were assessed from study drug dosing up to the end of the study (up to 52 days).
Treated Participants included enrolled participants who took study therapy (zavegepant or placebo).
|
3.5%
14/403 • Adverse events were assessed from study drug dosing up to the end of the study (up to 52 days).
Treated Participants included enrolled participants who took study therapy (zavegepant or placebo).
|
|
Respiratory, thoracic and mediastinal disorders
Nasal discomfort
|
1.3%
5/388 • Adverse events were assessed from study drug dosing up to the end of the study (up to 52 days).
Treated Participants included enrolled participants who took study therapy (zavegepant or placebo).
|
1.3%
5/394 • Adverse events were assessed from study drug dosing up to the end of the study (up to 52 days).
Treated Participants included enrolled participants who took study therapy (zavegepant or placebo).
|
5.2%
21/403 • Adverse events were assessed from study drug dosing up to the end of the study (up to 52 days).
Treated Participants included enrolled participants who took study therapy (zavegepant or placebo).
|
0.25%
1/403 • Adverse events were assessed from study drug dosing up to the end of the study (up to 52 days).
Treated Participants included enrolled participants who took study therapy (zavegepant or placebo).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60