A Study in Migraine Prevention

The definition of a migraine (a headache lasting 4 to 72 hours) was based on the International Headache Society (IHS) diagnostic criteria. The number of migraine attacks per month was normalized to a 28-day month and calculated as the (number of migraine attacks\*28 days)/number of days in the specified month.

Time frame: Baseline and Month 3

Population: Randomized participants (pts) who had at least 4 migraines and/or probable migraine headaches during the baseline period, who received at least 1 dose of study drug, and for whom had at least 1 post-randomization efficacy data for the specified endpoint was available.

The duration of migraine symptoms was the amount of time from the beginning of each individual migraine attack to the end of each migraine attack. Two attacks separated by \<24 hours were considered part of the same migraine and duration was calculated as such. Migraine symptoms included photophobia, phonophobia, nausea, and vomiting. No data collected for aura and vomiting's migraine symptoms.

Time frame: Baseline and Month 3

Population: Randomized participants (pts) who had at least 4 migraines/probable migraines during the baseline period, who received at least 1 dose of study drug, and had at least 1 post-randomization efficacy data for the specified endpoint.No data collected for aura and vomiting's migraine symptoms.

The CGI-I was a 1-item scale that measured the clinician's perception of the improvement in migraine symptoms compared with the start of treatment. Scores ranged from 1 (very much improved) to 7 (very much worse). A score of 4 indicated no change.

Time frame: Baseline(Day 28) and Week 12 (Day 84)

Population: Randomized participants who had at least 4 migraines and/or probable migraine headaches during the baseline period, who received at least 1 dose of study drug and, for whom at least 1 post-randomization efficacy data for the specified endpoint was available.

MIBS-4 was a 4-item self-administered scale that assessed the impact of headaches on the participant's life between headache attacks. Each item measured a specific domain (impairment in work or school, impairment in family and social life, difficulty making plans or commitments, or emotional/affective and cognitive distress). For each item and domain, scores were weighted as follows: Don't know (0), Never (0), Rarely (1), Some of the time (2), Much of the time (3), and All of the time (4). The overall weighted score was the sum of the domain scores and ranged from 0 to 16. Higher scores indicated a greater impact of headaches on the participant's life between headache attacks.

Time frame: Baseline and Week 12

Population: Randomized participants who had at least 4 migraines and/or probable migraine headaches during the baseline period, who received at least 1 dose of study drug, and for whom at least 1 post-randomization efficacy data for the specified endpoint was available.

The MSQ was a 14-item self-administered scale that assessed the participant's perception of quality of life for 3 dimensions \[role restriction or restrictive function (Items 1-7), role prevention or preventive function (Items 8-11), and emotional function (Items 12-14)\]. Participants rated each item from 1 (none of the time) to 6 (all of the time). Since each item was presented as a negative statement, participant responses were recoded before item scores were calculated. Then, dimension scores were calculated as the sum of the recoded items for that specific dimension. Each dimension score was transformed into a score that ranged from 0 to 100. The transformation formula for the restrictive function = \[(dimension score-7)\*100\]/35, for the preventive function = \[(dimension score-4)\*100\]/20, and for the emotional function = \[(dimension score-3)\*100\]/15. A lower score indicated a poorer quality of life associated with that domain.

Time frame: Baseline and Week 12

Population: Randomized participants who had at least 4 migraines and/or probable migraine headaches during the baseline period, who received at least 1 dose of study drug, and for whom at least 1 post-randomization efficacy data for the specified endpoint was available.

The PGI-I was a 1-item scale that measured the participant's perception of improvement in migraine symptoms compared with the start of treatment. Scores ranged from 1 (very much improved) to 7 (very much worse). A score of 4 indicated no change.

Time frame: Baseline (Day 28) and Week 12 (Day 84)

Population: Randomized participants who had at least 4 migraines and/or probable migraine headaches during the baseline period, who received at least 1 dose of study drug, and for whom at least 1 post-randomization efficacy data for the specified endpoint was available.

The participant-reported severity of migraines was rated on a 3-point categorical scale (Mild, Moderate, or Severe). Participants could report a severity of none (score = 0), mild (1), moderate (2), or severe (3). In general, if a headache was mild, daily activities could be resumed and little to no medication was taken. Moderate headaches required medication and effected daily activities. Severe headaches were debilitating and required medication. If a participant had multiple migraines during Month 3 (normalized to 28 days), the most severe migraine was analyzed.

Time frame: Baseline and Month 3

Population: Randomized participants who had at least 4 migraines and/or probable migraine headaches during the baseline period, who received at least 1 dose of study drug, and for whom at least 1 post-randomization efficacy data for the specified endpoint was available.

A migraine day was any day with a migraine attack (a headache lasting 4 to 72 hours). The number of migraine days per month was normalized to a 28-day month and calculated as the (number of migraine days\*28)/number of days in the specified month.

Time frame: Baseline and Month 3

Population: Randomized participants (pts) who had at least 4 migraines and/or probable migraine headaches during the baseline period, who received at least 1 dose of study drug, and for whom at least 1 post-randomization efficacy data for the specified endpoint was available.

Participants were allowed to use a pre-approved list of medications for the treatment of breakthrough migraines during the study, as long as the treatments were the same as those used and reported during the baseline period. Any medications or procedures to prevent migraines were not allowed. Percentage of participants = (number of participants using breakthrough medication/total number of participants)\*100. Each month was normalized to a 28-day month.

Time frame: Month 3

Population: Randomized participants who had at least 4 migraines and/or probable migraine headaches during the baseline period, who received at least 1 dose of study drug, and for whom at least 1 post-randomization efficacy data for the specified endpoint was available.

Time frame: Baseline and Week 8 (1 to 3 hours postdose), Weeks 2 and 4 (predose and 1 to 3 hours postdose), Week 12 (predose, 1 to 3 hours postdose, and 5 hours postdose)

Population: Participants who received at least 1 dose of study drug and had at least 1 evaluable pharmacokinetic sample.

Participants were allowed to use a pre-approved list of medications for the treatment of breakthrough migraines during the study, as long as the treatments were the same as those used and reported during the baseline period. Any medications or procedures to prevent migraines were not allowed. The mean number was calculated by the breakthrough (BH) medications (meds) per migraine used by each participant per month. Each month was normalized to a 28-day month.

Time frame: Baseline, Week 12

Population: Randomized participants who had at least 4 migraines and/or probable migraine headaches during the baseline period, who received at least 1 dose of study drug, and for whom at least 1 post-randomization efficacy data for the specified endpoint was available.