Trial Outcomes & Findings for Long-Term Safety of Treximet (Sumatriptan/Naproxen Sodium) for Migraine in Adolescents (NCT NCT00488514)

Results Overview

The number of participants with a drug-related adverse event (AE). Frequency threshold for reporting a drug-related AE: \>=2% participants recorded as having at least one occurrence of a reported drug-related AE.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

656 participants

Primary outcome timeframe

Baseline through End of Study (up to Month 12)

Results posted on

2017-05-18

Participant Flow

Participant milestones

Participant milestones
Measure	85 mg Sumatriptan/500 mg Naproxen Sodium Combination Tablet: 85 milligrams (mg) sumatriptan and 500 mg naproxen sodium. A single Combination Tablet was supplied for each migraine attack, not to exceed one tablet in 24 hours.
Overall Study STARTED	656
Overall Study COMPLETED	363
Overall Study NOT COMPLETED	293

Reasons for withdrawal

Reasons for withdrawal
Measure	85 mg Sumatriptan/500 mg Naproxen Sodium Combination Tablet: 85 milligrams (mg) sumatriptan and 500 mg naproxen sodium. A single Combination Tablet was supplied for each migraine attack, not to exceed one tablet in 24 hours.
Overall Study Adverse Event	41
Overall Study Lost to Follow-up	44
Overall Study Protocol Violation	32
Overall Study Withdrawal by Subject	106
Overall Study Lack of Efficacy	28
Overall Study Did not meet criteria for treatment	30
Overall Study Postive drug screen	1
Overall Study Withdrawn per medical monitor decision	2
Overall Study Investigator decision	1
Overall Study Participant had too few migraines	5
Overall Study Increase in number of migraines	2
Overall Study Increased use of concomitant medication	1

Baseline Characteristics

Long-Term Safety of Treximet (Sumatriptan/Naproxen Sodium) for Migraine in Adolescents

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	85 mg Sumatriptan/500 mg Naproxen Sodium n=622 Participants Combination Tablet: 85 milligrams (mg) sumatriptan and 500 mg naproxen sodium.
Age, Continuous	14.7 Years STANDARD_DEVIATION 1.68 • n=5 Participants
Sex: Female, Male Female	367 Participants n=5 Participants
Sex: Female, Male Male	255 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	527 participants n=5 Participants
Race/Ethnicity, Customized Africian American	71 participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaskan Native	10 participants n=5 Participants
Race/Ethnicity, Customized Asian	4 participants n=5 Participants
Race/Ethnicity, Customized African American/African Heritage and Asian	2 participants n=5 Participants
Race/Ethnicity, Customized African American/African Heritage and White	3 participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaskan Native and White	5 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline through End of Study (up to Month 12)

Population: Enrolled Population: all participants entered into the trial and dispensed the Combination Tablet, regardless of whether they ever took the Combination Tablet

The number of participants with a drug-related adverse event (AE). Frequency threshold for reporting a drug-related AE: \>=2% participants recorded as having at least one occurrence of a reported drug-related AE.

Outcome measures

Outcome measures
Measure	6 Month Completer Population n=333 Participants Participants in the Enrolled Population who were treated with at least one dose of the combination tablet, completed at least one study visit (3- or 6-month visit), provided data for at least 6 migraines, and who continued in the study for at least 166 days	12 Month Completer Population n=181 Participants Participants in the Enrolled and 6 Month Completer Populations who completed at least one study visit in the second six-month period (9- or 12-month visit), provided data for at least 12 migraines, and who continued in the study for at least 346 days. The 12 Month Completer Population is a subset of those participants who completed or remained in the study for at least 346 days.	Safety Population n=622 Participants Participants in the Enrolled Population who took at least one dose of the combination tablet
Number of Participants With the Indicated Drug-related Adverse Events At least one drug-related adverse event	93 participants	46 participants	170 participants
Number of Participants With the Indicated Drug-related Adverse Events Nausea	19 participants	11 participants	44 participants
Number of Participants With the Indicated Drug-related Adverse Events Dizziness	7 participants	3 participants	20 participants
Number of Participants With the Indicated Drug-related Adverse Events Muscle tightness	10 participants	5 participants	18 participants
Number of Participants With the Indicated Drug-related Adverse Events Chest discomfort	10 participants	3 participants	16 participants
Number of Participants With the Indicated Drug-related Adverse Events Paresthesia	8 participants	2 participants	14 participants
Number of Participants With the Indicated Drug-related Adverse Events Throat tightness	11 participants	6 participants	14 participants
Number of Participants With the Indicated Drug-related Adverse Events Somnolence	9 participants	2 participants	14 participants
Number of Participants With the Indicated Drug-related Adverse Events Neck pain	6 participants	3 participants	12 participants
Number of Participants With the Indicated Drug-related Adverse Events Flushing	5 participants	2 participants	8 participants

SECONDARY outcome

Timeframe: Baseline through End of Study (up to Month 12)

Population: Enrolled Population: all participants entered into the trial and dispensed the Combination Tablet, regardless of whether they ever took the Combination Tablet

The number of participants with at least one mild (an event that is easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities), moderate (an event that is sufficiently discomforting to interfere with normal everyday activities), or severe adverse event (an event that prevents normal everyday activities) was recorded.

Outcome measures

Outcome measures
Measure	6 Month Completer Population n=333 Participants Participants in the Enrolled Population who were treated with at least one dose of the combination tablet, completed at least one study visit (3- or 6-month visit), provided data for at least 6 migraines, and who continued in the study for at least 166 days	12 Month Completer Population n=181 Participants Participants in the Enrolled and 6 Month Completer Populations who completed at least one study visit in the second six-month period (9- or 12-month visit), provided data for at least 12 migraines, and who continued in the study for at least 346 days. The 12 Month Completer Population is a subset of those participants who completed or remained in the study for at least 346 days.	Safety Population n=622 Participants Participants in the Enrolled Population who took at least one dose of the combination tablet
Number of Participants With Any Adverse Event Categorized by Severity Mild	74 participants	43 participants	127 participants
Number of Participants With Any Adverse Event Categorized by Severity Moderate	140 participants	72 participants	220 participants
Number of Participants With Any Adverse Event Categorized by Severity Severe	24 participants	14 participants	44 participants

SECONDARY outcome

Timeframe: Baseline through End of Study (up to Month 12)

Population: Enrolled Population: all participants entered into the trial and dispensed the Combination Tablet, regardless of whether they ever took the Combination Tablet

The number of participants with an adverse event occurring in either the first six months of the study (months 0-6; \<=194 days) or the second six months of the study (months 6-12; =\>194 days until end of study) was recorded.

Outcome measures

Outcome measures
Measure	6 Month Completer Population n=333 Participants Participants in the Enrolled Population who were treated with at least one dose of the combination tablet, completed at least one study visit (3- or 6-month visit), provided data for at least 6 migraines, and who continued in the study for at least 166 days	12 Month Completer Population n=181 Participants Participants in the Enrolled and 6 Month Completer Populations who completed at least one study visit in the second six-month period (9- or 12-month visit), provided data for at least 12 migraines, and who continued in the study for at least 346 days. The 12 Month Completer Population is a subset of those participants who completed or remained in the study for at least 346 days.	Safety Population n=622 Participants Participants in the Enrolled Population who took at least one dose of the combination tablet
Number of Participants With Any Adverse Event Categorized Over Time Second six months of study	143 participants	85 participants	191 participants
Number of Participants With Any Adverse Event Categorized Over Time First six months of study	208 participants	112 participants	348 participants

SECONDARY outcome

Timeframe: Baseline through End of Study (up to Month 12)

Population: Enrolled Population: all participants entered into the trial and dispensed the Combination Tablet, regardless of whether they ever took the Combination Tablet

The number of participants with any adverse event by age group (12-14 and 15-17 years) is recorded.

Outcome measures

Outcome measures
Measure	6 Month Completer Population n=333 Participants Participants in the Enrolled Population who were treated with at least one dose of the combination tablet, completed at least one study visit (3- or 6-month visit), provided data for at least 6 migraines, and who continued in the study for at least 166 days	12 Month Completer Population n=181 Participants Participants in the Enrolled and 6 Month Completer Populations who completed at least one study visit in the second six-month period (9- or 12-month visit), provided data for at least 12 migraines, and who continued in the study for at least 346 days. The 12 Month Completer Population is a subset of those participants who completed or remained in the study for at least 346 days.	Safety Population n=622 Participants Participants in the Enrolled Population who took at least one dose of the combination tablet
Number of Participants With Any Adverse Event Categorized by Participant Age Ages 12-14	104 participants	57 participants	175 participants
Number of Participants With Any Adverse Event Categorized by Participant Age Ages 15-17	135 participants	73 participants	218 participants

SECONDARY outcome

Timeframe: Baseline through End of Study (up to Month 12)

Population: Safety Population: all participants in the Enrolled Population who took at least one dose of the combination tablet

The number of participants with any adverse event was categorized by race. The category "Other" captures : American Indian or Alaskan Native; Asian, Native Hawaiian, or Other Pacific Islander; African American/African Heritage and Asian; African American/African Heritage and White; and American Indian or Alaskan Native and White.

Outcome measures

Outcome measures
Measure	6 Month Completer Population n=622 Participants Participants in the Enrolled Population who were treated with at least one dose of the combination tablet, completed at least one study visit (3- or 6-month visit), provided data for at least 6 migraines, and who continued in the study for at least 166 days	12 Month Completer Population Participants in the Enrolled and 6 Month Completer Populations who completed at least one study visit in the second six-month period (9- or 12-month visit), provided data for at least 12 migraines, and who continued in the study for at least 346 days. The 12 Month Completer Population is a subset of those participants who completed or remained in the study for at least 346 days.	Safety Population Participants in the Enrolled Population who took at least one dose of the combination tablet
Number of Participants With Any Adverse Event Categorized by Participant Race Caucasian	344 participants	—	—
Number of Participants With Any Adverse Event Categorized by Participant Race African American	35 participants	—	—
Number of Participants With Any Adverse Event Categorized by Participant Race Other	14 participants	—	—

SECONDARY outcome

Timeframe: Baseline through End of Study (up to Month 12)

Population: Safety Population: all participants in the Enrolled Population who took at least one dose of the combination tablet

The number of participants with adverse events by gender is recorded.

Outcome measures

Outcome measures
Measure	6 Month Completer Population n=622 Participants Participants in the Enrolled Population who were treated with at least one dose of the combination tablet, completed at least one study visit (3- or 6-month visit), provided data for at least 6 migraines, and who continued in the study for at least 166 days	12 Month Completer Population Participants in the Enrolled and 6 Month Completer Populations who completed at least one study visit in the second six-month period (9- or 12-month visit), provided data for at least 12 migraines, and who continued in the study for at least 346 days. The 12 Month Completer Population is a subset of those participants who completed or remained in the study for at least 346 days.	Safety Population Participants in the Enrolled Population who took at least one dose of the combination tablet
Number of Participants With Any Adverse Event Categorized by Participant Gender Female	238 participants	—	—
Number of Participants With Any Adverse Event Categorized by Participant Gender Male	155 participants	—	—

SECONDARY outcome

Timeframe: Baseline through End of Study (up to Month 12)

Population: Enrolled Population: all participants entered into the trial and dispensed the Combination Tablet, regardless of whether they ever took the Combination Tablet

The number of participants with adverse events that occurred within 3 or 5 days of their first dose of the Combination Tablet was recorded.

Outcome measures

Outcome measures
Measure	6 Month Completer Population n=333 Participants Participants in the Enrolled Population who were treated with at least one dose of the combination tablet, completed at least one study visit (3- or 6-month visit), provided data for at least 6 migraines, and who continued in the study for at least 166 days	12 Month Completer Population n=181 Participants Participants in the Enrolled and 6 Month Completer Populations who completed at least one study visit in the second six-month period (9- or 12-month visit), provided data for at least 12 migraines, and who continued in the study for at least 346 days. The 12 Month Completer Population is a subset of those participants who completed or remained in the study for at least 346 days.	Safety Population n=622 Participants Participants in the Enrolled Population who took at least one dose of the combination tablet
Number of Participants With Any Adverse Event That Occurred Within 3 or 5 Days of the First Dose of the Combination Tablet Within 3 days	66 participants	35 participants	128 participants
Number of Participants With Any Adverse Event That Occurred Within 3 or 5 Days of the First Dose of the Combination Tablet Within 5 days	66 participants	35 participants	130 participants

SECONDARY outcome

Timeframe: Baseline through End of Study (up to Month 12)

Population: Enrolled Population: all participants entered into the trial and dispensed the Combination Tablet, regardless of whether they ever took the Combination Tablet

The number of events that occurred within 3 or 5 days of dosing with the combination tablet on a per tablet basis. A total of 8413, 5876, and 9989 tablets were taken by the 6 Month Completer, 12 Month Completer, and the Safety Populations, respectively.

Outcome measures

Outcome measures
Measure	6 Month Completer Population n=333 Participants Participants in the Enrolled Population who were treated with at least one dose of the combination tablet, completed at least one study visit (3- or 6-month visit), provided data for at least 6 migraines, and who continued in the study for at least 166 days	12 Month Completer Population n=181 Participants Participants in the Enrolled and 6 Month Completer Populations who completed at least one study visit in the second six-month period (9- or 12-month visit), provided data for at least 12 migraines, and who continued in the study for at least 346 days. The 12 Month Completer Population is a subset of those participants who completed or remained in the study for at least 346 days.	Safety Population n=622 Participants Participants in the Enrolled Population who took at least one dose of the combination tablet
Number of Tablets Taken, After Which at Least One Adverse Event Occurred Within 3 or 5 Days of Dosing With That Combination Tablet Number of tablets with an AE within 3 days	917 tablets	667 tablets	1116 tablets
Number of Tablets Taken, After Which at Least One Adverse Event Occurred Within 3 or 5 Days of Dosing With That Combination Tablet Number of tablets with an AE within 5 days	970 tablets	706 tablets	1178 tablets

SECONDARY outcome

Timeframe: Baseline through End of Study (up to Month 12)

Population: Enrolled Population: all participants entered into the trial and dispensed the Combination Tablet, regardless of whether they ever took the Combination Tablet. The number of participants with an assessment may vary, depending on the number of assessments completed at each visit.

A shift from "normal to low," for example, indicates that a value was normal at baseline but low at the end of study visit. The value ranges were determined by the central laboratory. Reference ranges: ALT, 12 years old (y): 0-45 Units/liter (U/L), \>13 y: 0-48 U/L; AST, 12 y: 0-42 U/L, \>13 y 0-42 U/L; creatinine, 12 y: 27-88 micromoles/liter (UMOL/L), \>13 y: 44-124 UMOL/L; potassium, 12 y: 3.5-5.5 millimoles/liter (MMOL/L), \>13 y: 3.5-5.3 MMOL/L; BUN, 12-17 y: 24-101 milligrams (mg)/deciliter (dL).

Outcome measures

Outcome measures
Measure	6 Month Completer Population n=330 Participants Participants in the Enrolled Population who were treated with at least one dose of the combination tablet, completed at least one study visit (3- or 6-month visit), provided data for at least 6 migraines, and who continued in the study for at least 166 days	12 Month Completer Population n=179 Participants Participants in the Enrolled and 6 Month Completer Populations who completed at least one study visit in the second six-month period (9- or 12-month visit), provided data for at least 12 migraines, and who continued in the study for at least 346 days. The 12 Month Completer Population is a subset of those participants who completed or remained in the study for at least 346 days.	Safety Population n=565 Participants Participants in the Enrolled Population who took at least one dose of the combination tablet
Number of Participants With Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine, Potassium, and Blood Urea Nitrogen (BUN) Values of Interest That Shifted From Normal at Baseline to Abnormal at the End of Study Visit ALT, normal to high, n=330, 179, 565	2 participants	1 participants	3 participants
Number of Participants With Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine, Potassium, and Blood Urea Nitrogen (BUN) Values of Interest That Shifted From Normal at Baseline to Abnormal at the End of Study Visit ALT, normal to low, n=330, 179, 565	0 participants	0 participants	0 participants
Number of Participants With Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine, Potassium, and Blood Urea Nitrogen (BUN) Values of Interest That Shifted From Normal at Baseline to Abnormal at the End of Study Visit AST, normal to high, n=329, 179, 562	1 participants	1 participants	3 participants
Number of Participants With Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine, Potassium, and Blood Urea Nitrogen (BUN) Values of Interest That Shifted From Normal at Baseline to Abnormal at the End of Study Visit AST, normal to low, n=329, 179, 562	0 participants	0 participants	0 participants
Number of Participants With Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine, Potassium, and Blood Urea Nitrogen (BUN) Values of Interest That Shifted From Normal at Baseline to Abnormal at the End of Study Visit Creatinine, normal to high, n=330, 179, 565	0 participants	0 participants	0 participants
Number of Participants With Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine, Potassium, and Blood Urea Nitrogen (BUN) Values of Interest That Shifted From Normal at Baseline to Abnormal at the End of Study Visit Creatinine, normal to low, n=330, 179, 565	2 participants	1 participants	2 participants
Number of Participants With Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine, Potassium, and Blood Urea Nitrogen (BUN) Values of Interest That Shifted From Normal at Baseline to Abnormal at the End of Study Visit Potassium, normal to high, n=329, 179, 562	1 participants	0 participants	4 participants
Number of Participants With Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine, Potassium, and Blood Urea Nitrogen (BUN) Values of Interest That Shifted From Normal at Baseline to Abnormal at the End of Study Visit Potassium, normal to low, n=329, 179, 562	3 participants	2 participants	6 participants
Number of Participants With Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine, Potassium, and Blood Urea Nitrogen (BUN) Values of Interest That Shifted From Normal at Baseline to Abnormal at the End of Study Visit BUN, normal to high, n=330, 179, 565	0 participants	0 participants	1 participants
Number of Participants With Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine, Potassium, and Blood Urea Nitrogen (BUN) Values of Interest That Shifted From Normal at Baseline to Abnormal at the End of Study Visit BUN, normal to low, n=330, 179, 565	2 participants	0 participants	9 participants

SECONDARY outcome

Timeframe: Baseline through End of Study (up to Month 12)

Population: Enrolled Population: all participants entered into the trial and dispensed the Combination Tablet, regardless of whether they ever took the Combination Tablet. The number of participants with an assessment may vary, depending on the number of assessments completed at each visit.

A shift from "normal to low," for example, indicates that a value was normal at baseline but low at the end of study visit. The value ranges were determined by the central laboratory. Reference ranges: hemoglobin, 12-17 years old (y): 120-160 grams (g)/L; hematocrit (expressed as the percentage of blood occupied by red blood cells), 12-17 y: 0.360-0.490.

Outcome measures

Outcome measures
Measure	6 Month Completer Population n=318 Participants Participants in the Enrolled Population who were treated with at least one dose of the combination tablet, completed at least one study visit (3- or 6-month visit), provided data for at least 6 migraines, and who continued in the study for at least 166 days	12 Month Completer Population n=176 Participants Participants in the Enrolled and 6 Month Completer Populations who completed at least one study visit in the second six-month period (9- or 12-month visit), provided data for at least 12 migraines, and who continued in the study for at least 346 days. The 12 Month Completer Population is a subset of those participants who completed or remained in the study for at least 346 days.	Safety Population n=546 Participants Participants in the Enrolled Population who took at least one dose of the combination tablet
Number of Participants With Hematocrit and Hemoglobin Values of Interest That Shifted From Normal at Baseline to Abnormal at the End of Study Visit Hemoglobin, normal to high, n=318,176, 546	6 participants	0 participants	9 participants
Number of Participants With Hematocrit and Hemoglobin Values of Interest That Shifted From Normal at Baseline to Abnormal at the End of Study Visit Hemoglobin, normal to low, n=318,176, 546	10 participants	6 participants	20 participants
Number of Participants With Hematocrit and Hemoglobin Values of Interest That Shifted From Normal at Baseline to Abnormal at the End of Study Visit Hematocrit, normal to high, n=318,176, 546	2 participants	0 participants	4 participants
Number of Participants With Hematocrit and Hemoglobin Values of Interest That Shifted From Normal at Baseline to Abnormal at the End of Study Visit Hematocrit, normal to low, n=318,176, 546	17 participants	10 participants	29 participants

SECONDARY outcome

Timeframe: Screening and Months 3, 6, 9, and 12

Population: Safety Population: all participants in the Enrolled Population who took at least one dose of the combination tablet. The number of participants with an assessment may vary by visit, depending on the number of assessments completed at each visit.

Outcome measures

Outcome measures
Measure	6 Month Completer Population n=285 Participants Participants in the Enrolled Population who were treated with at least one dose of the combination tablet, completed at least one study visit (3- or 6-month visit), provided data for at least 6 migraines, and who continued in the study for at least 166 days	12 Month Completer Population n=337 Participants Participants in the Enrolled and 6 Month Completer Populations who completed at least one study visit in the second six-month period (9- or 12-month visit), provided data for at least 12 migraines, and who continued in the study for at least 346 days. The 12 Month Completer Population is a subset of those participants who completed or remained in the study for at least 346 days.	Safety Population n=622 Participants Participants in the Enrolled Population who took at least one dose of the combination tablet
Mean Height for All Study Participants at the Indicated Time Points Month 6, n=224, 249, 473	162.6 centimeters Standard Deviation 9.12	167.3 centimeters Standard Deviation 8.81	165.1 centimeters Standard Deviation 9.26
Mean Height for All Study Participants at the Indicated Time Points Month 12, n=178, 198, 376	165.3 centimeters Standard Deviation 8.86	167.9 centimeters Standard Deviation 8.70	166.7 centimeters Standard Deviation 8.86
Mean Height for All Study Participants at the Indicated Time Points Screening, n=285, 337, 622	160.2 centimeters Standard Deviation 9.15	167.0 centimeters Standard Deviation 8.80	163.9 centimeters Standard Deviation 9.57
Mean Height for All Study Participants at the Indicated Time Points Month 3, n=271, 308, 579	161.3 centimeters Standard Deviation 9.09	167.3 centimeters Standard Deviation 8.92	164.5 centimeters Standard Deviation 9.48
Mean Height for All Study Participants at the Indicated Time Points Month 9, n=198, 221, 419	163.8 centimeters Standard Deviation 8.92	167.6 centimeters Standard Deviation 8.39	165.8 centimeters Standard Deviation 8.84

SECONDARY outcome

Timeframe: Screening and Months 3, 6, 9, and 12

Population: Safety Population: all participants in the Enrolled Population who took at least one dose of the combination tablet. The number of participants with an assessment may vary, depending on the number of assessments completed at each visit.

Outcome measures

Outcome measures
Measure	6 Month Completer Population n=285 Participants Participants in the Enrolled Population who were treated with at least one dose of the combination tablet, completed at least one study visit (3- or 6-month visit), provided data for at least 6 migraines, and who continued in the study for at least 166 days	12 Month Completer Population n=337 Participants Participants in the Enrolled and 6 Month Completer Populations who completed at least one study visit in the second six-month period (9- or 12-month visit), provided data for at least 12 migraines, and who continued in the study for at least 346 days. The 12 Month Completer Population is a subset of those participants who completed or remained in the study for at least 346 days.	Safety Population n=622 Participants Participants in the Enrolled Population who took at least one dose of the combination tablet
Mean Weight for All Study Participants at the Indicated Time Points Screening, n=285, 337, 622	57.02 kilograms Standard Deviation 15.450	66.57 kilograms Standard Deviation 16.824	62.19 kilograms Standard Deviation 16.881
Mean Weight for All Study Participants at the Indicated Time Points Month 3, n=270, 306, 576	58.01 kilograms Standard Deviation 16.012	66.61 kilograms Standard Deviation 16.921	62.58 kilograms Standard Deviation 17.037
Mean Weight for All Study Participants at the Indicated Time Points Month 6, n=223, 248, 471	60.20 kilograms Standard Deviation 16.976	66.61 kilograms Standard Deviation 16.864	63.57 kilograms Standard Deviation 17.200
Mean Weight for All Study Participants at the Indicated Time Points Month 9, n=197, 220, 417	61.24 kilograms Standard Deviation 17.149	66.90 kilograms Standard Deviation 17.169	64.23 kilograms Standard Deviation 17.372
Mean Weight for All Study Participants at the Indicated Time Points Month 12, n=178, 198, 376	62.92 kilograms Standard Deviation 17.406	67.35 kilograms Standard Deviation 17.952	65.25 kilograms Standard Deviation 17.810

SECONDARY outcome

Timeframe: Screening and Months 3, 6, 9, and 12

Population: Safety Population: all participants in the Enrolled Population who took at least one dose of the combination tablet. The number of participants with an assessment may vary, depending on the number of assessments completed at each visit.

BMI = (Weight in kilograms)/(height in centimeters/100)\^2

Outcome measures

Outcome measures
Measure	6 Month Completer Population n=285 Participants Participants in the Enrolled Population who were treated with at least one dose of the combination tablet, completed at least one study visit (3- or 6-month visit), provided data for at least 6 migraines, and who continued in the study for at least 166 days	12 Month Completer Population n=337 Participants Participants in the Enrolled and 6 Month Completer Populations who completed at least one study visit in the second six-month period (9- or 12-month visit), provided data for at least 12 migraines, and who continued in the study for at least 346 days. The 12 Month Completer Population is a subset of those participants who completed or remained in the study for at least 346 days.	Safety Population n=622 Participants Participants in the Enrolled Population who took at least one dose of the combination tablet
Mean Body Mass Index (BMI) for All Study Participants at the Indicated Time Points Screening, n=285, 337, 622	22.01 kilograms per meters squared Standard Deviation 4.611	23.77 kilograms per meters squared Standard Deviation 5.249	22.97 kilograms per meters squared Standard Deviation 5.040
Mean Body Mass Index (BMI) for All Study Participants at the Indicated Time Points Month 3, n=270, 306, 576	22.09 kilograms per meters squared Standard Deviation 4.740	23.71 kilograms per meters squared Standard Deviation 5.267	22.95 kilograms per meters squared Standard Deviation 5.087
Mean Body Mass Index (BMI) for All Study Participants at the Indicated Time Points Month 12, n=178, 198, 376	22.81 kilograms per meters squared Standard Deviation 4.969	23.79 kilograms per meters squared Standard Deviation 5.633	23.33 kilograms per meters squared Standard Deviation 5.345
Mean Body Mass Index (BMI) for All Study Participants at the Indicated Time Points Month 6, n=223, 248, 471	22.54 kilograms per meters squared Standard Deviation 4.949	23.74 kilograms per meters squared Standard Deviation 5.455	23.17 kilograms per meters squared Standard Deviation 5.251
Mean Body Mass Index (BMI) for All Study Participants at the Indicated Time Points Month 9, n= 197, 220, 417	22.58 kilograms per meters squared Standard Deviation 4.904	23.74 kilograms per meters squared Standard Deviation 5.431	23.20 kilograms per meters squared Standard Deviation 5.215

SECONDARY outcome

Timeframe: Screening and Months 3, 6, 9, and 12

Population: Safety Population: all participants in the Enrolled Population who took at least one dose of the combination tablet. The number of participants with an assessment may vary, depending on the number of assessments completed at each visit.

At each visit, a participant's blood pressure was taken three times. The average of the three readings was then calculated for each participant at each visit (mean blood pressure). The outcome measure represents the average of the mean blood pressure of all of the study participants. SBP, systolic blood pressure; DBP, diastolic blood pressure.

Outcome measures

Outcome measures
Measure	6 Month Completer Population n=285 Participants Participants in the Enrolled Population who were treated with at least one dose of the combination tablet, completed at least one study visit (3- or 6-month visit), provided data for at least 6 migraines, and who continued in the study for at least 166 days	12 Month Completer Population n=337 Participants Participants in the Enrolled and 6 Month Completer Populations who completed at least one study visit in the second six-month period (9- or 12-month visit), provided data for at least 12 migraines, and who continued in the study for at least 346 days. The 12 Month Completer Population is a subset of those participants who completed or remained in the study for at least 346 days.	Safety Population n=622 Participants Participants in the Enrolled Population who took at least one dose of the combination tablet
Mean Blood Pressure for All Study Participants at the Indicated Time Points SBP, Month 12, n=178, 198, 376	111.0 millimeters of mercury (mmHg) Standard Deviation 10.78	112.1 millimeters of mercury (mmHg) Standard Deviation 10.22	111.5 millimeters of mercury (mmHg) Standard Deviation 10.49
Mean Blood Pressure for All Study Participants at the Indicated Time Points DBP, Month 6, n=224, 249, 473	66.1 millimeters of mercury (mmHg) Standard Deviation 7.29	68.4 millimeters of mercury (mmHg) Standard Deviation 7.68	67.3 millimeters of mercury (mmHg) Standard Deviation 7.58
Mean Blood Pressure for All Study Participants at the Indicated Time Points SBP, Screening, n=285, 337, 622	107.4 millimeters of mercury (mmHg) Standard Deviation 10.08	110.2 millimeters of mercury (mmHg) Standard Deviation 10.15	108.9 millimeters of mercury (mmHg) Standard Deviation 10.21
Mean Blood Pressure for All Study Participants at the Indicated Time Points SBP, Month 3, n=270, 308, 578	107.2 millimeters of mercury (mmHg) Standard Deviation 10.67	111.1 millimeters of mercury (mmHg) Standard Deviation 10.19	109.3 millimeters of mercury (mmHg) Standard Deviation 10.58
Mean Blood Pressure for All Study Participants at the Indicated Time Points SBP, Month 6, n=224, 249, 473	109.2 millimeters of mercury (mmHg) Standard Deviation 10.37	112.0 millimeters of mercury (mmHg) Standard Deviation 10.39	110.6 millimeters of mercury (mmHg) Standard Deviation 10.46
Mean Blood Pressure for All Study Participants at the Indicated Time Points SBP, Month 9, n=198, 221, 419	109.6 millimeters of mercury (mmHg) Standard Deviation 10.55	112.7 millimeters of mercury (mmHg) Standard Deviation 10.63	111.2 millimeters of mercury (mmHg) Standard Deviation 10.69
Mean Blood Pressure for All Study Participants at the Indicated Time Points DBP, Screening, n=285, 337, 622	66.2 millimeters of mercury (mmHg) Standard Deviation 7.72	69.0 millimeters of mercury (mmHg) Standard Deviation 7.24	67.7 millimeters of mercury (mmHg) Standard Deviation 7.58
Mean Blood Pressure for All Study Participants at the Indicated Time Points DBP, Month 3, n=270, 308, 578	65.7 millimeters of mercury (mmHg) Standard Deviation 7.33	68.4 millimeters of mercury (mmHg) Standard Deviation 7.84	67.1 millimeters of mercury (mmHg) Standard Deviation 7.72
Mean Blood Pressure for All Study Participants at the Indicated Time Points DBP, Month 9, n=198, 221, 419	65.6 millimeters of mercury (mmHg) Standard Deviation 6.79	68.9 millimeters of mercury (mmHg) Standard Deviation 7.30	67.3 millimeters of mercury (mmHg) Standard Deviation 7.25
Mean Blood Pressure for All Study Participants at the Indicated Time Points DBP, Month 12, n=178, 198, 376	66.6 millimeters of mercury (mmHg) Standard Deviation 8.40	69.9 millimeters of mercury (mmHg) Standard Deviation 7.35	68.3 millimeters of mercury (mmHg) Standard Deviation 8.03

SECONDARY outcome

Timeframe: Screening and Months 3, 6, 9, and 12

Population: Safety Population: all participants in the Enrolled Population who took at least one dose of the combination tablet. The number of participants with an assessment may vary, depending on the number of assessments completed at each visit.

A sitting heart rate was measured once for each participant at each visit.

Outcome measures

Outcome measures
Measure	6 Month Completer Population n=284 Participants Participants in the Enrolled Population who were treated with at least one dose of the combination tablet, completed at least one study visit (3- or 6-month visit), provided data for at least 6 migraines, and who continued in the study for at least 166 days	12 Month Completer Population n=336 Participants Participants in the Enrolled and 6 Month Completer Populations who completed at least one study visit in the second six-month period (9- or 12-month visit), provided data for at least 12 migraines, and who continued in the study for at least 346 days. The 12 Month Completer Population is a subset of those participants who completed or remained in the study for at least 346 days.	Safety Population n=620 Participants Participants in the Enrolled Population who took at least one dose of the combination tablet
Mean Heart Rate for All Study Participants at the Indicated Time Points Month 9, n=198, 221, 419	76.9 beats per minute Standard Deviation 11.43	75.4 beats per minute Standard Deviation 11.13	76.1 beats per minute Standard Deviation 11.28
Mean Heart Rate for All Study Participants at the Indicated Time Points Screening, n=284, 336, 620	75.8 beats per minute Standard Deviation 11.58	73.0 beats per minute Standard Deviation 10.20	7.43 beats per minute Standard Deviation 10.93
Mean Heart Rate for All Study Participants at the Indicated Time Points Month 3, n=266, 305, 571	76.9 beats per minute Standard Deviation 11.57	75.6 beats per minute Standard Deviation 11.57	76.2 beats per minute Standard Deviation 11.58
Mean Heart Rate for All Study Participants at the Indicated Time Points Month 6, n=221, 247, 468	77.5 beats per minute Standard Deviation 10.87	75.4 beats per minute Standard Deviation 10.22	76.4 beats per minute Standard Deviation 10.57
Mean Heart Rate for All Study Participants at the Indicated Time Points Month 12, n=178, 198, 376	76.8 beats per minute Standard Deviation 12.17	74.7 beats per minute Standard Deviation 10.41	75.7 beats per minute Standard Deviation 11.31

SECONDARY outcome

Timeframe: Screening and Final Visit (up to Month 12)

Population: Safety Population: all participants in the Enrolled Population who took at least one dose of the combination tablet. The number of participants with an assessment may vary, depending on the number of assessments completed at each visit.

The number of participants with an electrocardiogram (ECG) status of normal, abnormal, clinically significant (CS), or not clinically significant (NCS), as determined by the Investigator, was reported. Specific definitions of ECG categorizations were not provided; investigators were expected to apply reasonable standards of clinical judgment. Normal, all ECG parameters within accepted normal ranges; abnormal, ECG finding(s) outside of normal ranges; CS, ECG with a CS abnormality that meets exclusion criteria; NCS, ECG with an abnormality not CS or meeting exclusion criteria per investigator.

Outcome measures

Outcome measures
Measure	6 Month Completer Population n=284 Participants Participants in the Enrolled Population who were treated with at least one dose of the combination tablet, completed at least one study visit (3- or 6-month visit), provided data for at least 6 migraines, and who continued in the study for at least 166 days	12 Month Completer Population n=337 Participants Participants in the Enrolled and 6 Month Completer Populations who completed at least one study visit in the second six-month period (9- or 12-month visit), provided data for at least 12 migraines, and who continued in the study for at least 346 days. The 12 Month Completer Population is a subset of those participants who completed or remained in the study for at least 346 days.	Safety Population n=621 Participants Participants in the Enrolled Population who took at least one dose of the combination tablet
Number of Participants With Abnormal Electrocardiogram Findings at Screening and at the Final Visit as Assessed by the Investigator Final Visit, Normal, n=248, 294, 542	196 participants	220 participants	416 participants
Number of Participants With Abnormal Electrocardiogram Findings at Screening and at the Final Visit as Assessed by the Investigator Screening, normal, n=284, 337, 621	224 participants	270 participants	494 participants
Number of Participants With Abnormal Electrocardiogram Findings at Screening and at the Final Visit as Assessed by the Investigator Screening, abnormal, NCS, n=284, 337, 621	60 participants	67 participants	127 participants
Number of Participants With Abnormal Electrocardiogram Findings at Screening and at the Final Visit as Assessed by the Investigator Screening, abnormal, CS, n=284, 337, 621	0 participants	0 participants	0 participants
Number of Participants With Abnormal Electrocardiogram Findings at Screening and at the Final Visit as Assessed by the Investigator Final Visit, abnormal, NCS, n=248, 294, 542	52 participants	74 participants	126 participants
Number of Participants With Abnormal Electrocardiogram Findings at Screening and at the Final Visit as Assessed by the Investigator Final Visit, abnormal, CS, n=248, 294, 542	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline through End of Study (up to Month 12)

Population: Intent-to-Treat (ITT) Population: all participants who took at least one dose of study drug and had at least one post-treatment migraine assessment

The number of migraine attacks eligible for evaluation, not associated with rescue medication use, or prohibited medications, was summarized. Rescue medication was additional medication taken within 24 hours of Combination Tablet. Prohibited medications: ergot, opioid, barbiturate, 5-HT1 agonist, long-acting non-steroidal anti-inflammatory drug (NSAID), short-acting NSAID-containing compound, analgesic, anti-emetic, monoamine oxidase inhibitors, St. John's Wort, angiotensin-converting enzyme inhibitor, Angiotensin II receptor blockers, anti-coagulant, anti-platelet.

Outcome measures

Outcome measures
Measure	6 Month Completer Population n=591 Participants Participants in the Enrolled Population who were treated with at least one dose of the combination tablet, completed at least one study visit (3- or 6-month visit), provided data for at least 6 migraines, and who continued in the study for at least 166 days	12 Month Completer Population Participants in the Enrolled and 6 Month Completer Populations who completed at least one study visit in the second six-month period (9- or 12-month visit), provided data for at least 12 migraines, and who continued in the study for at least 346 days. The 12 Month Completer Population is a subset of those participants who completed or remained in the study for at least 346 days.	Safety Population Participants in the Enrolled Population who took at least one dose of the combination tablet
Number of Treated Migraine Attacks All Migraines	8517 treated migraine attacks	—	—
Number of Treated Migraine Attacks Migraines Without Rescue Medication	7791 treated migraine attacks	—	—
Number of Treated Migraine Attacks Migraines Without Rescue or Prohibited Medication	7657 treated migraine attacks	—	—

SECONDARY outcome

Timeframe: Baseline through End of Study (up to Month 12)

Population: ITT Population: all participants who took at least one dose of study drug and had at least one post-treatment migraine assessment

The number of migraine attacks eligible for evaluation, not associated with rescue medication use, and not associated with either rescue medication use or prohibited medications were counted. Migraine Pain Free was defined as the migraine attack ending \<= 24 hours after the participant was dosed with the Combination Tablet.

Outcome measures

Outcome measures
Measure	6 Month Completer Population n=591 Participants Participants in the Enrolled Population who were treated with at least one dose of the combination tablet, completed at least one study visit (3- or 6-month visit), provided data for at least 6 migraines, and who continued in the study for at least 166 days	12 Month Completer Population Participants in the Enrolled and 6 Month Completer Populations who completed at least one study visit in the second six-month period (9- or 12-month visit), provided data for at least 12 migraines, and who continued in the study for at least 346 days. The 12 Month Completer Population is a subset of those participants who completed or remained in the study for at least 346 days.	Safety Population Participants in the Enrolled Population who took at least one dose of the combination tablet
Number of Treated Attacks Classified as Migraine Pain-Free (MPF) Within 24 Hours of Dosing With the Combination Tablet All Migraines	6400 treated migraine attacks	—	—
Number of Treated Attacks Classified as Migraine Pain-Free (MPF) Within 24 Hours of Dosing With the Combination Tablet Migraines Without Rescue Medication	6142 treated migraine attacks	—	—
Number of Treated Attacks Classified as Migraine Pain-Free (MPF) Within 24 Hours of Dosing With the Combination Tablet Migraines Without Rescue or Prohibited Medication	6052 treated migraine attacks	—	—

SECONDARY outcome

Timeframe: Baseline through End of Study (up to Month 12)

Population: ITT Population: all participants who took at least one dose of study drug and had at least one post-treatment migraine assessment

The number of migraine attacks eligible for evaluation, not associated with rescue medication use, and not associated with either rescue medication use or prohibited medications were counted. Migraine Pain Free was defined as the migraine attack ending \<= 4 hours after the participant was dosed with the Combination Tablet.

Outcome measures

Outcome measures
Measure	6 Month Completer Population n=591 Participants Participants in the Enrolled Population who were treated with at least one dose of the combination tablet, completed at least one study visit (3- or 6-month visit), provided data for at least 6 migraines, and who continued in the study for at least 166 days	12 Month Completer Population Participants in the Enrolled and 6 Month Completer Populations who completed at least one study visit in the second six-month period (9- or 12-month visit), provided data for at least 12 migraines, and who continued in the study for at least 346 days. The 12 Month Completer Population is a subset of those participants who completed or remained in the study for at least 346 days.	Safety Population Participants in the Enrolled Population who took at least one dose of the combination tablet
Number of Treated Attacks Classified as Migraine Pain-Free (MPF) Within 4 Hours of Dosing With a Combination Tablet All Migraines	5076 treated migraine attacks	—	—
Number of Treated Attacks Classified as Migraine Pain-Free (MPF) Within 4 Hours of Dosing With a Combination Tablet Migraines Without Rescue Medication	5020 treated migraine attacks	—	—
Number of Treated Attacks Classified as Migraine Pain-Free (MPF) Within 4 Hours of Dosing With a Combination Tablet Migraines Without Rescue or Prohibited Medication	5017 treated migraine attacks	—	—

SECONDARY outcome

Timeframe: Baseline through End of Study (up to Month 12)

Population: ITT Population: all participants who took at least one dose of study drug and had at least one post-treatment migraine assessment

The number of migraine attacks eligible for evaluation, not associated with rescue medication use, and not associated with either rescue medication use or prohibited medications were counted. Migraine Pain Free was defined as the migraine attack ending \<= 4 hours after the participant was dosed with the Combination Tablet.

Outcome measures

Outcome measures
Measure	6 Month Completer Population n=591 Participants Participants in the Enrolled Population who were treated with at least one dose of the combination tablet, completed at least one study visit (3- or 6-month visit), provided data for at least 6 migraines, and who continued in the study for at least 166 days	12 Month Completer Population Participants in the Enrolled and 6 Month Completer Populations who completed at least one study visit in the second six-month period (9- or 12-month visit), provided data for at least 12 migraines, and who continued in the study for at least 346 days. The 12 Month Completer Population is a subset of those participants who completed or remained in the study for at least 346 days.	Safety Population Participants in the Enrolled Population who took at least one dose of the combination tablet
Number of Treated Attacks Classified as Migraine Pain-Free Within 4 Hours That Were Also Pain Free Within 2 Hours of Dosing With the Combination Tablet All Migraines	3623 treated migraine attacks	—	—
Number of Treated Attacks Classified as Migraine Pain-Free Within 4 Hours That Were Also Pain Free Within 2 Hours of Dosing With the Combination Tablet Migraines Without Rescue Medication	3598 treated migraine attacks	—	—
Number of Treated Attacks Classified as Migraine Pain-Free Within 4 Hours That Were Also Pain Free Within 2 Hours of Dosing With the Combination Tablet Migraines Without Rescue or Prohibited Medication	3596 treated migraine attacks	—	—

SECONDARY outcome

Timeframe: Baseline through End of Study (up to Month 12)

Population: Enrolled Population: all participants entered into the trial and dispensed the Combination Tablet, regardless of whether they ever took the Combination Tablet

The average number of headaches (non-migraine and migraine attacks), migraine attacks, and treated migraine attacks per month was calculated for each participant, based on their time in the study. The outcome measure represents the average of the mean number of the headaches, migraine headaches, and treated migraines per month of the study participants in the 6 Month, 12 Month, and ITT Populations. A treated attack is defined as a migraine treated with the Combination Tablet.

Outcome measures

Outcome measures
Measure	6 Month Completer Population n=333 Participants Participants in the Enrolled Population who were treated with at least one dose of the combination tablet, completed at least one study visit (3- or 6-month visit), provided data for at least 6 migraines, and who continued in the study for at least 166 days	12 Month Completer Population n=181 Participants Participants in the Enrolled and 6 Month Completer Populations who completed at least one study visit in the second six-month period (9- or 12-month visit), provided data for at least 12 migraines, and who continued in the study for at least 346 days. The 12 Month Completer Population is a subset of those participants who completed or remained in the study for at least 346 days.	Safety Population n=591 Participants Participants in the Enrolled Population who took at least one dose of the combination tablet
Average Number of Headaches, Migraine Attacks, and Treated Migraine Attacks Per Month Migraines	2.2 events Standard Deviation 1.17	2.6 events Standard Deviation 1.09	1.8 events Standard Deviation 1.23
Average Number of Headaches, Migraine Attacks, and Treated Migraine Attacks Per Month Treated migraine attacks	1.9 events Standard Deviation 1.05	2.4 events Standard Deviation 0.97	1.5 events Standard Deviation 1.11
Average Number of Headaches, Migraine Attacks, and Treated Migraine Attacks Per Month Headaches	3.3 events Standard Deviation 2.19	3.9 events Standard Deviation 2.29	3.0 events Standard Deviation 2.49

SECONDARY outcome

Timeframe: Baseline through End of Study (up to Month 12)

Population: Enrolled Population: all participants entered into the trial and dispensed the Combination Tablet, regardless of whether they ever took the Combination Tablet

The total number of migraine headaches and the number of migraine headaches treated with the Combination Tablet during the study were summarized.

Outcome measures

Outcome measures
Measure	6 Month Completer Population n=333 Participants Participants in the Enrolled Population who were treated with at least one dose of the combination tablet, completed at least one study visit (3- or 6-month visit), provided data for at least 6 migraines, and who continued in the study for at least 166 days	12 Month Completer Population n=181 Participants Participants in the Enrolled and 6 Month Completer Populations who completed at least one study visit in the second six-month period (9- or 12-month visit), provided data for at least 12 migraines, and who continued in the study for at least 346 days. The 12 Month Completer Population is a subset of those participants who completed or remained in the study for at least 346 days.	Safety Population n=591 Participants Participants in the Enrolled Population who took at least one dose of the combination tablet
Number of Total Migraines Headaches and Migraines Treated With the Combination Tablet Total Migraines	8290 migraine attacks	5851 migraine attacks	9937 migraine attacks
Number of Total Migraines Headaches and Migraines Treated With the Combination Tablet Treated Migraines	7318 migraine attacks	5234 migraine attacks	8517 migraine attacks

SECONDARY outcome

Timeframe: Baseline through End of Study (up to Month 12)

Population: Enrolled Population: all participants entered into the trial and dispensed the Combination Tablet, regardless of whether they ever took the Combination Tablet

The number of migraine attacks treated at the mild, moderate, or severe intensity were counted. Pain severity was assessed by participants based on a scale of 0-3: 0=no pain, 1=mild, 2= moderate, 3=severe.

Outcome measures

Outcome measures
Measure	6 Month Completer Population n=333 Participants Participants in the Enrolled Population who were treated with at least one dose of the combination tablet, completed at least one study visit (3- or 6-month visit), provided data for at least 6 migraines, and who continued in the study for at least 166 days	12 Month Completer Population n=181 Participants Participants in the Enrolled and 6 Month Completer Populations who completed at least one study visit in the second six-month period (9- or 12-month visit), provided data for at least 12 migraines, and who continued in the study for at least 346 days. The 12 Month Completer Population is a subset of those participants who completed or remained in the study for at least 346 days.	Safety Population n=591 Participants Participants in the Enrolled Population who took at least one dose of the combination tablet
Number of Migraine Attacks Rated With the Indicated Pain Severity No pain	0 treated migraine attacks	0 treated migraine attacks	0 treated migraine attacks
Number of Migraine Attacks Rated With the Indicated Pain Severity Mild	1373 treated migraine attacks	1009 treated migraine attacks	1619 treated migraine attacks
Number of Migraine Attacks Rated With the Indicated Pain Severity Moderate	3555 treated migraine attacks	2535 treated migraine attacks	4132 treated migraine attacks
Number of Migraine Attacks Rated With the Indicated Pain Severity Severe	2385 treated migraine attacks	1686 treated migraine attacks	2759 treated migraine attacks

SECONDARY outcome

Timeframe: Baseline through End of Study (up to Month 12)

Population: Enrolled Population: all participants entered into the trial and dispensed the Combination Tablet, regardless of whether they ever took the Combination Tablet

The number of treated migraine attacks with the reported migraine-associated symptoms of photophobia, phonophobia, nausea, neck pain, sinus pain, and vomiting were counted. Photophobia: sensitivity to light; phonophobia: sensitivity to sound.

Outcome measures

Outcome measures
Measure	6 Month Completer Population n=333 Participants Participants in the Enrolled Population who were treated with at least one dose of the combination tablet, completed at least one study visit (3- or 6-month visit), provided data for at least 6 migraines, and who continued in the study for at least 166 days	12 Month Completer Population n=181 Participants Participants in the Enrolled and 6 Month Completer Populations who completed at least one study visit in the second six-month period (9- or 12-month visit), provided data for at least 12 migraines, and who continued in the study for at least 346 days. The 12 Month Completer Population is a subset of those participants who completed or remained in the study for at least 346 days.	Safety Population n=591 Participants Participants in the Enrolled Population who took at least one dose of the combination tablet
Number of Treated Migraine Attacks With Photophobia, Phonophobia, Nausea, Neck Pain, Sinus Pain, and Vomiting Phonophobia	5221 treated migraine attacks	3725 treated migraine attacks	6063 treated migraine attacks
Number of Treated Migraine Attacks With Photophobia, Phonophobia, Nausea, Neck Pain, Sinus Pain, and Vomiting Sinus pain	2052 treated migraine attacks	1424 treated migraine attacks	2428 treated migraine attacks
Number of Treated Migraine Attacks With Photophobia, Phonophobia, Nausea, Neck Pain, Sinus Pain, and Vomiting Photophobia	5608 treated migraine attacks	4064 treated migraine attacks	6528 treated migraine attacks
Number of Treated Migraine Attacks With Photophobia, Phonophobia, Nausea, Neck Pain, Sinus Pain, and Vomiting Nausea	3120 treated migraine attacks	2173 treated migraine attacks	3690 treated migraine attacks
Number of Treated Migraine Attacks With Photophobia, Phonophobia, Nausea, Neck Pain, Sinus Pain, and Vomiting Neck pain	3050 treated migraine attacks	2172 treated migraine attacks	3540 treated migraine attacks
Number of Treated Migraine Attacks With Photophobia, Phonophobia, Nausea, Neck Pain, Sinus Pain, and Vomiting Vomiting	555 treated migraine attacks	375 treated migraine attacks	682 treated migraine attacks

SECONDARY outcome

Timeframe: Baseline and Months 3, 6, 9, and 12

Population: Enrolled Population: all participants entered into the trial and dispensed the Combination Tablet, regardless of whether they ever took the Combination Tablet. Due to data collection and/or assignment of a collected assessment to a visit, the number of participants analyzed at a given visit could vary.

The MSQ-A consists of 14 items measuring how migraines affect QOL: Role Function (RF)-Restrictive (items 1-7) and RF-Preventative (items 8-11), examining the degree to which performance of daily activities is limited or interrupted, respectively, by migraine; RF-Emotional (items 12-14, examining frustration/helplessness due to migraine). Dimensions (dim.) are scored independently. The 14 items are reverse coded onto a 1-6 scale; dim. are then created by summing specific item scores and transforming raw total score onto a 0-100 scale. For each dim., higher scores indicate better health status.

Outcome measures

Outcome measures
Measure	6 Month Completer Population n=457 Participants Participants in the Enrolled Population who were treated with at least one dose of the combination tablet, completed at least one study visit (3- or 6-month visit), provided data for at least 6 migraines, and who continued in the study for at least 166 days	12 Month Completer Population n=160 Participants Participants in the Enrolled and 6 Month Completer Populations who completed at least one study visit in the second six-month period (9- or 12-month visit), provided data for at least 12 migraines, and who continued in the study for at least 346 days. The 12 Month Completer Population is a subset of those participants who completed or remained in the study for at least 346 days.	Safety Population Participants in the Enrolled Population who took at least one dose of the combination tablet
Mean Change From Baseline in the Migraine Specific Quality of Life (QOL) Questionnaire for Adolescents (MSQ-A) Score at Months 3, 6, 9, and 12 Role restrictive, Month 3, n=457, 160	10.1 points on a scale Standard Error 1.145	9.0 points on a scale Standard Error 1.952	—
Mean Change From Baseline in the Migraine Specific Quality of Life (QOL) Questionnaire for Adolescents (MSQ-A) Score at Months 3, 6, 9, and 12 Role restrictive, Month 6, n=366, 160	10.5 points on a scale Standard Error 1.302	8.2 points on a scale Standard Error 1.972	—
Mean Change From Baseline in the Migraine Specific Quality of Life (QOL) Questionnaire for Adolescents (MSQ-A) Score at Months 3, 6, 9, and 12 Role restrictive, Month 9, n=315, 148	13.7 points on a scale Standard Error 1.475	9.0 points on a scale Standard Error 2.155	—
Mean Change From Baseline in the Migraine Specific Quality of Life (QOL) Questionnaire for Adolescents (MSQ-A) Score at Months 3, 6, 9, and 12 Role restrictive, Month 12, n=291, 153	15.7 points on a scale Standard Error 1.530	11.5 points on a scale Standard Error 2.117	—
Mean Change From Baseline in the Migraine Specific Quality of Life (QOL) Questionnaire for Adolescents (MSQ-A) Score at Months 3, 6, 9, and 12 Role preventative, Month 3, n=457, 160	7.9 points on a scale Standard Error 1.110	9.6 points on a scale Standard Error 1.974	—
Mean Change From Baseline in the Migraine Specific Quality of Life (QOL) Questionnaire for Adolescents (MSQ-A) Score at Months 3, 6, 9, and 12 Role preventative, Month 6, n=366, 160	6.8 points on a scale Standard Error 1.212	8.3 points on a scale Standard Error 1.890	—
Mean Change From Baseline in the Migraine Specific Quality of Life (QOL) Questionnaire for Adolescents (MSQ-A) Score at Months 3, 6, 9, and 12 Role preventative, Month 9, n=315, 148	9.4 points on a scale Standard Error 1.473	8.2 points on a scale Standard Error 2.234	—
Mean Change From Baseline in the Migraine Specific Quality of Life (QOL) Questionnaire for Adolescents (MSQ-A) Score at Months 3, 6, 9, and 12 Role preventative, Month 12, n=291, 153	9.8 points on a scale Standard Error 1.441	8.4 points on a scale Standard Error 1.959	—
Mean Change From Baseline in the Migraine Specific Quality of Life (QOL) Questionnaire for Adolescents (MSQ-A) Score at Months 3, 6, 9, and 12 Role emotional , Month 3, n=457, 160	7.1 points on a scale Standard Error 1.287	7.9 points on a scale Standard Error 2.223	—
Mean Change From Baseline in the Migraine Specific Quality of Life (QOL) Questionnaire for Adolescents (MSQ-A) Score at Months 3, 6, 9, and 12 Role emotional, Month 6, n=366, 160	6.6 points on a scale Standard Error 1.441	7.2 points on a scale Standard Error 2.136	—
Mean Change From Baseline in the Migraine Specific Quality of Life (QOL) Questionnaire for Adolescents (MSQ-A) Score at Months 3, 6, 9, and 12 Role emotional, Month 9, n=315, 148	10.5 points on a scale Standard Error 1.625	9.0 points on a scale Standard Error 2.411	—
Mean Change From Baseline in the Migraine Specific Quality of Life (QOL) Questionnaire for Adolescents (MSQ-A) Score at Months 3, 6, 9, and 12 Role emotional, Month 12, n=291, 153	11.4 points on a scale Standard Error 1.694	7.1 points on a scale Standard Error 2.461	—

SECONDARY outcome

Timeframe: Screening

Population: Enrolled Population: all participants entered into the trial and dispensed the Combination Tablet, regardless of whether they ever took the Combination Tablet. Due to data collection and/or assignment of a collected assessment to a visit, the number of participants analyzed at a given visit could vary.

The PPMQ-R is a fully validated 32-item questionnaire assessing participant satisfaction with acute migraine medication and includes 3 questions that assess satisfaction with respect to efficacy, side effects, and overall satisfaction (i.e., How effective the medication is overall, side effects of the medication, overall satisfaction with the medication). Each item is rated on a 7-point scale ranging from "very satisfied" (1) to "very dissatisfied" (7).

Outcome measures

Outcome measures
Measure	6 Month Completer Population n=562 Participants Participants in the Enrolled Population who were treated with at least one dose of the combination tablet, completed at least one study visit (3- or 6-month visit), provided data for at least 6 migraines, and who continued in the study for at least 166 days	12 Month Completer Population n=316 Participants Participants in the Enrolled and 6 Month Completer Populations who completed at least one study visit in the second six-month period (9- or 12-month visit), provided data for at least 12 migraines, and who continued in the study for at least 346 days. The 12 Month Completer Population is a subset of those participants who completed or remained in the study for at least 346 days.	Safety Population n=174 Participants Participants in the Enrolled Population who took at least one dose of the combination tablet
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionnaire-Revised (PPMQ-R) at the Screening Visit Side Effects, Somewhat Satisfied	77 participants	45 participants	26 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionnaire-Revised (PPMQ-R) at the Screening Visit Overall Treatment Satisfaction, Neutral	67 participants	35 participants	16 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionnaire-Revised (PPMQ-R) at the Screening Visit Overall Efficacy, Very Satisfied	36 participants	22 participants	11 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionnaire-Revised (PPMQ-R) at the Screening Visit Overall Efficacy, Satisfied	163 participants	102 participants	54 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionnaire-Revised (PPMQ-R) at the Screening Visit Overall Efficacy, Somewhat Satisfied	192 participants	113 participants	72 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionnaire-Revised (PPMQ-R) at the Screening Visit Overall Efficacy, Neutral	67 participants	30 participants	15 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionnaire-Revised (PPMQ-R) at the Screening Visit Overall Efficacy, Somewhat Dissatisfied	49 participants	23 participants	12 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionnaire-Revised (PPMQ-R) at the Screening Visit Overall Efficacy, Dissatisfied	43 participants	22 participants	8 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionnaire-Revised (PPMQ-R) at the Screening Visit Overall Efficacy, Very Dissatisfied	12 participants	4 participants	2 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionnaire-Revised (PPMQ-R) at the Screening Visit Side Effects, Very Satisfied	135 participants	89 participants	50 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionnaire-Revised (PPMQ-R) at the Screening Visit Side Effects, Satisfied	166 participants	87 participants	50 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionnaire-Revised (PPMQ-R) at the Screening Visit Side Effects, Neutral	127 participants	69 participants	36 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionnaire-Revised (PPMQ-R) at the Screening Visit Side Effects, Somewhat Dissatisfied	29 participants	13 participants	6 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionnaire-Revised (PPMQ-R) at the Screening Visit Side Effects, Dissatisfied	18 participants	6 participants	2 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionnaire-Revised (PPMQ-R) at the Screening Visit Side Effects, Very Dissatisfied	11 participants	7 participants	4 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionnaire-Revised (PPMQ-R) at the Screening Visit Overall Treatment Satisfaction, Very Satisfied	50 participants	30 participants	11 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionnaire-Revised (PPMQ-R) at the Screening Visit Overall Treatment Satisfaction, Satisfied	192 participants	113 participants	70 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionnaire-Revised (PPMQ-R) at the Screening Visit Overall Treatment Satisfaction, Somewhat Satisfied	164 participants	94 participants	56 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionnaire-Revised (PPMQ-R) at the Screening Visit Treatment Satisfaction, Somewhat Dissatisfied	31 participants	13 participants	9 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionnaire-Revised (PPMQ-R) at the Screening Visit Overall Treatment Satisfaction, Dissatisfied	43 participants	23 participants	9 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionnaire-Revised (PPMQ-R) at the Screening Visit Overall Treatment Satisfaction, Very Dissatisfied	15 participants	8 participants	3 participants

SECONDARY outcome

Timeframe: End of Study/Month 12

Population: Enrolled Population: all participants entered into the trial and dispensed the Combination Tablet, regardless of whether they ever took the Combination Tablet. Due to data collection and/or assignment of a collected assessment to a visit, the number of participants analyzed at a given visit could vary.

The PPMQ-R is a fully validated 32-item questionnaire assessing participant satisfaction with acute migraine medication and includes 3 questions that assess satisfaction with respect to efficacy, side effects, and overall satisfaction (i.e., How effective the medication is overall, side effects of the medication, overall satisfaction with the medication). Each item is rated on a 7-point scale ranging from "very satisfied" (1) to "very dissatisfied" (7).

Outcome measures

Outcome measures
Measure	6 Month Completer Population n=171 Participants Participants in the Enrolled Population who were treated with at least one dose of the combination tablet, completed at least one study visit (3- or 6-month visit), provided data for at least 6 migraines, and who continued in the study for at least 166 days	12 Month Completer Population n=144 Participants Participants in the Enrolled and 6 Month Completer Populations who completed at least one study visit in the second six-month period (9- or 12-month visit), provided data for at least 12 migraines, and who continued in the study for at least 346 days. The 12 Month Completer Population is a subset of those participants who completed or remained in the study for at least 346 days.	Safety Population n=110 Participants Participants in the Enrolled Population who took at least one dose of the combination tablet
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionaire-Revised (PPMQ-R) at Month 12 Overall Efficacy, Dissatisfied	1 participants	0 participants	0 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionaire-Revised (PPMQ-R) at Month 12 Overall Treatment Satisfaction, Satisfied	76 participants	61 participants	47 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionaire-Revised (PPMQ-R) at Month 12 Overall Efficacy, Very Satisfied	66 participants	59 participants	48 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionaire-Revised (PPMQ-R) at Month 12 Overall Efficacy, Satisfied	75 participants	63 participants	46 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionaire-Revised (PPMQ-R) at Month 12 Overall Efficacy, Somewhat Satisfied	20 participants	16 participants	12 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionaire-Revised (PPMQ-R) at Month 12 Overall Efficacy, Neutral	7 participants	5 participants	3 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionaire-Revised (PPMQ-R) at Month 12 Overall Efficacy, Somewhat Dissatisfied	2 participants	1 participants	1 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionaire-Revised (PPMQ-R) at Month 12 Overall Efficacy, Very Dissatisfied	0 participants	0 participants	0 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionaire-Revised (PPMQ-R) at Month 12 Side Effects, Very Satisfied	55 participants	49 participants	42 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionaire-Revised (PPMQ-R) at Month 12 Side Effects, Satisfied	61 participants	51 participants	40 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionaire-Revised (PPMQ-R) at Month 12 Side Effects, Somewhat Satisfied	24 participants	21 participants	14 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionaire-Revised (PPMQ-R) at Month 12 Side Effects, Neutral	11 participants	10 participants	6 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionaire-Revised (PPMQ-R) at Month 12 Side Effects, Somewhat Dissatisfied	12 participants	7 participants	3 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionaire-Revised (PPMQ-R) at Month 12 Side Effects, Dissatisfied	5 participants	4 participants	3 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionaire-Revised (PPMQ-R) at Month 12 Side Effects, Very Dissatisfied	3 participants	2 participants	2 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionaire-Revised (PPMQ-R) at Month 12 Overall Treatment Satisfaction, Very Satisfied	71 participants	64 participants	51 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionaire-Revised (PPMQ-R) at Month 12 Overall Treatment Satisfaction, Somewhat Satisfied	13 participants	10 participants	6 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionaire-Revised (PPMQ-R) at Month 12 Overall Treatment Satisfaction, Neutral	6 participants	5 participants	2 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionaire-Revised (PPMQ-R) at Month 12 Treatment Satisfaction, Somewhat Dissatisfied	3 participants	3 participants	3 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionaire-Revised (PPMQ-R) at Month 12 Overall Treatment Satisfaction, Dissatisfied	1 participants	0 participants	0 participants
Number of Participants Categorized by Response to Each of the 3 Global Satisfaction Questions From the Patient Perception Migraine Questionaire-Revised (PPMQ-R) at Month 12 Overall Treatment Satisfaction, Very Dissatisfied	1 participants	1 participants	1 participants

Adverse Events

Safety Population

Serious events: 4 serious events

Other events: 257 other events

Deaths: 0 deaths

6 Month Completer Population

Serious events: 3 serious events

Other events: 159 other events

Deaths: 0 deaths

12 Month Completer Population

Serious events: 1 serious events

Other events: 89 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Safety Population n=622 participants at risk Participants in the Enrolled Population who took at least one dose of the combination tablet	6 Month Completer Population n=333 participants at risk Participants in the Enrolled Population who were treated with at least one dose of the combination tablet, completed at least one study visit (3- or 6-month visit), provided data for at least 6 migraines, and who continued in the study for at least 166 days	12 Month Completer Population n=181 participants at risk Participants in the Enrolled and 6 Month Completer Populations who completed at least one study visit in the second six-month period (9- or 12-month visit), provided data for at least 12 migraines, and who continued in the study for at least 346 days. The 12 Month Completer Population is a subset of those participants who completed or remained in the study for at least 346 days.
Psychiatric disorders Suicide attempt	0.16% 1/622	0.30% 1/333	0.00% 0/181
Nervous system disorders Syncope	0.16% 1/622	0.30% 1/333	0.55% 1/181
Blood and lymphatic system disorders Hemolytic anemia	0.16% 1/622	0.30% 1/333	0.55% 1/181
Psychiatric disorders Suicidal ideation	0.16% 1/622	0.30% 1/333	0.00% 0/181
Pregnancy, puerperium and perinatal conditions Spontaneous abortion	0.16% 1/622	0.00% 0/333	0.00% 0/181

Other adverse events

Other adverse events
Measure	Safety Population n=622 participants at risk Participants in the Enrolled Population who took at least one dose of the combination tablet	6 Month Completer Population n=333 participants at risk Participants in the Enrolled Population who were treated with at least one dose of the combination tablet, completed at least one study visit (3- or 6-month visit), provided data for at least 6 migraines, and who continued in the study for at least 166 days	12 Month Completer Population n=181 participants at risk Participants in the Enrolled and 6 Month Completer Populations who completed at least one study visit in the second six-month period (9- or 12-month visit), provided data for at least 12 migraines, and who continued in the study for at least 346 days. The 12 Month Completer Population is a subset of those participants who completed or remained in the study for at least 346 days.
Gastrointestinal disorders Nausea	8.8% 55/622	8.4% 28/333	8.8% 16/181
Infections and infestations Upper respiratory tract infection	8.7% 54/622	11.7% 39/333	12.2% 22/181
Infections and infestations Nasopharyngitis	7.7% 48/622	10.5% 35/333	11.0% 20/181
Infections and infestations Sinusitis	5.9% 37/622	8.1% 27/333	10.5% 19/181
Nervous system disorders Dizziness	4.0% 25/622	3.0% 10/333	1.7% 3/181
Musculoskeletal and connective tissue disorders Neck pain	3.9% 24/622	3.6% 12/333	4.4% 8/181
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	3.5% 22/622	4.8% 16/333	5.5% 10/181
Nervous system disorders Migraine (worsening)	3.5% 22/622	1.8% 6/333	0.55% 1/181
Musculoskeletal and connective tissue disorders Arthralgia	3.4% 21/622	4.8% 16/333	5.5% 10/181
Musculoskeletal and connective tissue disorders Muscle tightness	3.2% 20/622	3.6% 12/333	3.3% 6/181
Musculoskeletal and connective tissue disorders Back pain	2.9% 18/622	3.9% 13/333	3.9% 7/181
Reproductive system and breast disorders Dysmenorrhoea	3.1% 19/622	4.2% 14/333	6.6% 12/181
General disorders Pyrexia	2.3% 14/622	3.6% 12/333	2.8% 5/181

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER