Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Results for the TRX109011 (NCT00573170) and TRX109013 (NCT00599157) studies were pooled for analysis. Individual studies were not analyzed or reported separately. The individual protocols were amended while ongoing to allow for pooling of study data for analysis.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Randomized participants were treated for three separate migraine attacks with three different investigational products, assigned in randomized order, as one of six possible treatment sequences. Not all participants enrolled in the study were randomized for treatment; those participants who were randomized are said to have "started" the study

Reporting Groups

	Description
Treximet, Placebo, Butalbital-containing Combo. Medication	Fixed dose combination (combo.) tablet of sumatriptan succinate (equivalent to sumatriptan 85 milligrams [mg]) and naproxen sodium 500 mg (Treximet) for treatment of first migraine attack, followed by a 7-day washout period; matching placebo for treatment of second migraine attack, followed by a 7-day washout period; comparator of acetaminophen 325 mg, caffeine 40 mg, and butalbital 50 mg (butalbital-containing combination medication), currently marketed as Fioricet, for treatment of third migraine attack. Treatment of each separate migraine attack had to be preceeded by a 24-hour pain-free period to ensure that a separate migraine attack was being treated.
Treximet, Butalbital-containing Combo. Medication, Placebo	Fixed dose combination tablet of sumatriptan succinate (equivalent to sumatriptan 85 milligrams [mg]) and naproxen sodium 500 mg (Treximet) for treatment of first migraine attack, followed by a 7-day washout period; comparator of acetaminophen 325 mg, caffeine 40 mg, and butalbital 50 mg (butalbital-containing combination medication), currently marketed as Fioricet, for treatment of second migraine attack, followed by a 7-day washout period; matching placebo for treatment of third migraine attack, followed by a 7-day washout period. Treatment of each separate migraine attack had to be preceeded by a 24-hour pain-free period to ensure that a separate migraine attack was being treated.
Butalbital-containing Combo. Medication, Treximet, Placebo	Comparator of acetaminophen 325 mg, caffeine 40 mg, and butalbital 50 mg (butalbital-containing combination medication), currently marketed as Fioricet, for treatment of first migraine attack, followed by a 7-day washout period; fixed dose combination tablet of sumatriptan succinate (equivalent to sumatriptan 85 milligrams [mg]) and naproxen sodium 500 mg (Treximet) for treatment of second migraine attack, followed by a 7-day washout period; matching placebo for treatment of third migraine attack, followed by a 7-day washout period. Treatment of each separate migraine attack had to be preceeded by a 24-hour pain-free period to ensure that a separate migraine attack was being treated.
Butalbital-containing Combo. Medication, Placebo, Treximet	Comparator of acetaminophen 325 mg, caffeine 40 mg, and butalbital 50 mg (butalbital-containing combination medication), currently marketed as Fioricet, for treatment of first migraine attack, followed by a 7-day washout period; matching placebo for treatment of second migraine attack, followed by a 7-day washout period; fixed dose combination tablet of sumatriptan succinate (equivalent to sumatriptan 85 milligrams [mg]) and naproxen sodium 500 mg (Treximet) for treatment of third migraine attack. Treatment of each separate migraine attack had to be preceeded by a 24-hour pain-free period to ensure that a separate migraine attack was being treated.
Placebo, Treximet, Butalbital-containing Combo. Medication	Matching placebo for treatment of first migraine attack, followed by a 7-day washout period; fixed dose combination tablet of sumatriptan succinate (equivalent to sumatriptan 85 milligrams [mg]) and naproxen sodium 500 mg (Treximet) for treatment of second migraine attack, followed by a 7-day washout period; comparator of acetaminophen 325 mg, caffeine 40 mg, and butalbital 50 mg (butalbital-containing combination medication), currently marketed as Fioricet, for treatment of third migraine attack. Treatment of each separate migraine attack had to be preceeded by a 24-hour pain-free period to ensure that a separate migraine attack was being treated.
Placebo, Butalbital-containing Combo. Medication, Treximet	Matching placebo for treatment of first migraine attack, followed by a 7-day washout period; comparator of acetaminophen 325 mg, caffeine 40 mg, and butalbital 50 mg (butalbital-containing combination medication), currently marketed as Fioricet, for treatment of second migraine attack, followed by a 7-day washout period; fixed dose combination tablet of sumatriptan succinate (equivalent to sumatriptan 85 milligrams [mg]) and naproxen sodium 500 mg (Treximet) for treatment of third migraine attack. Treatment of each separate migraine attack had to be preceeded by a 24-hour pain-free period to ensure that a separate migraine attack was being treated.

Participant Flow for 5 periods

Period 1:   First Treatment Period

	Treximet, Placebo, Butalbital-containing Combo. Medication	Treximet, Butalbital-containing Combo. Medication, Placebo	Butalbital-containing Combo. Medication, Treximet, Placebo	Butalbital-containing Combo. Medication, Placebo, Treximet	Placebo, Treximet, Butalbital-containing Combo. Medication	Placebo, Butalbital-containing Combo. Medication, Treximet
STARTED	64	60	60	66	63	62
COMPLETED	64	60	60	66	62	62
NOT COMPLETED	0	0	0	0	1	0
Did Not Treat Attack 1	0	0	0	0	1	0

Period 2:   First Washout Period

	Treximet, Placebo, Butalbital-containing Combo. Medication	Treximet, Butalbital-containing Combo. Medication, Placebo	Butalbital-containing Combo. Medication, Treximet, Placebo	Butalbital-containing Combo. Medication, Placebo, Treximet	Placebo, Treximet, Butalbital-containing Combo. Medication	Placebo, Butalbital-containing Combo. Medication, Treximet
STARTED	64	60	60	66	62	62
COMPLETED	56	58	59	61	59 [1]	55
NOT COMPLETED	8	2	1	5	3	7
Adverse Event	1	1	0	0	0	1
Lack of Efficacy	0	0	0	0	0	1
Lost to Follow-up	1	1	0	2	0	2
Withdrawal by Subject	2	0	0	2	3	3
Unknown	4	0	1	1	0	0

Period 3:   Second Treatment Period

	Treximet, Placebo, Butalbital-containing Combo. Medication	Treximet, Butalbital-containing Combo. Medication, Placebo	Butalbital-containing Combo. Medication, Treximet, Placebo	Butalbital-containing Combo. Medication, Placebo, Treximet	Placebo, Treximet, Butalbital-containing Combo. Medication	Placebo, Butalbital-containing Combo. Medication, Treximet
STARTED	56	58	59	61	59	55
COMPLETED	56	58	59	61	59	55
NOT COMPLETED	0	0	0	0	0	0

Period 4:   Second Washout Period

	Treximet, Placebo, Butalbital-containing Combo. Medication	Treximet, Butalbital-containing Combo. Medication, Placebo	Butalbital-containing Combo. Medication, Treximet, Placebo	Butalbital-containing Combo. Medication, Placebo, Treximet	Placebo, Treximet, Butalbital-containing Combo. Medication	Placebo, Butalbital-containing Combo. Medication, Treximet
STARTED	56	58	59	61	59	55
COMPLETED	51	54	55	56	51	53
NOT COMPLETED	5	4	4	5	8	2
Adverse Event	1	0	0	0	1	0
Protocol Violation	2	1	1	0	0	0
Withdrawal by Subject	1	1	2	0	1	0
Lost to Follow-up	0	0	0	1	0	0
Unknown	1	2	1	4	6	2

Period 5:   Third Treatment Period

	Treximet, Placebo, Butalbital-containing Combo. Medication	Treximet, Butalbital-containing Combo. Medication, Placebo	Butalbital-containing Combo. Medication, Treximet, Placebo	Butalbital-containing Combo. Medication, Placebo, Treximet	Placebo, Treximet, Butalbital-containing Combo. Medication	Placebo, Butalbital-containing Combo. Medication, Treximet
STARTED	51	54	55	56	51	53
COMPLETED	50	54	55	56	51	51
NOT COMPLETED	1	0	0	0	0	2
Withdrawal by Subject	1	0	0	0	0	0
Lost to Follow-up	0	0	0	0	0	2

Reporting Groups

	Description
All Study Participants Treated at Least Once	All study participants who were treated at least once with study medication

Baseline Measures

	All Study Participants Treated at Least Once
Number of Participants   [units: participants]	442
Age [1] [units: Years] Mean ± Standard Deviation	42.6  ± 11.23
Gender   [units: Participants]
Female	391
Male	51
Race/Ethnicity, Customized   [units: participants]
White-White/Caucasian/European Heritage	368
African American/African Heritage	61
Mixed Race	4
Asian - Central/South	2
Asian - South East Asian Heritage	2
White - Arabic/North African Heritage	2
American Indian or Native Alaskan	1
Asian - Japanese Heritage	1
Native Hawaiian or Other Pacific Islander	1

1.  Primary:

Number of Participants With a Sustained Pain-free (SPF) Response From 2 to 24 Hours Post-dose   [ Time Frame: From 2 to 24 hours post-dose. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed). ]

2.  Secondary:

Number of Participants With a Pain-free Response From 2 to 48 Hours Post-dose   [ Time Frame: At 2, 4, 6, 8, 24, and 48 hours post-dose for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed). ]

3.  Secondary:

Number of Participants Using Rescue Medication Within 48 Hours Post Dose   [ Time Frame: From dose time through 48 hours post-dose for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed). ]

4.  Secondary:

Mean Time to First Use of Rescue Medication for the First Attack Treated With Study Medication (Attack 1)   [ Time Frame: From dose time through 48 hours post-dose for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed). ]

5.  Secondary:

Mean Time to First Use of Rescue Medication for the Second Attack Treated With Study Medication (Attack 2)   [ Time Frame: From dose time through 48 hours post-dose for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed). ]

6.  Secondary:

Mean Time to First Use of Rescue Medication for the Third Attack Treated With Study Medication (Attack 3)   [ Time Frame: From dose time through 48 hours post-dose for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed). ]

7.  Secondary:

Number of Participants With a Migraine-free Response 2-48 Hours After Dosing   [ Time Frame: At 2, 4, 6, 8, 24, and 48 hours post-dose for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed). ]

8.  Secondary:

Number of Participants With Pain-freedom and Relief of Nausea at 2, 4, 6, 8, 24 and 48 Post-dose Time Points   [ Time Frame: At 2, 4, 6, 8, 24, and 48 hours post-dose for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed). ]

9.  Secondary:

Number of Participants With Pain-freedom and Relief of Photophobia at 2, 4, 6, 8, 24 and 48 Post-dose Time Points   [ Time Frame: At 2, 4, 6, 8, 24, and 48 hours post-dose for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed). ]

10.  Secondary:

Number of Participants With Pain-freedom and Relief of Phonophobia at 2, 4, 6, 8, 24 and 48 Post-dose Time Points   [ Time Frame: At 2, 4, 6, 8, 24, and 48 hours post-dose for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed). ]

11.  Secondary:

Number of Participants With Pain-freedom and Relief of Vomiting at 2, 4, 6, 8, 24 and 48 Hours Post-dose   [ Time Frame: At 2, 4, 6, 8, 24, and 48 hours post-dose for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed). ]

12.  Secondary:

Number of Participants With Relief From Sinus/Facial Pain at 2, 4, 6, 8, 24 and 48 Hours After Dosing in Those Who Also Had the Symptom at Dosing   [ Time Frame: At 2, 4, 6, 8, 24, and 48 hours post-dose for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed). ]

13.  Secondary:

Number of Participants With Relief From Neck Pain at 2, 4, 6, 8, 24 and 48 Hours After Dosing Who Also Had the Symptom at Baseline   [ Time Frame: At 2, 4, 6, 8, 24, and 48 hours post-dose for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed). ]

14.  Secondary:

Number of Participants With Pain Relief at 2, 4, 6, 8, 24 and 48 Hours After Dosing Moderate or Severe Baseline Pain   [ Time Frame: At 2, 4, 6, 8, 24, and 48 hours post-dose for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed). ]

15.  Secondary:

Number of Participants Who Reported a Complete Symptom-Free Response at 2, 4, 6, 8, 24 and 48 Hours After Dosing   [ Time Frame: At 2, 4, 6, 8, 24, and 48 hours post-dose for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed). ]

16.  Secondary:

Mean Performance Index (PI) Scores at Time of Dosing and at 2, 4, 6, 8, 24 and 48 Hours After Dosing   [ Time Frame: At time of dosing, and at 2, 4, 6, 8, 24, and 48 hours post-dose for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed). ]

17.  Secondary:

Mean Stanford Sleepiness (SS) Scale Scores at Time of Dosing and at 2, 4, 6, 8, 24 and 48 Hours After Dosing   [ Time Frame: Dose time, 2, 4, 6, 8, 24 and 48 hours post-dose. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed). ]

18.  Secondary:

Efficacy Subscore as Measured by the Revised Patient Perception of Migraine (PPMQ-R) Questionnaire 24 Hours After Treating a Migraine   [ Time Frame: At 24 hours after dosing for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed). ]

19.  Secondary:

Functionality Subscore as Measured by the Revised Patient Perception of Migraine (PPMQ-R) Questionnaire 24 Hours After Taking Study Medication   [ Time Frame: At 24 hours after dosing for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed). ]

20.  Secondary:

Ease-of-Use Subscore as Measured by the Revised Patient Perception of Migraine (PPMQ-R) Questionnaire 24 Hours After Taking Study Medication   [ Time Frame: At 24 hours after dosing for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed). ]

21.  Secondary:

Bothersomeness-of-side Effect Subscore as Measured by the Revised Patient Perception of Migraine (PPMQ-R) Questionnaire 24 Hours After Taking Study Medication   [ Time Frame: At 24 hours after dosing for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed). ]

22.  Secondary:

Total PPMQ-R Score as Measured With the Revised Patient Perception of Migraine (PPMQ-R) Questionnaire 24 Hours After Taking Study Medication   [ Time Frame: At 24 hours after dosing for each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed). ]

23.  Secondary:

Numbers of Participants Able to "Engage in Normal Activities Not Impaired" at Time of Dosing and 2, 4, 6, and 8 Hours After Dosing as Assessed by the CDQ (Clinical Disability Questionnaire)   [ Time Frame: At dosing and at 2, 4, 6 and 8 hours after dosing of each attack treated with study medication. All 3 migraine attacks were to have been treated within 19 weeks of randomization (when study medication was dispensed). ]