Purpose of the study is to evaluate dose response relationship, efficacy, safety and tolerability of target doses of GSK1838262 compared to placebo in the prophylactic treatment of migraine headache. Once subjects complete the baseline and meet the randomization criteria, they will complete a 5-wk flexible titration period and then enter the 12 week maintenance period.
MPX111381 is a multicenter, randomized, double-blind, placebo-controlled, parallel group, flexible-dose evaluation of GSK1838262 1200 mg/day, 1800 mg/day, 2400 mg/day and 3000 mg/day compared with placebo in the prophylactic treatment of migraine headache. Subjects 18 years of age must have experienced at least three migraine headache attacks (with or without aura according to 2004 International Headache Society \[IHS\] criteria 1.1 and 1.2.1) per month during the 3 months prior to screening and at least four migraine headache days but less than 15 total headache days (migraine or non-migraine) per month during the 3 months prior to screening and must maintain this requirement throughout the last 4 weeks of the baseline period. Approximately 528 subjects from approximately 53 centers in North America will be randomized in a 2:1:2:2:1 ratio to the following treatment groups: placebo, GSK1838262 1200 mg/day, 1800 mg/day, 2400 mg/day and 3000 mg/day. Investigational product will be administered twice daily (morning and evening) with food (e.g., meal or snack). The study will consist of six study periods for a total study duration of up to 30 weeks: Screening (2 weeks), baseline (including randomization, 6 weeks), flexible titration (5 weeks), maintenance (12 weeks), taper (3 weeks) and post-treatment (2 weeks). The flexible titration administration of investigational product is designed to allow subjects to reach the target dose for maintenance treatment or, if unable to reach this target dose, to achieve a maximum tolerated dose for maintenance treatment. Subjects will have the opportunity to undergo a single dose (600 mg/day) downward adjustment during the flexible titration period if intolerability at the current dose occurs. Subsequently, if a single dose downward adjustment has occurred, no further dose adjustments in the study (upward or downward) will be permitted.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
526
Flexible dosing: 1200 mg/day, 1800 mg/day, 2400 mg/day and 3000 mg/day
Placebo-control
Adjusted Mean Change From Baseline in the Number of Migraine Headache Days (MHD) During the Last 4 Weeks of Treatment Prior to Taper
A migraine headache day is defined as a calendar day with any occurrence of migraine headache pain of at least 30 minutes in duration. Change from baseline was calculated as the mean number of MHD over the last 4 weeks of treatment prior to taper minus the number at baseline using the Last Observation Carried Forward (LOCF). The last 4-week treatment phase is based on the last 4 weeks prior to taper for each participant.
Time frame: Baseline and last 4 weeks of treatment prior to taper (up to Week 17)
Mean Change From Baseline in the Number of MHD in All Study Phases
A migraine headache day is defined as a calendar day with any occurrence of migraine headache pain of at least 30 minutes in duration. Change from baseline and the last 4 weeks of treatment prior to taper were calculated means of the number of migraine headache days using the Last Observation Carried Forward (LOCF). Change from baseline is calculated as post-baseline minus baseline. The last 4-week treatment phase is based on the last 4 weeks prior to taper for each participant.
Time frame: Baseline and last 4 weeks of treatment prior to taper (up to Week 17)
Adjusted Mean Change From Baseline in the Number of Migraine Attacks
A migraine attack is defined as a migraine headache of at least 30 minutes in duration and may also include recurring non-migraine or migraine headaches . Change from baseline and the last 4 weeks of treatment prior to taper were calculated means of the number of migraine attacks using the Last Observation Carried Forward (LOCF). The last 4-week treatment phase is based on the last 4 weeks prior to taper for each participant.
Time frame: Baseline and last 4 weeks of treatment prior to taper (up to Week 17)
Mean Change From Baseline in the Number of Migraine Headache Periods (MHP)
A migraine headache period is a 24-hour block of time that begins at the onset of a migraine event . The 24-hour period is not linked directly with a calendar day. The change from baseline and the last 4 weeks of treatment prior to taper were calculated means of the number of migraine headache periods using the Last Observation Carried Forward (LOCF). The last 4-week treatment phase is based on the last 4 weeks prior to taper for each participant.
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GSK Investigational Site
Birmingham, Alabama, United States
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Phoenix, Arizona, United States
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Phoenix, Arizona, United States
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Anaheim, California, United States
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Santa Monica, California, United States
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Westlake Village, California, United States
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Colorado Springs, Colorado, United States
...and 49 more locations
Time frame: Baseline and last 4 weeks of treatment prior to taper (up to Week 17)
Change From Baseline in the Mean Migraine Attack Duration
The total duration of a migraine attack is measured from migraine attack onset until the resolution of the attack measured in hours and may include more than 1 headache event. The duration is assessed using a Daily Migraine Diary. Change from baseline and the last 4 weeks of treatment prior to taper were calculated means of the number of migraine headache days using the Last Observation Carried Forward (LOCF). Change from baseline is calculated as post-baseline minus baseline. The last 4-week treatment phase is based on the last 4 weeks prior to taper for each participant.
Time frame: Baseline and last 4 weeks of treatment prior to taper (up to Week 17)
Change From Baseline in the Mean Peak Migraine Pain Severity
Peak Migraine Pain Severity was measured using a 4-point scale (0=none, 1=mild, 2=moderate, or 3=severe) on a participant self assessed Daily Migraine Diary. The scale measured the maximum pain severity across all headache events considered to be one attack.. Change from baseline and the last 4 weeks of treatment prior to taper were calculated means of the number of migraine headache days using the Last Observation Carried Forward (LOCF). The last 4-week treatment phase is based on the last 4 weeks prior to taper for each participant.
Time frame: Baseline and last 4 weeks of treatment prior to taper (up to Week 17)
Mean Change From Baseline to the Last 4-Week Treatment Phase in the Number of Days of Acute Migraine Medication Use
The Number of Days of Acute Migraine Medication Use was assessed via the participant-assessed Daily Migraine Diary.
Time frame: Baseline and last 4 weeks of treatment prior to taper (up to Week 17)
Mean Change From Baseline to the Last 4-Week Treatment Phase in the Number of Acute Migraine Medication Doses Administered
The Number of Acute Migraine Medication Doses Administered was captured via the participant-assessed Daily Migraine Diary.
Time frame: Baseline and last 4 weeks of treatment prior to taper (up to Week 17)
Mean Change From Baseline to the Last 4-Week Treatment Phase in the Number of Acute Migraine Medication Doses Administered by Triptan Use
The Number of Acute Migraine Medication Administered was measured via the participant-assessed Daily Migraine Diary.
Time frame: Baseline and last 4 weeks of treatment prior to taper (up to Week 17)
Mean Change From Baseline to the Last 4-Week Treatment Phase in the Number of Acute Migraine Medication Doses Administered by Opioid Use
The Number of Acute Migraine Medication Doses Administered by Opioid Use was measured via the participant-assessed Daily Migraine Diary.
Time frame: Baseline and last 4 weeks of treatment prior to taper (up to Week 17)
Mean Change From Baseline to the Last 4-Week Treatment Phase in the Number of Acute Migraine Medication Doses Administered by Prescription Headache Medication Use
The Number of Acute Migraine Medication Doses Administered by Prescription Headache Medication use was measured via the participant-assessed Daily Migraine Diary.
Time frame: Baseline and last 4 weeks of treatment prior to taper (up to Week 17)
Mean Change From Baseline in Percentage of Migraine Attacks With Each of the Following Migraine Symptoms: Aura, Nausea, Vomiting, Photophobia, Phonophobia
The endpoint is defined as the percentage of attacks with each symptom (separately) for each study phase. Migraine symptoms aura, nausea, vomiting, photophobia, and phonophobia are defined as the presence of each migraine symptom during any of the headache events within an attack.
Time frame: Baseline and last 4 weeks of treatment prior to taper (up to Week 17)
Percentage of Participants Classified as Responders for Each of the Following Measures: Migraine Headache Days, Migraine Attacks, and Migraine Headache Periods
A responder is defined as a participant who achieved at least a 50% reduction from baseline for the indicated measures.
Time frame: Baseline to the Last 4 weeks of treatment
Number of Participants Who Were "Much Improved" or "Very Much Improved" on the 7-point Likert Patient Global Impression of Change (PGIC) Scale Using LOCF at Week 17
The PGIC is a single question measured on the 7-point Likert Scale (1 = "very much improved"; 2 = "much improved"; 7 = "very much worse"). A responder is defined as being "very much improved" or "much improved."
Time frame: Week 17
Number of Participants Who Were "Much Improved" or "Very Much Improved" (Responders) on the 7-point Likert Clinical Global Impression of Change (CGIC) Scale Using LOCF at Week 17
The CGIC is a single question measured on a 7-point Likert Scale. (1 = "very much improved"; 2= "much improved, and 7 = "very much worse") designed to give an assessment of treatment from a clinician's perspective. A responder is defined as being 'Very much improved' or 'much improved'.
Time frame: Week 17