Prevention Study in Adult Patients Suffering From Migraine Headaches
Condition: Migraine Disorders; Migraine
MeSH terms: Migraine Disorders; Headache
Intervention: GSK1838262; Placebo
Intervention description: Flexible dosing: 1200 mg/day, 1800 mg/day, 2400 mg/day and 3000 mg/day; Placebo-control
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 526.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: migraine; prophylaxis; prevention

Summary:

      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.
    

Eligibility criteria:

        Inclusion criteria:

          -  Outpatient subjects aged 18 years or older.

          -  Females of non-childbearing potential. If of child-bearing potential, is not lactating
             and has a negative pregnancy test 7 days prior to study treatment initiation and
             agrees to use one of the GlaxoSmithKline (GSK)-specified highly effective methods for
             avoiding pregnancy.

          -  Subjects suffering from migraine headache with or without aura, according to 2004 IHS
             criteria 1.1 and 1.2.1.

          -  Subject has had a history of migraine headache for at least one year, and the age of
             onset was prior to 50 years.

          -  Subject has consistent migraine headache over time (i.e., incidence and severity).

          -  Subject has had at least three migraine headache attacks per month during the 3 months
             prior to screening and maintains this requirement during the last 4 weeks of the
             baseline period

          -  Subject has had 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
             maintains this requirement during the last 4 weeks of the baseline period.

          -  Subject is able to distinguish migraine headache attacks as discrete from other
             headaches (i.e., tension-type headaches).

          -  Subject has the ability to read, comprehend and legibly and reliably record
             information in paper and electronic format as required by the protocol.

          -  Subject must be able to provide written informed consent prior to participation in the
             study. The contents and process of obtaining informed consent will be in accordance
             with all applicable regulatory requirements.

        Exclusion Criteria:

          -  Subject has a history of ergotamine, triptan, opioid, and/or combination pain
             medication use on >/=10 days per month on a regular basis for >/= 3 months.

          -  Subject has failed more than 2 adequate treatments of migraine prophylaxis -where
             failure is defined as a lack of efficacy with treatment duration of at least 8 weeks.

          -  Subject has history of simple analgesic use on >/=15 days per month for >/=3months.

          -  Subject is unable to discontinue prohibited medications during the 2-week screening
             period and throughout the duration of the study including beta-blockers,
             benzodiazepines, tricyclic antidepressants, calcium channel blockers, antiepileptic
             drugs, bupropion or serotonergic noradrenergic reuptake inhibitors (SNRIs).

          -  Subjects who have taken gabapentin or pregabalin previously for the prophylactic
             treatment of migraine headache. Subjects who have taken gabapentin or pregabalin for
             treatment of conditions other than migraine are eligible provided, (1) their total
             exposure to gabapentin and pregabalin is less than 3 months during the preceding 12
             months, and (2) the subject stopped taking gabapentin or pregabalin for at least 3
             months prior to baseline.

          -  Subject has a history of cluster headaches or basilar, ophthalmoplegic, hemiplegic, or
             transformed migraine headaches.

          -  Subject has a current or past history of seizure disorder.

          -  Subject has any of the following medical conditions, laboratory abnormalities or
             disorders:

          -  Hepatic impairment defined as alanine aminotransferase (ALT) or aspartate
             aminotransferase (AST) >2x upper limit of normal (ULN) or alkaline phosphatase or
             bilirubin >1.5x ULN

          -  Chronic hepatitis B or C with a positive Hepatitis B surface antigen (HBsAg) or
             Hepatitis C Core Antigen Antibody (Hep C antibody)

          -  Impaired renal function defined as either creatinine clearance <60 mL/min (estimation
             of creatinine clearance by Cockroft and Gault Method) or renal dysfunction requiring
             hemodialysis

          -  Corrected QT (QTc) interval >/= 450 msec based on the average QTc value of triplicate
             electrocardiograms (ECGs) obtained by the central ECG reader over a brief recording
             period

          -  QTc interval >/= 480 msec for subjects with Bundle Branch Block based on the average
             QTc value of triplicate ECGs obtained by the central ECG reader over a brief recording
             period

          -  Uncontrolled hypertension at screen or at time of randomization (sitting systolic
             blood pressure [SBP] >160 mmHg and/or sitting diastolic blood pressure [DBP] >90 mmHg)

          -  Medical condition or disorder that would interfere with the action, absorption,
             distribution, metabolism, or excretion of GSK1838262, or, in the investigator's
             judgement:

          -  Is considered to be clinically significant and may pose a safety concern, or,

          -  Could interfere with the accurate assessment of safety or efficacy, or,

          -  Could potentially affect a subject's safety or study outcome.

          -  Subject meets criteria as defined by the Diagnostic and Statistical Manual of Mental
             Disorders (DSM-IV-TR) for a major depressive episode or for active significant
             psychiatric disorders within the past year, including dementia, general anxiety
             disorder, psychotic disorders or bipolar disorder.

          -  Subjects with a history of depression that is in remission, with or without
             antidepressant treatment, may participate, unless a stable antidepressant regimen
             includes a prohibited medication.

          -  Antidepressant medication may not be changed or discontinued to meet entry criteria
             and must be stable for at least 3 months prior to screening.

          -  Subject has a history of clinically significant drug or alcohol abuse as defined by
             DSM IV TR or is unable to refrain from substance abuse throughout the study.

          -  Subject is currently participating in another clinical study in which the subject is,
             or will be exposed to an investigational or non-investigational drug or device.

          -  Subject has participated in a clinical study in which the subject was exposed to an
             investigational or non investigational drug or device:

          -  Within the preceding month for studies unrelated to the current illness (migraine
             headaches), or

          -  Within the preceding 3 months for studies related to the current illness (migraine
             headaches).

          -  Subjects who have taken botulinum toxin type A (Botox) within the past 6 months.

          -  Subject has a history of an allergic reaction, or a medically significant adverse
             reaction to the investigational product or excipients, which, in the opinion of the
             investigator, makes a subject unsuitable for participation in the study.

          -  Subject is felt to be at risk of non-compliance (e.g., for taking investigational
             product or for completing the electronic diary [e-diary]), in the investigator's
             opinion.

          -  Subject is a pregnant or nursing woman.