The Childhood and Adolescent Migraine Prevention Study

Inclusion Criteria:

• Migraine with or without aura (International Classification of Headache Disorders, 2ndEdition (ICHD-II) or chronic migraine (ICHD-II revised)

• Migraine frequency based upon prospective headache diary of 28 days must be ≥ 4.Migraine frequency defined as any migraine during one day in the 28 day baselineperiod (1)

• PedMIDAS Disability Score > 10, indicating at least mild disruption in dailyactivities and < 140, indicating extreme disability that may require morecomprehensive, multi-component therapy

• Females or males 8-17 years, inclusive

1. Migraine frequency is defined as the period from the onset to the stop time ofpainful migraine symptoms not to exceed 24 hours with the clock starting atmidnight. If painful symptoms last longer than 24 hours, this is considered a newand distinct migraine headache. If painful symptoms recur within 24 hours ofinitial onset, this is considered part of the initial migraine episode and wouldbe counted as one migraine.

Exclusion Criteria:

• Continuous migraine defined as an unrelenting headache for a 28 day period

• Weight less than 30 kg or greater than 120 kg

• Unwilling to avoid taking non-specific acute medication such as NSAIDS (e.g.,ibuprofen), more than 3 times per week, or migraine specific acute medications such astriptans more than 6 times per month

• Currently taking other prophylactic anti-migraine medication within a periodequivalent to 2 weeks of that medication before entering the screening phase, or theuse of Botulinum toxin (Botox®) within 3 months of entering the screening phase

• Subjects who have previously failed an adequate trial of AMI or TPM for prophylaxis ofat least 3 months duration at doses recommended for migraine relief because of lack ofefficacy or adverse events(2)

• Current use of disallowed medications/products: opioids, antipsychotics, antimanics,barbiturates, benzodiazepines, muscle relaxants, sedatives, tramadol, nutraceuticals,SSRIs, or SSNRIs

• Known history of allergic reaction or anaphylaxis to AMI or TPM

• Abnormal findings on ECG at baseline, particularly lengthening of the QT intervalgreater than or equal to 450 msec

• Subject is pregnant or has a positive pregnancy test

• Subject is sexually active and not using a medically acceptable form of contraception

• Diagnosis of epilepsy or other neurological diseases

• History of kidney stones

• Inability to swallow pills after using behavioral techniques if indicated betweenscreening visit and baseline visit (3)

• Present psychiatric disease as defined by the Diagnostic and Statistical Manual ofMental Disorders, 4th Edition (DSM IV) (e.g. psychosis, bipolar disorder, majordepression, generalized anxiety disorder), alcohol or drug dependence, or documenteddevelopmental delays or impairments (e.g., autism, cerebral palsy, or mentalretardation) that, in the opinion of the site investigator, would interfere withadherence to study requirements or safe participation in the trial

• Any and all other diagnoses or conditions which in the opinion of the siteinvestigator, that would prevent the patient from being a suitable candidate for thestudy or interfere with the medical care needs of the study subject

(2)"Previously failed an adequate trial of AMI or TPM" is defined as: dosage of 1mg/kg/day of AMI or 2 mg/kg/day of TPM; trial of at least 3 months duration; efficacyof having at least a 50% decrease in migraine frequency in response to drug therapy;or unable to tolerate taking the medication due to treatment-related side effects.

(3)Subjects who cannot swallow pills at the time of the screening visit will be givena training session using behavioral techniques. Upon return for baseline visit, if thesubject continues to be unable to swallow pills, the subject will be excluded from thestudy.