A Study to Evaluate the Tolerability of Botox and Topiramate or Botox and Placebo and Effect on Cognitive Efficiency

Inclusion Criteria

• must be outpatient, male or female, of any race, between 18 and 65 years of age.
• if female of child bearing potential must have a negative pregnancy test result at the Screening Visit and practice a reliable method of contraception.

A female is considered of childbearing potential unless she is post-menopausal for at least 12 months prior to administration of study drug, without a uterus and/or both ovaries or has been surgically sterilized for at least 6 months prior to study drug administration.

Reliable methods of contraception are:

Complete abstinence from intercourse from 2 weeks prior to administration of the investigational product. Throughout the study, and for a time interval (5 days) after completion or premature discontinuation from the study. History of bilateral tubal ligation Sterilization of male partner; or, Implants of levonorgestrel; or, Injectable progestogen, or, Oral contraceptive (combination therapy with ethinyl estradiol plus a progestin) with a placebo week every 1-3 months; or, Any intrauterine device (IUD) with published data showing that the highest expected failure rate is less than 1% per year (not all IUD's meet this criterion) in use at least 30 days prior to study drug administration; or, Spermicide plus a mechanical barrier (e.g., spermicide plus a male condom or a female diaphragm); or, Any other barrier methods (only is used in combination with any of the above acceptable methods) in use at least 14 days prior to study drug administration; or, Any other methods with published data showing that the highest expected failure rate for that method is less than 1% per year.

• must have history of chronic migraine (with or without aura) according to the criteria proposed by the Headache Classification Committee of the International Headache Society (IHS) for at least 3 months prior to enrollment.
• must be able to understand the requirements of the study including maintaining a headache Diary, and signing informed consent.
• must be in good general health as determined by investigator.
• if taking migraine preventive, must be on a stable dose of preventive medication for at least 6 weeks prior to screening.
• must have daily access to internet for completion of online daily headache diary.

Exclusion Criteria

• if female, is pregnant, planning to become pregnant during the study period, are breast feeding, or are of childbearing potential and not practicing a reliable form of birth control.
• has headache disorders outside IHS-defined chronic migraine definition.
• has evidence of underlying pathology contributing to their headaches.
• has any medical condition that may increase their risk with exposure to OnabotulinumtoxinA including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, or any other significant disease that might interfere with neuromuscular function.
• has profound atrophy or weakness of muscles in the target areas of injection.
• has skin conditions or infections at any injection site.
• has allergy or sensitivities to any component of the test medication.
• has previously received onabotulinumtoxinA for migraine prevention.
• has previously received topiramate.
• who in the opinion of the investigator, has active major psychiatric or depressive disorders including alcohol/drug abuse.
• meets International Headache Society criteria for Medication Overuse Headache with opioid or butalbital containing products.
• who in the opinion of the investigator, is taking opioid or butalbital containing products more than once a week that could be contributing to a pattern of increased headaches or cognitive decline.
• is planning or requiring surgery during the study.
• has a history of poor compliance with medical treatment.
• is currently participating in an investigational drug study or has participated in an investigational drug study within the previous 30 days of the screening visit.