Clinical trial NCT00332007: Tonabersat in the Prophylaxis of Migraine With Aura
Official title: A Single Centre, Double-blind, Randomised, Placebo Controlled Crossover Study to Evaluate the Efficacy and Tolerability of Tonabersat in the Prophylaxis of Migraine in Patients Presenting With Migraine With Aura
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Migraine With Aura
Lead sponsor: Minster Research Ltd
Sponsor class: INDUSTRY
Collaborators: name: University of Copenhagen
First posted: 2006-05-31
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: Overall trial objectives:

1. Can treatment with tonabersat reduce the number of days with aura and/or migraine headache in patients with migraine with aura
2. How well tolerated is treatment with tonabersat

The study is based on the hypothesis that the unique mechanism of action of tonabersat will inhibit some of the early events in the generation of aura and migraine headache and so be effective as prophylactic treatment


Eligibility criteria: Inclusion Criteria:

* Patients with an established history of migraine of at least one year meeting the diagnostic criteria of the International Classification of Headache Disorders - Edition 2 (Appendix 2) and who experience at least one aura a month.
* Male or female patients between 18-65 years of age
* Women of child bearing potential must be using a reliable form of contraception (defined in the protocol) for at least 3 months prior to enrolment and they must have a negative pregnancy test at screening with no intention of becoming pregnant during the study period

Exclusion Criteria:

* Patients experiencing headache other than migraine or tension headache
* Overuse of acute migraine treatments defined as more than 14 daily doses per month with analgesics or more than 9 daily doses per month of ergots or triptans within the last two months
* Migraine prophylactic treatment within two months prior to entry to the trial
* Patients taking any of the following medications for migraine: beta-blockers, tricyclic antidepressants (during the last 2 months), antiepileptic dugs (during the last 2 months), calcium channel blockers, monoamine oxidase inhibitors, daily NSAIDs, daily paracetamol, high dose magnesium supplements (600mg/day). Parenteral administration of botulinum toxin is also excluded. These drugs are permitted when given for diseases other than migraine provided that, in the opinion of the investigator the dose can be kept constant throughout the trial.
* Patients who, in the opinion of the investigator, have significant cerebrovascular disease e.g. transient ischaemic attacks, stroke
* Patients who, in the opinion of the investigator, have clinically significant cardiovascular disease
* Patients suffering from a current clinical diagnosis of a major depressive disorder or schizophrenia
* Patients with renal dysfunction , defined as a serum creatinine of greater than 125% of the upper limit of normal for their age group
* Patients with hepatic dysfunction defined as a liver function test (AST, ALT, alkaline phosphatase, bilirubin) of greater than twice the upper limit of normal for their age group
* Patients with known alcohol or other substance abuse
* Use of an investigational drug (for any indication) within 30 days or 5 half-lives, whichever is the longer, prior to screening
* Women who are pregnant or breast feeding
* Women of childbearing potential not using a reliable form of contraception
* Patients with any other clinically significant condition which, in the investigators opinion, would render them unsuitable for this study

Primary outcomes:
measure: Difference in the mean number of aura attacks experienced between treatment groups
timeFrame: 12 week treatment period
measure: Difference in the mean number of migraine headache days between treatment groups
timeFrame: 12 week treatment period
measure: Incidence of adverse events
timeFrame: 12 week treatment period
Secondary outcomes:
measure: Mean number of headache days in each treatment period.
timeFrame: 12 week treatment period
measure: Mean number of auras followed by headache in each treatment period.
timeFrame: 12 week treatment period
measure: Mean number of headache days in each month of treatment in each treatment period.
timeFrame: Mean monthly
measure: Mean number of auras and/or migraine headache during each treatment period.
timeFrame: 12 week treatment period
measure: Mean number of migraine headache attacks in each treatment period.
timeFrame: 12 week treatment period
measure: Speed of effect of treatment.
timeFrame: First month for which difference between treatments identified
measure: Mean monthly consumption of rescue medication.
timeFrame: Mean monthly
measure: Mean duration of auras in each treatment period.
timeFrame: Mean over 12 week treatment period
measure: Mean number of symptoms associated with auras in each treatment period.
timeFrame: 12 week treatment period
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Danish Headache Centre, Department of Neurology, Glostrup Hospital
Study officials:
affiliation: University of Copenhagen, Department of Neurology, Glostrup Hospital
name: Jes Olesen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: International Headache Society Clinical Trials Subcommittee. Guidelines for controlled trials of drugs in migraine (second edition). Cephalalgia 2000; 20:765-86. Committee for Proprietary Medicinal Products. Note for guidance on clinical investigation of medicinal products for the treatment of migraine, CPMP/EWP/788/01/Final. London, 17 December 2003.
citation: Committee for Proprietary Medicinal Products. Note for guidance on clinical investigation of medicinal products for the treatment of migraine, CPMP/EWP/788/01/Final. London, 17 December 2003.
citation: Hauge AW, Asghar MS, Schytz HW, Christensen K, Olesen J. Effects of tonabersat on migraine with aura: a randomised, double-blind, placebo-controlled crossover study. Lancet Neurol. 2009 Aug;8(8):718-23. doi: 10.1016/S1474-4422(09)70135-8. Epub 2009 Jun 29.