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Randomized, double-blind, placebo-controlled, proof-of-concept study of the cortical spreading depression inhibiting agent tonabersat in migraine prophylaxis.
Cephalalgia 2009; 29(7):742-50C

Abstract

Tonabersat is a novel putative migraine prophylactic agent with an unique stereospecific binding site in the brain. Tonabersat has been shown, in animal models, to inhibit experimentally induced cortical spreading depression, the likely underlying mechanism for migraine aura, and cerebrovascular responses to trigeminal nerve stimulation. The aim was to study the potential for tonabersat as a migraine preventive. A randomized, double-blind, placebo-controlled, multicentre, parallel group study recruited patients with migraine with and without aura experiencing between two and six migraine attacks per month. After a 1-month baseline they received tonabersat 20 mg daily for 2 weeks and 40 mg daily for a further 10 weeks. The primary end-point was the change in mean number of migraine headache days between the third month and the baseline period in the intention-to-treat population comparing the placebo (n = 65) and tonabersat (n = 58) groups. At the primary end-point there was a 1.0-day (95% confidence interval -0.33, 2.39; P = 0.14) difference in reduction in migraine days between tonabersat and placebo. There were 10 secondary efficacy end-points, of which two were statistically significant. In month 3 of treatment, the responder rate, defined as a 50% reduction in migraine attacks, was 62% for tonabersat and 45% for placebo (P < 0.05), and the rescue medication use was reduced in the tonabersat group compared with placebo by 1.8 days (P = 0.02). Placebo responses were particularly high for all end-points. At least one treatment-emergent adverse event was reported in the tonabersat group in 61% of patients compared with 51% in the placebo group; none was worrisome. Placebo responses were unexpectedly high in this trial, complicating straightforward interpretation of the study results. The good tolerability and promising efficacy results support further exploration of higher doses of tonabersat in larger controlled trials.

Authors+Show Affiliations

Headache Group, Institute of Neurology, London, UK. peter.goadsby@ucsf.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19222510

Citation

Goadsby, P J., et al. "Randomized, Double-blind, Placebo-controlled, Proof-of-concept Study of the Cortical Spreading Depression Inhibiting Agent Tonabersat in Migraine Prophylaxis." Cephalalgia : an International Journal of Headache, vol. 29, no. 7, 2009, pp. 742-50.
Goadsby PJ, Ferrari MD, Csanyi A, et al. Randomized, double-blind, placebo-controlled, proof-of-concept study of the cortical spreading depression inhibiting agent tonabersat in migraine prophylaxis. Cephalalgia. 2009;29(7):742-50.
Goadsby, P. J., Ferrari, M. D., Csanyi, A., Olesen, J., & Mills, J. G. (2009). Randomized, double-blind, placebo-controlled, proof-of-concept study of the cortical spreading depression inhibiting agent tonabersat in migraine prophylaxis. Cephalalgia : an International Journal of Headache, 29(7), pp. 742-50. doi:10.1111/j.1468-2982.2008.01804.x.
Goadsby PJ, et al. Randomized, Double-blind, Placebo-controlled, Proof-of-concept Study of the Cortical Spreading Depression Inhibiting Agent Tonabersat in Migraine Prophylaxis. Cephalalgia. 2009;29(7):742-50. PubMed PMID: 19222510.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Randomized, double-blind, placebo-controlled, proof-of-concept study of the cortical spreading depression inhibiting agent tonabersat in migraine prophylaxis. AU - Goadsby,P J, AU - Ferrari,M D, AU - Csanyi,A, AU - Olesen,J, AU - Mills,J G, AU - ,, Y1 - 2009/02/13/ PY - 2009/2/19/entrez PY - 2009/2/19/pubmed PY - 2009/8/20/medline SP - 742 EP - 50 JF - Cephalalgia : an international journal of headache JO - Cephalalgia VL - 29 IS - 7 N2 - Tonabersat is a novel putative migraine prophylactic agent with an unique stereospecific binding site in the brain. Tonabersat has been shown, in animal models, to inhibit experimentally induced cortical spreading depression, the likely underlying mechanism for migraine aura, and cerebrovascular responses to trigeminal nerve stimulation. The aim was to study the potential for tonabersat as a migraine preventive. A randomized, double-blind, placebo-controlled, multicentre, parallel group study recruited patients with migraine with and without aura experiencing between two and six migraine attacks per month. After a 1-month baseline they received tonabersat 20 mg daily for 2 weeks and 40 mg daily for a further 10 weeks. The primary end-point was the change in mean number of migraine headache days between the third month and the baseline period in the intention-to-treat population comparing the placebo (n = 65) and tonabersat (n = 58) groups. At the primary end-point there was a 1.0-day (95% confidence interval -0.33, 2.39; P = 0.14) difference in reduction in migraine days between tonabersat and placebo. There were 10 secondary efficacy end-points, of which two were statistically significant. In month 3 of treatment, the responder rate, defined as a 50% reduction in migraine attacks, was 62% for tonabersat and 45% for placebo (P < 0.05), and the rescue medication use was reduced in the tonabersat group compared with placebo by 1.8 days (P = 0.02). Placebo responses were particularly high for all end-points. At least one treatment-emergent adverse event was reported in the tonabersat group in 61% of patients compared with 51% in the placebo group; none was worrisome. Placebo responses were unexpectedly high in this trial, complicating straightforward interpretation of the study results. The good tolerability and promising efficacy results support further exploration of higher doses of tonabersat in larger controlled trials. SN - 1468-2982 UR - https://www.unboundmedicine.com/medline/citation/19222510/Randomized_double_blind_placebo_controlled_proof_of_concept_study_of_the_cortical_spreading_depression_inhibiting_agent_tonabersat_in_migraine_prophylaxis_ L2 - http://journals.sagepub.com/doi/full/10.1111/j.1468-2982.2008.01804.x?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -