Abstract | OBJECTIVE: To examine total migraine freedom (TMF), defined as pain freedom and absence of associated symptoms, using rizatriptan clinical trial data and to explore advantages of TMF as a single primary composite efficacy endpoint. BACKGROUND: The FDA has set a higher regulatory hurdle for registration of new migraine agents requiring both pain freedom (or relief) and absence of each associated symptom ( phonophobia, photophobia, and nausea). METHODS: Twelve studies representing phase III + efficacy/safety studies of rizatriptan 10 mg in adults treating migraine were included in the meta-analysis. The percentage of patients achieving TMF at 2 hours by study and combined by treatment group was summarized by treatment paradigm (early/mild pain, moderate/severe, menstrual migraine). To demonstrate the impact of the strict migraine regulatory hurdle on clinical trial design and to compare it to TMF, simulation via bootstrap sampling was used. RESULTS: Odds ratios ( rizatriptan vs placebo, all P < .001) for TMF were 6.2 (95% CI: [4.9, 7.7]) for moderate/severe, 2.7 (95% CI: [1.8, 4.0]) for menstrual, and 3.1 (95% CI: [2.4, 4.0]) for early/mild. Most with moderate/severe migraine reported photophobia and/or phonophobia at baseline, but only half had nausea. Simulation results showed a substantial loss of power analyzing absence of pain and each symptom compared with the composite TMF endpoint across all treatment paradigms. CONCLUSION:
Rizatriptan 10 mg was superior to placebo in achieving TMF at 2 hours post-dose across all treatment paradigms. Given that the majority of patients with migraine do not exhibit all 3 associated symptoms, the TMF endpoint has significant advantages vs establishing efficacy on pain and each symptom individually.
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Authors | Anthony J Rodgers, Carolyn M Hustad, Roger K Cady, Vincent T Martin, Paul Winner, Karen E Ramsey, Tony W Ho |
Journal | Headache
(Headache)
Vol. 51
Issue 3
Pg. 356-368
(Mar 2011)
ISSN: 1526-4610 [Electronic] United States |
PMID | 21039453
(Publication Type: Comparative Study, Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't)
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Copyright | © 2010 American Headache Society. |
Chemical References |
- Serotonin Receptor Agonists
- Triazoles
- Tryptamines
- rizatriptan
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Topics |
- Adult
- Clinical Trials, Phase III as Topic
- Databases, Factual
- Endpoint Determination
- Female
- Humans
- Male
- Migraine Disorders
(drug therapy)
- Serotonin Receptor Agonists
(therapeutic use)
- Treatment Outcome
- Triazoles
(therapeutic use)
- Tryptamines
(therapeutic use)
- United States
- United States Food and Drug Administration
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