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3D-Neuronavigation In Vivo Through a Patient's Brain During a Spontaneous Migraine Headache
Published on: June 2, 2014
Total migraine freedom, a potential primary endpoint to assess acute treatment in migraine: comparison to the current
Anthony J Rodgers1, Carolyn M Hustad1, Roger K Cady1
1From Merck, North Wales, PA, USA (A.J. Rodgers, C.M. Hustad, K.E. Ramsey, and T.W. Ho); Banyan Group Inc., Springfield, MO, USA (R.K. Cady); University of Cincinnati, Cincinnati, OH, USA (V.T. Martin); Palm Beach Headache Center, Nova Southeastern University, West Palm Beach, FL, USA (P. Winner).
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.
