Abstract Details

Title How Adverse Events Are Collected and Reported: Differences Between Randomized Phase 2 and Phase 3 Clinical Trials for Lasmiditan

Topic Headache

Presentation(s) P2 - Poster Session 2 (5:30 PM-6:30 PM)

Poster/Presentation
Number 13-011

Objective We explore factors potentially contributing to differences in reported incidence and severity of treatment-emergent adverse events (TEAEs) in phase 2 and 3 lasmiditan clinical trials for acute treatment of migraine.

Background Double-blind, placebo-controlled, phase 2 and phase 3 (SAMURAI, SPARTAN) randomized clinical trials showed that lasmiditan (selective 5-HT_1F receptor agonist) is generally safe and effective as an acute treatment for migraine. A higher frequency and greater severity of TEAEs were reported in phase 2 versus phase 3 studies.

Design/Methods We compared the protocols, informed consent documents, and data collection methods between the phase 2 study and the phase 3 studies to identify factors explaining these differences.

Results Of patients receiving lasmiditan 100 mg and 200 mg, 59/82 (72%) and 61/71 (86%) in phase 2, 229/630 (36%) and 229/635 (36%) in SAMURAI, and 260/609 (43%) and 253/649 (39%) in SPARTAN reported TEAEs. Most commonly reported were dizziness, fatigue, paresthesia, vertigo, somnolence, nausea, and lethargy. Severe TEAEs were reported by 26% (102/391) of patients in phase 2, 2% (43/1856) in SAMURAI, and 2% (43/2583) in SPARTAN. In phase 2, patients recorded the type and severity of adverse events (AEs) in a paper journal which included warnings about drowsiness and dizziness. In phase 3, patients recorded any unusual feelings not previously felt with a migraine in an electronic diary; the type and severity of AE was then characterized by a call from the study site. The phase 2 consent form was more descriptive of AEs. Assessment and documentation of the AEs vertigo and dizziness differed between the phase 2 and phase 3 studies.

Conclusions Differences in informed consent, AE collection methodology, and translation may have contributed to a marked difference in the frequency and severity of AE reporting between phase 2 and 3 studies in this migraine clinical development program.

Authors/Disclosures
David B. Kudrow, MD (David Kudrow MD) PRESENTER	Dr. Kudrow has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AbbVie. Dr. Kudrow has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for AbbVie.
John H. Krege	John H. Krege has received personal compensation for serving as an employee of Eli Lilly. John H. Krege has received stock or an ownership interest from Eli Lilly.
	No disclosure on file
Hans Hundemer, MD (Lilly Deutschland GmbH)	No disclosure on file
Paul H. Berg, MS (Eli Lilly and Company)	No disclosure on file
	No disclosure on file
Patricia Pozo-Rosich, MD, PhD	Dr. Pozo-Rosich has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for AbbVie. Dr. Pozo-Rosich has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Teva Pharmaceuticals. Dr. Pozo-Rosich has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lundbeck. Dr. Pozo-Rosich has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pfizer. Dr. Pozo-Rosich has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Organon. Dr. Pozo-Rosich has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Dr. Reddy's. Dr. Pozo-Rosich has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Sociedad Española Neurologia.

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