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Issues Impacting Adverse Event Frequency and Severity: Differences Between Randomized Phase 2 and Phase 3 Clinical Trials for Lasmiditan
- Source :
- Headache, Dipòsit Digital de Documents de la UAB, Universitat Autònoma de Barcelona
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
Abstract
- Objective We explore factors that may have contributed to differences in treatment-emergent adverse events in the phase 2 and phase 3 lasmiditan clinical trials. Background Phase 2 and phase 3 trials showed that the centrally penetrant 5-HT1F agonist, lasmiditan, was effective; higher frequency and severity of adverse events (AEs) were seen in phase 2. Methods This work represents a hybrid of a review of primary documents and study reports with additional post hoc analyses. Protocols, informed consents, data collection forms, and methodologies were reviewed. This information was supplemented by results from the clinical study reports and post hoc analyses of individual patient data from each trial. Results For lasmiditan 100 and 200 mg, in phase 2, the incidence of ≥1 AE was 72-86% (26% severe), while in phase 3 was 36-43% (2% severe). The most common AEs in all studies were CNS-related. The phase 2 consent form was more descriptive of AEs than phase 3. In phase 2, patients recorded AEs and severity in a paper diary that warned about drowsiness and dizziness. In phase 3, patients recorded in electronic diaries whether they experienced unusual feelings after dosing with lasmiditan that they had not felt with a migraine before, and were contacted to determine if an AE had occurred. In phase 2, the AE Schwindel was variably translated from German as "vertigo" or "dizziness," while phase 3 vertigo cases were queried to ensure there was a sensation of rotation or movement. History of recurrent dizziness and/or vertigo was exclusionary in phase 3. Conclusions This work illustrates how informed consent wording, AE collection methods, translation, exclusion criteria, and other factors may be important determinants for reporting of the frequency and severity of AEs in clinical trials.
- Subjects :
- Male
Pyridines
chemistry.chemical_compound
0302 clinical medicine
Treatment-emergent adverse event
Piperidines
Informed consent
Vertigo
030212 general & internal medicine
Episodic migraine
Informed Consent
biology
treatment‐emergent adverse event
migraine headache
Incidence (epidemiology)
Forms as Topic
Middle Aged
Lasmiditan
Serotonin Receptor Agonists
Neurology
Benzamides
lasmiditan
Female
Adult
medicine.medical_specialty
Drug-Related Side Effects and Adverse Reactions
Migraine Disorders
Migraine headache
Research Submissions
03 medical and health sciences
Clinical Trials, Phase II as Topic
medicine
Humans
Patient Reported Outcome Measures
Dosing
Adverse effect
business.industry
Translating
biology.organism_classification
medicine.disease
adverse events
Clinical trial
Clinical Trials, Phase III as Topic
Migraine
chemistry
Adverse events
Physical therapy
episodic migraine
Neurology (clinical)
business
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 15264610 and 00178748
- Volume :
- 60
- Database :
- OpenAIRE
- Journal :
- Headache: The Journal of Head and Face Pain
- Accession number :
- edsair.doi.dedup.....957a2b7ec2085c0de6ada55bcec04cc0