PMID- 31943195
OWN - NLM
STAT- MEDLINE
DCOM- 20210729
LR  - 20210729
IS  - 1526-4610 (Electronic)
IS  - 0017-8748 (Print)
IS  - 0017-8748 (Linking)
VI  - 60
IP  - 3
DP  - 2020 Mar
TI  - Issues Impacting Adverse Event Frequency and Severity: Differences Between 
      Randomized Phase 2 and Phase 3 Clinical Trials for Lasmiditan.
PG  - 576-588
LID - 10.1111/head.13731 [doi]
AB  - 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-HT(1F) 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.
CI  - (c) 2020 Eli Lilly and Company. Headache: The Journal of Head and Face Pain 
      published by Wiley Periodicals, Inc., on behalf of American Headache Society.
FAU - Kudrow, David
AU  - Kudrow D
AD  - California Medical Clinic for Headache, Santa Monica, CA, USA.
AD  - Neurology, David Geffen UCLA School of Medicine, Los Angeles, CA, USA.
FAU - Krege, John H
AU  - Krege JH
AD  - Eli Lilly and Company, Indianapolis, IN, USA.
FAU - Hundemer, Hans P
AU  - Hundemer HP
AD  - Eli Lilly and Company, Bad Homburg, Germany.
FAU - Berg, Paul H
AU  - Berg PH
AD  - Eli Lilly and Company, Indianapolis, IN, USA.
FAU - Khanna, Rashna
AU  - Khanna R
AD  - Eli Lilly and Company, Erl Wood, UK.
FAU - Ossipov, Michael H
AU  - Ossipov MH
AD  - Syneos Health, Clinical Division, Raleigh, NC, USA.
FAU - Pozo-Rosich, Patricia
AU  - Pozo-Rosich P
AD  - Headache & Craniofacial Pain Unit, Neurology Department, Hospital Universitari 
      Vall d'Hebron, Barcelona, Spain.
AD  - Headache Research Group, VHIR, Universitat Autonoma de Barcelona, Barcelona, 
      Spain.
LA  - eng
GR  - NA/Eli Lilly and Company/International
PT  - Comparative Study
PT  - Journal Article
DEP - 20200113
PL  - United States
TA  - Headache
JT  - Headache
JID - 2985091R
RN  - 0 (Benzamides)
RN  - 0 (Piperidines)
RN  - 0 (Pyridines)
RN  - 0 (Serotonin Receptor Agonists)
RN  - 760I9WM792 (lasmiditan)
SB  - IM
MH  - Adult
MH  - Benzamides/administration & dosage/adverse effects/*pharmacology
MH  - *Clinical Trials, Phase II as Topic
MH  - *Clinical Trials, Phase III as Topic
MH  - *Drug-Related Side Effects and Adverse Reactions
MH  - Female
MH  - *Forms as Topic
MH  - Humans
MH  - *Informed Consent
MH  - Male
MH  - Middle Aged
MH  - Migraine Disorders/*drug therapy
MH  - *Patient Reported Outcome Measures
MH  - Piperidines/administration & dosage/adverse effects/*pharmacology
MH  - Pyridines/administration & dosage/adverse effects/*pharmacology
MH  - Serotonin Receptor Agonists/administration & dosage/adverse effects/*pharmacology
MH  - Translating
PMC - PMC7064990
OTO - NOTNLM
OT  - adverse events
OT  - episodic migraine
OT  - lasmiditan
OT  - migraine headache
OT  - treatment-emergent adverse event
EDAT- 2020/01/17 06:00
MHDA- 2021/07/30 06:00
PMCR- 2020/03/11
CRDT- 2020/01/17 06:00
PHST- 2019/11/14 00:00 [accepted]
PHST- 2020/01/17 06:00 [pubmed]
PHST- 2021/07/30 06:00 [medline]
PHST- 2020/01/17 06:00 [entrez]
PHST- 2020/03/11 00:00 [pmc-release]
AID - HEAD13731 [pii]
AID - 10.1111/head.13731 [doi]
PST - ppublish
SO  - Headache. 2020 Mar;60(3):576-588. doi: 10.1111/head.13731. Epub 2020 Jan 13.