Bruce Hughes1, Mark Cascione2, Mark S Freedman3, Mark Agius4, Daniel Kantor5, Mark Gudesblatt6, Lawrence P Goldstick7, Neetu Agashivala8, Lesley Schofield9, Kevin McCague10, Ron Hashmonay11, Luigi Barbato12. 1. Mercy Ruan Neuroscience Center, Des Moines, IA, USA. Electronic address: brucehughes@mac.com. 2. Tampa Neurology Associates, Tampa, FL, USA. Electronic address: me@markcascione.com. 3. University of Ottawa and the Ottawa Hospital Research Institute, Ottawa, ON, Canada. Electronic address: MFREEDMAN@Ottawahospital.on.ca. 4. University of California Davis, Veterans Affairs Northern California Health Care System (VANCHCS), CA, USA. Electronic address: markaagius@hotmail.com. 5. Neurologique Foundation, Inc., Jacksonville, FL, USA. Electronic address: dkantor@neurologique.org. 6. Multiple Sclerosis Comprehensive Care Center, St Islip, NY, USA. Electronic address: mgudesbl@southshoreneurologic.com. 7. Neurology Specialists Inc, Dayton, OH, USA. Electronic address: lgoldstick@hotmail.com. 8. Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. Electronic address: neetu.agashivala@novartis.com. 9. Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. Electronic address: lesley.schofield@novartis.com. 10. Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. Electronic address: kevin.mccague@novartis.com. 11. Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. Electronic address: ronny.hashmonay@novartis.com. 12. Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. Electronic address: lou.barbato@novartis.com.
Abstract
BACKGROUND: In pivotal phase 3 studies, fingolimod treatment initiation was associated with a transient reduction in heart rate (HR). Atrioventricular (AV) conduction delays, which were typically asymptomatic, were detected in a small minority of patients. OBJECTIVE: We report the first-dose effects of fingolimod in patients who switched from injectable therapies during the Evaluate Patient OutComes (EPOC) study (ClinicalTrials.gov Identifier: NCT01216072). METHODS: This was a phase 4, 6-month, randomized, active-comparator, open-label, multicenter study. It included over 900 fingolimod-treated patients with relapsing multiple sclerosis, with subgroups of individuals who were receiving common concomitant HR-lowering medications or had pre-existing cardiac conditions (PCCs). Vital signs were recorded hourly for 6h post-dose. A 12-lead electrocardiogram was obtained at baseline and at 6h post-dose. RESULTS: A transient decrease in mean HR and blood pressure occurred within 6h of the first fingolimod dose. The incidence of symptomatic bradycardia was low (1%); eight patients reported dizziness and there was one case each of fatigue, palpitations, dyspnea, cardiac discomfort, and gait disturbance. These symptomatic events were typically mild or moderate in severity and all resolved spontaneously, without intervention or fingolimod discontinuation. CONCLUSION: First-dose effects in patients with PCCs and in those receiving concomitant HR-lowering medications were consistent with effects observed in the overall study population and with results from previous clinical trials. The EPOC study provides additional data demonstrating the transient and generally benign nature of fingolimod first-dose effects on HR and AV conduction in a large population that is more representative of patients encountered in routine clinical practice than in the pivotal trials.
RCT Entities:
BACKGROUND: In pivotal phase 3 studies, fingolimod treatment initiation was associated with a transient reduction in heart rate (HR). Atrioventricular (AV) conduction delays, which were typically asymptomatic, were detected in a small minority of patients. OBJECTIVE: We report the first-dose effects of fingolimod in patients who switched from injectable therapies during the Evaluate Patient OutComes (EPOC) study (ClinicalTrials.gov Identifier: NCT01216072). METHODS: This was a phase 4, 6-month, randomized, active-comparator, open-label, multicenter study. It included over 900 fingolimod-treated patients with relapsing multiple sclerosis, with subgroups of individuals who were receiving common concomitant HR-lowering medications or had pre-existing cardiac conditions (PCCs). Vital signs were recorded hourly for 6h post-dose. A 12-lead electrocardiogram was obtained at baseline and at 6h post-dose. RESULTS: A transient decrease in mean HR and blood pressure occurred within 6h of the first fingolimod dose. The incidence of symptomatic bradycardia was low (1%); eight patients reported dizziness and there was one case each of fatigue, palpitations, dyspnea, cardiac discomfort, and gait disturbance. These symptomatic events were typically mild or moderate in severity and all resolved spontaneously, without intervention or fingolimod discontinuation. CONCLUSION: First-dose effects in patients with PCCs and in those receiving concomitant HR-lowering medications were consistent with effects observed in the overall study population and with results from previous clinical trials. The EPOC study provides additional data demonstrating the transient and generally benign nature of fingolimod first-dose effects on HR and AV conduction in a large population that is more representative of patients encountered in routine clinical practice than in the pivotal trials.
Authors: Brandon Brown; Jamie L Weiss; Scott Kolodny; Xiangyi Meng; Ian M Williams; John A Osborne Journal: BMC Neurol Date: 2019-11-15 Impact factor: 2.474