Design of a multicenter study of eslicarbazepine acetate as a first add-on to initial levetiracetam or lamotrigine monotherapy and as later adjunctive therapy for uncontrolled partial-onset seizures
Abstract number :
1.288
Submission category :
7. Antiepileptic Drugs / 7B. Clinical Trials
Year :
2017
Submission ID :
342671
Source :
www.aesnet.org
Presentation date :
12/2/2017 5:02:24 PM
Published date :
Nov 20, 2017, 11:02 AM
Authors :
John Hixson, University of California, San Francisco, CA, USA; Barry E. Gidal, University of Wisconsin; Andrei Pikalov, Sunovion Pharmaceuticals Inc.; Todd Grinnell, Sunovion Pharmaceuticals Inc.; David Cantu, Sunovion Pharmaceuticals Inc.; JungAh Jung, S
Rationale: Eslicarbazepine acetate (ESL) is a once-daily, oral antiepileptic drug (AED) for partial-onset seizures (POS), i.e., focal seizures. Most clinical trials of AEDs involve highly treatment-resistant patients who have used multiple AEDs throughout their clinical course. Data on AEDs in patients at an earlier stage in their treatment trajectory are limited; behavioral, mood-related, and quality of life (QoL) outcomes following initiation of AEDs also require further study. This study will investigate the efficacy and safety of ESL (as well as impact on behavior and QoL) taken as a first adjunctive therapy to levetiracetam (LEV) or lamotrigine (LTG) monotherapy, and as later adjunctive therapy in treatment-resistant patients with POS in a real-world setting. Methods: A multicenter, 2-arm, open-label, non-randomized study of adjunctive ESL in patients aged =18 years with POS. Patients with prior exposure to ESL or current treatment with oxcarbazepine are excluded. Arm 1: ESL as first add-on to LEV or LTG in patients with inadequate response to treatment. Arm 2: ESL as a later add-on, following prior use of adjunctive therapy, in patients who require a new therapeutic option. Both groups will be maintained on stable treatment (group 1: LEV or LTG, group 2: 1–2 AEDs) for =28 days prior to screening. Patients (~190) will be enrolled at centers in North America. The trial comprises screening (1–2 weeks) followed by 2-week titration, 24-week maintenance, and 4-week ESL taper/safety follow-up periods (see Figure). Results: Primary endpoint: retention rate during maintenance (24 weeks). This endpoint recognizes that both efficacy and tolerability contribute to a patient’s willingness to continue therapy. Secondary endpoints: standardized seizure frequency (SSF); 50% and 75% responder rates (reductions in SSF from baseline); relative reduction from baseline in SSF; seizure-free rate; time on ESL. Safety and tolerability endpoints: adverse events; mood/depressive symptoms; aggression; QoL; Clinical Global Impression of Improvement; Patient Global Impression of Change. Exploratory endpoints: assess the accuracy of an investigational, wearable device (Embrace watch) in detecting seizures, and the temporal correlation of these measurements with seizure diary entries. The Embrace watch measures movement, skin conductance and body temperature to identify seizure activity. Conclusions: This study will provide new information about the efficacy, safety and tolerability of adjunctive ESL in patients early in the course of their disease, and will further examine the effectiveness of ESL in treatment-resistant patients, in a design reflective of a real-world setting. Additionally, the study will advance understanding of the effects of ESL on mood, behavior, and QoL in patients with POS. The study will also provide novel data on seizure monitoring during drug treatment, by means of a wearable seizure detection device. Funding: Study sponsored by Sunovion Pharmaceuticals Inc.
Antiepileptic Drugs