A Study of Lorcaserin as Adjunctive Treatment in Participants With Dravet Syndrome

Study Overview
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Brief Summary
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The primary purpose of the study is to demonstrate that lorcaserin has superior efficacy compared to placebo on percent change in frequency of convulsive seizures per 28 days in participants with Dravet syndrome.

Official Title
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A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Study With Open-Label Extension Phase of Lorcaserin as Adjunctive Treatment in Subjects With Dravet Syndrome

Conditions
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Epilepsies, Myoclonic

Intervention / Treatment
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* Drug: Placebo
* Drug: Lorcaserin


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Participants must meet all of the following criteria to be included in this study: Male or female, age 2 years and older at the time of informed consent Diagnosis of epilepsy with Dravet syndrome Has at least 4 convulsive seizures during the 4 weeks of baseline Current treatment with antiepileptic drugs must be stable for at least 4 weeks before screening, and be expected to remain stable throughout the study Key Exclusion Criteria: Participants who meet any of the following criteria will be excluded from this study: Use of lorcaserin within 4 weeks before screening, or any history of it being discontinued due to lack of efficacy or adverse reactions Use of fenfluramine within 2 months before screening, any history of lack of fenfluramine efficacy, or any history of valvulopathy at baseline with history of fenfluramine use Recent or concomitant use of serotonergic medications or monoamine oxidase inhibitors Presence of progressive central nervous system disease other than Dravet syndrome

Ages Eligible for Study
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Minimum Age: 2 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lorcaserin (Core Study and Open-label Extension Phase)<br>Participants will be randomized to receive lorcaserin administered as an oral suspension, twice daily for 14 weeks during the core treatment period. Dose will be based on body weight as follows: target dose for participants weighing 10 to less than (<) 20, 20 to <40, and greater than or equal to (>=) 40 kilogram (kg) will be 5, 10, and 20 milligram per day (mg/day) respectively. Based on clinical response and tolerability and within 2 weeks of treatment, dose can be increased up to 10, 20 mg/day for participants weighing 10 to <20, 20 to <40 kg respectively. Participants completing the core treatment period will enter a 12-week extension phase and will receive lorcaserin. | Drug: Lorcaserin<br>* Lorcaserin oral tablet, administered as oral suspension.<br>* Other names: E2023;|
| Placebo Comparator: Placebo (Core Study) + Lorcaserin (Open-label Extension Phase)<br>Participants will be randomized to receive lorcaserin matching placebo administered as an oral suspension, twice daily for 14 weeks during the core treatment period. Dose will be based on body weight as follows: target dose for participants weighing 10 to <20, 20 to <40, and >=40 kg will be 5, 10, and 20 mg/day respectively. Based on clinical response and tolerability and within 2 weeks of treatment, dose can be increased up to 10, 20 mg/day for participants weighing 10 to <20, 20 to <40 kg respectively. Participants completing the core treatment period will enter a 12-week extension phase and will receive lorcaserin. | Drug: Placebo<br>* Placebo matching to lorcaserin oral tablet, administered as oral suspension.<br>Drug: Lorcaserin<br>* Lorcaserin oral tablet, administered as oral suspension.<br>* Other names: E2023;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Convulsive Seizure Frequency Per 28 Days During the Core Treatment Period (14 Weeks) | Seizure frequency will be based on number of seizures per 28 days, calculated during the baseline period and treatment period as the number of seizures during each respective period divided by the number of non-missing days during each respective period, multiplied by 28. | Baseline to Week 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of 50% Responders for Convulsive Seizures in the Core Treatment Period (14 Weeks) Compared to Baseline | A 50 percent (%) responder is defined as a participant with at least 50% reduction in frequency of convulsive seizures per 28 days compared to baseline. | Baseline to Week 14 | 
| Percentage of Participants who are Free From Convulsive Seizures in the Core Treatment Period (14 Weeks) |  | Up to 14 Weeks | 
| Maximum Lorcaserin Plasma Concentration at Steady-state (Cmax,ss) in the Core Treatment Period (14 Weeks) |  | Up to 14 Weeks | 
| Area Under the Plasma Lorcaserin Concentration-time Curve at Steady-state (AUC,ss) in the Core Treatment Period (14 Weeks) |  | Up to 14 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dravet Syndrome, Lorcaserin, E2023, Epilepsy, Seizures