Epilepsies, Myoclonic
Conditions
Keywords
Dravet Syndrome, Lorcaserin, E2023, Epilepsy, Seizures
Brief summary
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.
Interventions
DRUGPlacebo
Placebo matching to lorcaserin oral tablet, administered as oral suspension.
DRUGLorcaserin
Lorcaserin oral tablet, administered as oral suspension.
Sponsors
Eisai Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: Participants must meet all of the following criteria to be included in this study: 1. Male or female, age 2 years and older at the time of informed consent 2. Diagnosis of epilepsy with Dravet syndrome 3. Has at least 4 convulsive seizures during the 4 weeks of baseline 4. 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: 1. Use of lorcaserin within 4 weeks before screening, or any history of it being discontinued due to lack of efficacy or adverse reactions 2. 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 3. Recent or concomitant use of serotonergic medications or monoamine oxidase inhibitors 4. Presence of progressive central nervous system disease other than Dravet syndrome
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Core Study: Percent Change From Baseline in Convulsive Seizure Frequency Per 28 Days During the Treatment Period | Baseline up to Week 14 | Seizure frequency for convulsive seizures was based on number of seizures per 28 days, calculated during the baseline period (Week -4 to Week 0) and 14-week 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. Percent change from baseline was calculated as: (\[post-baseline value minus the baseline value\] / baseline value) \*100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Core Study: Percentage of Participants With 50% or Greater Response for Convulsive Seizures in the Treatment Period Compared to Baseline | Baseline up to Week 14 | A responder was defined as a participant who experienced a reduction of 50% or greater in the frequency of convulsive seizures during the 14-week treatment period compared to the baseline period (Week -4 to Week 0). Seizure frequency was based on number of seizures per 28 days, calculated during the baseline period (Week -4 to Week 0) 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. |
| Core Study: Percentage of Participants Who Were Free From Convulsive Seizures in the Treatment Period | Baseline up to Week 14 | A responder was a participant who experienced a 100% reduction (seizure freedom) in convulsive seizure frequency in the 14-week treatment period relative to the baseline period (Week -4 to Week 0). Seizure frequency was based on number of seizures per 28 days, calculated during the baseline period (Week -4 to Week 0) 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. |
| Core Study: Plasma Concentrations of Lorcaserin | Weeks 1, 2, 6, 15: Pre-dose and 1 to 2 hours post-dose; Weeks 4,10: Pre-dose, 1 to 2 hours and 3 to 6 hours post-dose | Plasma Concentrations of Lorcaserin was evaluated and reported. |
| Core Study: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | From first dose of study drug up to end of 4 weeks of follow up after last dose of study drug (up to Week 18) | A TEAE was defined as an adverse event (AE) that emerges during treatment, was absent at pretreatment (baseline) or reemerges during treatment, was present at pretreatment (baseline) but stopped before treatment or worsens in severity during treatment relative to the pretreatment state, when the AE was continuous. An AE was any untoward medical occurrence in a participant or clinical investigation participant administered an investigational product. An AE did not necessarily have a causal relationship with the medicinal product. |
Countries
Canada, United States
Participant flow
Recruitment details
Participants took part at 15 investigative sites in Canada and the United States from 23 September 2020 to 15 August 2024.
Pre-assignment details
The study was conducted in two phases (Core Study and an Open-label Extension Phase). A total of 27 participants were screened, of which 5 were screen failures and 22 were enrolled to receive study treatment. This study was terminated due to sponsor decision, and not due to safety concerns. As pre-planned, the data collection and analysis were based on treatments (placebo or lorcaserin) in Core Study and Extension Phase. The dose level wise data was not collected in this study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo/ Lorcaserin Participants received lorcaserin-matching placebo, oral suspension, twice daily for 14 weeks in Core Study followed by lorcaserin, oral suspension based on body weight as the target dose for participants weighing 10 to \<20 kg, 20 to \<40 kg, and \>=40 kg was 5 mg/day, 10 mg/day, and 20 mg/day, respectively for first 6 weeks in Extension Phase. Based on clinical response and tolerability, the dose was increased up to 10 mg/day for participants weighing 10 to \<20 kg and up to 20 mg/day for those weighing 20 to \<40 kg and \>=40 kg for second 6 weeks in Extension Phase. The total treatment duration in Core Study was 14 weeks and 12 weeks in Extension Phase. | 10 |
| Lorcaserin/ Lorcaserin Participants weighing 10 to \<20 kg, 20 to \<40 kg, and \>=40 kg received lorcaserin oral suspension, at dose of 5 mg/day, 10 mg/day, and 20 mg/day, respectively in Core Study. During the first 2 weeks of the treatment, depending on the participant's clinical response and tolerability, the dose was increased up to 10 mg/day for participants weighing 10 to \<20 kg and up to 20 mg/day for those weighing 20 to \<40 kg and \>=40 kg. During Extension Phase, participants continued the same dose of Core Study for first 6 weeks in Extension Phase. Based on clinical response and tolerability, the dose increased up to 10 mg/day for participants weighing 10 to \<20 kg and up to 20 mg/day for those weighing 20 to \<40 kg and \>=40 kg during second 6 weeks in Extension Phase. The total treatment duration in Core Study was 14 weeks and 12 weeks in Extension Phase. | 11 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Core Study: 14 Weeks | Adverse Event | 1 | 2 | 0 | 0 |
| Core Study: 14 Weeks | Randomized but not treated | 1 | 0 | 0 | 0 |
| Core Study: 14 Weeks | Subject choice | 0 | 2 | 0 | 0 |
| Core Study: 14 Weeks | Withdrawal of consent | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Lorcaserin/ Lorcaserin | Total | Placebo/ Lorcaserin |
|---|---|---|---|
| Age, Continuous | 12.7 year STANDARD_DEVIATION 7.71 | 12.8 year STANDARD_DEVIATION 8.81 | 12.9 year STANDARD_DEVIATION 10.32 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 4 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 17 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 4 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) White | 4 Participants | 12 Participants | 8 Participants |
| Sex: Female, Male Female | 7 Participants | 10 Participants | 3 Participants |
| Sex: Female, Male Male | 4 Participants | 11 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 11 | 0 / 7 | 0 / 7 |
| other Total, other adverse events | 7 / 10 | 8 / 11 | 4 / 7 | 3 / 7 |
| serious Total, serious adverse events | 0 / 10 | 1 / 11 | 0 / 7 | 1 / 7 |
Outcome results
Primary
Core Study: Percent Change From Baseline in Convulsive Seizure Frequency Per 28 Days During the Treatment Period
Seizure frequency for convulsive seizures was based on number of seizures per 28 days, calculated during the baseline period (Week -4 to Week 0) and 14-week 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. Percent change from baseline was calculated as: (\[post-baseline value minus the baseline value\] / baseline value) \*100.
Time frame: Baseline up to Week 14
Population: The FAS was the group of randomized participants who received at least 1 dose of study drug and had at least 1 post-dose primary efficacy measurement.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Core Study: Placebo | Core Study: Percent Change From Baseline in Convulsive Seizure Frequency Per 28 Days During the Treatment Period | 18.78 percent change |
| Core Study: Lorcaserin | Core Study: Percent Change From Baseline in Convulsive Seizure Frequency Per 28 Days During the Treatment Period | -78.88 percent change |
95% CI: [-144.01, -28.14]
Secondary
Core Study: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
A TEAE was defined as an adverse event (AE) that emerges during treatment, was absent at pretreatment (baseline) or reemerges during treatment, was present at pretreatment (baseline) but stopped before treatment or worsens in severity during treatment relative to the pretreatment state, when the AE was continuous. An AE was any untoward medical occurrence in a participant or clinical investigation participant administered an investigational product. An AE did not necessarily have a causal relationship with the medicinal product.
Time frame: From first dose of study drug up to end of 4 weeks of follow up after last dose of study drug (up to Week 18)
Population: The Safety Analysis Set was the group of participants who received at least 1 dose of study drug and had at least 1 post-dose safety assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Core Study: Placebo | Core Study: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 7 Participants |
| Core Study: Lorcaserin | Core Study: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 9 Participants |
Secondary
Core Study: Percentage of Participants Who Were Free From Convulsive Seizures in the Treatment Period
A responder was a participant who experienced a 100% reduction (seizure freedom) in convulsive seizure frequency in the 14-week treatment period relative to the baseline period (Week -4 to Week 0). Seizure frequency was based on number of seizures per 28 days, calculated during the baseline period (Week -4 to Week 0) 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.
Time frame: Baseline up to Week 14
Population: The FAS was the group of randomized participants who received at least 1 dose of study drug and had at least 1 post-dose primary efficacy measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Core Study: Placebo | Core Study: Percentage of Participants Who Were Free From Convulsive Seizures in the Treatment Period | 0.0 percentage of participants |
| Core Study: Lorcaserin | Core Study: Percentage of Participants Who Were Free From Convulsive Seizures in the Treatment Period | 10.0 percentage of participants |
Secondary
Core Study: Percentage of Participants With 50% or Greater Response for Convulsive Seizures in the Treatment Period Compared to Baseline
A responder was defined as a participant who experienced a reduction of 50% or greater in the frequency of convulsive seizures during the 14-week treatment period compared to the baseline period (Week -4 to Week 0). Seizure frequency was based on number of seizures per 28 days, calculated during the baseline period (Week -4 to Week 0) 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.
Time frame: Baseline up to Week 14
Population: The FAS was the group of randomized participants who received at least 1 dose of study drug and had at least 1 post-dose primary efficacy measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Core Study: Placebo | Core Study: Percentage of Participants With 50% or Greater Response for Convulsive Seizures in the Treatment Period Compared to Baseline | 20.0 percentage of participants |
| Core Study: Lorcaserin | Core Study: Percentage of Participants With 50% or Greater Response for Convulsive Seizures in the Treatment Period Compared to Baseline | 60.0 percentage of participants |
95% CI: [0.81, 44.35]
Secondary
Core Study: Plasma Concentrations of Lorcaserin
Plasma Concentrations of Lorcaserin was evaluated and reported.
Time frame: Weeks 1, 2, 6, 15: Pre-dose and 1 to 2 hours post-dose; Weeks 4,10: Pre-dose, 1 to 2 hours and 3 to 6 hours post-dose
Population: The Pharmacokinetic (PK) analysis set was the group of all randomized participants from whom at least measurable lorcaserin plasma concentration was obtained with associated documented dosing history. Here 'n' refers to number of participants analyzed at different timepoints for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Core Study: Placebo | Core Study: Plasma Concentrations of Lorcaserin | Week 4: 1 to 2 hours post-dose | 107 nanograms per milliliter (ng/mL) | Standard Deviation 76.9 |
| Core Study: Placebo | Core Study: Plasma Concentrations of Lorcaserin | Week 1: Pre-dose | 52.0 nanograms per milliliter (ng/mL) | — |
| Core Study: Placebo | Core Study: Plasma Concentrations of Lorcaserin | Week 1: 1 to 2 hours post-dose | 106 nanograms per milliliter (ng/mL) | — |
| Core Study: Placebo | Core Study: Plasma Concentrations of Lorcaserin | Week 2: Pre-dose | 22.1 nanograms per milliliter (ng/mL) | Standard Deviation 14.5 |
| Core Study: Placebo | Core Study: Plasma Concentrations of Lorcaserin | Week 2: 1 to 2 hours post-dose | 32.7 nanograms per milliliter (ng/mL) | Standard Deviation 22.7 |
| Core Study: Placebo | Core Study: Plasma Concentrations of Lorcaserin | Week 4: Pre-dose | 48.5 nanograms per milliliter (ng/mL) | Standard Deviation 13.2 |
| Core Study: Placebo | Core Study: Plasma Concentrations of Lorcaserin | Week 4: 3 to 6 hours post-dose | 60.5 nanograms per milliliter (ng/mL) | Standard Deviation 36 |
| Core Study: Placebo | Core Study: Plasma Concentrations of Lorcaserin | Week 6: Pre-dose | 22.7 nanograms per milliliter (ng/mL) | Standard Deviation 11.8 |
| Core Study: Placebo | Core Study: Plasma Concentrations of Lorcaserin | Week 6: 1 to 2 hours post-dose | 41.0 nanograms per milliliter (ng/mL) | Standard Deviation 20.6 |
| Core Study: Placebo | Core Study: Plasma Concentrations of Lorcaserin | Week 10: Pre-dose | 32.9 nanograms per milliliter (ng/mL) | — |
| Core Study: Placebo | Core Study: Plasma Concentrations of Lorcaserin | Week 10: 1 to 2 hours post-dose | 52.4 nanograms per milliliter (ng/mL) | — |
| Core Study: Placebo | Core Study: Plasma Concentrations of Lorcaserin | Week 10: 3 to 6 hours post-dose | 66.7 nanograms per milliliter (ng/mL) | Standard Deviation 33.7 |
| Core Study: Placebo | Core Study: Plasma Concentrations of Lorcaserin | Week 15: Pre-dose | 33.6 nanograms per milliliter (ng/mL) | — |
| Core Study: Placebo | Core Study: Plasma Concentrations of Lorcaserin | Week 15: 1 to 2 hours post-dose | 31.4 nanograms per milliliter (ng/mL) | — |