The primary purpose of this study is evaluate the safety and tolerability of fenfluramine hydrochloride (HCl) 0.2 to 0.8 mg/kg/day in infants 1 year to less than 2 years of age with Dravet syndrome.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
25
The study drug, fenfluramine HCl, is an oral solution to be administered in equal doses twice daily (BID). It will be based on the current dose and participant's weight (kg).
Ep0213 105
Memphis, Tennessee, United States
Ep0213 107
Dallas, Texas, United States
Ep0213 103
Seattle, Washington, United States
Ep0213 502
Brussels, Belgium
Change from Baseline in QT interval corrected by Fridericia (QTcF) at Visit 13 (End of Treatment/Early Termination (EOT/ET))
QTcF is the QT interval corrected for heart rate according to Fridericia's formula. Higher values correspond to prolongation of QT interval.
Time frame: Week 52 (Visit 13; EOT/ET), compared to Baseline
Occurrence of a treatment-emergent (ie, post-Baseline through Visit 13 [EOT/ET]) result which meets the FDA case definition of drug associated valvulopathy
Drug associated valvulopathy refers to aortic regurgitation with severity mild or greater and/or mitral regurgitation with severity moderate or greater.
Time frame: From post-Baseline (Day 1) through Visit 13 (EOT/ET) (up to 52 weeks)
Occurrence of treatment-emergent (ie, post-Baseline through Visit 13 [EOT/ET]) clinically confirmed valvular heart disease (VHD)
Clinically confirmed VHD is an aortic regurgitation with mild or greater severity and/or a mitral regurgitation with moderate or greater severity.
Time frame: From post-Baseline (Day 1) through Visit 13 (EOT/ET) (up to 52 weeks)
Change from Baseline in body weight (Z-score) at each visit
Body weight (Z-score) refers to the number of standard deviations a participant's body weight lies from the mean, when compared to others of similar gender and age.
Time frame: Week 1 (Visit 3), Week 4 (Visit 5), Week 8 (Visit 7), Week 12 (Visit 8), Week 16 (Visit 9), Week 20 (Visit 10), Week 26 (Visit 11), Week 39 (Visit 12), Week 52 (Visit 13), Postdose Safety Follow-Up (Visit 14), compared to Baseline
Change from Baseline in recumbent length (Z-score) at each visit
Recumbent length (Z-score) refers to the number of standard deviations a participant's body weight lies from the mean, when compared to others of similar gender and age.
Time frame: Week 1 (Visit 3), Week 4 (Visit 5), Week 8 (Visit 7), Week 12 (Visit 8), Week 16 (Visit 9), Week 20 (Visit 10), Week 26 (Visit 11), Week 39 (Visit 12), Week 52 (Visit 13), Postdose Safety Follow-Up (Visit 14), compared to Baseline
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Ep0213 501
Edegem, Belgium
Ep0213 303
Bielefeld, Germany
Ep0213 202
Florence, Italy
Ep0213 203
Genova, Italy
Ep0213 201
Roma, Italy
Ep0213 204
Roma, Italy
...and 2 more locations
Occurrence of a clinically significant abnormality on the neurological examination at each visit
A complete neurological examination will be conducted by the investigator for each participant covering cranial nerves, muscle strength and tone, reflexes, coordination, sensory function, and gait.
Time frame: Week 1 (Visit 3), Week 4 (Visit 5), Week 8 (Visit 7), Week 12 (Visit 8), Week 16 (Visit 9), Week 20 (Visit 10), Week 26 (Visit 11), Week 39 (Visit 12), Week 52 (Visit 13), Postdose Safety Follow-Up (Visit 14), compared to Baseline
Percentage change from the Baseline Period (ie, Baseline) in monthly (28 days) countable motor seizure frequency (CMSF), during Weeks 9 through 20
The percentage change from the Baseline Period (Baseline) in "monthly (28 days) countable motor seizure frequency," or CMSF, during Weeks 9 through 20
Time frame: During Weeks 9 to 20, compared to Baseline
Percentage change from Baseline in CMSF during Weeks 1 through 20
The percentage change from the Baseline Period (Baseline) in "monthly (28 days) countable motor seizure frequency," or CMSF, during Weeks 1 through 20
Time frame: During Weeks 1 to 20, compared to Baseline
Percentage change from Baseline in CMSF during the Treatment Period (Week 1 through the EOT/ET Visit)
The percentage change from the Baseline Period (Baseline) in "monthly (28 days) countable motor seizure frequency," or CMSF, during the Treatment Period (Week 1 through the EOT/ET Visit; up to 52 weeks)
Time frame: During the Treatment Period (Week 1 through EOT/ET) (up to 52 weeks), compared to Baseline
Achievement of a Clinical Global Impression - Improvement (CGI-I) rating of "much improved" or "very much improved" as assessed by the Principal Investigator at Week 20
The CGI-I rating scale permits a global evaluation of the participant's improvement over time by the investigator on a 7-point scale.
Time frame: At Week 20
Achievement of a CGI-I rating of "much improved" or "very much improved" as assessed by the parent/caregiver at Week 20
The CGI-I rating scale permits a global evaluation of the participant's improvement over time by the parent/caregiver on a 7-point scale.
Time frame: At Week 20
Steady-state maximum plasma concentration (Cmax) of fenfluramine and norfenfluramine at Week 12
Mean peak (maximum) plasma concentration of fenfluramine and norfenfluramine will be reported at Study Week 12 when participants are in the Maintenance Period.
Time frame: At Week 12
Steady-state minimum plasma concentration (Cmin) of fenfluramine and norfenfluramine at Week 12
Mean minimum plasma concentration of fenfluramine and norfenfluramine will be reported at Study Week 12 when participants are in the Maintenance Period.
Time frame: At Week 12
Area under the plasma concentration time curve from time zero to 24 hours (AUC0 24) for steady-state fenfluramine and norfenfluramine at Week 12
Mean AUC0-24 values of fenfluramine and norfenfluramine will be reported at Study Week 12 when participants are in the Maintenance Period.
Time frame: At Week 12