Trial Outcomes & Findings for Fenfluramine in CDKL5 Deficiency Disorder (CDD) (NCT NCT03861871)
NCT ID: NCT03861871
Last Updated: 2023-10-04
Results Overview
Change between baseline and Week 14 in the median number of monthly convulsive seizures.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
7 participants
Primary outcome timeframe
Baseline, Week 14
Results posted on
2023-10-04
Participant Flow
Participant milestones
| Measure |
Fenfluramine Hydrochloride
Study medication will be administered as equal doses twice a day in the morning and in the evening approximately 12 hours apart.
Patients will first be titrated over 14 days to a dose of ZX008 0.8 mg/kg/day (maximum dose 30 mg/d).
After completion of the Titration Period, patients will continue to receive the ZX008 0.8 mg/kg/day dose and be treated for an additional 12 weeks (Maintenance Period). Study medication will continue to be administered twice a day in the morning and in the evening, approximately 12 hours apart.
After completion of the Maintenance Period, patients will enter the Taper Period, where they will decrease from 0.8 mg/kg twice a day to a dose of 0.4 mg/kg twice a day (maximum 30 mg/day). After 4 days at this dose level, patients will decrease their dose to 0.2 mg/kg/day. On day 9 of the Taper Period, all participants will stop taking study medication.
Fenfluramine Hydrochloride: Oral aqueous solution of fenfluramine hydrochloride buffered to pH 5 and provided in concentrations of 2.5 mg/mL. Manufactured by Andersonbrecon, Inc. on behalf of Zogenix International Limited.
|
|---|---|
|
Overall Study
STARTED
|
7
|
|
Overall Study
COMPLETED
|
7
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Fenfluramine in CDKL5 Deficiency Disorder (CDD)
Baseline characteristics by cohort
| Measure |
Fenfluramine Hydrochloride
n=7 Participants
Study medication will be administered as equal doses twice a day in the morning and in the evening approximately 12 hours apart.
Patients will first be titrated over 14 days to a dose of ZX008 0.8 mg/kg/day (maximum dose 30 mg/d).
After completion of the Titration Period, patients will continue to receive the ZX008 0.8 mg/kg/day dose and be treated for an additional 12 weeks (Maintenance Period). Study medication will continue to be administered twice a day in the morning and in the evening, approximately 12 hours apart.
After completion of the Maintenance Period, patients will enter the Taper Period, where they will decrease from 0.8 mg/kg twice a day to a dose of 0.4 mg/kg twice a day (maximum 30 mg/day). After 4 days at this dose level, patients will decrease their dose to 0.2 mg/kg/day. On day 9 of the Taper Period, all participants will stop taking study medication.
Fenfluramine Hydrochloride: Oral aqueous solution of fenfluramine hydrochloride buffered to pH 5 and provided in concentrations of 2.5 mg/mL. Manufactured by Andersonbrecon, Inc. on behalf of Zogenix International Limited.
|
|---|---|
|
Age, Continuous
|
12.7 years
STANDARD_DEVIATION 7.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
7 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 14Change between baseline and Week 14 in the median number of monthly convulsive seizures.
Outcome measures
| Measure |
Fenfluramine Hydrochloride
n=7 Participants
Study medication will be administered as equal doses twice a day in the morning and in the evening approximately 12 hours apart.
Patients will first be titrated over 14 days to a dose of ZX008 0.8 mg/kg/day (maximum dose 30 mg/d).
After completion of the Titration Period, patients will continue to receive the ZX008 0.8 mg/kg/day dose and be treated for an additional 12 weeks (Maintenance Period). Study medication will continue to be administered twice a day in the morning and in the evening, approximately 12 hours apart.
After completion of the Maintenance Period, patients will enter the Taper Period, where they will decrease from 0.8 mg/kg twice a day to a dose of 0.4 mg/kg twice a day (maximum 30 mg/day). After 4 days at this dose level, patients will decrease their dose to 0.2 mg/kg/day. On day 9 of the Taper Period, all participants will stop taking study medication.
Fenfluramine Hydrochloride: Oral aqueous solution of fenfluramine hydrochloride buffered to pH 5 and provided in concentrations of 2.5 mg/mL. Manufactured by Andersonbrecon, Inc. on behalf of Zogenix International Limited.
|
|---|---|
|
Change From Baseline in Median Monthly Convulsive Seizure Frequency
|
88.429 Number of monthly seizures
Standard Deviation 122.44
|
SECONDARY outcome
Timeframe: Baseline, Week 14The CGIC is a 1-item, parent/caregiver-completed assessment used determine how much their child/care-recipient has improved with treatment. The instrument asks parents/caregivers to rate their child's/care-recipient's improvement as: 1) very much improved; 2) much improved; 3) minimally improved; 4) unchanged; 5) a little worse; 6) much worse; 7) very much worse; the total score correspondingly ranges from 1-7.
Outcome measures
| Measure |
Fenfluramine Hydrochloride
n=7 Participants
Study medication will be administered as equal doses twice a day in the morning and in the evening approximately 12 hours apart.
Patients will first be titrated over 14 days to a dose of ZX008 0.8 mg/kg/day (maximum dose 30 mg/d).
After completion of the Titration Period, patients will continue to receive the ZX008 0.8 mg/kg/day dose and be treated for an additional 12 weeks (Maintenance Period). Study medication will continue to be administered twice a day in the morning and in the evening, approximately 12 hours apart.
After completion of the Maintenance Period, patients will enter the Taper Period, where they will decrease from 0.8 mg/kg twice a day to a dose of 0.4 mg/kg twice a day (maximum 30 mg/day). After 4 days at this dose level, patients will decrease their dose to 0.2 mg/kg/day. On day 9 of the Taper Period, all participants will stop taking study medication.
Fenfluramine Hydrochloride: Oral aqueous solution of fenfluramine hydrochloride buffered to pH 5 and provided in concentrations of 2.5 mg/mL. Manufactured by Andersonbrecon, Inc. on behalf of Zogenix International Limited.
|
|---|---|
|
Change in Caregiver Global Impression of Change (CGIC) Score
|
-2.429 score on a scale
Standard Deviation 1.988
|
SECONDARY outcome
Timeframe: Baseline, Week 14The IGIC is a 1-item, investigator-completed assessment used determine how much a patient has improved with treatment. The instrument asks the investigator to rate patients' improvement as: 1) very much improved; 2) much improved; 3) minimally improved; 4) unchanged; 5) a little worse; 6) much worse; 7) very much worse; the total score correspondingly ranges from 1-7.
Outcome measures
| Measure |
Fenfluramine Hydrochloride
n=7 Participants
Study medication will be administered as equal doses twice a day in the morning and in the evening approximately 12 hours apart.
Patients will first be titrated over 14 days to a dose of ZX008 0.8 mg/kg/day (maximum dose 30 mg/d).
After completion of the Titration Period, patients will continue to receive the ZX008 0.8 mg/kg/day dose and be treated for an additional 12 weeks (Maintenance Period). Study medication will continue to be administered twice a day in the morning and in the evening, approximately 12 hours apart.
After completion of the Maintenance Period, patients will enter the Taper Period, where they will decrease from 0.8 mg/kg twice a day to a dose of 0.4 mg/kg twice a day (maximum 30 mg/day). After 4 days at this dose level, patients will decrease their dose to 0.2 mg/kg/day. On day 9 of the Taper Period, all participants will stop taking study medication.
Fenfluramine Hydrochloride: Oral aqueous solution of fenfluramine hydrochloride buffered to pH 5 and provided in concentrations of 2.5 mg/mL. Manufactured by Andersonbrecon, Inc. on behalf of Zogenix International Limited.
|
|---|---|
|
Change in Investigator Global Impression of Change (IGIC) Score
|
1.571 score on a scale
Standard Deviation 0.787
|
SECONDARY outcome
Timeframe: Baseline, Week 14Parent/caregiver-completed assessment assessing how epilepsy affects day-to-day functioning of their child/care-recipient in various life areas. Each item is ranked on a 5-point Likert scale from 1 (response correlated with the lowest possible quality of life) to 5 (response correlated with the highest possible quality of life). Item scores are then transformed to a 0-100 scale as follows: 1 = 0, 2 = 25, 3 = 50, 4=75, and 5=100. The total score is the average of all item scores and ranges from 0-100. Higher scores indicate greater quality of life; an increase in scores indicates quality of life increased during the observational period.
Outcome measures
| Measure |
Fenfluramine Hydrochloride
n=7 Participants
Study medication will be administered as equal doses twice a day in the morning and in the evening approximately 12 hours apart.
Patients will first be titrated over 14 days to a dose of ZX008 0.8 mg/kg/day (maximum dose 30 mg/d).
After completion of the Titration Period, patients will continue to receive the ZX008 0.8 mg/kg/day dose and be treated for an additional 12 weeks (Maintenance Period). Study medication will continue to be administered twice a day in the morning and in the evening, approximately 12 hours apart.
After completion of the Maintenance Period, patients will enter the Taper Period, where they will decrease from 0.8 mg/kg twice a day to a dose of 0.4 mg/kg twice a day (maximum 30 mg/day). After 4 days at this dose level, patients will decrease their dose to 0.2 mg/kg/day. On day 9 of the Taper Period, all participants will stop taking study medication.
Fenfluramine Hydrochloride: Oral aqueous solution of fenfluramine hydrochloride buffered to pH 5 and provided in concentrations of 2.5 mg/mL. Manufactured by Andersonbrecon, Inc. on behalf of Zogenix International Limited.
|
|---|---|
|
Change in Quality of Life in Childhood Epilepsy (QOLCE) Score
|
-0.429 score on a scale
Standard Deviation 1.512
|
SECONDARY outcome
Timeframe: Baseline, Week 14The PedsQL Epilepsy Module is a 29-item measure with five scales: Impact, Cognitive, Sleep, Executive Function, and Mood/Behavior. The Impact scale (nine items) assesses how epilepsy interferes with daily activities, interacting with peers, independence, and increased disease burden due to treatment. The Cognitive Scale (six items) assesses memory, ability to learn new materials, school-related difficulties, and reading difficulties. The Sleep Scale (three items) assesses fatigue and sleep difficulties. The Executive Function Scale (six items) assesses organization, task initiation, impulsivity, and inattention. The Mood/Behavior Scale (five items) assesses feelings of anger, sadness, worries, and frustration tolerance. Scores range from 0-100 for each subscale, with higher scores representing better quality of life. The raw score is the sum of each subscale score and ranges from 0-500.
Outcome measures
| Measure |
Fenfluramine Hydrochloride
n=7 Participants
Study medication will be administered as equal doses twice a day in the morning and in the evening approximately 12 hours apart.
Patients will first be titrated over 14 days to a dose of ZX008 0.8 mg/kg/day (maximum dose 30 mg/d).
After completion of the Titration Period, patients will continue to receive the ZX008 0.8 mg/kg/day dose and be treated for an additional 12 weeks (Maintenance Period). Study medication will continue to be administered twice a day in the morning and in the evening, approximately 12 hours apart.
After completion of the Maintenance Period, patients will enter the Taper Period, where they will decrease from 0.8 mg/kg twice a day to a dose of 0.4 mg/kg twice a day (maximum 30 mg/day). After 4 days at this dose level, patients will decrease their dose to 0.2 mg/kg/day. On day 9 of the Taper Period, all participants will stop taking study medication.
Fenfluramine Hydrochloride: Oral aqueous solution of fenfluramine hydrochloride buffered to pH 5 and provided in concentrations of 2.5 mg/mL. Manufactured by Andersonbrecon, Inc. on behalf of Zogenix International Limited.
|
|---|---|
|
Change in Pediatric Quality Of Life (PEDS-QL) Epilepsy Module Raw Score
|
-103.571 score on a scale
Standard Deviation 424.124
|
Adverse Events
Fenfluramine Hydrochloride
Serious events: 1 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Fenfluramine Hydrochloride
n=7 participants at risk
Study medication will be administered as equal doses twice a day in the morning and in the evening approximately 12 hours apart.
Patients will first be titrated over 14 days to a dose of ZX008 0.8 mg/kg/day (maximum dose 30 mg/d).
After completion of the Titration Period, patients will continue to receive the ZX008 0.8 mg/kg/day dose and be treated for an additional 12 weeks (Maintenance Period). Study medication will continue to be administered twice a day in the morning and in the evening, approximately 12 hours apart.
After completion of the Maintenance Period, patients will enter the Taper Period, where they will decrease from 0.8 mg/kg twice a day to a dose of 0.4 mg/kg twice a day (maximum 30 mg/day). After 4 days at this dose level, patients will decrease their dose to 0.2 mg/kg/day. On day 9 of the Taper Period, all participants will stop taking study medication.
Fenfluramine Hydrochloride: Oral aqueous solution of fenfluramine hydrochloride buffered to pH 5 and provided in concentrations of 2.5 mg/mL. Manufactured by Andersonbrecon, Inc. on behalf of Zogenix International Limited.
|
|---|---|
|
Infections and infestations
Clostridium dificile infection
|
14.3%
1/7 • 14 Weeks
Monitored via safety phone calls and at all visits.
|
|
Infections and infestations
Respiratory infection
|
14.3%
1/7 • 14 Weeks
Monitored via safety phone calls and at all visits.
|
|
Infections and infestations
Aspiration pneumonia
|
14.3%
1/7 • 14 Weeks
Monitored via safety phone calls and at all visits.
|
Other adverse events
| Measure |
Fenfluramine Hydrochloride
n=7 participants at risk
Study medication will be administered as equal doses twice a day in the morning and in the evening approximately 12 hours apart.
Patients will first be titrated over 14 days to a dose of ZX008 0.8 mg/kg/day (maximum dose 30 mg/d).
After completion of the Titration Period, patients will continue to receive the ZX008 0.8 mg/kg/day dose and be treated for an additional 12 weeks (Maintenance Period). Study medication will continue to be administered twice a day in the morning and in the evening, approximately 12 hours apart.
After completion of the Maintenance Period, patients will enter the Taper Period, where they will decrease from 0.8 mg/kg twice a day to a dose of 0.4 mg/kg twice a day (maximum 30 mg/day). After 4 days at this dose level, patients will decrease their dose to 0.2 mg/kg/day. On day 9 of the Taper Period, all participants will stop taking study medication.
Fenfluramine Hydrochloride: Oral aqueous solution of fenfluramine hydrochloride buffered to pH 5 and provided in concentrations of 2.5 mg/mL. Manufactured by Andersonbrecon, Inc. on behalf of Zogenix International Limited.
|
|---|---|
|
Gastrointestinal disorders
Diarrhea
|
28.6%
2/7 • 14 Weeks
Monitored via safety phone calls and at all visits.
|
|
General disorders
Lethargy
|
85.7%
6/7 • 14 Weeks
Monitored via safety phone calls and at all visits.
|
|
General disorders
Crying episode
|
28.6%
2/7 • 14 Weeks
Monitored via safety phone calls and at all visits.
|
|
General disorders
Screaming episode
|
14.3%
1/7 • 14 Weeks
Monitored via safety phone calls and at all visits.
|
|
General disorders
Low appetite
|
85.7%
6/7 • 14 Weeks
Monitored via safety phone calls and at all visits.
|
|
Infections and infestations
Upper respiratory infection
|
42.9%
3/7 • 14 Weeks
Monitored via safety phone calls and at all visits.
|
|
Infections and infestations
Common cold
|
42.9%
3/7 • 14 Weeks
Monitored via safety phone calls and at all visits.
|
|
General disorders
Teething
|
14.3%
1/7 • 14 Weeks
Monitored via safety phone calls and at all visits.
|
|
Infections and infestations
Urinary tract infection
|
14.3%
1/7 • 14 Weeks
Monitored via safety phone calls and at all visits.
|
|
Gastrointestinal disorders
Vomitting
|
14.3%
1/7 • 14 Weeks
Monitored via safety phone calls and at all visits.
|
|
General disorders
Weight Loss
|
28.6%
2/7 • 14 Weeks
Monitored via safety phone calls and at all visits.
|
|
Gastrointestinal disorders
Constipation
|
28.6%
2/7 • 14 Weeks
Monitored via safety phone calls and at all visits.
|
|
Infections and infestations
Pneumonia
|
14.3%
1/7 • 14 Weeks
Monitored via safety phone calls and at all visits.
|
|
Infections and infestations
Low grade fever
|
14.3%
1/7 • 14 Weeks
Monitored via safety phone calls and at all visits.
|
|
General disorders
Bite on finger
|
14.3%
1/7 • 14 Weeks
Monitored via safety phone calls and at all visits.
|
|
Gastrointestinal disorders
Intestinal gas
|
14.3%
1/7 • 14 Weeks
Monitored via safety phone calls and at all visits.
|
|
General disorders
Grinding teeth
|
14.3%
1/7 • 14 Weeks
Monitored via safety phone calls and at all visits.
|
|
General disorders
Rash on face
|
14.3%
1/7 • 14 Weeks
Monitored via safety phone calls and at all visits.
|
|
General disorders
Hair loss
|
14.3%
1/7 • 14 Weeks
Monitored via safety phone calls and at all visits.
|
|
Gastrointestinal disorders
Regurgitation after meals
|
14.3%
1/7 • 14 Weeks
Monitored via safety phone calls and at all visits.
|
|
Gastrointestinal disorders
Loose bowel
|
14.3%
1/7 • 14 Weeks
Monitored via safety phone calls and at all visits.
|
|
General disorders
Low tone
|
14.3%
1/7 • 14 Weeks
Monitored via safety phone calls and at all visits.
|
|
Gastrointestinal disorders
Loose stool
|
14.3%
1/7 • 14 Weeks
Monitored via safety phone calls and at all visits.
|
|
Infections and infestations
Mucus plug in throat
|
14.3%
1/7 • 14 Weeks
Monitored via safety phone calls and at all visits.
|
|
General disorders
Irritability
|
14.3%
1/7 • 14 Weeks
Monitored via safety phone calls and at all visits.
|
|
Infections and infestations
SARS-CoV2 infection
|
14.3%
1/7 • 14 Weeks
Monitored via safety phone calls and at all visits.
|
|
General disorders
Sialorrhea
|
14.3%
1/7 • 14 Weeks
Monitored via safety phone calls and at all visits.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place