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Trial record 1 of 1 for:    ZX008-1504
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A 2-Part Study to Investigate the Dose-Ranging Safety and Pharmacokinetics, Followed by the Efficacy and Safety of ZX008 (Fenfluramine Hydrochloride) Oral Solution as an Adjunctive Therapy in Children ≥ 2 Years Old and Young Adults With Dravet Syndrome

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02926898
Recruitment Status : Completed
First Posted : October 6, 2016
Results First Posted : October 19, 2022
Last Update Posted : November 2, 2022
Sponsor:
Information provided by (Responsible Party):
UCB Pharma ( Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Dravet Syndrome
Interventions Drug: ZX008 (Fenfluramine Hydrochloride)
Drug: Matching Placebo
Enrollment 87
Recruitment Details A total of 28 study sites in Canada, France, Germany, the Netherlands, Spain, the United Kingdom, and the United States enrolled participants for Study 1504 Cohort 2.
Pre-assignment Details A total of 115 subjects were screened for eligibility to participate in Study 1504 Cohort 2. Of these, 87 subjects were enrolled and randomized.
Arm/Group Title Cohort 2: ZX008 0.5 mg/kg/Day Cohort 2: Matching Placebo
Hide Arm/Group Description ZX008 0.5 mg/kg/day (maximum 20 mg/day) administered twice a day (BID) in equally divided doses. Matching placebo administered twice a day (BID) in equally divided doses.
Period Title: Overall Study
Started 43 44
Completed 36 41
Not Completed 7 3
Arm/Group Title Cohort 2: ZX008 0.5 mg/kg/Day Cohort 2: Matching Placebo Total
Hide Arm/Group Description ZX008 0.5 mg/kg/day (maximum 20 mg/day) dose administered twice a day (BID) in equally divided doses. Matching placebo administered twice a day (BID) in equally divided doses. Total of all reporting groups
Overall Number of Baseline Participants 43 44 87
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Cohort 2 Number Analyzed 43 participants 44 participants 87 participants
8.8  (4.56) 9.4  (5.05) 9.1  (4.80)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Cohort 2 Number Analyzed 43 participants 44 participants 87 participants
Female
20
  46.5%
17
  38.6%
37
  42.5%
Male
23
  53.5%
27
  61.4%
50
  57.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 43 participants 44 participants 87 participants
Hispanic or Latino
3
   7.0%
7
  15.9%
10
  11.5%
Not Hispanic or Latino
25
  58.1%
22
  50.0%
47
  54.0%
Unknown or Not Reported
15
  34.9%
15
  34.1%
30
  34.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Cohort 2 Number Analyzed 43 participants 44 participants 87 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
2
   4.7%
1
   2.3%
3
   3.4%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   2.3%
2
   4.5%
3
   3.4%
White
23
  53.5%
29
  65.9%
52
  59.8%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
17
  39.5%
12
  27.3%
29
  33.3%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 43 participants 44 participants 87 participants
Netherlands
8
  18.6%
2
   4.5%
10
  11.5%
France
13
  30.2%
10
  22.7%
23
  26.4%
Canada
4
   9.3%
3
   6.8%
7
   8.0%
United States
11
  25.6%
11
  25.0%
22
  25.3%
Germany
0
   0.0%
3
   6.8%
3
   3.4%
Spain
4
   9.3%
6
  13.6%
10
  11.5%
United Kingdom
3
   7.0%
9
  20.5%
12
  13.8%
1.Primary Outcome
Title Change in Convulsive Seizure Frequency (CSF) From the Baseline Period (Baseline) to the Combined Titration + Maintenance (T+M) Period
Hide Description Monthly (28 day) convulsive seizure frequency (CSF) was based on electronic diary data obtained for each participant. Convulsive seizures included hemiclonic, focal with clear observable motor signs, generalized tonic clonic, secondarily generalized tonic clonic, tonic, clonic, and drop seizures (tonic/atonic). The number of convulsive seizures reported during the entire time interval was divided by the number of nonmissing diary days and the result was then multiplied by 28 to get a 28-day CSF.
Time Frame 15 weeks (combined Titration + Maintenance Period)
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intent-to-treat (mITT) Population, defined as all randomized subjects who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.
Arm/Group Title Cohort 2: ZX008 0.5 mg/kg/Day Cohort 2: Matching Placebo
Hide Arm/Group Description:
ZX008 0.5 mg/kg/day (maximum 20 mg/day) administered twice a day (BID) in equally divided doses.
Matching placebo administered twice a day (BID) in equally divided doses.
Overall Number of Participants Analyzed 43 44
Mean (Standard Deviation)
Unit of Measure: Convulsive seizures per 28 days
-3.18  (44.121) -0.65  (8.767)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 2: ZX008 0.5 mg/kg/Day, Cohort 2: Matching Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Analysis of covariance (ANCOVA) model with treatment group (ZX008 or placebo) and age group (< 6 years, ≥ 6 years) as factors, and with log baseline frequency as a covariate, and log CSF as the outcome variable.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Percent difference
Estimated Value -54.0
Confidence Interval (2-Sided) 95%
-67.2 to -35.6
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants Who Achieved ≥ a 50% Reduction in Convulsive Seizure Frequency From Baseline to the Combined Titration + Maintenance Period
Hide Description Percentage of participants who achieved ≥ a 50% reduction in convulsive seizure frequency from Baseline compared to the combined Titration + Maintenance Periods in the ZX008 0.5 mg/kg/day vs placebo groups.
Time Frame 15 weeks (combined Titration + Maintenance Period)
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intent-to-treat (mITT) Population, defined as all randomized subjects who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.
Arm/Group Title Cohort 2: ZX008 0.5 mg/kg/Day Cohort 2: Matching Placebo
Hide Arm/Group Description:
ZX008 0.5 mg/kg/day (maximum 20 mg/day) administered twice a day (BID) in equally divided doses.
Matching placebo administered twice a day (BID) in equally divided doses.
Overall Number of Participants Analyzed 43 44
Measure Type: Number
Unit of Measure: Percentage of participants
53.5 4.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 2: ZX008 0.5 mg/kg/Day, Cohort 2: Matching Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Logistic
Comments A logistic regression model using a categorical response variable as a function of Treatment group, Baseline seizure frequency, and age group.
3.Secondary Outcome
Title Longest Convulsive Seizure-Free Interval (Days)
Hide Description Comparison of the duration of the longest convulsive seizure-free interval (days) during the combined Titration + Maintenance Periods for the ZX008 0.5 mg/kg/day and placebo groups.
Time Frame 15 weeks (combined Titration + Maintenance Period)
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intent-to-treat (mITT) Population, defined as all randomized subjects who received at least 1 dose of ZX008 or placebo and for whom at least 1 week of diary data were available.
Arm/Group Title Cohort 2: ZX008 0.5 mg/kg/Day Cohort 2: Matching Placebo
Hide Arm/Group Description:
ZX008 0.5 mg/kg/day (maximum 20 mg/day) administered twice a day (BID) in equally divided doses.
Matching placebo administered twice a day (BID) in equally divided doses.
Overall Number of Participants Analyzed 43 44
Median (Full Range)
Unit of Measure: Days
22.0
(3.0 to 105.0)
13.0
(1.0 to 40.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 2: ZX008 0.5 mg/kg/Day, Cohort 2: Matching Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Time Frame The period of observation for Adverse Events extended from the time the subject gave informed consent until the end of the Follow-up Visit (up to Day 120 [Visit 13]).
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Cohort 2: ZX008 0.5 mg/kg/Day Cohort 2: Matching Placebo
Hide Arm/Group Description ZX008 0.5 mg/kg/day (maximum 20 mg/day) dose administered twice a day (BID) in equally divided doses. Matching placebo administered twice a day (BID) in equally divided doses.
All-Cause Mortality
Cohort 2: ZX008 0.5 mg/kg/Day Cohort 2: Matching Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/43 (0.00%)   0/44 (0.00%) 
Hide Serious Adverse Events
Cohort 2: ZX008 0.5 mg/kg/Day Cohort 2: Matching Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   6/43 (13.95%)   7/44 (15.91%) 
Gastrointestinal disorders     
Abdominal pain † 1  0/43 (0.00%)  1/44 (2.27%) 
General disorders     
Pyrexia † 1  0/43 (0.00%)  1/44 (2.27%) 
Infections and infestations     
Gastroenteritis viral † 1  0/43 (0.00%)  1/44 (2.27%) 
Lower respiratory tract infection † 1  0/43 (0.00%)  1/44 (2.27%) 
Pneumonia † 1  0/43 (0.00%)  1/44 (2.27%) 
Musculoskeletal and connective tissue disorders     
Osteochondritis † 1  1/43 (2.33%)  0/44 (0.00%) 
Nervous system disorders     
Generalised tonic-clonic seizure † 1  0/43 (0.00%)  1/44 (2.27%) 
Lethargy † 1  1/43 (2.33%)  0/44 (0.00%) 
Seizure † 1  1/43 (2.33%)  4/44 (9.09%) 
Seizure cluster † 1  0/43 (0.00%)  1/44 (2.27%) 
Status epilepticus † 1  3/43 (6.98%)  0/44 (0.00%) 
1
Term from vocabulary, MedDRA (19.0)
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cohort 2: ZX008 0.5 mg/kg/Day Cohort 2: Matching Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   42/43 (97.67%)   42/44 (95.45%) 
Gastrointestinal disorders     
Diarrhea † 1  10/43 (23.26%)  3/44 (6.82%) 
Constipation † 1  4/43 (9.30%)  1/44 (2.27%) 
Vomiting † 1  2/43 (4.65%)  3/44 (6.82%) 
General disorders     
Fatigue † 1  11/43 (25.58%)  2/44 (4.55%) 
Pyrexia † 1  11/43 (25.58%)  4/44 (9.09%) 
Asthenia † 1  3/43 (6.98%)  2/44 (4.55%) 
Infections and infestations     
Bronchitis † 1  5/43 (11.63%)  2/44 (4.55%) 
Ear Infection † 1  4/43 (9.30%)  2/44 (4.55%) 
Nasopharyngitis † 1  7/43 (16.28%)  15/44 (34.09%) 
Rhinitis † 1  3/43 (6.98%)  1/44 (2.27%) 
Sinusitis † 1  1/43 (2.33%)  3/44 (6.82%) 
Upper respiratory tract infection † 1  4/43 (9.30%)  3/44 (6.82%) 
Investigations     
Blood glucose decreased † 1  6/43 (13.95%)  2/44 (4.55%) 
Blood pressure diastolic increased † 1  0/43 (0.00%)  3/44 (6.82%) 
Blood pressure increased † 1  0/43 (0.00%)  3/44 (6.82%) 
Echocardiogram abnormal † 1  4/43 (9.30%)  0/44 (0.00%) 
Weight decreased † 1  4/43 (9.30%)  1/44 (2.27%) 
Metabolism and nutrition disorders     
Decreased appetite † 1  19/43 (44.19%)  5/44 (11.36%) 
Nervous system disorders     
Lethargy † 1  6/43 (13.95%)  2/44 (4.55%) 
Seizure † 1  2/43 (4.65%)  7/44 (15.91%) 
Generalized tonic-clonic seizure † 1  0/43 (0.00%)  3/44 (6.82%) 
Somnolence † 1  3/43 (6.98%)  3/44 (6.82%) 
Status epilepticus † 1  5/43 (11.63%)  0/44 (0.00%) 
Tremor † 1  5/43 (11.63%)  0/44 (0.00%) 
Psychiatric disorders     
Abnormal behavior † 1  4/43 (9.30%)  1/44 (2.27%) 
Irritability † 1  4/43 (9.30%)  2/44 (4.55%) 
1
Term from vocabulary, MedDRA (19.0)
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: UCB
Organization: Cares
Phone: 001 844 599 2273
EMail: UCBCares@ucb.com
Publications of Results:
Nabbout R, Mistry A, Zuberi S, Villeneuve N, Gil-Nagel A, Sanchez-Carpintero R, Stephani U, Laux L, Wirrell E, Knupp K, Chiron C, Farfel G, Galer BS, Morrison G, Lock M, Agarwal A, Auvin S; FAiRE, DS Study Group. Fenfluramine for Treatment-Resistant Seizures in Patients With Dravet Syndrome Receiving Stiripentol-Inclusive Regimens: A Randomized Clinical Trial. JAMA Neurol. 2020 Mar 1;77(3):300-308. doi: 10.1001/jamaneurol.2019.4113.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: UCB Pharma ( Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc. )
ClinicalTrials.gov Identifier: NCT02926898    
Other Study ID Numbers: ZX008-1504
First Submitted: August 10, 2016
First Posted: October 6, 2016
Results First Submitted: June 10, 2021
Results First Posted: October 19, 2022
Last Update Posted: November 2, 2022