CDKL5 DEFICIENCY DISORDER MedDRA version: 22.1 Level: PT Classification code 10083005 Term: CDKL5 deficiency disorder System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: Fenfluramine hydrochloride
Product Code: ZX008
Pharmaceutical Form: Oral solution
INN or Proposed INN: FENFLURAMINE HYDROCHLORIDE
CAS Number: 404-82-0
Current Sponsor code: ZX008
Other d
Sponsors
Zogenix International Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subject has a confirmed pathogenic or likely pathogenic mutation in the CDKL5 gene and a clinical diagnosis of CDD with epilepsy onset in the first year of life, plus motor and developmental delays. 2. Subject is male or female, aged 1 to 35 years, inclusive, as of the day of the Screening Visit. Subjects aged 1 to =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Subject has a known hypersensitivity to fenfluramine or any of the excipients in the study drug. 2. Subject has a diagnosis of pulmonary arterial hypertension. 3. Subject has a clinically significant medical condition, including chronic obstructive pulmonary disease, interstitial lung disease, or portal hypertension, or has had clinically relevant symptoms or a clinically significant illness currently or in the 4 weeks prior to the Screening Visit, other than epilepsy, that would negatively impact study participation, collection of study data, or pose a risk to the subject. 4. Subject has current or past history of cardiovascular or cerebrovascular disease, such as cardiac valvulopathy, myocardial infarction or stroke, severe ventricular arrhythmias, or clinically significant structural cardiac abnormality, including but not limited to mitral valve prolapse, atrial or ventricular septal defects, patent ductus arteriosus, and patent foramen ovale with reversal of shunt. (Note: Patent foramen ovale or a bicuspid aortic valve are not considered exclusionary.) 5. Subject has current eating disorder that suggests anorexia nervosa or bulimia. 6. Subject has a current or past history of glaucoma. 7. Subject is taking > 4 concomitant ASMs. Rescue medications are not included in the count. 8. Subject is receiving concomitant treatment with cannabidiol (CBD) other than Epidiolex/Epidyolex or is being actively treated with tetrahydrocannabinol (THC) or any marijuana product for any condition. Disallowed medications are subject to wash-out requirements. 9. Subject has moderate to severe hepatic impairment, assessed based on the Child-Pugh system. 10. Subject has moderate to severe renal impairment (estimated glomerular filtration rate < 50 mL/min/1.73 m2 calculated with the Isotope Dilution Mass Spectrometry [IDMS] Traceable Schwartz equation for children and the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation for adults, using actual body weight). 11. Subject is receiving concomitant therapy with any of the following: centrally-acting anorectic agents; monoamine-oxidase inhibitors; any centrally-acting compound with clinically appreciable amount of serotonin agonist or antagonist properties, including serotonin reuptake inhibition; other centrally-acting noradrenergic agonists, including atomoxetine; or cyproheptadine. (Note: Short-term requirements for prohibited medications will be handled on a per case basis by the Medical Monitor.) 12. Subject has participated in another interventional clinical trial within 30 days of the Screening Visit or is currently receiving an investigational product. 13. Female subjects of childbearing potential must not be pregnant or breastfeeding. Female subjects of childbearing potential must have a negative urine or serum pregnancy test at Screening. Subjects of childbearing or child-fathering potential must be willing to use an approved method of highly effective contraception, which includes abstinence, while participating in this study and for 90 days after the last dose of study drug. 14. Subject is known to be human immunodeficiency virus positive. 15. Subject is known to have active viral hepatitis B or C. 16. Subject is institutionalized in a facility that does not provide skilled epilepsy care. 17. Subject has previously been treated with Fintepla® (fenfluramine) prior to the Screening Visit.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1 Objectives: Efficacy • To demonstrate that ZX008 0.8 mg/kg/day is superior to placebo as an adjunctive therapy for pediatric and adult subjects with CDD • To assess global improvement with ZX008 treatment in pediatric and adult subjects with CDD Safety • To characterize the safety and tolerability of ZX008 in pediatric and adult subjects with CDD Pharmacokinetics • To assess the pharmacokinetics (PK) of ZX008 at steady-state in pediatric and adult subjects with CDD Part 2 Objectives: Efficacy • To assess long-term effectiveness of ZX008 as an adjunctive therapy for pediatric and adult subjects with CDD • To assess global improvement with ZX008 treatment in pediatric and adult subjects with CDD Safety • To characterize the long-term safety and tolerability of ZX008 in pediatric and adult subjects with CDD;Secondary Objective: Not applicable;Primary end point(s): The primary endpoint of Part 1 is the primary endpoint of the entire study: • The median percentage change from the Baseline Period (Baseline) in "monthly (28 days) countable motor seizure frequency," or CMSF, during the combined Titration and Maintenance Periods (T+M) in the ZX008 0.8 mg/kg/day group compared with the placebo group;Timepoint(s) of evaluation of this end point: One time point at end of 14 weeks (T + M) period. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary: • The percentage of subjects who achieve a = 50% reduction from Baseline in CMSF during T+M in the ZX008 0.8 mg/kg/day group compared with the placebo group • The percentage of subjects who achieve a CGI-I rating of much or very much improved as assessed by the Investigator at the end of T+M in the ZX008 0.8 mg/kg group compared with the placebo group • The median percentage change from Baseline in monthly GTC seizure frequency during T+M in the ZX008 0.8 mg/kg/day group compared with the placebo group;Timepoint(s) of evaluation of this end point: One time point at end of 14 weeks (T + M) period. | — |
Countries
Austria, Belgium, Germany, Ireland, Israel, Italy, Japan, Netherlands, Portugal, Spain, United States
Contacts
Public ContactLonnissa Nguyen
Zogenix, Inc.
Outcome results
None listed