Clinical trial NCT02829827: A Phase 2 Study of Radiprodil in Subjects With Drug-resistant Infantile Spasms (IS)
Official title: An Open-label Adaptive Study for the Assessment of Safety, Tolerability, Pharmacokinetics, and Efficacy of Multiple Doses of Radiprodil in Subjects With Drug-resistant Infantile Spasms
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Infantile Spasms (IS)
Keywords: Radiprodil
Infantile spasms
IS
Infantile
Spasms
Epilepsy
Paediatrics
Drug-resistant
West Syndrome
Hypsarrhythmia
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2016-07-12
Enrollment: 3
Sex: ALL
Minimum age (years): 2
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to evaluate the safety and tolerability, the pharmacokinetics and the efficacy of radiprodil in abolishing clinical spasms in subjects with drug-resistant infantile spasms

Detailed description: The study is divided into 3 parts:

Part A - exploratory, Part B - confirmatory, Part C - open label extension

Eligibility criteria: Inclusion Criteria:

Part A and B:

* Subject is male or female between 2 and 14 months of age
* The diagnosis of infantile spasms (IS)
* Subject has drug-resistant IS

Part C:

* Subject participated in EP0078 Part A and received 2 radiprodil treatment cycles
* Subject experienced a relapse of spasms during the down taper or within 5 half-lives (3 days) discontinuation of radiprodil treatment in Cycle 2 of Part A
* Electroencephalogram (EEG) on baseline Part C is compatible with the diagnosis of infantile spasms

Exclusion Criteria:

Part A and B:

* More than 6 months have passed since the diagnosis of Infantile Spasms (IS)
* Current treatment with cannabinoids
* Subject has hematocrit greater than 60
* Subject has any medical condition that, in the opinion of the Investigator, could jeopardize or would compromise the subject's ability to participate in this study
* Subject has a history or current condition predisposing to respiratory dysfunction
* Current treatment with felbamate
* Current treatment with perampanel
* Ketogenic diet
* Clinically significant lab abnormalities
* Clinically significant abnormality on ECG that, in the opinion of the Investigator, increases the safety risks of participating in the study
* Subject has a lethal or potentially lethal condition other than IS, with a significant risk of death before 18 months of age such as non-ketotic hyperglycinemia
* Body weight is below 4 kg
* Known history of severe anaphylactic reaction secondary to medication intake or serious blood dyscrasias

Part C:

* Subject experienced any acute tolerability issues in either treatment cycle in Part A which the investigator and the sponsor medical monitor consider a risk for further participation
* Subject met any withdrawal criteria in Part A
* Subject has experienced any adverse effects or developed any new medical conditions since enrollment in Part A which the investigator considers could significantly increase the safety risks of participating in Part C

Primary outcomes:
measure: Percentage of subjects with clinical response on Day 14 of treatment with the maintenance dose of radiprodil
timeFrame: Day 14, counting from the first day of radiprodil at maintenance dose
measure: Estimates of exposure generated from a population-Pharmacokinetic modelling
timeFrame: Samples will be taken at baseline (time during Day -14 to -1 prior to dosing) and 3, 4, 5 & 12hr after the 1st dose on Day 1 of radiprodil low, mid & high dose. Blood samples will be taken at same timepoints after 1st dose on Day 2 of radiprodil low dose
measure: Percentage of subjects with electro-clinical response on Day 14 of treatment with the maintenance dose of radiprodil
timeFrame: Day 14, counting from the first day of radiprodil at maintenance dose
measure: Incidence of Adverse Events (AEs) during the study
timeFrame: From Baseline (Day -1) to the end of the Post-treatment Period (28 days post last dosing)
Secondary outcomes:
measure: Percentage of subjects with electro-clinical response on Day 14 of treatment with the maintenance dose of radiprodil
timeFrame: Day 14, counting from the first day of radiprodil at maintenance dose
measure: Percentage of subjects with clinical response on Day 14 of treatment with the maintenance dose of radiprodil
timeFrame: Day 14, counting from Day 14 of treatment with the maintenance dose of radiprodil
measure: Estimates of exposure generated from a population-Pharmacokinetic modelling
timeFrame: Pharmacokinetic samples will be collected on Day 1 of radiprodil low dose, mid dose and high dose. Additionally, blood samples will be taken after 1st dose on Day 2 of radiprodil low dose.
measure: Time to cessation of spasms
timeFrame: During the first 14 days of treatment with radiprodil
measure: Percentage of responders with clinical relapse
timeFrame: 12 months, counting from Day 14 of treatment with the maintenance dose of radiprodil
measure: Time to clinical relapse from the day of spasm cessation
timeFrame: From day of spasms cessation up to 42 months of age
measure: Percentage of electro-clinical responders with electro-clinical relapse
timeFrame: 12 months, counting from Day 14 of treatment with the maintenance dose of radiprodil
measure: Time to electro-clinical relapse from the day of spasm cessation
timeFrame: From day of spasms cessation up to 42 months of age
measure: Percentage of subjects with extended clinical response
timeFrame: 28 days, counting from Day 14 (inclusive) of treatment with the maintenance dose of radiprodil
measure: Percentage of subjects with extended electro-clinical response
timeFrame: 28 days, counting from Day 14 (inclusive) of treatment with the maintenance dose of radiprodil
measure: Percentage of subjects with extended clinical response to each additional treatment cycle on Day 14 of treatment with the maintenance dose of radiprodil
timeFrame: 28 days, counting from Day 14 (inclusive) of maintenance dose
measure: Number of treatment cycles per subject
timeFrame: During Part C (Day -1 to Day 28 of the Maintenance Period)
measure: Percentage of subjects with electro-clinical response to each additional treatment cycle on Day 14 of treatment with the maintenance dose of radiprodil
timeFrame: Day 14, counting from the first day of maintenance dose
measure: Time to clinical relapse from the first day of no witnessed spasms for each treatment cycle
timeFrame: From day of no witnessed spasms up to 42 months of age
Other outcomes:
Locations:
city: Paris
country: France
facility: Ep0078 401
Study officials:
affiliation: +1 8445992273 (UCB)
name: UCB Cares
role: STUDY_DIRECTOR
References: