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
Overview
- Phase
- Phase 2
- Intervention
- Radiprodil
- Conditions
- Infantile Spasms (IS)
- Sponsor
- UCB Biopharma S.P.R.L.
- Enrollment
- 3
- Locations
- 1
- Primary Endpoint
- Percentage of subjects with clinical response on Day 14 of treatment with the maintenance dose of radiprodil
- Status
- Terminated
- Last Updated
- 6 years ago
Overview
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
Investigators
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
- •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
Arms & Interventions
Radiprodil
Each subject will enter an individualized dose titration schedule.
Intervention: Radiprodil
Outcomes
Primary Outcomes
Percentage of subjects with clinical response on Day 14 of treatment with the maintenance dose of radiprodil
Time Frame: Day 14, counting from the first day of radiprodil at maintenance dose
Clinical response is defined as no spasms on Day 14 of treatment with the maintenance dose of radiprodil. This is the primary efficacy variable for Part A.
Estimates of exposure generated from a population-Pharmacokinetic modelling
Time Frame: 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
This is a primary variable for Part A.
Percentage of subjects with electro-clinical response on Day 14 of treatment with the maintenance dose of radiprodil
Time Frame: Day 14, counting from the first day of radiprodil at maintenance dose
Electro-clinical response is defined as no spasms and resolution of hypsarrythmia on Day 14 of treatment with the maintenance dose of radiprodil. This is the primary efficacy variable for Part B.
Incidence of Adverse Events (AEs) during the study
Time Frame: From Baseline (Day -1) to the end of the Post-treatment Period (28 days post last dosing)
An AE is any untoward medical occurrence in a subject or trial subject that is administered a drug or biologic (medicinal product) or that is using a medical device. The event does not necessarily have a causal relationship with that treatment or usage. This is a primary variable for all parts.
Secondary Outcomes
- Percentage of subjects with electro-clinical response on Day 14 of treatment with the maintenance dose of radiprodil(Day 14, counting from the first day of radiprodil at maintenance dose)
- Percentage of subjects with clinical response on Day 14 of treatment with the maintenance dose of radiprodil(Day 14, counting from Day 14 of treatment with the maintenance dose of radiprodil)
- Estimates of exposure generated from a population-Pharmacokinetic modelling(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.)
- Time to cessation of spasms(During the first 14 days of treatment with radiprodil)
- Percentage of responders with clinical relapse(12 months, counting from Day 14 of treatment with the maintenance dose of radiprodil)
- Time to clinical relapse from the day of spasm cessation(From day of spasms cessation up to 42 months of age)
- Percentage of electro-clinical responders with electro-clinical relapse(12 months, counting from Day 14 of treatment with the maintenance dose of radiprodil)
- Time to electro-clinical relapse from the day of spasm cessation(From day of spasms cessation up to 42 months of age)
- Percentage of subjects with extended clinical response(28 days, counting from Day 14 (inclusive) of treatment with the maintenance dose of radiprodil)
- Percentage of subjects with extended electro-clinical response(28 days, counting from Day 14 (inclusive) of treatment with the maintenance dose of radiprodil)
- Percentage of subjects with extended clinical response to each additional treatment cycle on Day 14 of treatment with the maintenance dose of radiprodil(28 days, counting from Day 14 (inclusive) of maintenance dose)
- Number of treatment cycles per subject(During Part C (Day -1 to Day 28 of the Maintenance Period))
- Percentage of subjects with electro-clinical response to each additional treatment cycle on Day 14 of treatment with the maintenance dose of radiprodil(Day 14, counting from the first day of maintenance dose)
- Time to clinical relapse from the first day of no witnessed spasms for each treatment cycle(From day of no witnessed spasms up to 42 months of age)