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Proposal 1558

Title of the Proposed Research

Development of historical control using placebo data from pediatric epilepsy studies

Lead Researcher

Anthony Daniels

Affiliation

UCB BioSciences, Inc
8010 Arco Corporate Drive
Suite 175
Raleigh NC 27613

Funding Source

UCB BioSciences, Inc. will perform the analyses internally and provide necessary funding.

Potential Conflicts of Interest

Employee of UCB BioSciences

Data Sharing Agreement Date

19 January 2017

Lay Summary

In the development of new drugs, pharmaceutical companies need to conduct clinical studies in the pediatric population for a medication that has been approved for the same indication in adults where the disease has similar characteristics and the same response to treatment is expected. To prove that the new treatment works in children, there needs to be a standard to which the new medication data can be compared to show it performs better than no treatment.

Clinical studies in the pediatric population are often more difficult to enroll than those conducted in adults; especially in the population of children younger than 4 years of age. Challenges in study design, ethical questions about exposing children to placebo, and logistics of a pediatric subjects participating in a clinical trial contribute to the difficulty in enrollment. To limit the number of pediatric subjects exposed to placebo, it is proposed to perform a combined analysis of the placebo responses observed in completed studies in children with epilepsy (especially partial-onset seizures) to create a historical control for reference in future studies.

In 2015, the PEACE initiative examined the concept of extrapolation of efficacy data from adults to pediatric subjects to show that if a pharmaceutical company’s study data proved an anti-epileptic drug worked in adults then the drug could be shown to work in children without conducting a placebo-controlled study due to the similarity of the disease between adults and children. Companies are still required to conduct studies to observe the safety of the subjects taking the investigational drug and measure the levels of the medication in a subject’s system. The initiative was able to show that efficacy of anti-epileptic drugs in adults based on clinical trial data and drug concentration data, could be used to predict efficacy of anti-epileptic drugs in pediatric population.

The goal of this project is to create an estimate of a historical control rate using the data from several anti-epileptic drugs (eg, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, topiramate) that could be used as a comparator to future new anti-epileptic drugs. This would possibly reduce the number of pediatric subjects required to be randomized to the placebo arm, and would minimize the exposure of a larger number of pediatric subjects with potentially life-threatening seizures to placebo. In addition, leveraging historical control placebo response may shorten development timelines, allowing quicker access to additional treatment options for epilepsy in the pediatric population.

After analysis is completed, the results would be published in a journal available to the public.

Study Data Provided

Study GSK-LAM100036: A Multicenter, Double-blind, Randomized, Parallel-group Evaluation of LAMICTAL Extended-Release Adjunctive Therapy in Patients with Primary Generalized Tonic-Clonic Seizures-
Study GSK-LAM100034: A Multicenter, Double-Blind, Randomized, Parallel-group Evaluation of LAMICTAL Extended-release Adjunctive Therapy in Subjects with Partial Seizures
Study GSK-LAM40097: A Multi-Center, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Evaluation of Lamotrigine Adjunctive Therapy in Subjects wtih Primary Generalized Tonic-Clonic Seizures
Study GSK-LAM20006: A Double-Blind, Placebo-Controlled, Add-On Clinical Trial of the Safety, Pharmacokinetics and Efficacy of Lamictal in Pediatric Age Subjects (1-24 months)
Study GSK-105-123: Lamotrigine as add-on therapy in patients with a clinical diagnosis of a Lennox-Gastaut syndrome (severe generalised epilepsy of childhood onset). A multicentre, double-blind, placebo-controlled, parallel group study.
Study GSK-105-040: A Multicenter, Double-Blind, Placebo-Controlled, Parallel-Design Evaluation of LAMICTAL for Add-on Treatment of Partial Seizures in Pediatric Patients
Study NOVARTIS-CTRI476E2339: A Multicenter, Rater-blind, Randomized, Age-stratified, Parallel-group Study Comparing Two Doses of Oxcarbazepine as Monotherapy in Pediatric Patients With Inadequately-controlled Partial Seizures
Study NOVARTIS-CTRI476E2340: A Multicenter, Rater-blind, Randomized, Age-stratified, Parallel-group Study Comparing Two Doses of Oxcarbazepine as Adjunctive Therapy in Pediatric Patients With Inadequately-controlled Partial Seizures

Statistical Analysis Plan

Publication Citation

The publication citation will be added after the research is published.

Summary Results

Results summary or link will be posted when available.