At the Center for Translational Medicine (CTM), faculty and staff are involved in integrating efficacy knowledge across pediatrics and adults for adjunct treatment of partial seizures.
Pharmacometric bridging (dose/exposure-response) has been utilized for extrapolating efficacy in pediatrics based on adult data in lieu of an efficacy trial for partial seizures in monotherapy settings, such as oxcarbazapine (Trileptal®) and Topiramate (Topamax®).
However, this approach has not been utilized for approval of anti-epileptics in pediatrics for adjunctive therapies. We are working to investigate the possibility of leveraging the information from drugs already approved in adults and pediatrics to extrapolate efficacy for new AEDs in pediatrics for adjunctive therapy based only on adult clinical trials. A database will be constructed for drugs that are approved for both adults and pediatrics for partial seizures in adjunctive setting. This database will be used to establish and compare exposure-response relationships between adult and pediatrics.
Eventually, the established exposure-response findings of the approved drugs will form the basis of approval of new AEDs for partial seizures in the adjunctive setting, thus alleviating the need of efficacy trials in pediatrics in this setting. This project is a joint collaboration between Pediatric Epilepsy Academic Consortium for Extrapolation (PEACE), the Food and Drug Administration (FDA), and CTM.
Faculty and staff at CTM are involved in integrating pre-clinical, Hyperinsulinemic-euglycemic clamp PKPD studies in healthies and patients together with innovative designs to guide the formulation and development of biosimilars.
The CTM is also involved in integrating pre-clinical PKPD studies in healthy individuals and patients together with innovative designs to guide dose selection and probability of technical success of early and late phase clinical trials.
Currently, there exists no decision tool kit for “go/no-go” decisions based on MRI lesion counts collected at an early drug development stage (6-12 months). In registration trials for relapsing remitting multiple sclerosis (RRMS), the annualized relapse rate (ARR) is the clinical endpoint measured at 24 months.
We propose to predict the late stage trial outcome for any investigational compound, based on MRI lesion count data (clinical endpoint used in dose ranging studies) using an existing MRI (12 months) –ARR (24 months) relationship. The objective is to optimize the early phase trial design with respect to sample size, duration, and late stage trial outcome (ARR at 24 months) predictability. The validity of the predictive nature of trial simulations will be evaluated by comparing the observed data published in the literature. This design can aid in making key drug development decisions at an early stage for compounds in the pipeline for treatment of RRMS.
With a wealth of prior knowledge on anti-hypertensives, CTM’s research involves integrating mechanistic reasoning and innovative quantitative approaches to provide efficient trial designs for your single and combination anti-hypertensive therapies. CTM can provide:Probability of Technical Success for your new or combination therapy to make go-no go decisions
Lastly, faculty and staff at CTM are involved in exploring the best endpoints and designs for early NSCLC patient trials.