Strategies Considered in Designing an FTIH Trial

• Activity Number: 686
• Type: Contributed
• Date/Time: Thursday, August 8, 2013 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Yu Lou*+ and Jianjun Gan
• Companies: GlaxoSmithKline and GlaxoSmithKline
• Keywords: FTIH ; Bayesian ; Adaptive

Abstract

The cost of discovering and developing new medicines has increased dramatically in recent years. Many assumptions will be made in first time in human (FTIH) trial design to account for the uncertainty in the clinical safety, pharmacokinetics, and pharmacological activity of a new compound. Bayesian adaptive trial approaches for FTIH have the potential to reduce development costs, identify the right doses, and increase the trial success rate. These approaches are well suited to flexible development strategies tailored to meet an asset's unique challenges (i.e., differential development). Specific questions can be addressed using more focused FTIH trial design prior to large investments in a full development program. An example will be provided to demonstrate how Bayesian adaptive design was used to design the FTIH trial for an antiviral compound, where specific criteria and predictions were applied to guide the dose escalation relative to the nonclinical toxicological coverage, select doses to define the exposure-antiviral response relationship. In addition, the adaptive randomization and enrollment strategies will be discussed.