First Time in Humans
Every new clinical entity heading for regulatory approval has to start human clinical trials somewhere, and of course your initial protocol needs to be included in your Investigational New Drug application and meet with both Agency and Institutional Review Board approval.
The safety of the participants is always the primary concern, while seeking to provide you with the pharmacokinetic and/or pharmacodynamic data needed for a decision regarding further compound development.
There are many issues. Even with good preclinical toxicology data, extrapolating to humans may not be straightforward, especially if there are considerable differences between species. Should you use a microdose strategy? Should you be looking for genomics markers? What is the best starting dose? What should you plan as the range of doses? When do you want to draw your PK samples? What safety and pharmacodynamic parameters need to be monitored? If specialized assays or equipment are being considered, are they cost effective? What should be your cohort size? Do you need placebo recipients, and what should be the active:placebo ratio? What are your stop dose criteria, and who should be involved with the safety monitoring and dose escalation decisions? And of course the Inclusion/Exclusion criteria need to strike a balance allowing feasible recruitment while avoiding confounding variables.
Beyond the traditional Single Ascending Dose then Multiple Ascending Dose protocol designs, there are multiple options including "adaptive" and hybrid designs, use of "sentinel" subjects, overlapping cohorts, incorporation of women, elderly, or other special populations, and early inclusion of patients with a target indication for incorporation of biomarkers. Appropriate use of strategies such as these can deliver data with proof of concept far sooner than traditional methods.
With 13 years of ìon the shop floorî experience with Phase I studies, including First Time In Humans studies with both large and small molecules, Dr. Ruckle brings a practical, real world Investigator perspective to the protocol design discussion. In collaboration with Toxicologists, Pharmacologists, regulatory experts and others, Pacific Pharma Group seeks to provide balanced guidance so you may efficiently reach your end points.
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