April 11, 2016

Preclinical

Comprehensive preclinical research is the most critical element of an IND. Once a clinical candidate is selected, preclinical research focuses on identifying both the limits of safe dosing and the specific adverse event risks, thus paving the way for safe dosing in humans.

  • Pharmacology studies elucidate primary and secondary responses, efficacious doses, dose-response relationships and appropriate dose regimens
  • Drug metabolism and pharmacokinetics (DMPK) studies reveal (i) disposition in the body, (ii) bioavailability, (iii) primary clearance pathways, (iv) dose frequency, and, (iv) drug-drug interaction potential. These studies also enable selection of the appropriate species for toxicology studies
  • Toxicology and Safety Pharmacology studies (in vitro and in vivo) predict the safety of the drug in humans. At least two animal models are used to determine dose-limiting toxicities and no-observed-adverse-effect-limits (NoAEL), and cellular models are used to assess the potential for triggering mutagenesis or life-threatening arrhythmias

Comprehensive Preclinical Support

Preclinical research on your clinical candidate focuses on identifying both the limits of safe dosing and the specific adverse event liabilities, thus minimizing risks to clinical subjects as well as risks to your program. Be it Pharmacology, DMPK or Toxicology studies, we will assemble the senior preclinical experts and project management support to:

  • Develop a global preclinical plan to support the clinical development plan
  • Design the right studies
  • Find the vendors for the studies and audit them if necessary
  • Develop the protocols
  • Monitor the studies
  • Interpret the results
  • Review reports and support their preparation
  • Summarize results and incorporate them into your IND or other submission
  • Act as your champion before FDA and other regulatory bodies

Single Study Support

Every program is different and some require only a quick Proof-of-Concept pharmacology study or a bridging toxicology study.  We will help you design, outsource, and oversee the study as well as interpreting results and writing them up for your filing. Preclinical data tell our experts whether a compound has a wide enough therapeutic index to be viable and, if so, what dose the first human recipient should receive and what signs clinicians need to watch out for. PharmaDirections provides the expertise, the experience and the project team to design, oversee and execute complete IND enabling preclinical programs.

PK Modeling

With the exception of topically active drugs, what matters is not the dose itself, but how much gets into the bloodstream, when it gets in, and how long it stays there.  Pharmacokinetic modeling can be a powerful and cost-effective tool for developing, optimizing and de-risking clinical trial designs.

PharmaDirections pharmacokineticists use software packages such as WinNonLin® and GastroPlus® as well as internally developed tools to develop predictive models of in vivo drug release, absorption, distribution, metabolism, and excretion.  Once built and validated against independent data sets, these model are used to predict clinical outcomes from animal data that go beyond just allometric scaling as well as to assess outcomes of different dosing regimens to find the one most likely to give the desired plasma concentration profile.

Read more about PK Modeling