10 Things A PK clinical Trial Should Know Before Receiving Clinical Trial Samples

Clinical Trial

Planning a pharmacokinetic (PK) study is one of the most crucial aspects to consider while planning a first-in-human clinical trial. Although PK studies in early drug development provide vital information about drug doses for subsequent clinical trials, limited recommendations are available from regulatory bodies for viewing and interpreting PK data in clinical trials.

PK studies require robust approaches for assay development in drug discovery and development studies. Besides, there are several factors researchers must consider while conducting PK studies in clinical trials. Hence, the current article highlights ten things a PK clinical trial should know before receiving clinical trial samples.

  1. It is beneficial to gather appropriate PK data during first in human (FIH) studies. Hence most FIH studies have PK analysis as one of the early study objectives. Typically, SAD/MAD studies are included in FIH studies. SAD studies investigate the effect of single doses, whereas MAD studies provide PK data over multiple study doses.
  2. PK data in FIH clinical trials form a core component of the registration documents submitted to the US FDA. Hence, a rigorous PK analysis is of utmost importance. Although the FDA guidelines provide PK-related sections for FIH trials, they don’t have a precise methodology for PK analysis.
  3. Cmax, Tmax, AUC, and elimination half-life are the primary parameters researchers must assess while conducting PK clinical trials. Besides, plasma clearance and volume of distribution must also be calculated during PK assessments.
  4. PK analysis and the recorded documents are interconnected during a clinical workflow. Hence, only a thorough estimation of PK parameters will accurately interpret study results. Moreover, researchers must ensure that each assay step is followed meticulously for accurate results.
  5. During FIH studies, researchers must review the data before beginning the analysis. As the number of study subjects is limited in FIH studies, researchers must aim at having a large study population for PK clinical trials.
  6. While reviewing PK data in clinical trials, the primary objective must also assess unanticipated PK profiles. These unexpected profiles could be complex or simple. Besides, unexpected or abnormal profiles could be due to an accidental switch of samples or may indicate adverse events or concomitant medications.
  7. Draw conclusions based on primary and essential PK parameters while assessing and interpreting FIH results. Besides, consider dose-normalized PK parameters whenever necessary. These considerations will remove issues related to small dose groups with high inter-subject variability.
  8. Sometimes, a  perfect graphical presentation can be tedious. However, an appropriate selection of graphical ranges is vital for data representation. Consider using a longer drug concentration time frame while keeping the maximum concentration and timing with a shorter time frame on the original scale.
  9. Some clinical trials, such as BA/BE studies, require power calculation while investigating study hypotheses and demonstrating the statistical difference between treatments. Although FIH trials are exploratory and therefore do not requires a formal power calculator.
  10. If the significance threshold values are higher than standard 0.05, they can be acceptable, though sponsors must provide an adequate rationale. However, confidence intervals lie on the same scale with the same units. Hence, they are preferred while reporting PK data.

Leave a reply