First-in-Human

First-in-human (FIH) trials constitute a milestone step in drug development and serve as the first link between preclinical and clinical research. Typically, FIH trials are carried out with healthy volunteers to mitigate the impact of confounding factors associated with patients, such as comorbidities and concurrent medication usage. Nevertheless, certain patient groups may also be deemed appropriate for inclusion in FIH trials, and there appears to be an emerging trend towards an earlier involvement of patients in clinical research.

FIH trials usually encompass one single ascending dose (SAD) part followed by a multiple ascending dose (MAD) part conducted under a single, or two separate, protocol(s). All FIH trials are characterised by extensive safety monitoring in line with the European Medicines Agencies (EMAs) guideline outlining strategies to identify and mitigate risks in early clinical trials. Trial outcomes include stop/go data on safety, tolerability, and pharmacokinetics of a new drug candidate. If possible, pharmacodynamic endpoints are also evaluated.

Before the start of a FIH trial, specialists at CTC’s DMPK and Clinical Pharmacology department assist in the translation of animal data to a human setting by determining an appropriate starting dose, and a suitable dose escalation scheme, taking safety and PK margins established during animal testing into account. Through a cross-functional collaboration, involving the Sponsor and CTC’s advisory team of scientists and medical experts, the optimal study design, endpoints, assessments, and the definition of the trial population criteria are meticulously crafted and refined. CTC’s own FIH unit with 12 beds is located at Uppsala University Hospital, Sweden, adjacent to the intensive care unit (ICU), PET centre and MRI facilities. We run 6 to 8 FIH trials each year.