From FIM to PoC and beyond
While traditionally clinical development was divided in 3 sequential phases (I, II, and III) up to registration, we prefer to divide this process into an Exploratory Phase followed by a Confirmatory Phase ensuring an integrated continuous analysis to guide potential modifications to the clinical development plan as it progresses, with potential cost savings offered by the reduced development times and improved decision-making.
Significant milestones are met during the Exploratory Phase. The first milestone is the First administration to human (First In Man, FIM), when safety and tolerability is first assessed in humans, either healthy volunteers or patients. At the same time the pharmacokinetic profile of the new compound is being tested as well as the pharmacodynamic profile. The following significant milestone met during this phase is the Proof of Concept (PoC), i.e. the first demonstration in humans that the compound is efficacious. These results usually form the basis to decide on large future investments on the compound. During the Confirmatory Phase all the different studies which are required by regulatory authorities to register a new compound are conducted.
Different skills are required during this integrated drug development:
- Design & Implementation of Clinical Plans (In accordance with ICH/FDA, EMEA requirements, based on the analysis of differentiation factors & unmet needs with an Integrated analysis of Preclinical & Clinical data);
- Medical Governance;
- Medical & Scientific writing;
- Design & implementation of Clinical Studies (Design, Conduct, Analysis & Interpretation of HV & Patient Studies; FIM, Repeated-dose studies; Safety Studies; Efficacy & Pharmacodynamic studies; Pharmacokinetic studies);
- Translational & Experimental Medicine approaches (imaging studies such as PET, MRI structural & functional, EEG, TMS; human laboratory models; cognition, addiction, anxiety, sedation, pain; applied clinical pharmacogenomics);
- End to end study operational leadership; management of sites and vendors;
- Pharmacometric services (high statistical & PK competence for planning, executing and reporting both standard and innovative clinical trials; advanced statistical methodologies i.e. Bayesian approach; modeling & simulation; development of predictive models; population PK & PK/PD modeling);
- Due diligence & in-licensing support.
In addition, to design the most valuable and cost effective package in support of the clinical plan the following activities can be performed: Integrated DMPK strategy to clinical evaluation in accordance with the FDA guidance (including Definitive identification and quantification of human metabolites and assessment of clinical DDI potential; Clinical bioanalysis support including DBS and definitive assessment of human metabolites toxicological cover) and non-clinical assessment of safety (Pre-clinical investigative & problem solving studies, customized, fit-for-purpose, integrated assessment of multiple endpoints; Regulatory general toxicology studies).
The formulation refinement and optimization of the dosage form, based on the clinical PK readouts and the asset target product profile, is conducted if appropriate in line with the QbD concepts, to assure consistent high quality and in vivo performance of the clinical supplied product and to meet the regulatory filing requirements.
In conclusion, Aptuit offers original and unique integrated services in clinical development to deliver innovative new chemical entities according to the sponsor’s requests with potential cost savings offered by the reduced development times and improved decision-making associated with integrated approaches.
The following disciplines support stand alone or integrated services for FIM to PoC and beyond: