A phase 1 or ‘first in human’ study is carried out to generate data on safety, tolerability (whether a treatment is acceptable to patients) and exposure (levels of a drug in different parts of the body, particularly the site of the infection being targeted).
The design of a phase 1 study must be agreed by regulatory authorities. It must also be seen as appropriate by clinicians who will carry out the study, who must have confidence that the drug being tested has the potential to become a viable treatment.
A trial can only start when clinical trial authorization (CTA) and ethical approval has been obtained. A trial sponsormust submit a detailed application describing the studies to be carried out. This application will include results from pre-clinical studies, which must demonstrate that the drug to be tested is active against the targeted pathogen and is an effective treatment in animal models.
Pre-clinical studies should also demonstrate safety – that there is minimal risk of harm when the drug is given to people. A justification of the dose and dosing schedule to be used in the trial should also be provided.
The data required for clinical trial authorization will come from a combination of microbiology, non-clinical safety and pharmacokinetic/pharmacodynamics studies.
General trial essentials
Trial registration: All studies evaluating a drug in patients must be publicly posted before a trial starts, for example at clinicaltrials.gov or Eudract.
Good Clinical Practice (GCP): To ensure the safety of participants and the reliability of data, all clinical trials must comply with GCP.
Other considerations
Generally, antibiotics are directed against bacterial targets, in order to kill them or to disable mechanisms that they use to render antibiotics ineffective (e.g. enzymes such as beta-lactamases that inactivate beta-lactam antibiotics). Special considerations apply to antibiotics that act in other ways.