1. Introduction

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Human pharmacology represents the first stage of testing in human participants, ‘first-in-human’ studies. Although the treatment will have been thoroughly tested in laboratory and animal studies, side-effects in participants cannot be completely known ahead of time. For this reason, phase I studies may involve significant risks. These trials are often conducted in a dedicated inpatient clinic (with/near an intensive care unit) where the participant can be observed by full-time staff, and all possible safety provisions are in place in the event of an unexpected serious adverse reaction. Phase I studies usually have non-therapeutic objectives and are conducted in healthy volunteer participants. A minority of all phase I trials are conducted in patients rather than in healthy volunteers. The reasons for this is that some medicines are too toxic (e.g., anticancer medicine) to be given to healthy participants. Such Phase I trials may provide some early information about efficacy based on surrogate endpoints.

Phase I studies typically involve one or a combination of the following aspects:
  • Estimation of initial safety & tolerability - In order to determine the tolerability of the dose range (single and multiple administrations) expected to be needed for later studies.

  • Pharmacokinetics – Characterises the absorption, distribution, metabolism, and excretion of a medicine by the body. They also assess the clearance of the medicine (measurement of the renal excretion), anticipate possible accumulation, and look at the effects of food on bioavailability. Information is gathered on sub-populations: patient with impaired (renal or hepatic) elimination, the elderly, children, male/female, ethnic subgroups, etc. It is also important to study if any medicines interactions occur. PK may guide the dosage and dose regimens in later studies.

  • Assessment of pharmacodynamics - these data can provide early estimates of activity and potential efficacy and may guide the dosage and dose regimens in later studies.

  • Early measurement of medicine activity - generally performed in later studies. Payment to participants may be provided in Phase I clinical research in accordance with local laws as long as the study has non-therapeutic objectives, multiple procedures and/or long periods of residence, the payments serve as compensation.
Payment must never be related to risk. The amount must be stated in the informed consent document and accepted by the Ethics Committee.