Clinical trials investigate new medical interventions like drugs, vaccines, or treatments in human volunteers. These regulated studies progress through stages to gather data on a new treatment’s effects, aiming to determine if it is safe and effective for broader use. Phase 0 clinical trials represent a very early, exploratory step in this process.
Understanding Phase 0 Clinical Trials
A Phase 0 clinical trial is an initial, exploratory human study, often called an exploratory Investigational New Drug (IND) study. These trials administer very low, sub-therapeutic doses of a new drug, known as microdosing. A microdose is typically less than 1/100th of the expected pharmacological dose, or a maximum of 100 micrograms for small molecules, whichever is lower.
The purpose of these low doses is to gather preliminary data on the drug’s behavior in the human body without expecting therapeutic effects or significant side effects. Subjects usually receive the drug for a limited period, often no more than seven days. This approach provides early human data not always predictable from animal studies.
Core Objectives of Phase 0 Trials
The main objective of Phase 0 trials is to gather early pharmacokinetic (PK) and pharmacodynamic (PD) data. Pharmacokinetics describes how the body handles the drug, including its absorption, distribution, metabolism, and excretion. Pharmacodynamics focuses on how the drug affects the body, including its mechanism of action and any biochemical or physiological changes it induces.
This early data helps researchers decide if a drug candidate warrants further clinical development. By identifying compounds unlikely to succeed early, Phase 0 trials can save time and resources in drug development. The insights gained guide the selection of promising compounds, optimizing subsequent trial designs.
How Phase 0 Differs from Later Clinical Trial Phases
Phase 0 trials differ from later clinical trial phases (Phase I, II, and III) in dose, participant numbers, primary goals, and risk profiles. In Phase 0, the drug is administered at sub-therapeutic microdoses, not expected to have therapeutic effects. Phase I trials, conversely, test ascending therapeutic doses for safety and optimal dosage, while Phase II and III trials use therapeutic doses to assess efficacy and broader safety.
Phase 0 trials involve a small number of participants, usually 10 to 15 healthy volunteers or patients. This contrasts sharply with later phases: Phase I typically has 20-100 participants, Phase II expands to dozens to a few hundred patients, and Phase III includes hundreds to thousands of participants to confirm efficacy and monitor for less common side effects.
The primary goal of Phase 0 is exploratory, focusing on preliminary PK/PD data to understand drug behavior in humans. Phase I trials, however, prioritize safety, dose-finding, and initial observations of side effects. Phase II trials then evaluate the drug’s effectiveness and continue to monitor for side effects in a larger patient population. Phase III trials aim to confirm efficacy on a large scale, compare the new treatment to existing standards, and gather extensive safety data.
Due to the microdosing approach, the risk profile in Phase 0 trials is generally very low, as the doses are too small to cause significant adverse effects. As the trials progress to Phase I, II, and III, the potential for side effects increases with higher, therapeutic doses, necessitating more rigorous safety monitoring. Finally, Phase 0 studies are often conducted under an exploratory Investigational New Drug (IND) application, which has reduced regulatory requirements compared to the full IND required for traditional therapeutic trials.