Clinical trials of drugs are the final stage of a long and laborious process of their development. Clinical trials of drugs before their official authorization for medical use are conducted in 4 stages, traditionally called “Phases of clinical trials.”
I Phase of clinical trials
(clinical pharmacological, biomedical testing)
The first trials in humans of a new drug (active ingredient) with its preliminary evaluation. Usually, such tests are conducted on a small group (up to 100) of healthy volunteers.
At this stage, we study:
- tolerability of a single dose of the drug
- pharmacokinetic parameters
- pharmacodynamic effects
The importance of Phase I clinical trials is to obtain data on the tolerability and safety of the drug in order to decide whether to further develop or discontinue research.
The aim is to obtain preliminary data on the safety and tolerability of the drug, to make a primary characteristic of the pharmacodynamic and pharmacokinetic properties of the drug in humans, and sometimes also to determine the initial efficacy in human trials
Why do healthy volunteers usually participate? Healthy volunteers (usually male, young) are a homogeneous, highly selective, resistant to potential adverse events, a sample from the general population. In addition, volunteers are easier to recruit and observe. Eliminates the ethical problem associated with the appointment of patients with treatment with unproven efficacy.
In the early stages of Phase I trials, the initial dose, multiplicity and route of administration of the drug are usually established in preclinical trials (in laboratory animals). However, due to differences in pharmacokinetics and pharmacodynamics in humans and animals, such doses may require correction.
II Phase of clinical trials
If the drug is safe and well tolerated, the clinical trial goes to Phase II. This phase requires the inclusion of more subjects, but with a disease (or condition) for which (the diagnosis and/or prophylaxis) of which the active ingredient is intended.
Early Phase II trials are often called pilot trials, as the results provide optimal planning for more expensive and extensive Phase III trials.
The goal of Phase II clinical trials is
- to prove the clinical efficacy of the drug in a certain group of patients
- assess the short-term safety of the active ingredient
- determination of the therapeutic dose level of the drug
- Dosing regimens
Sometimes Phase II clinical trials are divided into Phases IIa and IIb.
Pilot clinical trials, designed primarily to determine the level of drug safety in patients with a disease or syndrome for which the drug is used.
During Phase IIa, it is necessary to verify
- activity of the substance under study
- assess short-term security
- establish a contingent of patients
- Dosing Regimen
- find out the dependence of the effect on the dose
- determine the criteria for assessing the effectiveness of
More extensive basic clinical trials (pivotal trials). They are planned to determine both the effectiveness and safety of the drug’s effects on patients.
The main objective of Phase II6 is to determine the optimal dose level of the drug in order to continue its study in Phase III clinical trials.
Phase II trials are the most important step necessary to decide whether to continue developing a new drug.
Such tests imply the existence of a planned design, clear inclusion/exclusion criteria, randomization, dazzling, follow-up procedures. In other words, such studies are methodologically similar to Phase III trials.