New Drug Development: From Preclinical Research to Clinical Trials

New Drug Development: From Preclinical Research to Clinical Trials

Developing a new drug requires demonstrating its safety and efficacy.

Questions:

• Is combining two known drugs with circulating doses considered a new drug?

• Yes.

• Is it necessary for all preclinical studies (TLS) to be completed before human trials?

• Important TLS must be conducted first.

• In-depth TLS, which is not crucial, can be conducted later.

• What are the requirements for a generic drug?

• Pharmacokinetic parameters should be similar from 80% to 125%.

• When is it necessary to prove bioequivalence (BE)?

• Most drugs need to demonstrate BE.

• Injectable drugs and topical drugs do not need to demonstrate BE.

Objectives of Preclinical Research:

• Determine toxicity.

• Prove safety.

• Demonstrate pharmacological effects and mechanisms of action.

• Determine pharmacokinetics.

Exceptions:

• Vaccines, traditional medicine, and drugs derived from medicinal plants are exempted from pharmacokinetic and toxicokinetic studies.

Important Parameters:

• Acute toxicity:

• LD50 (lethal dose 50%).

• Repeated doses:

• LOAEL (lowest observed adverse effect level).

• NOAEL (no observed adverse effect level).

Repeated Dose Studies in Animals:

• Use different animal species (at least one non-rodent species).

Results of TLS:

• Provide evidence with a high degree of reliability.

Clinical Trial Stages:

• Phase I:

• First human study.

• Healthy volunteers.

• Determine initial pharmacokinetics and safety.

• Sample size: < 100.

• In what cases are Phase I clinical trials conducted on patients?

• Drugs with high toxicity, only treating rare, difficult-to-treat diseases.

• Phase II:

• Patients.

• Find optimal dose.

• Sample size: 100 – 300, multicenter.

• Phase III:

• Patients.

• Confirm safety and efficacy, dose from Phase II.

• Sample size: Thousands, multicenter.

• Study for approval:

• Key study.

• Phase IV:

• Patients.

• Collect safety and efficacy information after approval.

Principles of Clinical Trial Design:

• Ensure that subjects have an equal chance of participating in treatment groups:

• Randomization (gold standard).

• Exclude the influence of factors on the effect:

• Natural progression of the disease.

• Researcher’s desire.

• …

• Control.

• Exclude the influence of subjects on the accuracy of research results:

• Blinding.

• Prove that the new treatment is superior to previous treatments:

• Superiority trial.

• Prove that the new treatment is similar or superior to previous treatments:

• Non-inferiority trial.

• Prove that there is no difference between the two treatments:

• Equivalence trial (equivalence range 80% – 125%).

• Local study to extrapolate results from foreign populations:

• Bridge trial.