L16: Drug clinical trials phase I-III

Phase I trial main goals

Starting dose & Escalation

PK/PD

Safety decisions

Phase II main goals

Dose optimisation

Proof of concept

Phase III main goals

Confirmatory evidence & benefit-risk

Phase I Primary objectives

-Characterizes safety and tolerability across planned exposures

-Identify dose-limiting or clinically-important findings

Phase I secondary objectives

-Describe [Pharmacokinetics] PK after single and repeated dosing

-Including Cmax, AUC, half-life, accumulation and variability

Phase I: Exploratory objectives (tertiary)

-Assess target engagement

-Pharmacodynamics (PD) biomarkers

-immunogenicity where relevant

-preliminary activity in patient studie

What type of participants enrolled in phase I

Healthy participants

Patients (if healthy volunteer exposure is unethical or uninformative)

Pharmacokinetics -

-Time-Matched Blood + (when needed) Urine sampling characterize exposure, distribution and elimination.

-What Body does to → Drug

Pharmacodynamics

-Biomarkers assess target engagement, pathway response or physiological effect and help interpret exposure-response

-What the Drug does to → Body

Phase II study population

Generally have the target condition (but with limited comorbidities)

What does phase II need to establish

1) Dose and regimen selection (compare tolerability, PD, efficacy)

2) Proof of concept (demonstrate credible effect on clinically meaningful endpoint)

3) Program readiness (refine endpoint definitions, event rates, variance, safety surveillance for phase III)

Phase III purpose

Confirm efficacy and characterise safety in the intended-use population