PGx and Drug Development

Question 1

Phase I

Answer 1

PK/PD exploration

Question 2

Phase II-III

Answer 2

PK/PD modeling and simulation
PD studies in pts response to therapy
Biomarkers

Question 3

Does Phase IV have a control group?

Answer 3

NO!

since it is during marketing

Question 4

Goals of clinical studies

Answer 4

• ID a safe starting dose w/ possible activity
• Determine end-organ toxicities and reversibility
• Guide dosing regimens and escalation scheme

Question 5

Phase 0

Answer 5

Proof-of-concept in clinic testing; fail early and fast
Target development (Phase 0) –> Target assessment (Phase I-II) –> Target validation (Phase III)
FDA reviews it differently (need exploratory IND rather than regular IND)
Much smaller scale in ALL the phases with Phase 0

Question 6

Types of Phase 0 Trials

Answer 6

• Microdose= 2 purposes (PK and imaging/ labeling)
• Pharmacologically Relevant Doses= move on to higher than microdose study then accumulate safety data (Primarily looking for safety and secondarily looks at PD endpoints)
• Pharmacodynamic endpoint studies= evaluate response to drug at molecular level; find biomarkers