Exam 2 lecture 13 Flashcards Preview

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Flashcards in Exam 2 lecture 13 Deck (24):
1

preclinical & phase 0

- preparation for human studies: gene ID, SNPs, linked to PK (ADME) & PD (targeting); gene (SNP) linked to disease progression
- data collection & exploratory studies: GWAS (untreated & treated pts), RNA microarray (disease & treatment response)

2

Phase 1

PK/PD in healthy volunteers or pts: drug metabolizing enzymes (phase I & II), transporter, molecular targets

3

phase II/III

- PK in pts
- PK/PD modeling & simulation
- PD studies in pts response to therapy (targeted genes, SNPs, disease associated genes & SNPs, genes or SNPs previously linked to similar drugs)
- exploratory studies & biomarkers: GWAS (treated pts), RNA microarray (Disease & treated response)

4

key components of clinical pharmacology

- optimal use of existing meds
- evaluation of new drugs

5

what phase do most drugs fail?

phase 2

6

discovery phase

- consultation on selection of lead compounds
- assistance in preclinical pharm/tox studies
- consultation on SAR study
- participating in GO/NO GO decision
- assistance in formulation/pharmaceuticals
- participating in GLP/GMP/quality evaluation
- participating in pre-IND meeting & IND filing

7

development phase

- clinical PK/PD studies (phase 0-III)
- population PK
- dose-response modeling/simulation
-PG trial
-phase IV

8

preclinical pharmacology PK & bioavailability

- protocol
- analytical methods
- PK analysis
- statistical methods
- justification for bioavailability study
-discussion

9

clinical pharmacology PK & bioavailability

- protocol (ADME)
- analytical methods
- PK analysis
- statistical methods
- bioavailability study (blood level)
-individual study report

10

types of clinical trials

treatment
prevention
screening/early detection
diagnostic
genetics
QOL/supportive care

11

phase I primary objectives

15-30 people
- what dosage is safe
-how should treatment be given
- how does treatment affect the body

12

phase II primary obectives

<100 people
- dose treatment do what it is supposed to
- how does treatment affect the body

13

phase III

100-thousands
- compare new treatment with current standard

14

phase IV

hundreds- thousands
- usually takes place after drug is approved
- used to further evaluate long-term safety & efficacy

15

conclusion of phase I trial

toxicity- acute/ delayed
response- target for phase II
max tolerated dose

16

phase 0

-proof of concept in clinic setting
- target development

17

phase 0 trials need a

exploratory IND

18

microdose studies

PK or imaging as endpoints

19

pharmacologically relevant doses

doses higher than microdose; more safety data needed; PD enpoints

20

pharmacodynamic endpoint studies

PD biomarker endpoints

21

PD assay criteria

accuracy
dynamic range
precision
sensitivity
reproducibility
robustness

22

PD assay is required for

phase 0 trial

23

potential benefits of phase 0 trial

- early human trial w/ reduced pharm/tox data
- small # of patients
- relatively low cost
- facilitate rational drug discovery/lead selection
-streamline phase I trial & reduce development time

24

Phase 0 trial limitaions

- no data on efficacy or safety
- no intent to replace phase I
- not ideal for candidates w.out a defined target
- increased costs in PD assay development
- if the target is incorrectly ID, an effective drug may be eliminated
- PD effects are not necessarily shown in low doses & dose-dependent
- not for all agents