Designing a phase 1 clinical trial

Question 1

Determining PK linearity, F and safety. List the info you need from the pre-cliicl package

Answer 1

• Cl, Vd and T1/2 from rodent PK and Transporter and CYP affinity and F, use these to determine likely PK profile in man via PBPK scaling approach
• NOAEL in mice used to determine first in human dose via allometry

Question 2

Determining PK linearity, F and safety. Describe patient flow through the study

Answer 2

• Cross over design
• greater than 5 half life wash out period
• PK/PD data analysed by IRB before proceeding to the next dose level

Question 3

Determining PK linearity, F and safety: describe the PK/OD data

Answer 3

• 12 blood samples per dose
• urine (0-dose interval), metabolites, faeces
• PD: ECG (QT interval elongation), BP, HR, renal and kidney function, ask about side effects which may correlate to those presented by lab animals

Question 4

Following the success of the SAD study, the development team wants you to conduct a MAD study. Describe patient flow, key data you would use from the previous study

Answer 4

• Parallel study, 3 dose groups bracketing the EC50. IRB Required before proceeding to next dose group
• Need AUC and accumulation from the previous study to determine Cav,ss.
• Need side effects from previous study to determine if they are worsened by chronic dosing