Hello everybody,
I'm running an NCA for the following study design for a customer:
Phase 1 randomized study to assess pharmacokinetics of multiple (MAD) ascending doses of oral drug X in healthy participants.
The endpoints are plasma concentration-time curves (area under the concentration-time curve [AUC]), maximum observed plasma concentration (Cmax), time to maximum plasma concentration (Tmax), and terminal half-life (t½), among others.
Extensive plasma sampling is applied to day 1 and 14 to characterize the PK of first and second dose. On days 3 to 13 predose sample is collected per day.
The PK after multiple doses was assessed after last administered dose, the second dose of Day 14.
Here comes the issue: the drug is administered from Day 1 to Day 14 in a BID regime (= total daily dose administered as 2 doses per day). The first dose is given in the morning and 8 hours later, the second dose is given. Then they dose again after 16 hours.
This makes it difficult for us to run the NCA with a regular Tau, as we already know how to do it within WNL.
We need to run NCA analysis across two doses as well as with separate doses (Dose 1 and Dose 2)
I would like to know your possible/best approaches to execute this analysis within basic WNL-NCA object (no modelling/simulations).
Related with separate doses we are thinking about putting a column for Dose 1/Dose 2 and also including this column in the "sort" within NCA (apart from subject, visit, cohort), so we will compute PK parameters for each subject/visit/cohort/dose, but we are not sure how to work with "across two doses" as there isn't a regular Tau.
Example based in our case study: one subject, for a particular visit and cohort has an actual dose of X mg, but this means this dose is given twice, so in total this subject is taking 2X mg with the posology explained above (Dose 1 = X mg + Dose 2 = X mg).
Due to confidentiality reasons I can't post any part of the data nor the project here, but let's start the discussion and I'll see if we can create any mock data to solve this issue.
I'll answer any doubt just in case I haven't explained very well.
Thanks in advance to everybody who contributes.
Aramis Rojas
Edited by aramisrojas_, 04 August 2023 - 07:08 AM.
