full replicate study for drug not highly variable - EMA perspective [Regulatives / Guidelines]
Background information:
We are working on designing a multiple-dose steady state Pharmacokinetic (PK) Bioequivalence (BE) study of an Immediate Release (IR) Solid Oral Dosage form on cancer patients for EMA submission. We are exploring alternate study design due to the inherent challenges related to the recruitment and retention of cancer patients in PK BE study and have following questions.
Question: To address the challenges related to recruitment of cancer patients in PK BE study, we want to plan a full replicate design study. Will the EMA agency accept this approach even if we are not suspecting the drug to be highly variable?
As per EMA guidance, “If an applicant suspects that a drug product can be considered as highly variable in its rate and/or extent of absorption, a replicate cross-over design study can be carried out.”
As per USFDA guidance “A replicate crossover study design (either partial or fully replicate) is appropriate for drugs whether the reference product is a highly variable drug or not. A replicate design can have the advantage of using fewer subjects compared to a non-replicate design, although each subject in a replicate design study would receive more treatments”.
We understand that widening criteria will be applied only to Cmax if we observe Swr > 0.294 or else conventional BE criteria will be applied. The reason we want to take this approach is to reduce the number of patients to be randomized in the trial.
We are working on designing a multiple-dose steady state Pharmacokinetic (PK) Bioequivalence (BE) study of an Immediate Release (IR) Solid Oral Dosage form on cancer patients for EMA submission. We are exploring alternate study design due to the inherent challenges related to the recruitment and retention of cancer patients in PK BE study and have following questions.
Question: To address the challenges related to recruitment of cancer patients in PK BE study, we want to plan a full replicate design study. Will the EMA agency accept this approach even if we are not suspecting the drug to be highly variable?
As per EMA guidance, “If an applicant suspects that a drug product can be considered as highly variable in its rate and/or extent of absorption, a replicate cross-over design study can be carried out.”
As per USFDA guidance “A replicate crossover study design (either partial or fully replicate) is appropriate for drugs whether the reference product is a highly variable drug or not. A replicate design can have the advantage of using fewer subjects compared to a non-replicate design, although each subject in a replicate design study would receive more treatments”.
We understand that widening criteria will be applied only to Cmax if we observe Swr > 0.294 or else conventional BE criteria will be applied. The reason we want to take this approach is to reduce the number of patients to be randomized in the trial.
Complete thread:
- full replicate study for drug not highly variable - EMA perspectiveAnkit Parikh 2024-07-11 04:40
- EMA: Full replicate study Helmut 2024-07-15 09:13