Bioequivalence and Bioavailability Forum

Hi everyone,

I’m working on the design of a study that needs to be done under both fasting and fed conditions. Normally these would be two separate studies, but to save time we’re thinking of running them together in a single 4-period study.

My question is: would it be acceptable to give all subjects the fasting treatments first (Periods 1–2) and then the fed treatments (Periods 3–4)? Or do we need to randomize subjects so that fasting and fed are mixed across periods?

For example:

A = Test, fasting
B = Reference, fasting
C = Test, fed
D = Reference, fed

Possible randomization options I’m considering:

Option 1:
S1: A → B → C → D
S2: B → C → D → A
S3: C → D → A → B
S4: D → A → B → C

Option 2:
S1: A → B → C → D
S2: B → A → D → C
S3: A → B → D → C
S4: B → A → C → D

Option 3:
S1: A → B → C → D
S2: B → A → D → C

Which approach would regulators (e.g. EMA) accept?

Also, would the same logic apply to studies of orally inhaled products where we compare “with charcoal” vs “without charcoal” (instead of fasting vs fed)?

Thanks in advance!

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Edit: Category changed; see also this post #1. [Helmut]