Bioequivalence and Bioavailability Forum

❝ ❝ What are the sample size “benefits” or “efficiencies” of undertaking this study as a replicate CO design (e.g., Test 50 x 2; Ref 50 x 2) versus a 2-way CO (Test 100 x 2; Ref 100 x 2). Any help would be much appreciated.

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❝ None. In both cases you risk a Refuse-to-Receive because you deviate from the guidance (recommending the 20 µg strength administered as a 60 µg dose). Theoretically you could deviate from the guidance if you have good reasons for doing so and initiate a Controlled Correspondence. However, I think your chance is close to nil because the guidance offers the option of biowaivers for the strengths 13, 25, 50, 75, 88, 100, 112, 125, 137, 150, and 175 µg. Only if you can’t perform a study with the 20 µg strength – because you don’t have in your line of strengths – you can give it a try.

Hi Helmut

Many thanks for your response. This is my first time responding on this forum. I am not even sure if I need to reply before or after your text. Is it possible you misunderstood my question? What I meant to ask is if I do replicate crossover, i.e., 50 subjects on Test x 2 periods and 50 subjects on Reference x 2 periods (replicate crossover, 2X2X4) as opposed to 100 subjects on test x 1 period and 100 subjects on Reference x 1 period (2X2X2), do I gain any sample size (or power) efficiency using FDA 3-tests (per PSG) for Levothyroxine? Many thanks!