General BE topics [Design Issues]

posted by ElMaestro  – Denmark, 2017-06-06 02:20 (2488 d 08:06 ago) – Posting: # 17445
Views: 16,399

Hello VSL,

❝ 1 Half-life: Is half life independent of formulation effect? I mean, IR vs. MR products of the same substance. I am asking as protocol design depends a lot on it.


Half-life can refer to the intrinsic half-life, or to the apparent half-life (what you observe in practice, given the formulation etc). The latter is what guides it.

❝ 2. High variable drug substance vs. High variable drug products, Is there is any demarcation for protocol design aspects?


No. Observed CV is what matters.

❝ 3. If there are two strengths, say, tablet, 10 and 20 mg and 20 mg is RLD. The company wishes to market only 10 mg strength but 10 mg is not RLD. What should be RLD in BE study? Is comparison of 10mg x2 tablets (test) vs. 20mg RLD right?


2x10mg, probably, but you should contact OGD.

❝ 4. What is the minimum sample size for parallel group BE study?


Wrong question. You will most likely not show BE in any parallel study at the minimum sample size. If you try, it might be unethical.

❝ 5. For endogenous substances, how many and for how much time duration (-48 hours etc.) baseline samples should be collected?


There is no rule if it isn't mentioned in the product-specific guidance.

❝ 6 Why passing ratio is high for BE studies (especially pivotal studies) conducted in India compared to foreign countries? Is there any geographical/ethnic/staff expertise/deliberate effect?


Wow, this one is toxic. :-D:-D:-D
Perhaps companies are powering their studies higher e.g. 90% rather than 80% when conducting them in India??
VSL, sometimes failure is not an option and sometimes shortcuts are taken to cut down effort/cost or to stay within agreed timelines. Google Semler, GVK Bio, MTR... I am sure you know the issues already.
Anyways, I never saw official passing statistics for India compared to other places. Can you show a reference?

❝ 7. For some therapeutic class drugs BE study, I have not seen any PD effect. Example, For Antihypertensive drugs, no change in BP in vital recordings even at/around Cmax. Please explain.


Some modern antihypertensives often have little effect in healthy volunteers. They are very, very safe. E.g. Telmisartan, Perindopril etc. But be aware you have nothing to compare with in BE trials since both arms are active and no placebo recording is available. If there is an effect you won't see it. Comparing BP at baseline to BP at Tmax is not particularly informative.

Have a good day.

Pass or fail!
ElMaestro

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