2 way fasting and 3 way fed pilot results analysis [Study As­sess­ment]

posted by unique_one – India, 2015-10-17 11:33 (3085 d 13:15 ago) – Posting: # 15569
Views: 6,555

Dear All,

We conducted a fasting (2-way crossover) and fed (3 way reference replicate scaled average BE) pilot studies for one of the molecules.

N=16 for fasting pilot and N=18 for fed pilot.

The results are as below:

Fasting Pilot:

Parameter     Ratios  CI 90_L  CI 90_U  Power   IS CV (%)
Ln(Cmax)      98.58    77.47   128.41   0.4194   43.13
Ln(AUC last)  93.86    82.05   110.32   0.8307   22.51
Ln(AUC INF)   89.75    72.47   111.56   0.5223   33.65


Fed pilot:

Parameter  SwR   Reference ISCV(%)
Cmax      0.333      33.13%
AUCt      0.244      26.32%
AUCi      0.325      35.48%

Parameter  T/R ratio  theta  95% upper CI
Cmax          0.86     0.79     0.044
AUCi          0.82     0.79     0.143

Parameter RLSM  Test LSM  Ref GM    Test GM    T/R        90% CI       power
AUCt      8.350   8.220   4712.223  4170.343  87.23%  74.25%-106.25%    0.69


Below are the considerations:
  1. As per the literature, this molecule has a food effect and food decreases bioavailability of Cmax and AUC, by approximately 40% - 45% and 20% - 23%, respectively.

  2. This molecule shows high variablity when administered with food and therefore a reference replicate pilot study was planned.
Queries:
  1. Looking to the above results, it is seen that the Test product is behaving fast in comparison to the Reference in fasting pilot study. However in contradiction, the test product is behaving slow in comparison to the reference in fed pilot study.

    Do we need to do any change in the formulation at this point? Because any change (fastening/slowing) will effect both fasting and fed pivotal studies.

  2. What would be the sample size recommended for fasting 2 way crossover pivotal study and pivotal fed reference replicate scaled average BE study?

  3. As per my dissolution media results, the product is a bit slower in one of the dissolution media. Any correlation from this aspect?

  4. What should be the best strategy to plan the pivotal studies for above molecule with respect to the current formulation and process and the pivotal studies design so as to get good results in the pivotal studies?

Thanks everyone in Advance.
Unique_One.


Edit: Category changed. Why are you shouting as us? All-capitals ⇒ lowercase. Use series of blanks enclosed in BBCodes instead of tabs[Helmut]

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