Пробный перевод (тест) по клиническим испытаниям медицинского препарата



Fingolimod is a sphingosine 1-phosphate receptor modulator indicated for the treatment of patients
with relapsing forms of multiple sclerosis (MS) to reduce the frequency of clinical exacerbations and to delay the accumulation of physical disability.


The Tmax of fingolimod is 12-16 hours. The apparent absolute oral bioavailability is 93%. Food intake does not alter Cmax or exposure (AUC) of fingolimod or fingolimod-phosphate. Therefore fingolimod may be taken without regard to meals. Steady-state blood concentrations are reached within 1 to 2 months following once-daily administration and steady-state levels are approximately 10-fold greater than with the initial dose.

Sample Size Calculations:

In a 2-way crossover, single dose, fasting bioequivalence study of fingolimod 3 x 0.5 mg capsules with 24 completed healthy subjects, the following geometric mean ratios (GMR) and intra-subject coefficients of variation (CV) were obtained:

Parameter       GMR (%)      CV (%)
Cmax                   98.19          6.11
AUC0-72             100.34          5.14

Assuming a GMR between 95% and 105%, to achieve an 80% power for demonstrating bioequivalence between the test and reference formulations (i.e. 90% CI of the GMR is within the limits of 80 – 125%) using the method presented in Hauschke D, Steinijans VW, Diletti E & Burke M. (Sample size determination for bioequivalence assessment  using a multiplicative model. J Pharmacokin Biopharm 1992; 20:557-561), the following sample sizes are required for a 2-way crossover study:
CV (%)       Sample Size
   10                     8
   20                    20
Consequently, a sample size of 26 subjects (with a minimum of 22 completing) has been selected for this study. In the event that the number of completing subjects falls below 22, replacement subjects may be recruited.

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