Purpose. The overall aim of the present study was to investigate retrospect
ively the feasibility and utility of model-based clinical trial simulation
as applied to the clinical development of naratriptan with effect measured
on a categorical scale.
Methods. A PK-PD model for naratriptan was developed by using information g
athered from previous naratriptan and sumatriptan preclinical and clinical
trials. The phase IIa naratriptan data were used to check the PK-PD model i
n its ability to describe future data. A further PK-PD model was developed
by using the phase IIa naratriptan data, and a phase IIb trial was designed
by simulation with the use of Matlab. The design resulting from clinical t
rial simulation was compared with that derived by using D-optimal design.
Results. The PK-PD model showed reasonable agreement with the data observed
in the phase IIa naratriptan clinical trial. Clinical trial simulation res
ulted in a design with four or five arms at 0 mg, 2.5 and/or 5 mg, 10 mg, a
nd 20 mg, PD measurements to be taken at 0, 2, and 4 or 6 li and at least 1
50 patients per arm, A sub-D-optimal design resulted in two dosing arms at
0 and 10 mg and PD measurements to be taken at I and 2 h.
Conclusions. Clinical trial simulation is a useful tool for the quantitativ
e assessment of the influence of the controllable factors and is the only t
ool for the quantitative assessment of the uncontrollable factors on the po
wer of a clinical trial.