For bioequivalence studies of immediate-release and modified-release formulations, the US Food and Drug Administration FDAA) generally recommends using a single-dose study design, rather than a multiple-dose design, because the single-dose study is considered to be more sensitive.
It is pointed out that the interaction studies generally need to be of multiple-dose design.
Therefore the present subacute (28-day) study was carried out to evaluate a multiple dose study design and to compare the results with the common OECD design.
Comparison of the results demonstrated that the multiple dose (7×5) design led to a more reliable result than the OECD (4×10) design, despite the smaller total number of animals.
The second study, SNAB, was a two-part study, the first of which followed a typical multiple ascending dose design, and the second evaluated SERT occupancy using positron electron tomography.
This was a single centre study of randomised, double-blind, double-dummy, placebo controlled, 3-way multiple dose, cross-over design.
Antipsychotics were dosed within a specified range at clinician discretion, except in one study in which multiple fixed-dose design was used [ 16].
Forty-eight beef×Friesian cows formed eight replicates of six treatments in a 2 (no steroid versus steroid)×3 (none, single or multiple dose(s) of FSH) factorial design in which follicles were aspirated once weekly for 3 weeks.
Six subjects in the first, second and third cohorts received 3.6 mg, 7.2 mg, or 10.8 mg MSF, respectively, and two subjects in each cohort received placebo in an ascending single dose and a multiple dose randomized, double-blind, placebo-controlled design.
Although the study included multiple dose levels of LY, it was not designed to provide precise dose-response relationships because of limitations of sample size.
