for theparison of the AUCs of M with M-FP-mono and M-AZE-mo respective thereby  glucitol assuming a true treatment ratio of and a coefficient of variation of 0. For this scenario a sample size of 4 subjects was calculated for each study to achieve 0 power. To account for potential drop-outs and for robustness in case of deviations from these assumptions a total of 0 subjects were randomised into each study. Metrics indicating peak exposure total exposure and elimination were analyzed by using a cross-over analysis of variance after logarithmic transformation. The model included fixed effects treatme period and sequence. The covariance structure over the treatments was unspecified.

A Satterthwaite approximation was applied to the degrees of freedom. This model was  TAK-875 used to provide geometric mean point estimates and 0-confidence intervals for ratios M /M-FP-mono and M /FP-BI or M /M-AZE-mono or M /Astelin , respectively. 0 The Authors British Journal of Clinical Pharmacology The British Pharmacological Society Accepted Article Safety and Tolerability Assessments Safety evaluations included the assessment and documentation of the subjectswell being throughout the study in terms of natu severity and incidence of adverse events. Medical histo ECG recordin haematolo blood chemist and urinalysis variables were assessed and a full physical examination performed as criteria for study enrolment. Vital signs were monitored at the beginning and end of the study. RESULTS Subject demographics and disposition Baseline demographic data of the study populations are given in Table .

Both study populations had similar demographic characteristics. Study : 0 subjects were randomised and exposed to at least one dose of study medication. Two subjects  Fesoterodine 286930-03-8 discontinued the study prematurely; one subject because of a positive drug screening and another withdrew consent. Twenty-eight subjectspleted all three study periods. Nine of them did not qualify for the PP analysis due to observed self-administration issues on at least one occasion . Because dosing technique could affect PK resul PK analysis used the PP population of 9 subjects and safety data included 0 subjects. A sensitivity analysis that included patients with documented administration issues yielded results consistent with the PP population and is included in the online supplement . Study : 0 subjects were randomised and all subjectspleted the three study periods. Four subjects were excluded from the PP analysis because of protocol 1 The Authors British Journal of Clinical Pharmacology The British Pharmacological Society Accepted Article deviations with possible relevance for the PK analyses: Two had noted administration issues and two had local nasal findings with possible impact on local  buy naratriptan absorption . PK results refer to a PP population of 6 subjects and safety data to 0 subjects.

Safety and Tolerability All investigational treatments were well tolerated . Pharmacokinetics Mean concentration-time profiles of FP and AZE of all five investigational nasal sprays are displayed in Figures and . Geometric and arithmetic mean PK parameter rang standard  organelles deviations and ANOVA derived coefficients of variations are presented in Tables and , for FP and A respectively. Table lists the mean point estimates along .