Table 3.

Ratios and 90% confidence limits of des-CIC pharmacokinetic parameter estimates on Day 7 (per-protocol population).

Geometric least squares means for des-CIC
Variable	Treatment A 160 μg CIC with spacer (Test)	Treatment C 160 μg CIC no spacer (Reference)	Ratio [% Ref]	90% Confidence interval#
AUCτ (μg*h/L)	0.601	0.475	127	107–149
Cmax (μg/L)	0.190	0.123	155	132–181
Variable	Treatment B 80 μg CIC with spacer (Test)	Treatment C 160 μg CIC no spacer (Reference)	Ratio [% Ref]	90% Confidence interval#
AUCτ (μg*h/L)	0.599	0.475	126	106–149
Cmax (μg/L)	0.201	0.123	163	140–190

^#90% Confidence Interval for difference between the treatments. AUC, Area under the AUC_τ, AUC over the dosage interval τ (at steady-state).

For the ANOVA, sequence and period were considered as fixed and patient nested in a sequence as random effect, resulting in a 90% CI for the ratio of the expected means. Each PK characteristic was log-transformed prior to analysis and for each log-transformed variable, a 90% CI was computed for the difference of means between the treatments under comparison. The limits of the 90% CI on the log-scale were log-transformed resulting in confidence limits on the original scale for the ratio of geometric means expressed as percentages.