Statistics
The population analyzed for pain, tolerability, preference, skin
imaging, and pharmacodynamic endpoints included all randomized subjects
(n = 24 subjects). The population analyzed for PK parameters and PK
modelling included injections in which no spillage during treatment
administration was reported (n = 43 injections). Repeated pain injection
data (VAS and FPSR) were analyzed with a repeated measures ANOVA with
fixed factors treatment, method, time, treatment by method, treatment by
time, method by time, treatment by method by time, random factor subject
and repeated factor time within subject by treatment by method. The
injection pain score of the Mantoux intradermal injection at screening
was used as covariate. Single measured pain insertion data (VAS and
FPSR) were analyzed with a repeated measures model ANOVA with fixed
factors treatment, method, treatment by method, and repeated factor
method within subject. The insertion pain score of the Mantoux
intradermal injection at screening was used as covariate. Repeated
cytokines data were analyzed with a repeated measures ANOVA with fixed
factors method, time, method by time, repeated factor time within
subject and the baseline as covariate. The contrasts of interest were
s.c. vs. i.d. and s.c. vs. i.d. within compound. For imaging analyses a
subset of data was used as some variables were zero in some conditions
or timepoints. If applicable, the factors of the mixed model were
adjusted.