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.