Statistical analysis
treatment-emergent adverse
REGRESSION, DISEASE, SKIN LESION
A minimum of 50 patients per treatment arm was estimated to provide a precision estimate of 10% with 95% CI, based on an anticipated cure rate of 85% at 12 months. Five patients were added to allow for 10% loss of patients during follow-up, resulting in a sample size of 55 patients per treatment arm and an overall sample size of 110. This was a non-comparative trial.A computer-generated randomization code was used for patient treatment allocation to one of the two treatment arms in a 1:1 ratio. A set of individual opaque, sealed, and sequentially numbered envelopes was provided to the treatment sites, with one envelope per patient containing the identity of the treatment.The primary efficacy analysis was performed on the modified intention-to-treat (mITT, all randomized patients receiving at least one dose of treatment; in case of erroneous treatment allocation, the actual treatment received was to be used in the analysis) and per protocol (PP, patients in the mITT with no major protocol deviations) population sets. Missing efficacy outcome at 12 months was considered as treatment failure. A sensitivity analysis of the primary efficacy analysis was performed using the sets of completers (subsets of patients belonging to the mITT or PP who had an outcome at 12 months follow-up i.e., patients with missing efficacy outcome at 12 months were excluded). The primary efficacy endpoint was reported as the proportion of cured patients with a corresponding 95% confidence interval (CI). No interim efficacy analysis was planned; a data safety monitoring board monitored the study to ensure the safety of the participants.Skin lesion score, distribution grade, and density grade were presented graphically, and Kaplan-Meier survival curves were produced to demonstrate the time to treatment failure and the time to complete cure by treatment arm and for the overall population.Univariate logistic regression was used to assess the association of baseline PKDL grade, initial disease status, duration of PKDL onset, age, and sex with the risk of failure. The results were presented as odds ratios with the corresponding 95% confidence interval.The safety analysis was performed on the mITT set, based on treatment-emergent adverse events (TEAEs). The numbers and percentages of patients presenting TEAEs were summarized by treatment arm and overall. All AEs were categorized by system organ class (SOC) and preferred term (PT) according to the Medical Dictionary for Regulatory Activities (MedDRA) Version 24.0, severity (based on the CTCAE v4.03), seriousness and by causal relationship to study drugs. This trial is registered at ClinicalTrials.gov, NCT03399955.For the pharmacokinetic analysis, a skin to plasma concentration ratio was calculated for each individual for whom a paired skin drug concentration and plasma drug concentration (measured on the same end of treatment day) was available.