Statistics
PK/PD
EVENTS
Since the primary endpoints were safety and tolerability, no formal sample size estimations were performed. A sample size of six participants (four in the nedosiran arm and two in the placebo arm) was considered sufficient to provide an initial assessment of the safety and PK/PD profile of nedosiran in patients with PH3. Analyses of safety, stone events, and fluid intake were evaluated in all participants exposed to study intervention, analyzed according to the intervention received. Urine analyses were evaluated in the modified intent-to-treat population (mITT), defined as all participants who were randomly assigned, received a partial or full dose of study intervention, and had post-dose 24-h Uox values collected at ≥ 2 consecutive visits. Pharmacokinetic analysis was assessed in all participants who received a full dose of nedosiran and had ≥ 1 evaluable post-dose PK assessment.Three prespecified sensitivity analyses were performed for the primary PD endpoint using BSA-adjusted 24-h Uox excretion for all participants, all Uox excretion concentrations (including those not meeting completeness criteria), and last observation carried forward (LOCF) imputation for missing 24-h Uox excretion data if they were missing or if no measurement met the completeness criteria at a scheduled visit (N.B., if the Day 29 sample was missing or incomplete, baseline was not carried forward).