The purposes of the amendment were to: • Remove requirement that body weight be ≥30 kg. • Clarify that the primary endpoints comprise PK assessments from data collected on Day 7 and Day 14. • Revise justification for dose selection using an updated popPK model. • Add electrocardiograms to safety endpoints. • Add the following: Following completion of study drug dosing on Day 14 or early discontinuation, the subject will be transitioned to local standard of care for 14 days during the Follow-up Period. • Addition of inclusion and exclusion criteria. • Clarify instructions for administration of study drug by specifying when study drug will be taken. • Provide additional instructions for recording date/time of each dose and actions required for missed study drug doses and missed visits/poor compliance. • Differentiate timing of PK blood samples between Days 7 and 14. Sodium heparin vacutainer collection tubes were specified. • Add bone fracture and hematologic abnormalities as adverse event of special interest. • Add urine pregnancy tests for female participants who had experienced menarche to protocol-required safety laboratory assessments. • Add Tanner staging to the physical examination. • Remove the measurement of electrocardiogram intervals, and specify that electrocardiograms were to be read and interpreted centrally by a pediatric cardiologist. • Define the pharmacodynamic population to include participants who received at least 1 dose of study drug and had sufficient pH data to support calculation of pharmacodynamic parameters. • Include a potential popPK analysis of interim data from a subset of participants prior to completion of enrollment to assess whether plasma exposure in pediatric participants aged ≥6 to <12 years was within the range observed in adults receiving the same dose. • Add appendices for contraceptive guidance, Tanner Staging criteria and growth charts.

The purposes of the amendment were to: • Change exclusion criterion for creatinine from >2 mg/dL (>177 µmol/L) to >0.8 mg/dL (>70 µmol/L). • Change the reporting period for pregnancy during administration of active study drug from ‘after Visit 2 or within 4 weeks of the last dose of active study drug’ to ‘after Visit 2 or within 2 weeks of the last dose of active study drug’. • Remove the requirement for an 8-hour fast before obtaining a glucose measurement. • Require participants to be dressed in light clothing and without shoes when body weight was measured. • Remove the telephone call at the Day 14 in-clinic visit from the schedule of assessments.