- Changes to study eligibility: pregnancy test results and use of medications known to inhibit CYP2D6 were to be evaluated prior to randomisation, and not prior to dosing; pathological bone involvement was to be evaluated in consultation with the central bone reviewer; acid glucosidase activity was to be evaluated in leukocytes, and not whole blood; documentation of anemia due to causes other than GD1 was to be based on folate, iron, and vitamin B-12 only, and not RBC. - A T2-weighted MRI of the femur was to be obtained, and not short T1 inversion recovery (STIR). Bone disease assessments were also added to the safety endpoints and safety analyses for completeness.

- Listed duration of each subjects in study. Updated risk/benefit & dose rationale information. Extension in screening period. Opened enrollment of broader subject population, including subjects who were >65 years of age, had received ERT more recently or had a prior history of cancer. - Removed contraception requirement for male subjects & allowed use of certain hormonal contraceptives in female subjects. - Modified restriction of CYP2D6 inhibitors use, temporary use of CYP3A4 inducers & strong inhibitors of CYP2D6 & CYP3A4 after completion of dose adjustment in each treatment period & exception for chronic medications after completion of dose adjustment in LTTP. Outlined specific actions were taken during temporary use based on type of concomitant medication, subject's CYP2D6 phenotype & treatment period. - Added second dose adjustment to 150 mg BID LTTP for subjects not achieved target trough conc. >5 ng/mL. - Added serial PK sampling after second dose adjustment, with 24-hour sampling for subjects receiving 150 mg BID. -Reduced PK sampling after single 50-mg dose on Day 1 & during study periods when subjects had received 50 mg BID or 100 mg BID. -Added and updated PK sampling in concomitant medications that had potential to alter Genz-112638 exposure based on revised PK sampling scheme. -Moved Wk 43 clinical laboratory tests & ECGs to Wk 45 & Wk 47,to better align with timing of second dose adjustment. -Added optional blood collection for pharmacogenetics analyses, to permit evaluation of emerging clinical issues. -Added GM3 as an exploratory marker to confirm lack of inhibition of the GL-1 pathway. Revised time points for biomarkers & exploratory biomarkers to reduce total number of measurements. -Added measurement of spleen & liver volume of subjects withdrew prior Week 26 & missing data was handled for subjects withdrew prior to Week 39. -Changed AE causality assessment as per National Cancer Institute Common Toxicology Criteria for Adverse Events.

- Planned enrollment was reduced from 36 subjects to 28 subjects. Underlying sample size assumptions were unchanged, and study remained adequately powered for primary efficacy endpoint (85% power for 28 subjects compared with a previous estimate of 92% power for 36 subjects) and all secondary endpoints. - Broadened target subject population to included following subjects, as data from the Phase 2 study (GZGD00304) and/or Gaucher Registry (for subjects on Cerezyme) suggested that such subjects might benefit from eliglustat therapy: Spleen volume as low as 6 MN (previously 8 MN) Platelet count as high as 130,000/mm³ (previously 100,000/mm³) - Radiological evidence of bone involvement in the absence of clinical symptoms (previously any documented bone involvement was an exclusion) - The analysis of organ volume measurements in subjects who had a repeat measurement (due to a >30% increase in volume on the original measurement) was modified such that only the repeat measurement was to be used in statistical analyses, rather than the average of the original and repeat measurements. This change was made because the original >30% increase in organ volume could potentially be due to a transient condition unrelated to Gaucher disease or treatment response. - Study visits in the LTTP were scheduled relative to the start of that study period, and not relative to the start of the Primary Analysis Period, given the duration of time required to complete specified assessments between study periods. - A PK sample was to be obtained at the Early Withdrawal visit only for subjects who withdrew due to an AE.

- The principal change was the implementation of additional monitoring in subjects with a peak plasma concentration ≥150 ng/mL. In such subjects, the dose of eliglustat was to be temporarily interrupted while the subject returned to the site for further evaluations. The nature of these evaluations and any subsequent dose modifications were dependent on the subject's observed peak plasma concentration and the treatment period in which it occurred, any concurrent safety findings, and the feasibility of adjusting any concomitant medications. Management of subjects with peak plasma concentrations ≥150 ng/mL. - Added 2-hour post-dose PK sampling at additional study visits. - Added a secondary analysis of within-subject changes in spleen volume, hemoglobin, liver volume, and platelet count for all randomised subjects with 39 weeks of treatment on eliglustat in the Primary Analysis Period (eliglustat group) or LTTP (placebo group). - Added an exception for temporary use of medications known to prolong QTc interval, after completion of the dose adjustment in either treatment period. - Clarified that, for the purpose of concomitant medication management, CYP2D6 indeterminate metabolizers would be considered poor metabolizers if neither allele was known to be active and non-poor metabolizer if 1 allele was known to be active. - Expanded the definition of MEOIs to include syncope from any cause, and not just syncope that may be a result of arrhythmia. Clarified that MEOIs occurring prior to initiation of study treatment were not required to be reported. - Clarified which assessments were required to be repeated during re-screening.

- Sample size, which had been adjusted downward to 28 subjects, was reverted to 36 subjects. - Extended the total study duration (due to the delay in enrollment). - Added an exploratory analysis of bone biomarkers (to investigate the role of impaired bone formation vs. accelerated bone resorption in the pathophysiology of Gaucher-related osteopenia and the mechanism of eliglustat effects on bone). - Updated / clarified concomitant medication guidance: - Added a definition of concomitant medications. - Added requirements to (1) notify the Sponsor's Medical Monitor in the event of temporary use of a CYP3A4 inducer and (2) interrupt the dose of eliglustat during temporary use of strong inhibitors of CYP2D6 or CYP3A4. - Added a statement about the potential for eliglustat to increase the exposure of P gp substrate drugs. - Clarified that the only subjects who should be on chronic therapy when entering the Long-term Treatment Period are CYP2D6 non-poor metabolizers, and that chronic therapy in these subjects is limited to a strong inhibitor of CYP2D6 or CYP3A4 (but not both). - Clarified that PK samples would be collected only in the event of changes in chronic use (not temporary use) of strong inhibitors of CYP2D6 or CYP3A4 or inducers of CYP3A4, and further clarified that discontinuation of a chronic medication would necessitate such PK sampling. - Added annual neurological examinations from Week 78 through the end of study, to allow detection of clinical signs or symptoms suggestive of nerve conduction abnormalities during LTTP. - Reduced the frequency of ECGs to every 6 months (previously every 3 months) during the Long-term Treatment Period, as this is deemed sufficient to monitor cardiac safety and will reduce the burden on subjects. - Updated risk/benefit information based on recently completed clinical studies.

- Updated concomitant medication guidance as based on the information provided in the investigator letter.