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Trial record 11 of 11 for:    eliglustat

A Study of Eliglustat Tartrate (Genz-112638) in Patients With Gaucher Disease to Evaluate Once Daily Versus Twice Daily Dosing (EDGE)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01074944
First Posted: February 24, 2010
Last Update Posted: February 6, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )
Results First Submitted: October 7, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Gaucher Disease
Intervention: Drug: Eliglustat tartrate

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study was conducted at 45 centers in 17 countries between 1 June 2010 and 6 October 2015. A total of 219 participants were screened, out of which 170 entered into the lead in period (LIP). Remaining 48 participants were screen failures and 1 participant withdrew before entering into the LIP.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participant flow divided into 4 periods: LIP:to assess randomization criteria. Primary analysis period (PAP):to assess therapeutic efficacy at 2 dosing regimen in randomized participants. Long-term treatment period (LTTP): to assess long term efficacy. Extended treatment period (ETP):those who were non-randomized after LIP continued in this period.

Reporting Groups
  Description
LIP, Eliglustat All participants (except in Japan) received eliglustat 50 mg, twice daily (BID) on Day 1 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual pharmacokinetics (PK) data for up to 78 weeks. All participants in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks.
PAP, Eliglustat: Once Daily All participants who were randomized after meeting all randomization criteria (defined as: no more than 1 bone crisis and was free of other clinically symptomatic bone disease [such as bone pain attributable to osteonecrosis and/or pathological fractures) during the first 6 months of the LIP; mean hemoglobin level of ≥11 g/dL [if female] and ≥12 g/dL [if male]; mean platelet count ≥100,000/mm^3; spleen volume ≤10 times of normal; liver volume ≤1.5 times of normal; had a dose of 50 mg BID or 100 mg BID of eliglustat for at least 4 months and a peak (2-hour) Genz-99067 plasma concentration of <50 ng/mL) after either 26, 52 or 78 weeks of LIP received eliglustat capsules at the total daily dose (TDD) of 100 mg or 200 mg (the TDD they were on before randomization) once daily (QD) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
PAP, Eliglustat: Twice Daily All participants who were randomized after meeting all randomization criteria (defined as: no more than 1 bone crisis and was free of other clinically symptomatic bone disease [such as bone pain attributable to osteonecrosis and/or pathological fractures) during the first 6 months of the LIP; mean hemoglobin level of ≥11 g/dL [if female] and ≥12 g/dL [if male]; mean platelet count ≥100,000/mm^3; spleen volume ≤10 times of normal; liver volume ≤1.5 times of normal; had a dose of 50 mg BID or 100 mg BID of eliglustat for at least 4 months and a peak (2-hour) Genz-99067 plasma concentration of <50 ng/mL) after either 26, 52 or 78 weeks of LIP, received eliglustat at the TDD 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
LTTP, Eliglustat All participants who entered PAP continued their blinded randomized treatment for first 4 weeks. Participants who at Week 52 of PAP maintained their therapeutic goals (defined as: no more than 2 bone crisis during PAP [with no more than 1 bone crisis during either first 6 months or later 6 months of PAP] and is free of other clinically symptomatic bone disease during PAP; hemoglobin level not decreased by >1.5 g/dL from Baseline for PAP [defined as last available assessment prior to randomization]; platelet count not decreased by >25% from Baseline for PAP; spleen volume not increased by 25% from Baseline for PAP; liver volume not increased by >20% from Baseline for PAP), continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) QD till the end of the study. The participants who did not maintain all their therapeutic goals continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) BID till the end of the study.
ETP, Eliglustat All participants who did not meet all the randomization criteria at Week 78 of the LIP continued in the ETP and received eliglustat capsules at the same dose as they were receiving at the end of LIP till the end of the study.

Participant Flow for 4 periods

Period 1:   Lead-in Period (up to 78 Weeks)
    LIP, Eliglustat   PAP, Eliglustat: Once Daily   PAP, Eliglustat: Twice Daily   LTTP, Eliglustat   ETP, Eliglustat
STARTED   170 [1]   0   0   0   0 
COMPLETED   157   0   0   0   0 
NOT COMPLETED   13   0   0   0   0 
Adverse Event                2                0                0                0                0 
Non-Compliance With Protocol                1                0                0                0                0 
Pregnancy                4                0                0                0                0 
Withdrawal by Subject                6                0                0                0                0 
[1] LIP conducted to assess randomization criteria of all participants in single reporting arm.

Period 2:   Primary Analysis Period (up to 52 Weeks)
    LIP, Eliglustat   PAP, Eliglustat: Once Daily   PAP, Eliglustat: Twice Daily   LTTP, Eliglustat   ETP, Eliglustat
STARTED   0   65 [1]   66 [1]   0   0 
COMPLETED   0   54   60   0   0 
NOT COMPLETED   0   11   6   0   0 
Adverse Event                0                2                3                0                0 
Treatment Failure                0                6                1                0                0 
Withdrawal by Subject                0                1                1                0                0 
Pregnancy                0                1                0                0                0 
Non-Compliant to Protocol                0                1                1                0                0 
[1] Participants who were randomized after LIP received treatment in PAP.

Period 3:   Long Term Treatment
    LIP, Eliglustat   PAP, Eliglustat: Once Daily   PAP, Eliglustat: Twice Daily   LTTP, Eliglustat   ETP, Eliglustat
STARTED   0   0   0   121 [1]   0 
COMPLETED   0   0   0   95   0 
NOT COMPLETED   0   0   0   26   0 
Adverse Event                0                0                0                3                0 
Lost to Follow-up                0                0                0                2                0 
Transitioned to Commercial Eliglustat                0                0                0                18                0 
Entered in Period, But Not Treated                0                0                0                1                0 
Withdrawal by Subject                0                0                0                2                0 
[1] Participants who completed PAP (114) including those who considered as treatment failure in PAP (7).

Period 4:   Extended Treatment (up to 42 Months)
    LIP, Eliglustat   PAP, Eliglustat: Once Daily   PAP, Eliglustat: Twice Daily   LTTP, Eliglustat   ETP, Eliglustat
STARTED   0   0   0   0   25 [1] 
COMPLETED   0   0   0   0   20 
NOT COMPLETED   0   0   0   0   5 
Pregnancy                0                0                0                0                2 
Transitioned to Commercial Eliglustat                0                0                0                0                3 
[1] Participants who were failed to meet the randomization criteria during the lead-in period.



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All treated (AT) analysis set included all participants who received at least 1 dose of eliglustat during LIP.

Reporting Groups
  Description
All Participants All participants who received treatment in LIP (eliglustat 50 mg BID on Day 1 titrated up to 100 mg BID [50 or 100 mg capsules] based on their individual PK data for up to 78 weeks [except for the participants in Japan]. Participants in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID [50 or 100 mg capsules] based on their individual PK data for up to 78 weeks) and assessed for randomization.

Baseline Measures
   All Participants 
Overall Participants Analyzed 
[Units: Participants]
 170 
Age 
[Units: Years]
Mean (Standard Deviation)
 37.7  (15.1) 
Gender 
[Units: Participants]
Count of Participants
 
Female      81  47.6% 
Male      89  52.4% 


  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   PAP: Percentage of Participants Who Remained Stable for 52 Weeks During the PAP   [ Time Frame: PAP Baseline up to the end of PAP (Week 52) ]

Measure Type Primary
Measure Title PAP: Percentage of Participants Who Remained Stable for 52 Weeks During the PAP
Measure Description Participants were considered as stable if they met all of the following criteria: 1) no more than 2 bone crisis during PAP (with no more than 1 bone crisis during either the first 6 months or the later 6 months of the period), and were free of other clinically symptomatic bone disease during the entire 52-week PAP; 2) hemoglobin level not decreased >1.5 g/dL from Baseline for PAP; 3) platelet count not decreased >25% from Baseline for PAP; 4) spleen volume (in multiples of normal [MN]) did not increase >25% from Baseline for PAP; 5) liver volume (in MN) did not increase >20% from Baseline for PAP. Baseline for PAP was defined as the last assessment prior to randomization.
Time Frame PAP Baseline up to the end of PAP (Week 52)  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on per protocol (PP) population which included all participants who were at least 80% compliant with investigational medicinal product (IMP) dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations.

Reporting Groups
  Description
PAP, Eliglustat: Once Daily All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
PAP, Eliglustat: Twice Daily All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).

Measured Values
   PAP, Eliglustat: Once Daily   PAP, Eliglustat: Twice Daily 
Participants Analyzed 
[Units: Participants]
 56   59 
PAP: Percentage of Participants Who Remained Stable for 52 Weeks During the PAP 
[Units: Percentage of participants]
Number (95% Confidence Interval)
 80.4 
 (67.6 to 89.8) 
 83.1 
 (71.0 to 91.6) 


Statistical Analysis 1 for PAP: Percentage of Participants Who Remained Stable for 52 Weeks During the PAP
Groups [1] All groups
Statistical Test Type [2] Non-Inferiority or Equivalence
Difference in Percentage Stable [3] -2.7
95% Confidence Interval -17.7 to 11.9
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Eliglustat QD treatment was declared non-inferior to BID treatment if the lower bound of the 95% confidence interval (CI) for the difference was within the non-inferiority margin of -0.15 (or -15%).
[3] Other relevant estimation information:
  No text entered.



2.  Secondary:   PAP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26 and 52   [ Time Frame: Baseline, Week 26, Week 52 ]

Measure Type Secondary
Measure Title PAP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26 and 52
Measure Description No text entered.
Time Frame Baseline, Week 26, Week 52  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PP population included all participants who were at least 80% compliant with IMP dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. Here 'n' signifies number of participants with available data at specified time points for each arm respectively.

Reporting Groups
  Description
PAP, Eliglustat: Once Daily All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
PAP, Eliglustat: Twice Daily All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).

Measured Values
   PAP, Eliglustat: Once Daily   PAP, Eliglustat: Twice Daily 
Participants Analyzed 
[Units: Participants]
 56   59 
PAP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26 and 52 
[Units: g/dL]
Mean (Standard Deviation)
   
Baseline (n=56, 59)   13.641  (1.214)   13.691  (1.273) 
Week 26 (n=56, 57)   13.677  (1.377)   13.946  (1.509) 
Week 52 (n=56, 59)   13.605  (1.432)   13.824  (1.442) 

No statistical analysis provided for PAP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26 and 52



3.  Secondary:   PAP: Mean Platelet Count at Baseline, Weeks 26, 52   [ Time Frame: Baseline, Week 26, Week 52 ]

Measure Type Secondary
Measure Title PAP: Mean Platelet Count at Baseline, Weeks 26, 52
Measure Description No text entered.
Time Frame Baseline, Week 26, Week 52  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PP population included all participants who were at least 80% compliant with IMP dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. Here 'n' signifies number of participants with available data at specified time points for each arm respectively.

Reporting Groups
  Description
PAP, Eliglustat: Once Daily All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
PAP, Eliglustat: Twice Daily All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).

Measured Values
   PAP, Eliglustat: Once Daily   PAP, Eliglustat: Twice Daily 
Participants Analyzed 
[Units: Participants]
 56   59 
PAP: Mean Platelet Count at Baseline, Weeks 26, 52 
[Units: Platelets*10^9 /L]
Mean (Standard Deviation)
   
Baseline (n=56, 59)   204.01  (81.49)   171.09  (63.50) 
Week 26 (n=56, 57)   195.75  (66.65)   173.94  (65.61) 
Week 52 (n=56, 59)   207.20  (80.62)   176.10  (62.01) 

No statistical analysis provided for PAP: Mean Platelet Count at Baseline, Weeks 26, 52



4.  Secondary:   PAP: Mean Spleen Volume at Baseline, Weeks 26, 52   [ Time Frame: Baseline, Week 26, Week 52 ]

Measure Type Secondary
Measure Title PAP: Mean Spleen Volume at Baseline, Weeks 26, 52
Measure Description No text entered.
Time Frame Baseline, Week 26, Week 52  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PP population included all participants who were at least 80% compliant with IMP dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. Here 'n' signifies number of participants with available data for specified category for each arm respectively.

Reporting Groups
  Description
PAP, Eliglustat: Once Daily All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
PAP, Eliglustat: Twice Daily All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).

Measured Values
   PAP, Eliglustat: Once Daily   PAP, Eliglustat: Twice Daily 
Participants Analyzed 
[Units: Participants]
 56   59 
PAP: Mean Spleen Volume at Baseline, Weeks 26, 52 
[Units: MN]
Mean (Standard Deviation)
   
Baseline (n= 39, 45)   3.309  (1.465)   3.787  (1.623) 
Week 26 (n= 39, 45)   3.066  (1.299)   3.504  (1.365) 
Week 52 (n= 39, 45)   3.017  (1.381)   3.394  (1.305) 

No statistical analysis provided for PAP: Mean Spleen Volume at Baseline, Weeks 26, 52



5.  Secondary:   PAP: Mean Liver Volume at Baseline, Weeks 26, 52   [ Time Frame: Baseline, Week 26 and Week 52 ]

Measure Type Secondary
Measure Title PAP: Mean Liver Volume at Baseline, Weeks 26, 52
Measure Description No text entered.
Time Frame Baseline, Week 26 and Week 52  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PP population included all participants who were at least 80% compliant with IMP dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations.

Reporting Groups
  Description
PAP, Eliglustat: Once Daily All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
PAP, Eliglustat: Twice Daily All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).

Measured Values
   PAP, Eliglustat: Once Daily   PAP, Eliglustat: Twice Daily 
Participants Analyzed 
[Units: Participants]
 56   59 
PAP: Mean Liver Volume at Baseline, Weeks 26, 52 
[Units: MN]
Mean (Standard Deviation)
   
Baseline (n=56, 59)   0.981  (0.187)   1.040  (0.198) 
Week 26 (n=56, 59)   0.987  (0.190)   1.024  (0.179) 
Week 52 (n=56, 59)   0.970  (0.170)   1.009  (0.196) 

No statistical analysis provided for PAP: Mean Liver Volume at Baseline, Weeks 26, 52



6.  Secondary:   PAP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26 and Week 52   [ Time Frame: Baseline, Week 26, Week 52 ]

Measure Type Secondary
Measure Title PAP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26 and Week 52
Measure Description Chitotriosidase biomarker was assayed from plasma.
Time Frame Baseline, Week 26, Week 52  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PP population which all participants who were at least 80% compliant with IMP dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. Here, 'n' signifies number of participants with available data for specified category for each arm respectively.

Reporting Groups
  Description
PAP, Eliglustat: Once Daily All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
PAP, Eliglustat: Twice Daily All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).

Measured Values
   PAP, Eliglustat: Once Daily   PAP, Eliglustat: Twice Daily 
Participants Analyzed 
[Units: Participants]
 56   59 
PAP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26 and Week 52 
[Units: nmol/hr/mL]
Mean (Standard Deviation)
   
Baseline (n=55, 59)   1523.7  (2556.6)   1554.9  (1895.0) 
Week 26 (n=52, 54)   1279.6  (2328.1)   1242.0  (2012.6) 
Week 52 (n=54, 55)   1076.6  (1855.8)   1170.1  (1683.3) 

No statistical analysis provided for PAP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26 and Week 52



7.  Secondary:   PAP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26 and Week 52   [ Time Frame: Baseline, Week 26 and week 52 ]

Measure Type Secondary
Measure Title PAP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26 and Week 52
Measure Description GL-1 on DBS biomarker was assayed from dried blood spot (DBS).
Time Frame Baseline, Week 26 and week 52  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PP population included all participants who were at least 80% compliant with IMP dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. Here 'n' signifies number of participants with available data at specified time points for each arm respectively.

Reporting Groups
  Description
PAP, Eliglustat: Once Daily All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
PAP, Eliglustat: Twice Daily All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).

Measured Values
   PAP, Eliglustat: Once Daily   PAP, Eliglustat: Twice Daily 
Participants Analyzed 
[Units: Participants]
 56   59 
PAP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26 and Week 52 
[Units: mcg/mL]
Mean (Standard Deviation)
   
GL-1 on DBS: Baseline (n=54, 55)   2.257  (0.835)   2.425  (1.378) 
GL-1 on DBS: week 26 (n=54, 54)   2.481  (1.037)   2.563  (1.100) 
GL-1 on DBS: week 52 (n=53, 55)   2.853  (1.383)   2.707  (1.443) 

No statistical analysis provided for PAP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26 and Week 52



8.  Secondary:   PAP: Mean Biomarker Macrophage Inflammatory Protein-1 Beta (MIP1-beta) Value at Baseline, Weeks 26, 52   [ Time Frame: Baseline, Week 26, Week 52 ]

Measure Type Secondary
Measure Title PAP: Mean Biomarker Macrophage Inflammatory Protein-1 Beta (MIP1-beta) Value at Baseline, Weeks 26, 52
Measure Description MIP1-beta biomarker was assayed from plasma.
Time Frame Baseline, Week 26, Week 52  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PP population included all participants who were at least 80% compliant with dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. Here, 'n' signifies number of participants with available data for specified category for each arm respectively.

Reporting Groups
  Description
PAP, Eliglustat: Once Daily All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
PAP, Eliglustat: Twice Daily All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).

Measured Values
   PAP, Eliglustat: Once Daily   PAP, Eliglustat: Twice Daily 
Participants Analyzed 
[Units: Participants]
 56   59 
PAP: Mean Biomarker Macrophage Inflammatory Protein-1 Beta (MIP1-beta) Value at Baseline, Weeks 26, 52 
[Units: pg/mL]
Mean (Standard Deviation)
   
Baseline (n=54, 58)   77.7  (74.4)   118.8  (156.3) 
Week 26 (n=52, 54)   74.5  (68.0)   121.0  (204.4) 
Week 52 (n=54, 55)   81.3  (82.8)   117.9  (165.3) 

No statistical analysis provided for PAP: Mean Biomarker Macrophage Inflammatory Protein-1 Beta (MIP1-beta) Value at Baseline, Weeks 26, 52



9.  Secondary:   PAP: Bone Mineral Density (BMD) at Baseline and Week 52   [ Time Frame: Baseline, Week 52 ]

Measure Type Secondary
Measure Title PAP: Bone Mineral Density (BMD) at Baseline and Week 52
Measure Description BMD measurements of the spine and bilateral femur were acquired by dual-energy x-ray absorptiometry (DXA) scan.
Time Frame Baseline, Week 52  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PP population included all participants who were at least 80% compliant with IMP dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. Here, 'n' signifies number of participants with available data at specified time points for each arm respectively.

Reporting Groups
  Description
PAP, Eliglustat: Once Daily All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
PAP, Eliglustat: Twice Daily All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).

Measured Values
   PAP, Eliglustat: Once Daily   PAP, Eliglustat: Twice Daily 
Participants Analyzed 
[Units: Participants]
 56   59 
PAP: Bone Mineral Density (BMD) at Baseline and Week 52 
[Units: G/cm^2]
Mean (Standard Deviation)
   
Lumbar Spine: Baseline (n=51, 55)   1.073  (0.177)   1.081  (0.172) 
Lumbar Spine: Week 52 (n=51, 55)   1.089  (0.183)   1.086  (0.177) 
Left Femur: Baseline (n=48, 47)   0.979  (0.219)   1.000  (0.199) 
Left Femur: Week 52 (n=48, 47)   0.972  (0.211)   0.990  (0.196) 
Right Femur: Baseline (n=48, 47)   0.971  (0.217)   0.996  (0.184) 
Right Femur: Week 52 (n=48, 47)   0.967  (0.213)   0.981  (0.177) 

No statistical analysis provided for PAP: Bone Mineral Density (BMD) at Baseline and Week 52



10.  Secondary:   PAP: Total T-Scores for BMD at Baseline and Week 52   [ Time Frame: Baseline, Week 52 ]

Measure Type Secondary
Measure Title PAP: Total T-Scores for BMD at Baseline and Week 52
Measure Description Images of the spine and bilateral femur were obtained by DXA to determine T-score for each bone area and total bone mineral density. The T-score bone density categories were: normal (score >-1), osteopenia (score -2.5 to <=-1), and osteoporosis (score <= -2.5).
Time Frame Baseline, Week 52  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PP population included all participants who were at least 80% compliant with IMP dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. Here 'n' signifies number of participants with available data at specified time points for each arm respectively.

Reporting Groups
  Description
PAP, Eliglustat: Once Daily All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
PAP, Eliglustat: Twice Daily All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).

Measured Values
   PAP, Eliglustat: Once Daily   PAP, Eliglustat: Twice Daily 
Participants Analyzed 
[Units: Participants]
 56   59 
PAP: Total T-Scores for BMD at Baseline and Week 52 
[Units: T-score]
Mean (Standard Deviation)
   
Lumbar Spine T-Score: Baseline (n=49, 52)   -0.722  (1.415)   -0.771  (1.217) 
Lumbar Spine T-Score: Week 52 (n=49, 52)   -0.580  (1.476)   -0.717  (1.271) 
Left Femur T-Score: Baseline (n=46, 44)   -0.459  (1.385)   -0.368  (1.347) 
Left Femur T-Score: Week 52 (n=46, 44)   -0.509  (1.342)   -0.441  (1.326) 
Right Femur T-score: Baseline (n=46, 44)   -0.574  (1.327)   -0.382  (1.282) 
Right Femur T-score: Week 52 (n=46, 44)   -0.607  (1.308)   -0.530  (1.236) 

No statistical analysis provided for PAP: Total T-Scores for BMD at Baseline and Week 52



11.  Secondary:   PAP: Total Z-scores for BMD at Baseline and Week 52   [ Time Frame: Baseline, Week 52 ]

Measure Type Secondary
Measure Title PAP: Total Z-scores for BMD at Baseline and Week 52
Measure Description Images of the spine and bilateral femur were obtained by DXA to determine Z-score for each bone area and total bone mineral density. The Z-score bone density categories are: normal (score >-2) and below normal (score <=-2).
Time Frame Baseline, Week 52  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PP population included all participants who were at least 80% compliant with IMP dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. Here 'n' signifies number of participants with available data for specified category for each arm respectively

Reporting Groups
  Description
PAP, Eliglustat: Once Daily All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
PAP, Eliglustat: Twice Daily All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).

Measured Values
   PAP, Eliglustat: Once Daily   PAP, Eliglustat: Twice Daily 
Participants Analyzed 
[Units: Participants]
 56   59 
PAP: Total Z-scores for BMD at Baseline and Week 52 
[Units: Z-score]
Mean (Standard Deviation)
   
Lumbar Spine Z-scores: Baseline (n=51, 55)   -0.492  (1.517)   -0.609  (1.166) 
Lumbar Spine Z-scores: Week 52 (n=51, 55)   -0.324  (1.559)   -0.555  (1.202) 
Left Femur Z-scores: Baseline (n= 48, 47)   -0.171  (1.316)   -0.115  (1.294) 
Left Femur Z-scores: Week 52 (n= 48, 47)   -0.202  (1.250)   -0.183  (1.274) 
Right Femur Z-scores: Baseline (n= 48, 47)   -0.235  (1.251)   -0.140  (1.194) 
Right Femur Z-scores: Week 52 (n= 48, 47)   -0.248  (1.214)   -0.260  (1.141) 

No statistical analysis provided for PAP: Total Z-scores for BMD at Baseline and Week 52



12.  Secondary:   PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52.   [ Time Frame: Baseline, Week 26 and Week 52 ]

Measure Type Secondary
Measure Title PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52.
Measure Description Mobility, i.e., ability to walk was assessed as a part of Gaucher disease assessment in participants. In this outcome, number of participants with their different mobility status along with the use of mobility aids (unrestricted mobility, walks with difficulty, walks with orthopaedic aid, requires wheelchair, bedridden) at specified time points were reported.
Time Frame Baseline, Week 26 and Week 52  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PP population included all participants who were at least 80% compliant with IMP dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations.

Reporting Groups
  Description
PAP, Eliglustat: Once Daily All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
PAP, Eliglustat: Twice Daily All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).

Measured Values
   PAP, Eliglustat: Once Daily   PAP, Eliglustat: Twice Daily 
Participants Analyzed 
[Units: Participants]
 56   59 
PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52. 
[Units: Participants]
   
MS, Unrestricted: Baseline (n=56, 59)   49   59 
MS, Unrestricted: Week 26 (n=55, 57)   46   56 
MS, Unrestricted: Week 52 (n=51, 58)   50   57 
MS, Walks with Difficulty: Baseline (n=56, 59)   6   0 
MS, Walks with Difficulty: Week 26 (n=55, 57)   8   1 
Ms, Walks with Difficulty: Week 52 (n=51, 58)   5   1 
MS, Walks with Orthopedic Aid: Baseline (n=56, 59)   1   0 
MS, Walks with Orthopedic Aid: Week 26 (n=55, 57)   1   0 
MS, Walks with Orthopedic Aid: Week 52 (n=51, 58)   0   0 
MS, Required Wheelchair: Baseline (n=56, 59)   0   0 
MS, Required Wheelchair: Week 26 (n=55, 57)   0   0 
MS, Required Wheelchair: Week 52 (n=51, 58)   1   0 
MS, Bedridden: Baseline (n=56, 59)   0   0 
MS, Bedridden: Week 26 (n=55, 57)   0   0 
MS, Bedridden: Week 52 (n=51, 58)   0   0 

No statistical analysis provided for PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52.



13.  Secondary:   PAP: Number of Participants With Bone Crises at Baseline, Weeks 26 and 52   [ Time Frame: Baseline, Week 26, and Week 52 ]

Measure Type Secondary
Measure Title PAP: Number of Participants With Bone Crises at Baseline, Weeks 26 and 52
Measure Description Bone crisis was assessed as a part of Gaucher disease assessment in participants. Acute, excruciating episodic bone pain is characteristic of Gaucher bone crisis, which typically causes debilitation lasting several days or longer and requires treatment with immobilization, hydration, and opioid analgesics. Participants were categorized as 0= no bone crisis, 1= 1 bone crisis, and 2= 2 bone crises during the assessment period. In this outcome, number of participants with different bone crises levels at specified time points were reported.
Time Frame Baseline, Week 26, and Week 52  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PP population included all participants who were at least 80% compliant with IMP dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations.

Reporting Groups
  Description
PAP, Eliglustat: Once Daily All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
PAP, Eliglustat: Twice Daily All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).

Measured Values
   PAP, Eliglustat: Once Daily   PAP, Eliglustat: Twice Daily 
Participants Analyzed 
[Units: Participants]
 56   59 
PAP: Number of Participants With Bone Crises at Baseline, Weeks 26 and 52 
[Units: Participants]
   
Bone Crisis (0): Baseline (n=56, 59)   55   57 
Bone Crisis (0): Week 26 (n=55,57)   54   56 
Bone Crisis (0): Week 52 (n=56, 58)   56   57 
Bone Crisis (1): Baseline (n=56, 59)   1   2 
Bone Crisis (1): Week 26 (n=55, 57)   0   1 
Bone Crisis (1): Week 52 (n=56, 58)   0   1 
Bone Crisis (2): Baseline (n=56, 59)   0   0 
Bone Crisis (2): week 26 (n=55, 57)   1   0 
Bone Crisis (2): week 52 (n=56, 58)   0   0 

No statistical analysis provided for PAP: Number of Participants With Bone Crises at Baseline, Weeks 26 and 52



14.  Secondary:   PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52   [ Time Frame: Baseline, Week 26, and Week 52 ]

Measure Type Secondary
Measure Title PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52
Measure Description Bone pain was assessed as a part of Gaucher disease assessment in participants. Participants were categorized as none (no bone pain), very mild bone pain, mild bone pain, moderate bone pain, severe bone pain and extreme bone pain during the past 4 weeks. In this outcome, number of participants with different level of bone pain during the past 4 weeks at specified time points were reported.
Time Frame Baseline, Week 26, and Week 52  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PP population included all participants who were at least 80% compliant with IMP dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations.

Reporting Groups
  Description
PAP, Eliglustat: Once Daily All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
PAP, Eliglustat: Twice Daily All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).

Measured Values
   PAP, Eliglustat: Once Daily   PAP, Eliglustat: Twice Daily 
Participants Analyzed 
[Units: Participants]
 56   59 
PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 
[Units: Participants]
   
None: Baseline (n=56, 59)   42   49 
None: Week 26 (n=55, 57)   42   49 
None: Week 52 (n=56, 58)   41   45 
Very Mild: Baseline (n=56, 59)   2   1 
Very Mild: Week 26 (n=55, 57)   3   4 
Very Mild: Week 52 (n=56, 58)   3   7 
Mild: Baseline (n=56, 59)   7   3 
Mild: Week 26 (n=55, 57)   5   3 
Mild: Week 52 (n=56, 58)   6   2 
Moderate: Baseline (n=56, 59)   4   5 
Moderate: Week 26 (n=55, 57)   5   1 
Moderate: Week 52 (56, 58)   6   2 
Severe: Baseline (n=56, 59)   1   1 
Severe: Week 26 (n=55, 57)   0   0 
Severe: Week 52 (n=56, 58)   0   2 
Extreme: Baseline (n=56, 59)   0   0 
Extreme: Week 26 (n=55, 57)   0   0 
Extreme: Week 52 (n=56, 58)   0   0 

No statistical analysis provided for PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52



15.  Secondary:   PAP: Total Bone Marrow Burden Score (BMB) at Baseline and Week 52   [ Time Frame: Baseline, Week 52 ]

Measure Type Secondary
Measure Title PAP: Total Bone Marrow Burden Score (BMB) at Baseline and Week 52
Measure Description BMB Score was measured using magnetic resonance imaging (MRI), range from 0 (no abnormalities) to 8 points (severe disease) for the lumbar spine and from 0 (no abnormalities) to 8 points (severe disease) for the femurs. The total score was calculated as the sum of scores for femur and lumbar spine regions which ranged from 0 (no abnormalities) -16 (severe disease) points. A higher BMB score signified more severe bone marrow involvement.
Time Frame Baseline, Week 52  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PP population included all participants who were at least 80% compliant with IMP dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. Here, 'n' signifies number of participants with available data at specified time points for each arm respectively.

Reporting Groups
  Description
PAP, Eliglustat: Once Daily All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
PAP, Eliglustat: Twice Daily All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).

Measured Values
   PAP, Eliglustat: Once Daily   PAP, Eliglustat: Twice Daily 
Participants Analyzed 
[Units: Participants]
 56   59 
PAP: Total Bone Marrow Burden Score (BMB) at Baseline and Week 52 
[Units: BMB Score]
Mean (Standard Deviation)
   
BMB Score: Baseline (n=52, 49)   8.276  (2.891)   9.136  (2.784) 
BMB Score: Week 52 (n=51, 48)   7.971  (2.689)   8.705  (2.633) 

No statistical analysis provided for PAP: Total Bone Marrow Burden Score (BMB) at Baseline and Week 52



16.  Secondary:   LIP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26, 52 and 78   [ Time Frame: Baseline, Week 26, Week, 52, and Week 78 ]

Measure Type Secondary
Measure Title LIP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26, 52 and 78
Measure Description No text entered.
Time Frame Baseline, Week 26, Week, 52, and Week 78  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on all treated (AT) analysis set which included all participants who received at least 1 dose of eliglustat during lead in period. Here 'n' signifies number of participants with available data at specified time points.

Reporting Groups
  Description
LIP: Eliglustat All participants (except in Japan) received eliglustat 50 mg BID on Day 1 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. All participants in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks.

Measured Values
   LIP: Eliglustat 
Participants Analyzed 
[Units: Participants]
 170 
LIP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26, 52 and 78 
[Units: g/dL]
Mean (Standard Deviation)
 
Baseline (n=170)   13.435  (1.560) 
Week 26 (n=163)   13.443  (1.382) 
Week 52 (n=74)   13.434  (1.497) 
Week 78 (n=41)   13.329  (1.528) 

No statistical analysis provided for LIP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26, 52 and 78



17.  Secondary:   LIP: Mean Platelet Count at Baseline, Weeks 26, 52 and 78   [ Time Frame: Baseline, Week 26, Week 52, Week 78 ]

Measure Type Secondary
Measure Title LIP: Mean Platelet Count at Baseline, Weeks 26, 52 and 78
Measure Description No text entered.
Time Frame Baseline, Week 26, Week 52, Week 78  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on AT analysis set which included all participants who received at least 1 dose of eliglustat during LIP. Here ‘n’ signifies number of participants with available data at specified time points.

Reporting Groups
  Description
LIP: Eliglustat All participants (except in Japan) received eliglustat 50 mg BID on Day 1 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. All participants in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks.

Measured Values
   LIP: Eliglustat 
Participants Analyzed 
[Units: Participants]
 170 
LIP: Mean Platelet Count at Baseline, Weeks 26, 52 and 78 
[Units: Platelets*10^9 /L]
Mean (Standard Deviation)
 
Baseline (n=170)   178.653  (92.732) 
Week 26 (n=163)   180.021  (85.426) 
Week 52 (n=74)   176.378  (79.880) 
Week 78 (n=41)   168.720  (74.117) 

No statistical analysis provided for LIP: Mean Platelet Count at Baseline, Weeks 26, 52 and 78



18.  Secondary:   LIP: Mean Liver Volume at Baseline, Weeks 26, 52 and 78   [ Time Frame: Baseline, Week 26, Week 52, Week 78 ]

Measure Type Secondary
Measure Title LIP: Mean Liver Volume at Baseline, Weeks 26, 52 and 78
Measure Description No text entered.
Time Frame Baseline, Week 26, Week 52, Week 78  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on AT participants which included all participants who received at least 1 dose of eliglustat during lead in period. Here, 'n' signifies number of participants with available data at specified time points.

Reporting Groups
  Description
LIP: Eliglustat All participants (except in Japan) received eliglustat 50 mg BID on Day 1 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. All participants in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks.

Measured Values
   LIP: Eliglustat 
Participants Analyzed 
[Units: Participants]
 170 
LIP: Mean Liver Volume at Baseline, Weeks 26, 52 and 78 
[Units: MN]
Mean (Standard Deviation)
 
Baseline (n=170)   1.044  (0.243) 
Week 26 (n=149)   1.040  (0.229) 
Week 52 (n=68)   1.059  (0.242) 
Week 78 (n=39)   1.062  (0.236) 

No statistical analysis provided for LIP: Mean Liver Volume at Baseline, Weeks 26, 52 and 78



19.  Secondary:   LIP: Mean Spleen Volume at Baseline, Weeks 26, 52 and 78   [ Time Frame: Baseline, Week 26, Week 52, Week 78 ]

Measure Type Secondary
Measure Title LIP: Mean Spleen Volume at Baseline, Weeks 26, 52 and 78
Measure Description No text entered.
Time Frame Baseline, Week 26, Week 52, Week 78  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on AT participants which included all participants who received at least 1 dose of eliglustat during lead in period. Here 'n' signifies number of participants with available data at specified time points.

Reporting Groups
  Description
LIP: Eliglustat All participants (except in Japan) received eliglustat 50 mg BID on Day 1 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. All participants in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks.

Measured Values
   LIP: Eliglustat 
Participants Analyzed 
[Units: Participants]
 170 
LIP: Mean Spleen Volume at Baseline, Weeks 26, 52 and 78 
[Units: MN]
Mean (Standard Deviation)
 
Baseline (n=119)   4.448  (2.314) 
Week 26 (n=106)   3.840  (1.801) 
Week 52 (n=52)   4.094  (1.767) 
Week 78 (n=30)   4.088  (2.089) 

No statistical analysis provided for LIP: Mean Spleen Volume at Baseline, Weeks 26, 52 and 78



20.  Secondary:   LIP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26, 52, and 78   [ Time Frame: Baseline, Week 26, Week 52 and Week 78 ]

Measure Type Secondary
Measure Title LIP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26, 52, and 78
Measure Description Chitotriosidase biomarker was assayed from plasma.
Time Frame Baseline, Week 26, Week 52 and Week 78  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on AT analysis set which included all participants who received at least 1 dose of eliglustat during LIP. Here ‘n’ signifies number of participants with available data at specified time points.

Reporting Groups
  Description
LIP: Eliglustat All participants (except in Japan) received eliglustat 50 mg, twice daily (BID) on Day 1 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. All participants in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks.

Measured Values
   LIP: Eliglustat 
Participants Analyzed 
[Units: Participants]
 170 
LIP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26, 52, and 78 
[Units: nmol/hr/mL]
Mean (Standard Deviation)
 
Chitotriosidase: Baseline (n=170)   2437.92  (3291.25) 
Chitotriosidase: week 26 (n=157)   1802.93  (2529.29) 
Chitotriosidase: week 52 (n=72)   1755.70  (2649.14) 
Chitotriosidase: week 78 (n=41)   1677.02  (2718.75) 

No statistical analysis provided for LIP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26, 52, and 78



21.  Secondary:   LIP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26, Week 52, and Week 78   [ Time Frame: Baseline, Week 26, Week 52 and Week 78 ]

Measure Type Secondary
Measure Title LIP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26, Week 52, and Week 78
Measure Description GL-1 on DBS biomarker was assayed from dried blood spot.
Time Frame Baseline, Week 26, Week 52 and Week 78  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on AT analysis set which included all participants who received at least 1 dose of eliglustat during LIP. Here ‘n’ signifies number of participants with available data at specified time points.

Reporting Groups
  Description
LIP: Eliglustat All participants (except in Japan) received eliglustat 50 mg, twice daily (BID) on Day 1 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. All participants in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks.

Measured Values
   LIP: Eliglustat 
Participants Analyzed 
[Units: Participants]
 170 
LIP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26, Week 52, and Week 78 
[Units: mcg/mL]
Mean (Standard Deviation)
 
GL-1 on DBS: Baseline (n=159)   4.358  (2.155) 
GL-1 on DBS: Week 26 (n=144)   2.340  (0.868) 
GL-1 on DBS: Week 52 (n=68)   2.279  (0.730) 
GL-1 on DBS: Week 78 (n=39)   2.495  (1.500) 

No statistical analysis provided for LIP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26, Week 52, and Week 78



22.  Secondary:   LIP: Mean Biomarker (MIP1-beta) Value at Baseline, Week 78   [ Time Frame: Baseline and Week 78 ]

Measure Type Secondary
Measure Title LIP: Mean Biomarker (MIP1-beta) Value at Baseline, Week 78
Measure Description MIP1-beta biomarker was assayed from plasma.
Time Frame Baseline and Week 78  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on AT analysis set which included all participants who received at least 1 dose of eliglustat during LIP. Here ‘n’ signifies number of participants with available data at specified time points.

Reporting Groups
  Description
LIP: Eliglustat All participants (except in Japan) received eliglustat 50 mg, twice daily (BID) on Day 1 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. All participants in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks.

Measured Values
   LIP: Eliglustat 
Participants Analyzed 
[Units: Participants]
 170 
LIP: Mean Biomarker (MIP1-beta) Value at Baseline, Week 78 
[Units: pg/mL]
Mean (Standard Deviation)
 
MIP-1beta: Baseline (n=170)   142.433  (125.961) 
MIP-1beta: Week 78 (n=41)   132.180  (189.454) 

No statistical analysis provided for LIP: Mean Biomarker (MIP1-beta) Value at Baseline, Week 78



23.  Secondary:   LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78   [ Time Frame: Baseline, Week 26, Week 52, Week 78 ]

Measure Type Secondary
Measure Title LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78
Measure Description Mobility, i.e., ability to walk was assessed as a part of Gaucher disease assessment in participants. In this outcome, number of participants with their different mobility status along with the use of mobility aids (unrestricted mobility, walks with difficulty, walks with orthopaedic aid, requires wheelchair, bedridden) at specified time points were reported.
Time Frame Baseline, Week 26, Week 52, Week 78  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on AT analysis set which included all participants who received at least 1 dose of eliglustat during LIP.

Reporting Groups
  Description
LIP: Eliglustat All participants (except in Japan) received eliglustat 50 mg, twice daily (BID) on Day 1 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. All participants in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks.

Measured Values
   LIP: Eliglustat 
Participants Analyzed 
[Units: Participants]
 170 
LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78 
[Units: Participants]
 
MS,Unrestricted: Baseline (n=163)   146 
MS,Unrestricted: Week 26 (n=161)   153 
MS,Unrestricted: Week 52 (n=72)   70 
MS,Unrestricted: Week 78 (n= 41)   39 
MS, Walks With Difficulty: Baseline (n=163)   12 
MS, Walks With Difficulty: Week 26 (n=161)   6 
MS, Walks With Difficulty: Week 52 (n=72)   1 
MS, Walks With Difficulty: Week 78 (n=41)   2 
MS, Walks With Orthopedic Aid: Baseline (n=163)   3 
MS, Walks With Orthopedic Aid: Week 26 (n=161)   1 
MS, Walks With Orthopedic Aid: Week 52 (n=72)   0 
MS, Walks With Orthopedic Aid: Week 78 (n=41)   0 
MS, Required wheelchair: Baseline (n=163)   2 
MS, Required wheelchair: Week 26 (n=161)   1 
MS, Required wheelchair: Week 52 (n=72)   1 
MS, Required wheelchair: Week 78 (n=41)   0 
MS, Bedridden: Baseline (n=163)   0 
MS, Bedridden: Week 26 (n=161)   0 
MS, Bedridden: Week 52 (n=72)   0 
MS, Bedridden: Week 78 (n=41)   0 

No statistical analysis provided for LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78



24.  Secondary:   LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78   [ Time Frame: Baseline, Week 26, Week 52, Week 78 ]

Measure Type Secondary
Measure Title LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78
Measure Description Bone crises was assessed as a part of Gaucher disease assessment in participants. Acute, excruciating episodic bone pain is characteristic of Gaucher bone crises, which typically causes debilitation lasting several days or longer and requires treatment with immobilization, hydration, and opioid analgesics. Participants were categorized as 0= no bone crisis, 1= 1 bone crisis, 2= 2 bone crises, 6= 6 bone crises, and 24= 24 bone crises during the assessment period. In this outcome, number of participants with different bone crises levels at specified time points were reported.
Time Frame Baseline, Week 26, Week 52, Week 78  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on AT analysis set which included all participants who received at least 1 dose of eliglustat during LIP.

Reporting Groups
  Description
LIP: Eliglustat All participants (except in Japan) received eliglustat 50 mg, twice daily (BID) on Day 1 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. All participants in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks.

Measured Values
   LIP: Eliglustat 
Participants Analyzed 
[Units: Participants]
 170 
LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78 
[Units: Participants]
 
Bone Crisis (0): Baseline (n=162)   151 
Bone Crisis (0): Week 26 (n=162)   159 
Bone Crisis (0): Week 52 (n=72)   72 
Bone Crisis (0): Week 78 (n=41)   41 
Bone Crisis (1): Baseline (n=162)   8 
Bone Crisis (1): Week 26 (n=162)   3 
Bone Crisis (1): Week 52 (n=72)   0 
Bone Crisis (1): Week 78 (n=41)   0 
Bone Crisis (2): Baseline (n=162)   1 
Bone Crisis (2): Week 26 (n=162)   0 
Bone Crisis (2): Week 52 (n=72)   0 
Bone Crisis (2): Week 78 (n=41)   0 
Bone Crisis (6): Baseline (n=162)   1 
Bone Crisis (6): Week 26 (n=162)   0 
Bone Crisis (6): Week 52 (n=72)   0 
Bone Crisis (6): Week 78 (n=41)   0 
Bone Crisis (24): Baseline (n=162)   1 
Bone Crisis (24): Week 26 (n=162)   0 
Bone Crisis (24): Week 52 (n=72)   0 
Bone Crisis (24): Week 78 (n=41)   0 

No statistical analysis provided for LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78



25.  Secondary:   LIP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78   [ Time Frame: Baseline, Week 26, Week 52, Week 78 ]

Measure Type Secondary
Measure Title LIP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78
Measure Description Bone pain was assessed as a part of Gaucher disease assessment in participants. Participants were categorized as none (no bone pain), very mild bone pain, mild bone pain, moderate bone pain, severe bone pain and extreme bone pain. In this outcome, number of participants with different type of bone pain during the past 4 weeks at specified time points were reported.
Time Frame Baseline, Week 26, Week 52, Week 78  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on AT analysis set which included all participants who received at least 1 dose of eliglustat during LIP.

Reporting Groups
  Description
LIP: Eliglustat All participants (except in Japan) received eliglustat 50 mg, twice daily (BID) on Day 1 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. All participants in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks.

Measured Values
   LIP: Eliglustat 
Participants Analyzed 
[Units: Participants]
 170 
LIP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78 
[Units: Participants]
 
None: Baseline (n=163)   112 
None: Week 26 (n=161)   125 
None: Week 52 (n=72)   62 
None: Week 78 (n=41)   39 
Very Mild: Baseline (n=163)   17 
Very Mild: Week 26 (n=161)   14 
Very Mild: Week 52 (n=72)   4 
Very Mild: Week 78 (n=41)   1 
Mild: Baseline (n=163)   22 
Mild: Week 26 (n=161)   10 
Mild: Week 52 (n=72)   3 
Mild: Week 78 (n=41)   0 
Moderate: Baseline (n=163)   8 
Moderate: Week 26 (n=161)   10 
Moderate: Week 52 (n=72)   3 
Moderate: Week 78 (n=41)   1 
Severe: Baseline (n=163)   4 
Severe: Week 26 (n=161)   2 
Severe: Week 52 (n=72)   0 
Severe: Week 78 (n=41)   0 
Extreme: Baseline (n=163)   0 
Extreme: Week 26 (n=161)   0 
Extreme: Week 52 (n=72)   0 
Extreme: Week 78 (n=41)   0 

No statistical analysis provided for LIP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78



26.  Secondary:   LTTP: Percentage of Participants Who Maintained a Stable Bone Criterion ,Hemoglobin Level, Platelet Count, Liver Volume and Spleen Volume at 1 Year and 2 Years   [ Time Frame: 1 Year, 2 Years ]

Measure Type Secondary
Measure Title LTTP: Percentage of Participants Who Maintained a Stable Bone Criterion ,Hemoglobin Level, Platelet Count, Liver Volume and Spleen Volume at 1 Year and 2 Years
Measure Description Participant were considered as stable if they met the following criteria: hemoglobin level did not decrease >1.5 g/dL from baseline for PAP, platelet count does not decrease >25% below Baseline for PAP, liver volume does not increase >20% above Baseline for PAP, spleen volume does not increase >25% above Baseline for PAP. Baseline for PAP was defined as last available assessment prior to randomization.
Time Frame 1 Year, 2 Years  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on intent to treat (ITT) population which included all participants who received at least 1 dose of eliglustat after randomization. Here ‘n’ signifies number of participants with available data at specified time points.

Reporting Groups
  Description
LTTP: Eliglustat All participants who entered PAP continued their blinded randomized treatment for first 4 weeks. Participants who at Week 52 of PAP maintained their therapeutic goals (defined as: no more than 2 bone crisis during PAP [with no more than 1 bone crisis during either first 6 months or later 6 months of PAP] and is free of other clinically symptomatic bone disease during PAP; hemoglobin level not decreased by >1.5 g/dL from Baseline for PAP [defined as last available assessment prior to randomization]; platelet count not decreased by >25% from Baseline for PAP; spleen volume not increased by 25% from Baseline for PAP; liver volume not increased by >20% from Baseline for PAP), continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) QD till the end of the study. The participants who did not maintain all their therapeutic goals continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) BID till the end of the study.

Measured Values
   LTTP: Eliglustat 
Participants Analyzed 
[Units: Participants]
 121 
LTTP: Percentage of Participants Who Maintained a Stable Bone Criterion ,Hemoglobin Level, Platelet Count, Liver Volume and Spleen Volume at 1 Year and 2 Years 
[Units: Percentage of participants]
Number (95% Confidence Interval)
 
Bone Criterion Stable at 1 year (n=104)   92.3 
 (85.4 to 96.6) 
Bone Criterion Stable at 2 years (n=32)   84.4 
 (67.2 to 94.7) 
Hemoglobin Level Stable at 1 year (n=104)   92.3 
 (85.4 to 96.6) 
Hemoglobin Level Stable at 2 years (n=32)   81.3 
 (63.6 to 92.8) 
Platelet Count Stable at 1 year (n=104)   93.3 
 (86.6 to 97.3) 
Platelet Count Stable at 2 years (n=32)   84.4 
 (67.2 to 94.7) 
Liver Volume Stable at 1 year (n=103)   93.2 
 (86.5 to 97.2) 
Liver Volume Stable at 2 years (n=31)   83.9 
 (66.3 to 94.5) 
Spleen Volume Stable at 1 year (n=72)   95.8 
 (88.3 to 99.1) 
Spleen Volume Stable at 2 years (n=20)   95.0 
 (75.1 to 99.9) 

No statistical analysis provided for LTTP: Percentage of Participants Who Maintained a Stable Bone Criterion ,Hemoglobin Level, Platelet Count, Liver Volume and Spleen Volume at 1 Year and 2 Years



27.  Secondary:   LTTP: Number of Participants With Mobility Status (MS) at Baseline, 1 Year and 2 Years   [ Time Frame: Baseline, 1 year, and 2 years ]

Measure Type Secondary
Measure Title LTTP: Number of Participants With Mobility Status (MS) at Baseline, 1 Year and 2 Years
Measure Description Mobility, i.e., ability to walk was assessed as a part of Gaucher disease assessment in participants. In this outcome, number of participants with their different mobility status along with the use of mobility aids (unrestricted mobility, walks with difficulty, walks with orthopaedic aid, requires wheelchair, bedridden) at specified time points were reported.
Time Frame Baseline, 1 year, and 2 years  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who received at least one dose of eliglustat during the LTTP.

Reporting Groups
  Description
LTTP: Eliglustat All participants who entered PAP continued their blinded randomized treatment for first 4 weeks. Participants who at Week 52 of PAP maintained their therapeutic goals (defined as: no more than 2 bone crisis during PAP [with no more than 1 bone crisis during either first 6 months or later 6 months of PAP] and is free of other clinically symptomatic bone disease during PAP; hemoglobin level not decreased by >1.5 g/dL from Baseline for PAP [defined as last available assessment prior to randomization]; platelet count not decreased by >25% from Baseline for PAP; spleen volume not increased by 25% from Baseline for PAP; liver volume not increased by >20% from Baseline for PAP), continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) QD till the end of the study. The participants who did not maintain all their therapeutic goals continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) BID till the end of the study.

Measured Values
   LTTP: Eliglustat 
Participants Analyzed 
[Units: Participants]
 121 
LTTP: Number of Participants With Mobility Status (MS) at Baseline, 1 Year and 2 Years 
[Units: Participants]
 
MS, Unrestricted: Baseline (n=120)   111 
MS, Unrestricted: 1 year (n=104)   97 
MS, Unrestricted: 2 years (n=32)   28 
MS, Walks with Difficulty: Baseline (n=120)   7 
MS, Walks with Difficulty: 1 year (n=104)   4 
Ms, Walks with Difficulty: 2 years (n=32)   2 
MS, Walks with Orthopedic Aid: Baseline (n=120)   0 
MS, Walks with Orthopedic Aid: 1 year (n=104)   1 
MS, Walks with Orthopedic Aid: 2 years (n=32)   0 
MS, Required Wheelchair: Baseline (n=120)   2 
MS, Required Wheelchair: 1 year (n=104)   2 
MS, Required Wheelchair: 2 years (n=32)   2 
MS, Bedridden: Baseline (n=120)   0 
MS, Bedridden: 1 year (n=104)   0 
MS, Bedridden: 2 years (n=32)   0 

No statistical analysis provided for LTTP: Number of Participants With Mobility Status (MS) at Baseline, 1 Year and 2 Years



28.  Secondary:   LTTP: Number of Participants With Bone Crises Assessment at Baseline, 1 Year and 2 Years   [ Time Frame: Baseline, 1 year and 2 years ]

Measure Type Secondary
Measure Title LTTP: Number of Participants With Bone Crises Assessment at Baseline, 1 Year and 2 Years
Measure Description Bone crises was assessed as a part of Gaucher disease assessment in participants. Acute, excruciating episodic bone pain is characteristic of Gaucher bone crises, which typically causes debilitation lasting several days or longer and requires treatment with immobilization, hydration, and opioid analgesics. Participants were categorized as 0= no bone crises, 1= 1 bone crisis during the assessment period. In this outcome, number of participants with different bone crises levels at specified time points were reported.
Time Frame Baseline, 1 year and 2 years  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who received at least one dose of eliglustat during the LTTP.

Reporting Groups
  Description
LTTP: Eliglustat All participants who entered PAP continued their blinded randomized treatment for first 4 weeks. Participants who at Week 52 of PAP maintained their therapeutic goals (defined as: no more than 2 bone crisis during PAP [with no more than 1 bone crisis during either first 6 months or later 6 months of PAP] and is free of other clinically symptomatic bone disease during PAP; hemoglobin level not decreased by >1.5 g/dL from Baseline for PAP [defined as last available assessment prior to randomization]; platelet count not decreased by >25% from Baseline for PAP; spleen volume not increased by 25% from Baseline for PAP; liver volume not increased by >20% from Baseline for PAP), continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) QD till the end of the study. The participants who did not maintain all their therapeutic goals continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) BID till the end of the study.

Measured Values
   LTTP: Eliglustat 
Participants Analyzed 
[Units: Participants]
 121 
LTTP: Number of Participants With Bone Crises Assessment at Baseline, 1 Year and 2 Years 
[Units: Participants]
 
Bone Crisis (0): Baseline (n=120)   119 
Bone Crisis (0): 1 year (n=104)   104 
Bone Crisis (0): 2 years (n=32)   32 
Bone Crisis (1): Baseline (n=120)   1 
Bone Crisis (1): 1 year (n=104)   0 
Bone Crisis (1): 2 years (n=32)   0 

No statistical analysis provided for LTTP: Number of Participants With Bone Crises Assessment at Baseline, 1 Year and 2 Years



29.  Secondary:   LTTP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, 1 Year, and 2 Years   [ Time Frame: Baseline, 1 year and 2 years ]

Measure Type Secondary
Measure Title LTTP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, 1 Year, and 2 Years
Measure Description Bone pain was assessed as a part of Gaucher disease assessment in participants. Participants were categorized as none (no bone pain), very mild bone pain, mild bone pain, moderate bone pain, severe bone pain and extreme bone pain. In this outcome, number of participants with different level of bone pain during the past 4 weeks at specified time points were reported.
Time Frame Baseline, 1 year and 2 years  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who received at least one dose of eliglustat during the LTTP.

Reporting Groups
  Description
LTTP: Eliglustat All participants who entered PAP continued their blinded randomized treatment for first 4 weeks. Participants who at Week 52 of PAP maintained their therapeutic goals (defined as: no more than 2 bone crisis during PAP [with no more than 1 bone crisis during either first 6 months or later 6 months of PAP] and is free of other clinically symptomatic bone disease during PAP; hemoglobin level not decreased by >1.5 g/dL from Baseline for PAP [defined as last available assessment prior to randomization]; platelet count not decreased by >25% from Baseline for PAP; spleen volume not increased by 25% from Baseline for PAP; liver volume not increased by >20% from Baseline for PAP), continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) QD till the end of the study. The participants who did not maintain all their therapeutic goals continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) BID till the end of the study.

Measured Values
   LTTP: Eliglustat 
Participants Analyzed 
[Units: Participants]
 121 
LTTP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, 1 Year, and 2 Years 
[Units: Participants]
 
None: Baseline (n=120)   91 
None: 1 year (n=104)   83 
None: 2 years (n=32)   32 
Very Mild: Baseline (n=120)   12 
Very Mild: 1 year (n=104)   9 
Very Mild: 2 years (n=32)   0 
Mild: Baseline (n=120)   8 
Mild: 1 year (n=104)   10 
Mild: 2 years (n=32)   0 
Moderate: Baseline (n=120)   7 
Moderate: 1 year (n=104)   1 
Moderate: 2 years (n=32)   0 
Severe: Baseline (n=120)   2 
Severe: 1 year (n=104)   0 
Severe: 2 years (n=32)   0 
Extreme: Baseline (n=120)   0 
Extreme: 1 year (n=104)   1 
Extreme: 2 years (n=32)   0 

No statistical analysis provided for LTTP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, 1 Year, and 2 Years



30.  Secondary:   LTTP: Bone Mineral Density (BMD) at Baseline, 1 Year, and 2 Years   [ Time Frame: Baseline, 1 year, and 2 years ]

Measure Type Secondary
Measure Title LTTP: Bone Mineral Density (BMD) at Baseline, 1 Year, and 2 Years
Measure Description BMD measurements of the spine and bilateral femur were acquired by DXA scan.
Time Frame Baseline, 1 year, and 2 years  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who received at least one dose of eliglustat during the LTTP.

Reporting Groups
  Description
LTTP: Eliglustat All participants who entered PAP continued their blinded randomized treatment for first 4 weeks. Participants who at Week 52 of PAP maintained their therapeutic goals (defined as: no more than 2 bone crisis during PAP [with no more than 1 bone crisis during either first 6 months or later 6 months of PAP] and is free of other clinically symptomatic bone disease during PAP; hemoglobin level not decreased by >1.5 g/dL from Baseline for PAP [defined as last available assessment prior to randomization]; platelet count not decreased by >25% from Baseline for PAP; spleen volume not increased by 25% from Baseline for PAP; liver volume not increased by >20% from Baseline for PAP), continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) QD till the end of the study. The participants who did not maintain all their therapeutic goals continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) BID till the end of the study.

Measured Values
   LTTP: Eliglustat 
Participants Analyzed 
[Units: Participants]
 121 
LTTP: Bone Mineral Density (BMD) at Baseline, 1 Year, and 2 Years 
[Units: G/cm^2]
Mean (Standard Deviation)
 
Lumbar Spine: Baseline (n=113)   1.087  (0.182) 
Lumbar Spine: 1 year (n=101)   1.083  (0.183) 
Lumbar Spine: 2 years (n=26)   1.082  (0.190) 
Left Femur: Baseline (n=107)   0.986  (0.205) 
Left Femur: 1 year (n=95)   0.994  (0.226) 
Left Femur: 2 years (n=22)   0.950  (0.220) 
Right Femur: Baseline (n=103)   0.983  (0.201) 
Right Femur: 1 year (n=91)   0.979  (0.202) 
Right Femur: 2 years (n=21)   0.908  (0.131) 

No statistical analysis provided for LTTP: Bone Mineral Density (BMD) at Baseline, 1 Year, and 2 Years



31.  Secondary:   LTTP: Total T-Scores for BMD at Baseline, 1 Year, and 2 Years   [ Time Frame: Baseline, 1 year, and 2 years ]

Measure Type Secondary
Measure Title LTTP: Total T-Scores for BMD at Baseline, 1 Year, and 2 Years
Measure Description Images of the spine and bilateral femur were obtained by DXA to determine T-score for each bone area and total bone mineral density. The T-score bone density categories were: normal (score >-1), osteopenia (score -2.5 to <=-1), and osteoporosis (score <= -2.5).
Time Frame Baseline, 1 year, and 2 years  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who received at least one dose of eliglustat during the LTTP.

Reporting Groups
  Description
LTTP: Eliglustat All participants who entered PAP continued their blinded randomized treatment for first 4 weeks. Participants who at Week 52 of PAP maintained their therapeutic goals (defined as: no more than 2 bone crisis during PAP [with no more than 1 bone crisis during either first 6 months or later 6 months of PAP] and is free of other clinically symptomatic bone disease during PAP; hemoglobin level not decreased by >1.5 g/dL from Baseline for PAP [defined as last available assessment prior to randomization]; platelet count not decreased by >25% from Baseline for PAP; spleen volume not increased by 25% from Baseline for PAP; liver volume not increased by >20% from Baseline for PAP), continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) QD till the end of the study. The participants who did not maintain all their therapeutic goals continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) BID till the end of the study.

Measured Values
   LTTP: Eliglustat 
Participants Analyzed 
[Units: Participants]
 121 
LTTP: Total T-Scores for BMD at Baseline, 1 Year, and 2 Years 
[Units: T-score]
Mean (Standard Deviation)
 
Lumbar Spine T-Score: Baseline (n=110)   -0.674  (1.383) 
Lumbar Spine T-Score: 1 year (n=98)   -0.718  (1.394) 
Lumbar Spine T-Score: 2 years (n=26)   -0.750  (1.370) 
Left Femur T-Score: Baseline (n=103)   -0.421  (1.377) 
Left Femur T-Score: 1 year (n=91)   -0.382  (1.551) 
Left Femur T-Score: 2 years (n=22)   -0.682  (1.532) 
Right Femur T-Score: Baseline (n=99)   -0.461  (1.360) 
Right Femur T-Score: 1 year (n=87)   -0.500  (1.381) 
Right Femur T-Score: 2 years (n=21)   -1.005  (0.931) 

No statistical analysis provided for LTTP: Total T-Scores for BMD at Baseline, 1 Year, and 2 Years



32.  Secondary:   LTTP: Total Z-scores for BMD at Baseline, 1 Year, and 2 Years   [ Time Frame: Baseline, 1 year, and 2 years ]

Measure Type Secondary
Measure Title LTTP: Total Z-scores for BMD at Baseline, 1 Year, and 2 Years
Measure Description Images of the spine and bilateral femur were obtained by DXA to determine Z-score for each bone area and total bone mineral density. The Z-score bone density categories are: normal (score >-2) and below normal (score <=-2).
Time Frame Baseline, 1 year, and 2 years  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who received at least one dose of eliglustat during the LTTP.

Reporting Groups
  Description
LTTP: Eliglustat All participants who entered PAP continued their blinded randomized treatment for first 4 weeks. Participants who at Week 52 of PAP maintained their therapeutic goals (defined as: no more than 2 bone crisis during PAP [with no more than 1 bone crisis during either first 6 months or later 6 months of PAP] and is free of other clinically symptomatic bone disease during PAP; hemoglobin level not decreased by >1.5 g/dL from Baseline for PAP [defined as last available assessment prior to randomization]; platelet count not decreased by >25% from Baseline for PAP; spleen volume not increased by 25% from Baseline for PAP; liver volume not increased by >20% from Baseline for PAP), continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) QD till the end of the study. The participants who did not maintain all their therapeutic goals continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) BID till the end of the study.

Measured Values
   LTTP: Eliglustat 
Participants Analyzed 
[Units: Participants]
 121 
LTTP: Total Z-scores for BMD at Baseline, 1 Year, and 2 Years 
[Units: Z-score]
Mean (Standard Deviation)
 
Lumbar Spine Z-Score: Baseline (n=113)   -0.460  (1.376) 
Lumbar Spine Z-Score: 1 year (n=101)   -0.512  (1.368) 
Lumbar Spine Z-Score: 2 years (n=26)   -0.385  (1.316) 
Left Femur Z-Score: Baseline (n=107)   -0.164  (1.277) 
Left Femur Z-Score: 1 year (n=95)   -0.132  (1.459) 
Left Femur Z-Score: 2 years (n=22)   -0.264  (1.525) 
Right Femur Z-Score: Baseline (n=103)   -0.214  (1.227) 
Right Femur Z-Score: 1 year (n=91)   -0.262  (1.270) 
Right Femur Z-Score: 2 years (n=21)   -0.605  (0.957) 

No statistical analysis provided for LTTP: Total Z-scores for BMD at Baseline, 1 Year, and 2 Years



33.  Secondary:   LTTP: Total Bone Marrow Burden Score (BMB) at Baseline, 1 Year, and 2 Years   [ Time Frame: Baseline, 1 year, and 2 years ]

Measure Type Secondary
Measure Title LTTP: Total Bone Marrow Burden Score (BMB) at Baseline, 1 Year, and 2 Years
Measure Description BMB Score was measured using MRI, range from 0 (no abnormalities) to 8 points (severe disease) for the lumbar spine and from 0 (no abnormalities) to 8 points (severe disease) for the femurs. The total score was calculated as the sum of scores for femur and lumbar spine regions which ranged from 0 (no abnormalities) -16 (severe disease) points. A higher BMB score signified more severe bone marrow involvement.
Time Frame Baseline, 1 year, and 2 years  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who received at least one dose of eliglustat during the LTTP.

Reporting Groups
  Description
LTTP: Eliglustat All participants who entered PAP continued their blinded randomized treatment for first 4 weeks. Participants who at Week 52 of PAP maintained their therapeutic goals (defined as: no more than 2 bone crisis during PAP [with no more than 1 bone crisis during either first 6 months or later 6 months of PAP] and is free of other clinically symptomatic bone disease during PAP; hemoglobin level not decreased by >1.5 g/dL from Baseline for PAP [defined as last available assessment prior to randomization]; platelet count not decreased by >25% from Baseline for PAP; spleen volume not increased by 25% from Baseline for PAP; liver volume not increased by >20% from Baseline for PAP), continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) QD till the end of the study. The participants who did not maintain all their therapeutic goals continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) BID till the end of the study.

Measured Values
   LTTP: Eliglustat 
Participants Analyzed 
[Units: Participants]
 121 
LTTP: Total Bone Marrow Burden Score (BMB) at Baseline, 1 Year, and 2 Years 
[Units: BMB Score]
Mean (Standard Deviation)
 
BMB Score: Baseline (n=115)   8.164  (2.646) 
BMB Score: 1 year (n=26)   7.853  (2.497) 
BMB Score: 2 years (n=17)   8.059  (1.918) 

No statistical analysis provided for LTTP: Total Bone Marrow Burden Score (BMB) at Baseline, 1 Year, and 2 Years



34.  Secondary:   LTTP: Mean Biomarker (Chitotriosidase) Value at Baseline, 1 Year, and 2 Years   [ Time Frame: Baseline, 1 year, and 2 years ]

Measure Type Secondary
Measure Title LTTP: Mean Biomarker (Chitotriosidase) Value at Baseline, 1 Year, and 2 Years
Measure Description Chitotriosidase biomarker was assayed from plasma.
Time Frame Baseline, 1 year, and 2 years  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who received at least one dose of eliglustat during the LTTP.

Reporting Groups
  Description
LTTP: Eliglustat All participants who entered PAP continued their blinded randomized treatment for first 4 weeks. Participants who at Week 52 of PAP maintained their therapeutic goals (defined as: no more than 2 bone crisis during PAP [with no more than 1 bone crisis during either first 6 months or later 6 months of PAP] and is free of other clinically symptomatic bone disease during PAP; hemoglobin level not decreased by >1.5 g/dL from Baseline for PAP [defined as last available assessment prior to randomization]; platelet count not decreased by >25% from Baseline for PAP; spleen volume not increased by 25% from Baseline for PAP; liver volume not increased by >20% from Baseline for PAP), continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) QD till the end of the study. The participants who did not maintain all their therapeutic goals continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) BID till the end of the study.

Measured Values
   LTTP: Eliglustat 
Participants Analyzed 
[Units: Participants]
 121 
LTTP: Mean Biomarker (Chitotriosidase) Value at Baseline, 1 Year, and 2 Years 
[Units: nmol/hr/mL]
Mean (Standard Deviation)
 
Chitotriosidase: Baseline (n=118)   1188.983  (1857.521) 
Chitotriosidase: 1 year (n=97))   1221.753  (2072.446) 
Chitotriosidase: 2 years (n=31)   598.161  (1463.603) 

No statistical analysis provided for LTTP: Mean Biomarker (Chitotriosidase) Value at Baseline, 1 Year, and 2 Years



35.  Secondary:   LTTP: Mean Biomarker (GL-1 on DBS) Value at Baseline, 1 Year, and 2 Years   [ Time Frame: Baseline, 1 year, and 2 years ]

Measure Type Secondary
Measure Title LTTP: Mean Biomarker (GL-1 on DBS) Value at Baseline, 1 Year, and 2 Years
Measure Description GL-1 on DBS biomarker was assayed from dried blood spot.
Time Frame Baseline, 1 year, and 2 years  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who received at least one dose of eliglustat during the LTTP.

Reporting Groups
  Description
LTTP: Eliglustat All participants who entered PAP continued their blinded randomized treatment for first 4 weeks. Participants who at Week 52 of PAP maintained their therapeutic goals (defined as: no more than 2 bone crisis during PAP [with no more than 1 bone crisis during either first 6 months or later 6 months of PAP] and is free of other clinically symptomatic bone disease during PAP; hemoglobin level not decreased by >1.5 g/dL from Baseline for PAP [defined as last available assessment prior to randomization]; platelet count not decreased by >25% from Baseline for PAP; spleen volume not increased by 25% from Baseline for PAP; liver volume not increased by >20% from Baseline for PAP), continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) QD till the end of the study. The participants who did not maintain all their therapeutic goals continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) BID till the end of the study.

Measured Values
   LTTP: Eliglustat 
Participants Analyzed 
[Units: Participants]
 121 
LTTP: Mean Biomarker (GL-1 on DBS) Value at Baseline, 1 Year, and 2 Years 
[Units: mcg/mL]
Mean (Standard Deviation)
 
GL-1 on DBS: Baseline (n=114)   2.725  (1.350) 
GL-1 on DBS: 1 year (n=98)   2.500  (1.031) 
GL-1 on DBS: 2 years (n=29)   2.238  (0.658) 

No statistical analysis provided for LTTP: Mean Biomarker (GL-1 on DBS) Value at Baseline, 1 Year, and 2 Years



36.  Secondary:   LTTP: Mean Biomarker (MIP1-beta) Value at Baseline, 1 Year, and 2 Years   [ Time Frame: Baseline, 1 year, and 2 years ]

Measure Type Secondary
Measure Title LTTP: Mean Biomarker (MIP1-beta) Value at Baseline, 1 Year, and 2 Years
Measure Description MIP1-beta biomarker was assayed from plasma.
Time Frame Baseline, 1 year, and 2 years  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who received at least one dose of eliglustat during the LTTP.

Reporting Groups
  Description
LTTP: Eliglustat All participants who entered PAP continued their blinded randomized treatment for first 4 weeks. Participants who at Week 52 of PAP maintained their therapeutic goals (defined as: no more than 2 bone crisis during PAP [with no more than 1 bone crisis during either first 6 months or later 6 months of PAP] and is free of other clinically symptomatic bone disease during PAP; hemoglobin level not decreased by >1.5 g/dL from Baseline for PAP [defined as last available assessment prior to randomization]; platelet count not decreased by >25% from Baseline for PAP; spleen volume not increased by 25% from Baseline for PAP; liver volume not increased by >20% from Baseline for PAP), continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) QD till the end of the study. The participants who did not maintain all their therapeutic goals continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) BID till the end of the study.

Measured Values
   LTTP: Eliglustat 
Participants Analyzed 
[Units: Participants]
 121 
LTTP: Mean Biomarker (MIP1-beta) Value at Baseline, 1 Year, and 2 Years 
[Units: pg/mL]
Mean (Standard Deviation)
 
MIP-1beta: Baseline (n=114)   97.857  (125.857) 
MIP-1beta: 1 year (n=94)   90.398  (90.549) 
MIP-1beta: 2 years (n=31)   68.445  (64.774) 

No statistical analysis provided for LTTP: Mean Biomarker (MIP1-beta) Value at Baseline, 1 Year, and 2 Years




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Trial Transparency Team
Organization: Sanofi
e-mail: Contact­US@sanofi.com


Publications:

Responsible Party: Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT01074944     History of Changes
Other Study ID Numbers: GZGD03109
2009-015811-42 ( EudraCT Number )
EFC12818 ( Other Identifier: Sanofi )
First Submitted: February 23, 2010
First Posted: February 24, 2010
Results First Submitted: October 7, 2016
Results First Posted: December 2, 2016
Last Update Posted: February 6, 2017