A Study of the Efficacy and Safety of Eliglustat Tartrate (Genz-112638) in Type 1 Gaucher Patients

• Sponsor: Genzyme, a Sanofi Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00358150
• Collaborator: (none)
• Enrollment: 26
• Locations: 17
• Arm: 1
• Duration (Months): 114
• Patients Per Site: 1.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

Gaucher disease is a genetic disease that results in a deficiency of an enzyme acid beta-glucosidase, also known as glucocerebrosidase. This enzyme is needed to digest a substrate (lipid) called glucosylceramide and, to a lesser degree, glucosylsphingosine. In participants with Gaucher disease, the liver, spleen, bone marrow and brain show increases in lipid concentration, specifically in cells derived from the monocyte/macrophage system.

Eliglustat tartrate (Genz-112638) is an oral drug that may regulate the Gaucher disease process by decreasing the synthesis of glucosylceramide. The primary objective of this study is to evaluate the efficacy, safety and pharmacokinetics (PK) of eliglustat tartrate, administered as an oral dose of either 50 milligram (mg) twice daily (BID) or 100 mg BID, to men and women with Gaucher disease Type 1 for 52 weeks.

Condition or Disease	Intervention/Treatment	Phase
Gaucher Disease, Type 1; Cerebroside Lipidosis Syndrome; Glucocerebrosidase Deficiency Disease; Glucosylceramide Beta-Glucosidase Deficiency Disease; Gaucher Disease, Non-Neuronopathic Form	Drug: Eliglustat tartrate	Phase 2

Detailed Description

This study consists of several phases: screening (-28 to -1 days), dose adjustment/treatment (Day 1 [treatment baseline] to Day 30), initial steady-state treatment (post-Day 30 through Week 52 post-baseline), a treatment interruption period (Week 52 through approximately Week 54), long-term steady-state treatment (approximately Week 54 through study completion), and safety follow-up (30 to 37 days after a participant withdraws from or completes the study). The Primary Analysis Period is from baseline through Week 52. The Extension Period is from Week 52 through study completion (that is, participant withdrawal, the study is terminated, eliglustat tartrate becomes commercially available, or where applicable, specific regulatory requirements have been met).

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Open-Label, Multi-Center Study Evaluating the Efficacy, Safety and Pharmacokinetics of Genz-112638 in Gaucher Type 1 Patients
• Study Start Date: Jun 1, 2006
• Actual Primary Completion Date: Aug 1, 2009
• Actual Study Completion Date: Dec 1, 2015

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Eliglustat tartrate

Drug: Eliglustat tartrate; Eliglustat (Genz-112638) capsule as single 50 mg dose on Day 1 then eliglustat 50 mg twice daily (BID) from Day 2 to Day 19, then either eliglustat 50 mg BID (if Genz-99067[active moiety of eliglustat in plasma] trough plasma concentration was greater than or equal to [>=]5 nanogram per milliliter [ng/mL] on Day 10) or eliglustat 100 mg BID(if Genz-99067 trough plasma concentration was less than [<] 5 ng/mL), from day 20 to Year 4. After primary completion date (Week 52) participants underwent treatment interruption period of approximately 2 weeks before continuing same treatment through study completion (Year 9). Participant receiving 100 mg BID could be considered for further dose increase to 150 mg BID at Week 24 if they met certain criteria (for example, had been on treatment for at least 24 months, had not reached therapeutic goals established for participants receiving Cerezyme, and if all other causes for lack of treatment effect had been evaluated and ruled out).; Other Names: Genz-112638

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Demonstrating A Meaningful Clinical Response [Baseline, Year 1]

   A meaningful clinical response was defined as an improvement in at least 2 of the 3 main efficacy parameters: a) an increase in hemoglobin of greater than or equal to (>=) 0.5 gram/deciliter from baseline, b) an increase in platelets of >=15 percent (%) from baseline, c) reduction in total spleen volume of >= 15% from baseline. As hemoglobin, platelets, total spleen volume were abnormal at baseline, within each participant, only those parameters were used in the evaluation of meaningful clinical response which were abnormal at baseline.

Secondary Outcome Measures

1. Percent Change From Baseline in Spleen Volume at Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study [Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study (Up to Year 9)]

   Percent change in spleen volume = ([spleen volume at specified time points minus spleen volume at baseline] divided by [spleen volume at baseline]) multiplied by 100, where all volumes are in multiples of normal.

2. Percent Change From Baseline in Liver Volume at Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study [Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study (Up to Year 9)]

   Percent change in liver volume = ([liver volume at specified time points minus liver volume at baseline] divided by [liver volume at baseline]) multiplied by 100, where all volumes are in multiples of normal.

3. Absolute Change From Baseline in Hemoglobin at Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study [Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study (Up to Year 9)]

   Absolute change = hemoglobin level at specified time points minus hemoglobin level at baseline.

4. Percent Change From Baseline in Platelet Count at Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study [Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study (Up to Year 9)]

   Percent change in platelet count = ([platelet count at specified time points minus platelet count at baseline] divided by [platelet count at baseline]) multiplied by 100.

5. Percent Change From Baseline in Biomarker (Angiotensin Converting Enzyme) Level at Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study [Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and End of Study (Up to Year 9)]

6. Percent Change From Baseline in Biomarker (Tartrate-Resistant Acid Phosphatase [TRAP]) Level at Year 1 and Year 2 [Baseline, Year 1, Year 2]

7. Percent Change From Baseline in Biomarker Chemokine Ligand 18 (CCL18) Level at Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and End of Study [Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and End of Study (Up to Year 9)]

8. Percent Change From Baseline in Biomarker (Chitotriosidase) Level at Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study [Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study (Up to Year 9)]

9. Change From Baseline in 36-Item Short Form (SF-36) Health Survey Scores at Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8 and Year 9 at End of Study [Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study (Up to Year 9)]

   The SF-36 questionnaire, version 2, investigates the participant's health-related quality of life (HRQL). It is a 36-item questionnaire measuring 8 domains (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health). Each domain score ranges from 0 (worst) to 100 (best), with higher scores reflecting best health-related quality of life. Two summary scale scores were computed from the 8 domain scores: the Physical Component Summary and the Mental Component Summary. Score range for both summary scale ranges from 0 (worst) to 100 (best), with higher scores reflecting best health-related quality of life.

10. Change From Baseline in Fatigue Severity Scale (FSS) Scores at Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study [Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study (Up to Year 9)]

    The FSS is an instrument consisting of 9 self-administered questions that measures the impact of severity of fatigue symptoms on everyday functioning, based on the recall over the past week. Score range for each question ranges from 1 (minimum) to 7 (maximum), where higher score indicates greater severity. FSS total score was calculated by averaging the results of all questions. Total FSS score ranges from 9 (minimum) to 63 (maximum), where higher scores indicates greater severity.

11. Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study [Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study (Up to Year 9)]

    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 and moderate bone pain. In this outcome, number of participants with different levels of bone pain at specified time points were reported.

12. Number of Participants With Mobility Status (MS) at Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study [Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study (Up to Year 9)]

    Mobillity, 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 (unrestricted mobility, walks with difficulty) at specified time points were reported.

13. Number of Participants With No Bone Crisis at Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study [Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study (Up to Year 9)]

    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 0= no bone crises levels at specified time points were reported.

14. Bone Marrow Infiltration: Number of Participants With Improvement From Baseline in Dark Marrow at Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8 and at End of Study (EOS) [Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8 and at End of Study (up to Year 9)]

    Bone marrow infiltration assessments were designed to evaluate improvements in dark marrow using MRI. Each MRI assessment was performed for both femurs and consisted of reviewing 6 different zones (the femoral head, greater trochanter, intertrochanteric region, shaft, distal metaphysis, and condyles). MRI images recorded dark marrow for each zone as either present or not present at baseline. In this outcome, number of participants (for whom dark marrow was present at baseline) with improvement from baseline in dark marrow at each specified time point were reported.

15. Lumbar Spine and Femur T-Scores for Bone Mineral Density (BMD) at Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study [Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study (up to Year 9)]

    Images of the lumbar spine and femur were obtained by dual energy X-ray absorptiometry (DXA) to determine T-score for each bone area and total bone mineral density. T-scores compares participant's bone density with that of healthy young participant of same gender. The T-score bone density categories were: normal (score >-1), osteopenia (score -2.5 to <=-1), and osteoporosis (score <= -2.5).

16. Lumbar Spine and Femur Z-Scores for BMD at Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study [Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study (up to Year 9)]

    Images of the lumbar spine and 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• The participant had a diagnosis of Gaucher Type I disease and a documented deficiency of glucocerebrosidase activity by enzyme assay and was willing and able to provide written informed consent prior to initiating any study-related procedures;

• The participant was 18 to 65 years old and weighed between 50 and 120 kilogram (kg) at enrollment;

• The participant had the following symptoms of Gaucher disease identified within 28 days of enrollment (at screening);

• Anemia - indicated by hemoglobin measurements taken during the screening phase (8 to 10 gram per deciliter (g/dL) if female, 8 to 11 g/dL if male);

• Thrombocytopenia - indicated by platelet count measurements taken during the screening phase (60000 to 100000 per cubic millimeter);

• Splenomegaly, as indicated by magnetic resonance imaging (MRI) or spiral computed tomography (CT) (>= 10 multiples of normal);

• Female participants of child-bearing potential must had a documented negative serum pregnancy test prior to dosing. Female participants agreed to use a reliable method of birth control throughout duration of trial.

Exclusion Criteria:

• Participant had a partial or total splenectomy or infarcted areas of the spleen;

• Participant had documented prior bleeding varices or liver infarction;

• Participant received miglustat within 12 months prior to study enrollment;

• The participant had received an investigational product within 30 days prior to study enrollment;

• Participant had neurologic or pulmonary involvement;

• Participant had new pathological bone involvement or bone crisis in the 12 months prior to enrollment;

• Participant was transfusion-dependent;

• Participant had a documented etiology of anemia due to causes other than Gaucher disease;

• The participant had cardiac functional and/or anatomical abnormalities, a history of cancer or tested positive for human immunodeficiency virus (HIV) antibody or Hepatitis;

• Participant had a clinically significant disease, other than Gaucher disease, including cardiovascular, renal, hepatic, gastrointestinal, pulmonary, neurologic, endocrine, metabolic, or psychiatric disease, other medical conditions, or serious intercurrent illnesses that, in the opinion of the Investigator, might preclude participation in the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	New York University	New York	New York	United States
2		New York	New York	United States
3	Aprillus Asistencia e Investigación	Buenos Aires		Argentina
4	Hospital de Oncologia Maria Curie	Buenos Aires		Argentina
5	IMAI	Buenos Aires		Argentina
6	Instituto Argentino de Diagnostico y Tratamiento (IADT)	Buenos Aires		Argentina
7		Buenos Aires		Argentina
8	Hospital Ramos Mejia	Ciudad Autonoma de Buenos Aires		Argentina
9	Rambam Medical Center	Haifa		Israel
10		Haifa		Israel
11	Sha'are Zedek Medical Centre	Jerusalem		Israel
12		Jerusalem		Israel
13	Universita degli Studi di Milano	Milano		Italy
14	Instituto Mexicano del Seguro Social	D.f.		Mexico
15		Mexico City		Mexico
16	Hematology Research Center of Ministry of Healthcare of the Russian Federation	Moscow		Russian Federation
17		Moscow		Russian Federation

Sponsors and Collaborators

• Genzyme, a Sanofi Company

Investigators

• Study Director: Medical Monitor, Genzyme, a Sanofi Company

Study Documents (Full-Text)

None provided.

More Information

Publications

• McEachern KA, Fung J, Komarnitsky S, Siegel CS, Chuang WL, Hutto E, Shayman JA, Grabowski GA, Aerts JM, Cheng SH, Copeland DP, Marshall J. A specific and potent inhibitor of glucosylceramide synthase for substrate inhibition therapy of Gaucher disease. Mol Genet Metab. 2007 Jul;91(3):259-67. Epub 2007 May 16.
• Peterschmitt MJ, Burke A, Blankstein L, Smith SE, Puga AC, Kramer WG, Harris JA, Mathews D, Bonate PL. Safety, tolerability, and pharmacokinetics of eliglustat tartrate (Genz-112638) after single doses, multiple doses, and food in healthy volunteers. J Clin Pharmacol. 2011 May;51(5):695-705. doi: 10.1177/0091270010372387. Epub 2010 Sep 23.

• Responsible Party: Genzyme, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT00358150
• Other Study ID Numbers: GZGD00304; 2005-004732-42; DRI12816
• First Posted: Jul 31, 2006
• Last Update Posted: Feb 15, 2017
• Last Verified: Dec 1, 2016

• Keywords provided by Genzyme, a Sanofi Company: Type 1 Gaucher Disease; Glucocerebrosidase Deficiency Disease
• Additional relevant MeSH terms: Gaucher Disease; Lipidoses; Deficiency Diseases; Eliglustat

Study Results

Participant Flow

Pre-assignment Detail	A total of 50 participants were screened of which 24 participants were screen failure. A total of 26 participants were enrolled in this study.

Arm/Group Title	Eliglustat
Arm/Group Description	Eliglustat (Genz-112638) capsule as single 50 milligram (mg) dose on Day 1 then eliglustat 50 mg twice daily (BID) from Day 2 to Day 19, and then either eliglustat 50 mg BID (if Genz-99067 [active moiety of eliglustat in plasma] trough plasma concentration was greater than or equal to [>=] 5 nanogram per milliliter [ng/mL] on Day 10) or eliglustat 100 mg BID (if Genz-99067 trough plasma concentration was less than [<] 5 ng/mL), from day 20 to Year 4. After primary completion date (Week 52) participants underwent treatment interruption period of approximately 2 weeks before continuing the same treatment up to Year 9. Participant receiving 100 mg BID could be considered for a further dose increase to 150 mg BID at Week 24 if they met certain criteria (for example, had been on treatment for at least 24 months, had not reached therapeutic goals established for participants receiving Cerezyme), and if all other causes for lack of treatment effect had been evaluated and ruled out).
Period Title: Overall Study
STARTED	26
COMPLETED	19
NOT COMPLETED	7

Baseline Characteristics

Arm/Group Title	Eliglustat
Arm/Group Description	Eliglustat (Genz-112638) capsule as single 50 mg dose on Day 1 then eliglustat 50 mg BID from Day 2 to Day 19, and then either eliglustat 50 mg BID (if Genz-99067 [active moiety of eliglustat in plasma] trough plasma concentration was greater than or equal to [>=] 5 ng/mL on Day 10) or eliglustat 100 mg BID (if Genz-99067 trough plasma concentration was less than [<] 5 ng/mL), from day 20 to Year 4. After primary completion date (Week 52) participants underwent treatment interruption period of approximately 2 weeks before continuing the same treatment up to Year 9. Participant receiving 100 mg BID could be considered for a further dose increase to 150 mg BID at Week 24 if they met certain criteria (for example, had been on treatment for at least 24 months, had not reached therapeutic goals established for participants receiving Cerezyme, and if all other causes for lack of treatment effect had been evaluated and ruled out).
Overall Participants	26
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34.47 (12.960)
Gender (Count of Participants)
Female	16 61.5%
Male	10 38.5%
Race/Ethnicity, Customized (participants) [Number]
Ashkenazi Jewish	7 26.9%
Non-Jewish Caucasian	16 61.5%
Hispanic	3 11.5%
Body Mass Index (BMI) (kilogram per square meter (kg/m^2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram per square meter (kg/m^2)]	22.56 (3.529)
Weight (kilogram (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram (kg)]	61.47 (11.018)
Height (centimeter (cm)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeter (cm)]	165.12 (9.747)
Hemoglobin (gram per deciliter (g/dL)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [gram per deciliter (g/dL)]	11.10 (1.674)
Platelet Count (10^9 cells per liter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [10^9 cells per liter]	66.423 (20.1413)
Spleen Volume (Multiples of normal) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Multiples of normal]	20.04 (12.798)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Demonstrating A Meaningful Clinical Response
Description	A meaningful clinical response was defined as an improvement in at least 2 of the 3 main efficacy parameters: a) an increase in hemoglobin of greater than or equal to (>=) 0.5 gram/deciliter from baseline, b) an increase in platelets of >=15 percent (%) from baseline, c) reduction in total spleen volume of >= 15% from baseline. As hemoglobin, platelets, total spleen volume were abnormal at baseline, within each participant, only those parameters were used in the evaluation of meaningful clinical response which were abnormal at baseline.
Time Frame	Baseline, Year 1

Outcome Measure Data

Analysis Population Description

Full analysis set consists of all participants who signed informed consent and received at least one dose of eliglustat.

Arm/Group Title	Eliglustat
Arm/Group Description	Eliglustat (Genz-112638) capsule as single 50 mg dose on Day 1 then eliglustat 50 mg BID from Day 2 to Day 19, and then either eliglustat 50 mg BID (if Genz-99067 [active moiety of eliglustat in plasma] trough plasma concentration was greater than or equal to [>=] 5 ng/mL on Day 10) or eliglustat 100 mg BID (if Genz-99067 trough plasma concentration was less than [<] 5 ng/mL), from day 20 to Year 4. After primary completion date (Week 52) participants underwent treatment interruption period of approximately 2 weeks before continuing the same treatment up to Year 9. Participant receiving 100 mg BID could be considered for a further dose increase to 150 mg BID at Week 24 if they met certain criteria (for example, had been on treatment for at least 24 months, had not reached therapeutic goals established for participants receiving Cerezyme, and if all other causes for lack of treatment effect had been evaluated and ruled out).
Measure Participants	26
Number [percentage of participants]	77 296.2%

2. Secondary Outcome

Title	Percent Change From Baseline in Spleen Volume at Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study
Description	Percent change in spleen volume = ([spleen volume at specified time points minus spleen volume at baseline] divided by [spleen volume at baseline]) multiplied by 100, where all volumes are in multiples of normal.
Time Frame	Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study (Up to Year 9)

Outcome Measure Data

Analysis Population Description

Full analysis set consists of all participants who signed informed consent and received at least one dose of eliglustat. Here 'n' signifies number of participants with available data at specified time points.

Arm/Group Title	Eliglustat
Arm/Group Description	Eliglustat (Genz-112638) capsule as single 50 mg dose on Day 1 then eliglustat 50 mg BID from Day 2 to Day 19, and then either eliglustat 50 mg BID (if Genz-99067 [active moiety of eliglustat in plasma] trough plasma concentration was greater than or equal to [>=] 5 ng/mL on Day 10) or eliglustat 100 mg BID (if Genz-99067 trough plasma concentration was less than [<] 5 ng/mL), from day 20 to Year 4. After primary completion date (Week 52) participants underwent treatment interruption period of approximately 2 weeks before continuing the same treatment up to Year 9. Participant receiving 100 mg BID could be considered for a further dose increase to 150 mg BID at Week 24 if they met certain criteria (for example, had been on treatment for at least 24 months, had not reached therapeutic goals established for participants receiving Cerezyme, and if all other causes for lack of treatment effect had been evaluated and ruled out).
Measure Participants	26
Change at Year 1 (n=22)	-38.5 (11.41)
Change at Year 2 (n=20)	-52.4 (10.73)
Change at Year 3 (n=19)	-59.1 (11.68)
Change at Year 4 (n=18)	-62.5 (11.63)
Change at Year 5 (n=19)	-63.9 (14.64)
Change at Year 6 (n=19)	-66.2 (15.72)
Change at Year 7 (n=19)	-67.8 (15.65)
Change at Year 8 (n=15)	-67.9 (17.11)
Change at Year 9 (n=4)	-52.6 (23.97)
Change at End of Study (n=19)	-68.6 (18.60)

3. Secondary Outcome

Title	Percent Change From Baseline in Liver Volume at Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study
Description	Percent change in liver volume = ([liver volume at specified time points minus liver volume at baseline] divided by [liver volume at baseline]) multiplied by 100, where all volumes are in multiples of normal.
Time Frame	Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study (Up to Year 9)

Outcome Measure Data

Analysis Population Description

Full analysis set consists of all participants who signed informed consent and received at least one dose of eliglustat. Here 'n' signifies number of participants with available data at specified time points.

Arm/Group Title	Eliglustat
Arm/Group Description	Eliglustat (Genz-112638) capsule as single 50 mg dose on Day 1 then eliglustat 50 mg BID from Day 2 to Day 19, and then either eliglustat 50 mg BID (if Genz-99067 [active moiety of eliglustat in plasma] trough plasma concentration was greater than or equal to [>=] 5 ng/mL on Day 10) or eliglustat 100 mg BID (if Genz-99067 trough plasma concentration was less than [<] 5 ng/mL), from day 20 to Year 4. After primary completion date (Week 52) participants underwent treatment interruption period of approximately 2 weeks before continuing the same treatment up to Year 9. Participant receiving 100 mg BID could be considered for a further dose increase to 150 mg BID at Week 24 if they met certain criteria (for example, had been on treatment for at least 24 months, had not reached therapeutic goals established for participants receiving Cerezyme, and if all other causes for lack of treatment effect had been evaluated and ruled out).
Measure Participants	26
Change at Year 1 (n=22)	-16.9 (10.48)
Change at Year 2 (n=20)	-23.9 (12.81)
Change at Year 3 (n=19)	-26.8 (12.28)
Change at Year 4 (n=18)	-28.0 (13.80)
Change at Year 5 (n=19)	-31.2 (13.90)
Change at Year 6 (n=19)	-28.4 (23.58)
Change at Year 7 (n=19)	-36.2 (13.49)
Change at Year 8 (n=15)	-31.1 (13.51)
Change at Year 9 (n=4)	-22.0 (18.49)
Change at End of Study (n=19)	-36.4 (14.91)

4. Secondary Outcome

Title	Absolute Change From Baseline in Hemoglobin at Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study
Description	Absolute change = hemoglobin level at specified time points minus hemoglobin level at baseline.
Time Frame	Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study (Up to Year 9)

Outcome Measure Data

Analysis Population Description

Full analysis set consists of all participants who signed informed consent and received at least one dose of eliglustat. Here 'n' signifies number of participants with available data at specified time points.

Arm/Group Title	Eliglustat
Arm/Group Description	Eliglustat (Genz-112638) capsule as single 50 mg dose on Day 1 then eliglustat 50 mg BID from Day 2 to Day 19, and then either eliglustat 50 mg BID (if Genz-99067 [active moiety of eliglustat in plasma] trough plasma concentration was greater than or equal to [>=] 5 ng/mL on Day 10) or eliglustat 100 mg BID (if Genz-99067 trough plasma concentration was less than [<] 5 ng/mL), from day 20 to Year 4. After primary completion date (Week 52) participants underwent treatment interruption period of approximately 2 weeks before continuing the same treatment up to Year 9. Participant receiving 100 mg BID could be considered for a further dose increase to 150 mg BID at Week 24 if they met certain criteria (for example, had been on treatment for at least 24 months, had not reached therapeutic goals established for participants receiving Cerezyme, and if all other causes for lack of treatment effect had been evaluated and ruled out).
Measure Participants	26
Change at Year 1 (n=22)	1.70 (1.274)
Change at Year 2 (n=20)	2.13 (1.507)
Change at Year 3 (n=18)	2.47 (1.406)
Change at Year 4 (n=19)	2.27 (1.451)
Change at Year 5 (n=19)	2.09 (1.746)
Change at Year 6 (n=18)	2.01 (1.326)
Change at Year 7 (n=19)	2.07 (1.485)
Change at Year 8 (n=16)	2.08 (1.748)
Change at Year 9 (n=4)	1.00 (1.480)
Change at End of Study (n=18)	2.01 (1.785)

5. Secondary Outcome

Title	Percent Change From Baseline in Platelet Count at Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study
Description	Percent change in platelet count = ([platelet count at specified time points minus platelet count at baseline] divided by [platelet count at baseline]) multiplied by 100.
Time Frame	Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study (Up to Year 9)

Outcome Measure Data

Analysis Population Description

Full analysis set consists of all participants who signed informed consent and received at least one dose of eliglustat. Here 'n' signifies number of participants with available data at specified time points.

Arm/Group Title	Eliglustat
Arm/Group Description	Eliglustat (Genz-112638) capsule as single 50 mg dose on Day 1 then eliglustat 50 mg BID from Day 2 to Day 19, and then either eliglustat 50 mg BID (if Genz-99067 [active moiety of eliglustat in plasma] trough plasma concentration was greater than or equal to [>=] 5 ng/mL on Day 10) or eliglustat 100 mg BID (if Genz-99067 trough plasma concentration was less than [<] 5 ng/mL), from day 20 to Year 4. After primary completion date (Week 52) participants underwent treatment interruption period of approximately 2 weeks before continuing the same treatment up to Year 9. Participant receiving 100 mg BID could be considered for a further dose increase to 150 mg BID at Week 24 if they met certain criteria (for example, had been on treatment for at least 24 months, had not reached therapeutic goals established for participants receiving Cerezyme, and if all other causes for lack of treatment effect had been evaluated and ruled out).
Measure Participants	26
Change at Year 1 (n=22)	41.3 (36.95)
Change at Year 2 (n=20)	81.5 (56.01)
Change at Year 3 (n=18)	87.9 (65.37)
Change at Year 4 (n=19)	95.1 (89.41)
Change at Year 5 (n=19)	90.9 (85.42)
Change at Year 6 (n=17)	114.3 (102.48)
Change at Year 7 (n=19)	99.4 (97.13)
Change at Year 8 (n=16)	109.8 (114.73)
Change at Year 9 (n=3)	45.4 (56.28)
Change at End of Study (n=18)	117.5 (116.91)

6. Secondary Outcome

Title	Percent Change From Baseline in Biomarker (Angiotensin Converting Enzyme) Level at Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study
Time Frame	Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and End of Study (Up to Year 9)

Outcome Measure Data

Analysis Population Description

Full analysis set consists of all participants who signed informed consent and received at least one dose of eliglustat. Here 'n' signifies number of participants with available data at specified time point.

Arm/Group Title	Eliglustat
Arm/Group Description	Eliglustat (Genz-112638) capsule as single 50 mg dose on Day 1 then eliglustat 50 mg BID from Day 2 to Day 19, and then either eliglustat 50 mg BID (if Genz-99067 [active moiety of eliglustat in plasma] trough plasma concentration was greater than or equal to [>=] 5 ng/mL on Day 10) or eliglustat 100 mg BID (if Genz-99067 trough plasma concentration was less than [<] 5 ng/mL), from day 20 to Year 4. After primary completion date (Week 52) participants underwent treatment interruption period of approximately 2 weeks before continuing the same treatment up to Year 9. Participant receiving 100 mg BID could be considered for a further dose increase to 150 mg BID at Week 24 if they met certain criteria (for example, had been on treatment for at least 24 months, had not reached therapeutic goals established for participants receiving Cerezyme, and if all other causes for lack of treatment effect had been evaluated and ruled out).
Measure Participants	26
Change at Year 1 (n=22)	-35.1 (18.87)
Change at Year 2 (n=20)	-53.5 (21.05)
Change at Year 3 (n=19)	-56.7 (19.33)
Change at Year 4 (n=18)	-60.7 (18.44)
Change at Year 5 (n=19)	-55.7 (22.51)
Change at Year 6 (n=17)	-61.5 (24.73)
Change at Year 7 (n=19)	-63.6 (24.64)
Change at Year 8 (n=16)	-59.2 (21.77)
Change at Year 9 (n=4)	-55.1 (32.58)
Change at End of Study (n=18)	-64.7 (23.38)

7. Secondary Outcome

Title	Percent Change From Baseline in Biomarker (Tartrate-Resistant Acid Phosphatase [TRAP]) Level at Year 1 and Year 2
Time Frame	Baseline, Year 1, Year 2

Outcome Measure Data

Analysis Population Description

Full analysis set consists of all participants who signed informed consent and received at least one dose of eliglustat. Here 'n' signifies number of participants with available data at specified time points. As per the change in planned analysis, TRAP was not assessed after Year 2.

Arm/Group Title	Eliglustat
Arm/Group Description	Eliglustat (Genz-112638) capsule as single 50 mg dose on Day 1 then eliglustat 50 mg BID from Day 2 to Day 19, and then either eliglustat 50 mg BID (if Genz-99067 [active moiety of eliglustat in plasma] trough plasma concentration was greater than or equal to [>=] 5 ng/mL on Day 10) or eliglustat 100 mg BID (if Genz-99067 trough plasma concentration was less than [<] 5 ng/mL), from day 20 to Year 4. After primary completion date (Week 52) participants underwent treatment interruption period of approximately 2 weeks before continuing the same treatment up to Year 9. Participant receiving 100 mg BID could be considered for a further dose increase to 150 mg BID at Week 24 if they met certain criteria (for example, had been on treatment for at least 24 months, had not reached therapeutic goals established for participants receiving Cerezyme, and if all other causes for lack of treatment effect had been evaluated and ruled out).
Measure Participants	26
Change at Year 1 (n=22)	-37.0 (11.64)
Change at Year 2 (n= 10)	-52.5 (10.61)

8. Secondary Outcome

Title	Percent Change From Baseline in Biomarker Chemokine Ligand 18 (CCL18) Level at Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and End of Study
Time Frame	Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and End of Study (Up to Year 9)

Outcome Measure Data

Analysis Population Description

Full analysis set consists of all participants who signed informed consent and received at least one dose of eliglustat. Here 'n' signifies number of participants with available data at specified time points.

Arm/Group Title	Eliglustat
Arm/Group Description	Eliglustat (Genz-112638) capsule as single 50 mg dose on Day 1 then eliglustat 50 mg BID from Day 2 to Day 19, and then either eliglustat 50 mg BID (if Genz-99067 [active moiety of eliglustat in plasma] trough plasma concentration was greater than or equal to [>=] 5 ng/mL on Day 10) or eliglustat 100 mg BID (if Genz-99067 trough plasma concentration was less than [<] 5 ng/mL), from day 20 to Year 4. After primary completion date (Week 52) participants underwent treatment interruption period of approximately 2 weeks before continuing the same treatment up to Year 9. Participant receiving 100 mg BID could be considered for a further dose increase to 150 mg BID at Week 24 if they met certain criteria (for example, had been on treatment for at least 24 months, had not reached therapeutic goals established for participants receiving Cerezyme, and if all other causes for lack of treatment effect had been evaluated and ruled out).
Measure Participants	26
Change at Year 1 (n=21)	-49.0 (24.89)
Change at Year 2 (n=15)	-72.1 (19.11)
Change at Year 3 (n=18)	-68.6 (17.27)
Change at Year 4 (n=18)	-80.2 (12.71)
Change at Year 5 (n=18)	-89.4 (8.48)
Change at Year 6 (n=18)	-82.7 (11.98)
Change at Year 7 (n=18)	-78.5 (17.83)
Change at Year 8 (n=16)	-79.8 (16.19)
Change at Year 9 (n=4)	-88.6 (6.30)
Change at End of Study (n=18)	-85.8 (12.92)

9. Secondary Outcome

Title	Percent Change From Baseline in Biomarker (Chitotriosidase) Level at Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study
Time Frame	Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study (Up to Year 9)

Outcome Measure Data

Analysis Population Description

Full analysis set consists of all participants who signed informed consent and received at least one dose of eliglustat. Here 'n' signifies number of participants with available data at specified time points.

Arm/Group Title	Eliglustat
Arm/Group Description	Eliglustat (Genz-112638) capsule as single 50 mg dose on Day 1 then eliglustat 50 mg BID from Day 2 to Day 19, and then either eliglustat 50 mg BID (if Genz-99067 [active moiety of eliglustat in plasma] trough plasma concentration was greater than or equal to [>=] 5 ng/mL on Day 10) or eliglustat 100 mg BID (if Genz-99067 trough plasma concentration was less than [<] 5 ng/mL), from day 20 to Year 4. After primary completion date (Week 52) participants underwent treatment interruption period of approximately 2 weeks before continuing the same treatment up to Year 9. Participant receiving 100 mg BID could be considered for a further dose increase to 150 mg BID at Week 24 if they met certain criteria (for example, had been on treatment for at least 24 months, had not reached therapeutic goals established for participants receiving Cerezyme, and if all other causes for lack of treatment effect had been evaluated and ruled out).
Measure Participants	26
Change at Year 1 (n=20)	-49.9 (17.17)
Change at Year 2 (n=18)	-73.5 (14.93)
Change at Year 3 (n=17)	-76.4 (12.78)
Change at Year 4 (n=17)	-79.2 (16.18)
Change at Year 5 (n=17)	-76.7 (19.16)
Change at Year 6 (n=17)	-74.1 (26.97)
Change at Year 7 (n=17)	-75.5 (27.88)
Change at Year 8 (n=14)	-72.5 (29.20)
Change at Year 9 (n=4)	-61.2 (36.45)
Change at End of Study (n=17)	-69.8 (36.59)

10. Secondary Outcome

Title	Change From Baseline in 36-Item Short Form (SF-36) Health Survey Scores at Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8 and Year 9 at End of Study
Description	The SF-36 questionnaire, version 2, investigates the participant's health-related quality of life (HRQL). It is a 36-item questionnaire measuring 8 domains (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health). Each domain score ranges from 0 (worst) to 100 (best), with higher scores reflecting best health-related quality of life. Two summary scale scores were computed from the 8 domain scores: the Physical Component Summary and the Mental Component Summary. Score range for both summary scale ranges from 0 (worst) to 100 (best), with higher scores reflecting best health-related quality of life.
Time Frame	Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study (Up to Year 9)

Outcome Measure Data

Analysis Population Description

Full analysis set consists of all participants who signed informed consent and received at least one dose of eliglustat. Here 'n' signifies number of participants with available data at specified time points.

Arm/Group Title	Eliglustat
Arm/Group Description	Eliglustat (Genz-112638) capsule as single 50 mg dose on Day 1 then eliglustat 50 mg BID from Day 2 to Day 19, and then either eliglustat 50 mg BID (if Genz-99067 [active moiety of eliglustat in plasma] trough plasma concentration was greater than or equal to [>=] 5 ng/mL on Day 10) or eliglustat 100 mg BID (if Genz-99067 trough plasma concentration was less than [<] 5 ng/mL), from day 20 to Year 4. After primary completion date (Week 52) participants underwent treatment interruption period of approximately 2 weeks before continuing the same treatment up to Year 9. Participant receiving 100 mg BID could be considered for a further dose increase to 150 mg BID at Week 24 if they met certain criteria (for example, had been on treatment for at least 24 months, had not reached therapeutic goals established for participants receiving Cerezyme, and if all other causes for lack of treatment effect had been evaluated and ruled out).
Measure Participants	26
Physical Functioning: Change at Year 1 (n=22)	8.41 (14.670)
Physical Functioning: Change at Year 2 (n=20)	9.50 (17.837)
Physical Functioning: Change at Year 3 (n=17)	12.65 (18.296)
Physical Functioning: Change at Year 4 (n=19)	11.32 (16.231)
Physical Functioning: Change at Year 5 (n=19)	10.76 (19.169)
Physical Functioning: Change at Year 6 (n=19)	12.63 (17.589)
Physical Functioning: Change at Year 7 (n=19)	11.58 (17.955)
Physical Functioning: Change at Year 8 (n=16)	11.56 (17.485)
Physical Functioning: Change at Year 9 (n=4)	1.25 (2.500)
Physical Functioning:Change at End of Study (n=19)	9.28 (17.085)
Role - Physical: Change at Year 1 (n=22)	4.55 (22.091)
Role - Physical: Change at Year 2 (n=20)	5.31 (27.824)
Role - Physical: Change at Year 3 (n=17)	9.56 (24.717)
Role - Physical: Change at Year 4 (n=19)	6.58 (26.391)
Role - Physical: Change at Year 5 (n=19)	7.57 (28.227)
Role - Physical: Change at Year 6 (n=19)	8.88 (25.964)
Role - Physical: Change at Year 7 (n=19)	7.89 (25.331)
Role - Physical: Change at Year 8 (n=16)	8.59 (29.393)
Role - Physical: Change at Year 9 (n=4)	-1.56 (18.663)
Role - Physical: Change at End of Study (n= 19)	10.53 (24.211)
Bodily Pain: Change at Year 1 (n= 22)	-0.77 (21.307)
Bodily Pain: Change at Year 2 (n= 20)	4.40 (25.050)
Bodily Pain: Change at Year 3 (n= 17)	4.24 (21.297)
Bodily Pain: Change at Year 4 (n= 19)	-2.53 (25.202)
Bodily Pain: Change at Year 5 (n= 19)	0.37 (23.104)
Bodily Pain: Change at Year 6 (n= 19)	-2.32 (26.268)
Bodily Pain: Change at Year 7 (n= 19)	1.74 (27.777)
Bodily Pain: Change at Year 8 (n= 16)	1.44 (25.532)
Bodily Pain: Change at Year 9 (n= 4)	1.00 (19.630)
Bodily Pain: Change at End of Study (n= 19)	6.11 (29.603)
General Health: Change at Year 1 (n= 22)	10.36 (19.822)
General Health: Change at Year 2 (n= 20)	11.30 (24.262)
General Health: Change at Year 3 (n= 17)	16.94 (23.485)
General Health: Change at Year 4 (n= 19)	15.53 (23.136)
General Health: Change at Year 5 (n= 19)	13.58 (23.710)
General Health: Change at Year 6 (n= 19)	12.83 (23.443)
General Health: Change at Year 7 (n= 19)	15.89 (23.278)
General Health: Change at Year 8 (n= 16)	18.19 (20.140)
General Health: Change at Year 9 (n= 4)	11.25 (11.087)
General Health: Change at End of Study (n= 19)	15.00 (21.422)
Vitality: Change at Year 1 (n= 22)	5.68 (17.242)
Vitality: Change at Year 2 (n= 20)	7.71 (26.127)
Vitality: Change at Year 3 (n= 17)	14.71 (21.188)
Vitality: Change at Year 4 (n= 19)	10.20 (20.005)
Vitality: Change at Year 5 (n= 19)	13.82 (23.623)
Vitality: Change at Year 6 (n= 19)	12.50 (23.936)
Vitality: Change at Year 7 (n= 19)	7.57 (22.782)
Vitality: Change at Year 8 (n= 16)	15.23 (23.493)
Vitality: Change at Year 9 (n= 4)	3.13 (10.825)
Vitality: Change at End of Study (n= 19)	15.13 (21.278)
Social Functioning: Change at Year 1 (n= 22)	-0.57 (23.298)
Social Functioning: Change at Year 2 (n= 20)	10.00 (26.470)
Social Functioning: Change at Year 3 (n= 17)	9.56 (19.024)
Social Functioning: Change at Year 4 (n= 19)	3.29 (25.291)
Social Functioning: Change at Year 5 (n= 19)	9.21 (23.140)
Social Functioning: Change at Year 6 (n= 19)	9.21 (26.628)
Social Functioning: Change at Year 7 (n= 19)	8.55 (20.435)
Social Functioning: Change at Year 8 (n= 16)	11.72 (24.778)
Social Functioning: Change at Year 9 (n= 4)	3.13 (6.250)
Social Functioning: Change at End of Study (n= 19)	9.21 (25.291)
Role - Emotional: Change at Year 1 (n= 22)	-3.03 (17.733)
Role - Emotional: Change at Year 2 (n= 20)	4.58 (20.675)
Role - Emotional: Change at Year 3 (n= 17)	2.45 (16.342)
Role - Emotional: Change at Year 4 (n= 19)	3.95 (18.916)
Role - Emotional: Change at Year 5 (n= 19)	2.19 (22.020)
Role - Emotional: Change at Year 6 (n= 19)	3.07 (23.110)
Role - Emotional: Change at Year 7 (n= 19)	0.44 (23.485)
Role - Emotional: Change at Year 8 (n= 16)	5.21 (19.927)
Role - Emotional: Change at Year 9 (n= 4)	-10.42 (12.501)
Role- Emotional: Change at End of study (n= 19)	1.32 (22.952)
Mental Health: Change at Year 1 (n= 22)	0.23 (17.827)
Mental Health: Change at Year 2 (n= 20)	1.75 (19.485)
Mental Health: Change at Year 3 (n=17)	7.65 (16.117)
Mental Health: Change at Year 4 (n= 19)	4.21 (19.809)
Mental Health: Change at Year 5 (n= 19)	6.84 (19.945)
Mental Health: Change at Year 6 (n= 19)	5.53 (22.785)
Mental Health: Change at Year 7 (n= 19)	6.05 (21.186)
Mental Health: Change at Year 8 (n= 16)	7.66 (19.989)
Mental Health: Change at Year 9 (n= 4)	3.75 (4.787)
Mental Health: Change at End of Study (n=19)	8.68 (20.196)
Physical Component Summary:Change at Year 1(n= 22)	3.58 (6.263)
Physical Component Summary:Change at Year 2(n= 20)	3.81 (7.968)
Physical Component Summary:Change at Year 3(n= 17)	5.17 (7.044)
Physical Component Summary:Change at Year 4(n= 19)	3.69 (8.195)
Physical Component Summary:Change at Year 5(n= 19)	3.75 (8.430)
Physical Component Summary:Change at Year 6(n= 19)	3.88 (6.038)
Physical Component Summary:Change at Year 7(n= 19)	4.57 (7.892)
Physical Component Summary:Change at Year 8(n= 16)	4.36 (6.946)
Physical Component Summary: Change at Year 9 (n=4)	1.98 (5.029)
Physical Component Summary: Change at EOS (n= 19)	4.70 (7.120)
Mental Component Summary: Change at Year 1 (n= 22)	-1.03 (8.703)
Mental Component Summary: Change at Year 2 (n= 20)	2.04 (10.476)
Mental Component Summary: Change at Year 3 (n= 17)	3.45 (7.881)
Mental Component Summary: Change at Year 4 (n= 19)	2.11 (10.013)
Mental Component Summary: Change at Year 5 (n= 19)	3.50 (10.963)
Mental Component Summary: Change at Year 6 (n= 19)	3.03 (12.535)
Mental Component Summary: Change at Year 7 (n= 19)	1.94 (10.982)
Mental Component Summary: Change at Year 8 (n= 16)	4.59 (10.106)
Mental Component Summary: Change at Year 9 (n= 4)	-0.52 (1.287)
Mental Component Summary: Change at EOS (n=19)	3.73 (11.243)

11. Secondary Outcome

Title	Change From Baseline in Fatigue Severity Scale (FSS) Scores at Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study
Description	The FSS is an instrument consisting of 9 self-administered questions that measures the impact of severity of fatigue symptoms on everyday functioning, based on the recall over the past week. Score range for each question ranges from 1 (minimum) to 7 (maximum), where higher score indicates greater severity. FSS total score was calculated by averaging the results of all questions. Total FSS score ranges from 9 (minimum) to 63 (maximum), where higher scores indicates greater severity.
Time Frame	Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study (Up to Year 9)

Outcome Measure Data

Analysis Population Description

Full analysis set consists of all participants who signed informed consent and received at least one dose of eliglustat. Here 'n' signifies number of participants with available data at specified time points.

Arm/Group Title	Eliglustat
Arm/Group Description	Eliglustat (Genz-112638) capsule as single 50 mg dose on Day 1 then eliglustat 50 mg BID from Day 2 to Day 19, and then either eliglustat 50 mg BID (if Genz-99067 [active moiety of eliglustat in plasma] trough plasma concentration was greater than or equal to [>=] 5 ng/mL on Day 10) or eliglustat 100 mg BID (if Genz-99067 trough plasma concentration was less than [<] 5 ng/mL), from day 20 to Year 4. After primary completion date (Week 52) participants underwent treatment interruption period of approximately 2 weeks before continuing the same treatment up to Year 9. Participant receiving 100 mg BID could be considered for a further dose increase to 150 mg BID at Week 24 if they met certain criteria (for example, had been on treatment for at least 24 months, had not reached therapeutic goals established for participants receiving Cerezyme, and if all other causes for lack of treatment effect had been evaluated and ruled out).
Measure Participants	26
Change at Year 1 (n=17)	-0.56 (1.169)
Change at Year 2 (n=16)	-0.63 (1.388)
Change at Year 3 (n=14)	-1.37 (1.983)
Change at Year 4 (n=16)	-1.41 (1.574)
Change at Year 5 (n=16)	-1.26 (1.418)
Change at Year 6 (n=15)	-1.21 (1.681)
Change at Year 7 (n=16)	-0.97 (1.429)
Change at Year 8 (n=13)	-1.22 (1.489)
Change at Year 9 (n=4)	-1.20 (1.192)
Change at End of Study (n=16)	-1.16 (1.665)

12. Secondary Outcome

Title	Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study
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 and moderate bone pain. In this outcome, number of participants with different levels of bone pain at specified time points were reported.
Time Frame	Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study (Up to Year 9)

Outcome Measure Data

Analysis Population Description

Full analysis set consists of all participants who signed informed consent and received at least one dose of eliglustat. Here 'n' signifies number of participants with available data at specified time points.

Arm/Group Title	Eliglustat
Arm/Group Description	Eliglustat (Genz-112638) capsule as single 50 mg dose on Day 1 then eliglustat 50 mg BID from Day 2 to Day 19, and then either eliglustat 50 mg BID (if Genz-99067 [active moiety of eliglustat in plasma] trough plasma concentration was greater than or equal to [>=] 5 ng/mL on Day 10) or eliglustat 100 mg BID (if Genz-99067 trough plasma concentration was less than [<] 5 ng/mL), from day 20 to Year 4. After primary completion date (Week 52) participants underwent treatment interruption period of approximately 2 weeks before continuing the same treatment up to Year 9. Participant receiving 100 mg BID could be considered for a further dose increase to 150 mg BID at Week 24 if they met certain criteria (for example, had been on treatment for at least 24 months, had not reached therapeutic goals established for participants receiving Cerezyme, and if all other causes for lack of treatment effect had been evaluated and ruled out).
Measure Participants	26
None: Baseline (n=26)	23 88.5%
None: Year 1 (n=22)	17 65.4%
None: Year 2 (n=20)	17 65.4%
None: Year 3 (n=19)	14 53.8%
None: Year 4 (n=19)	14 53.8%
None: Year 5 (n=19)	16 61.5%
None: Year 6 (n=19)	17 65.4%
None: Year 7 (n=19)	15 57.7%
None: Year 8 (n=16)	14 53.8%
None: Year 9 (n=4)	4 15.4%
None: End of Study (n=19)	18 69.2%
Very Mild: Baseline (n=26)	2 7.7%
Very Mild: Year 1 (n=22)	4 15.4%
Very Mild: Year 2 (n=20)	3 11.5%
Very Mild: Year 3 (n=19)	3 11.5%
Very Mild: Year 4 (n=19)	4 15.4%
Very Mild: Year 5 (n=19)	1 3.8%
Very Mild: Year 6 (n=19)	1 3.8%
Very Mild: Year 7 (n=19)	3 11.5%
Very Mild: Year 8 (n=16)	1 3.8%
Very Mild: Year 9 (n=4)	0 0%
Very Mild: End of Study (n=19)	1 3.8%
Mild: Baseline (n= 26)	1 3.8%
Mild: Year 1 (n= 22)	1 3.8%
Mild: Year 2 (n= 20)	0 0%
Mild: Year 3 (n=19)	2 7.7%
Mild: Year 4 (n=19)	1 3.8%
Mild: Year 5 (n=19)	2 7.7%
Mild: Year 6 (n=19)	1 3.8%
Mild: Year 7 (n=19)	1 3.8%
Mild: Year 8 (n=16)	1 3.8%
Mild: Year 9 (n=4)	0 0%
Mild: End of Study (n= 19)	0 0%
Moderate: Baseline (n=26)	0 0%
Moderate: Year 1 (n=22)	0 0%
Moderate: Year 2 (n=20)	0 0%
Moderate: Year 3 (n=19)	0 0%
Moderate: Year 4 (n=19)	0 0%
Moderate: Year 5 (n=19)	0 0%
Moderate: Year 6 (n=19)	0 0%
Moderate: Year 7 (n=19)	0 0%
Moderate: Year 8 (n=16)	0 0%
Moderate: Year 9 (n=4)	0 0%
Moderate: End of Study (n=19)	0 0%

13. Secondary Outcome

Title	Number of Participants With Mobility Status (MS) at Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study
Description	Mobillity, 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 (unrestricted mobility, walks with difficulty) at specified time points were reported.
Time Frame	Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study (Up to Year 9)

Outcome Measure Data

Analysis Population Description

Full analysis set consists of all participants who signed informed consent and received at least one dose of eliglustat. Here 'n' signifies number of participants with available data at specified time points.

Arm/Group Title	Eliglustat
Arm/Group Description	Eliglustat (Genz-112638) capsule as single 50 mg dose on Day 1 then eliglustat 50 mg BID from Day 2 to Day 19, and then either eliglustat 50 mg BID (if Genz-99067 [active moiety of eliglustat in plasma] trough plasma concentration was greater than or equal to [>=] 5 ng/mL on Day 10) or eliglustat 100 mg BID (if Genz-99067 trough plasma concentration was less than [<] 5 ng/mL), from day 20 to Year 4. After primary completion date (Week 52) participants underwent treatment interruption period of approximately 2 weeks before continuing the same treatment up to Year 9. Participant receiving 100 mg BID could be considered for a further dose increase to 150 mg BID at Week 24 if they met certain criteria (for example, had been on treatment for at least 24 months, had not reached therapeutic goals established for participants receiving Cerezyme, and if all other causes for lack of treatment effect had been evaluated and ruled out).
Measure Participants	26
MS: Unrestricted Mobility: Baseline (n=26)	24 92.3%
MS: Unrestricted Mobility: Year 1 (n=22)	22 84.6%
MS: Unrestricted Mobility: Year 2 (n=20)	20 76.9%
MS: Unrestricted Mobility: Year 3 (n=19)	19 73.1%
MS: Unrestricted Mobility: Year 4 (n=19)	19 73.1%
MS: Unrestricted Mobility: Year 5 (n=19)	19 73.1%
MS: Unrestricted Mobility: Year 6 (n=19)	19 73.1%
MS: Unrestricted Mobility: Year 7 (n=19)	19 73.1%
MS: Unrestricted Mobility: Year 8 (n=16)	16 61.5%
MS: Unrestricted Mobility: Year 9 (n=4)	4 15.4%
MS: Unrestricted Mobility: End of Study (n=19)	18 69.2%
MS: Walks with Difficulty: Baseline (n=26)	2 7.7%
MS: Walks with Difficulty: Year 1 (n=22)	0 0%
MS: Walks with Difficulty: Year 2 (n=20)	0 0%
MS: Walks with Difficulty: Year 3 (n=19)	0 0%
MS: Walks with Difficulty: Year 4 (n=19)	0 0%
MS: Walks with Difficulty: Year 5 (n=19)	0 0%
MS: Walks with Difficulty: Year 6 (n=19)	0 0%
MS: Walks with Difficulty: Year 7 (n=19)	0 0%
MS: Walks with Difficulty: Year 8 (n=16)	0 0%
MS: Walks with Difficulty: Year 9 (n=4)	0 0%
MS: Walks with Difficulty: End of Study (n=19)	1 3.8%

14. Secondary Outcome

Title	Number of Participants With No Bone Crisis at Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study
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 0= no bone crises levels at specified time points were reported.
Time Frame	Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study (Up to Year 9)

Outcome Measure Data

Analysis Population Description

Full analysis set consists of all participants who signed informed consent and received at least one dose of eliglustat. Here 'n' signifies number of participants with available data at specified time points.

Arm/Group Title	Eliglustat
Arm/Group Description	Eliglustat (Genz-112638) capsule as single 50 mg dose on Day 1 then eliglustat 50 mg BID from Day 2 to Day 19, and then either eliglustat 50 mg BID (if Genz-99067 [active moiety of eliglustat in plasma] trough plasma concentration was greater than or equal to [>=] 5 ng/mL on Day 10) or eliglustat 100 mg BID (if Genz-99067 trough plasma concentration was less than [<] 5 ng/mL), from day 20 to Year 4. After primary completion date (Week 52) participants underwent treatment interruption period of approximately 2 weeks before continuing the same treatment up to Year 9. Participant receiving 100 mg BID could be considered for a further dose increase to 150 mg BID at Week 24 if they met certain criteria (for example, had been on treatment for at least 24 months, had not reached therapeutic goals established for participants receiving Cerezyme, and if all other causes for lack of treatment effect had been evaluated and ruled out).
Measure Participants	26
Baseline (n=26)	26 100%
Year 1 (n=22)	22 84.6%
Year 2 (n=20)	20 76.9%
Year 3 (n=19)	19 73.1%
Year 4 (n=19)	19 73.1%
Year 5 (n=19)	19 73.1%
Year 6 (n=19)	19 73.1%
Year 7 (n=19)	19 73.1%
Year 8 (n=16)	16 61.5%
Year 9 (n=4)	4 15.4%
End of Study (n=19)	19 73.1%

15. Secondary Outcome

Title	Bone Marrow Infiltration: Number of Participants With Improvement From Baseline in Dark Marrow at Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8 and at End of Study (EOS)
Description	Bone marrow infiltration assessments were designed to evaluate improvements in dark marrow using MRI. Each MRI assessment was performed for both femurs and consisted of reviewing 6 different zones (the femoral head, greater trochanter, intertrochanteric region, shaft, distal metaphysis, and condyles). MRI images recorded dark marrow for each zone as either present or not present at baseline. In this outcome, number of participants (for whom dark marrow was present at baseline) with improvement from baseline in dark marrow at each specified time point were reported.
Time Frame	Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8 and at End of Study (up to Year 9)

Outcome Measure Data

Analysis Population Description

Full analysis set consists of all participants who signed informed consent and received at least one dose of eliglustat. Here 'n' signifies number of participants who were presented with dark marrow at baseline and had data available at specified time points.

Arm/Group Title	Eliglustat
Arm/Group Description	Eliglustat (Genz-112638) capsule as single 50 mg dose on Day 1 then eliglustat 50 mg BID from Day 2 to Day 19, and then either eliglustat 50 mg BID (if Genz-99067 [active moiety of eliglustat in plasma] trough plasma concentration was greater than or equal to [>=] 5 ng/mL on Day 10) or eliglustat 100 mg BID (if Genz-99067 trough plasma concentration was less than [<] 5 ng/mL), from day 20 to Year 4. After primary completion date (Week 52) participants underwent treatment interruption period of approximately 2 weeks before continuing the same treatment up to Year 8. Participant receiving 100 mg BID could be considered for a further dose increase to 150 mg BID at Week 24 if they met certain criteria (for example, had been on treatment for at least 24 months, had not reached therapeutic goals established for participants receiving Cerezyme, and if all other causes for lack of treatment effect had been evaluated and ruled out).
Measure Participants	26
Femoral Head: Improved: Year 1: (n=16)	3 11.5%
Femoral Head: Improved: Year 2: (n=14)	2 7.7%
Femoral Head: Improved: Year 3: (n=13)	2 7.7%
Femoral Head: Improved: Year 4: (n=13)	2 7.7%
Femoral Head: Improved: Year 5: (n=13)	4 15.4%
Femoral Head: Improved: Year 6: (n=12)	5 19.2%
Femoral Head: Improved: Year 7: (n=13)	5 19.2%
Femoral Head: Improved: Year 8: (n=13)	5 19.2%
Femoral Head: Improved: End of Study: (n=8)	3 11.5%
Greater Trochanter: Improved: Year 1 (n=8)	3 11.5%
Greater Trochanter: Improved: Year 2 (n=7)	2 7.7%
Greater Trochanter: Improved: Year 3 (n=6)	3 11.5%
Greater Trochanter: Improved: Year 4 (n=6)	3 11.5%
Greater Trochanter: Improved: Year 5 (n=7)	3 11.5%
Greater Trochanter: Improved: Year 6 (n=6)	1 3.8%
Greater Trochanter: Improved: Year 7 (n=7)	1 3.8%
Greater Trochanter: Improved: Year 8 (n=7)	1 3.8%
Greater Trochanter: Improved: End of Study (n=4)	0 0%
Intertrochanteric Regions: Improved: Year 1 (n=21)	1 3.8%
Intertrochanteric Regions: Improved: Year 2 (n=19)	3 11.5%
Intertrochanteric Regions: Improved: Year 3 (n=18)	3 11.5%
Intertrochanteric Regions: Improved: Year 4 (n=18)	3 11.5%
Intertrochanteric Regions: Improved: Year 5 (n=18)	5 19.2%
Intertrochanteric Regions: Improved: Year 6 (n=17)	6 23.1%
Intertrochanteric Regions: Improved: Year 7 (n=18)	6 23.1%
Intertrochanteric Regions: Improved: Year 8 (n=17)	7 26.9%
Intertrochanteric Regions: Improved: EOS (n=12)	5 19.2%
Shaft: Improved: Year 1 (n= 20)	1 3.8%
Shaft: Improved: Year 2 (n= 18)	3 11.5%
Shaft: Improved: Year 3 (n= 17)	3 11.5%
Shaft: Improved: Year 4 (n= 17)	3 11.5%
Shaft: Improved: Year 5 (n= 17)	4 15.4%
Shaft: Improved: Year 6 (n= 16)	5 19.2%
Shaft: Improved: Year 7 (n= 17)	5 19.2%
Shaft: Improved: Year 8 (n= 16)	5 19.2%
Shaft: Improved: End of Study (n=11)	4 15.4%
Distal Metaphysis: Improved: Year 1 (n=21)	2 7.7%
Distal Metaphysis: Improved: Year 2 (n=19)	3 11.5%
Distal Metaphysis: Improved: Year 3 (n=18)	4 15.4%
Distal Metaphysis: Improved: Year 4 (n=18)	3 11.5%
Distal Metaphysis: Improved: Year 5 (n=18)	7 26.9%
Distal Metaphysis: Improved: Year 6 (n=17)	8 30.8%
Distal Metaphysis: Improved: Year 7 (n=18)	8 30.8%
Distal Metaphysis: Improved: Year 8 (n=17)	8 30.8%
Distal Metaphysis: Improved: End of Study (n=12)	6 23.1%
Condyles: Improved: Year 1 (n=11)	3 11.5%
Condyles: Improved: Year 2 (n=9)	1 3.8%
Condyles: Improved: Year 3 (n=8)	1 3.8%
Condyles: Improved: Year 4 (n=8)	1 3.8%
Condyles: Improved: Year 5 (n=8)	2 7.7%
Condyles: Improved: Year 6 (n=7)	2 7.7%
Condyles: Improved: Year 7 (n=8)	2 7.7%
Condyles: Improved: Year 8 (n=8)	2 7.7%
Condyles: Improved: End of Study (n=5)	2 7.7%

16. Secondary Outcome

Title	Lumbar Spine and Femur T-Scores for Bone Mineral Density (BMD) at Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study
Description	Images of the lumbar spine and femur were obtained by dual energy X-ray absorptiometry (DXA) to determine T-score for each bone area and total bone mineral density. T-scores compares participant's bone density with that of healthy young participant of same gender. The T-score bone density categories were: normal (score >-1), osteopenia (score -2.5 to <=-1), and osteoporosis (score <= -2.5).
Time Frame	Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study (up to Year 9)

Outcome Measure Data

Analysis Population Description

Full analysis set consists of all participants who signed informed consent and received at least one dose of eliglustat. Here 'n' signifies number of participants with available data at specified time points.

Arm/Group Title	Eliglustat
Arm/Group Description	Eliglustat (Genz-112638) capsule as single 50 mg dose on Day 1 then eliglustat 50 mg BID from Day 2 to Day 19, and then either eliglustat 50 mg BID (if Genz-99067 [active moiety of eliglustat in plasma] trough plasma concentration was greater than or equal to [>=] 5 ng/mL on Day 10) or eliglustat 100 mg BID (if Genz-99067 trough plasma concentration was less than [<] 5 ng/mL), from day 20 to Year 4. After primary completion date (Week 52) participants underwent treatment interruption period of approximately 2 weeks before continuing the same treatment up to Year 9. Participant receiving 100 mg BID could be considered for a further dose increase to 150 mg BID at Week 24 if they met certain criteria (for example, had been on treatment for at least 24 months, had not reached therapeutic goals established for participants receiving Cerezyme, and if all other causes for lack of treatment effect had been evaluated and ruled out).
Measure Participants	26
Lumbar Spine T-Score: Baseline (n= 25)	-1.85 (1.094)
Lumbar Spine T-Score: Year 1 (n= 20)	-1.43 (1.015)
Lumbar Spine T-Score: Year 2 (n= 17)	-0.93 (1.268)
Lumbar Spine T-Score: Year 3 (n= 15)	-1.09 (1.143)
Lumbar Spine T-Score: Year 4 (n= 15)	-0.88 (1.258)
Lumbar Spine T-Score: Year 5 (n= 15)	-0.79 (1.116)
Lumbar Spine T-Score: Year 6 (n= 15)	-0.69 (1.313)
Lumbar Spine T-Score: Year 7 (n= 15)	-0.59 (1.265)
Lumbar Spine T-Score: Year 8 (n= 14)	-0.59 (1.294)
Lumbar Spine T-Score: Year 9 (n= 4)	0.00 (0.753)
Lumbar Spine T-Score: End of Study (n= 6)	-0.35 (1.613)
Femur T-Scores: Baseline (n= 23)	-0.47 (0.894)
Femur T-Scores: Year 1 (n= 19)	-0.24 (0.954)
Femur T-Scores: Year 2 (n= 15)	-0.09 (0.991)
Femur T-Scores: Year 3 (n= 13)	0.16 (0.987)
Femur T-Scores: Year 4 (n= 13)	0.13 (1.044)
Femur T-Scores: Year 5 (n= 13)	0.14 (1.016)
Femur T-Scores: Year 6 (n= 13)	0.19 (0.946)
Femur T-Scores: Year 7 (n= 13)	0.12 (1.021)
Femur T-Scores: Year 8 (n= 12)	0.33 (0.907)
Femur T-Scores: Year 9 (n= 4)	0.33 (0.618)
Femur T-Scores: End of Study (n= 6)	0.18 (1.278)

17. Secondary Outcome

Title	Lumbar Spine and Femur Z-Scores for BMD at Baseline, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study
Description	Images of the lumbar spine and 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, Year 1, Year 2, Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and at End of Study (up to Year 9)

Outcome Measure Data

Analysis Population Description

Full analysis set consists of all participants who signed informed consent and received at least one dose of eliglustat. Here 'n' signifies number of participants with available data at specified time points.

Arm/Group Title	Eliglustat
Arm/Group Description	Eliglustat (Genz-112638) capsule as single 50 mg dose on Day 1 then eliglustat 50 mg BID from Day 2 to Day 19, and then either eliglustat 50 mg BID (if Genz-99067 [active moiety of eliglustat in plasma] trough plasma concentration was greater than or equal to [>=] 5 ng/mL on Day 10) or eliglustat 100 mg BID (if Genz-99067 trough plasma concentration was less than [<] 5 ng/mL), from day 20 to Year 4. After primary completion date (Week 52) participants underwent treatment interruption period of approximately 2 weeks before continuing the same treatment up to Year 9. Participant receiving 100 mg BID could be considered for a further dose increase to 150 mg BID at Week 24 if they met certain criteria (for example, had been on treatment for at least 24 months, had not reached therapeutic goals established for participants receiving Cerezyme, and if all other causes for lack of treatment effect had been evaluated and ruled out).
Measure Participants	26
Lumbar Spine Z-Score: Baseline (n= 25)	-1.49 (1.055)
Lumbar Spine Z-Score: Year 1 (n= 20)	-1.11 (0.961)
Lumbar Spine Z-Score: Year 2 (n= 17)	-0.64 (0.999)
Lumbar Spine Z-Score: Year 3 (n= 15)	-0.63 (0.984)
Lumbar Spine Z-Score: Year 4 (n= 15)	-0.48 (1.073)
Lumbar Spine Z-Score: Year 5 (n= 15)	-0.37 (0.932)
Lumbar Spine Z-Score: Year 6 (n= 15)	-0.27 (1.100)
Lumbar Spine Z-Score: Year 7 (n= 15)	-0.14 (1.053)
Lumbar Spine Z-Score: Year 8 (n= 14)	-0.29 (1.088)
Lumbar Spine Z-Score: Year 9 (n= 4)	-0.05 (0.885)
Lumbar Spine Z-Score: End of Study (n= 6)	0.18 (0.968)
Femur Z-Scores: Baseline (n= 23)	-0.17 (0.783)
Femur Z-Scores: Year 1 (n= 19)	0.04 (0.813)
Femur Z-Scores: Year 2 (n= 15)	0.25 (0.787)
Femur Z-Scores: Year 3 (n= 13)	0.52 (0.704)
Femur Z-Scores: Year 4 (n= 13)	0.48 (0.773)
Femur Z-Scores: Year 5 (n= 13)	0.49 (0.741)
Femur Z-Scores: Year 6 (n= 13)	0.57 (0.665)
Femur Z-Scores: Year 7 (n= 13)	0.52 (0.683)
Femur Z-Scores: Year 8 (n= 12)	0.64 (0.693)
Femur Z-Scores: Year 9 (n= 4)	0.38 (0.793)
Femur Z-Scores: End of Study (n= 6)	0.73 (0.766)

Adverse Events

Time Frame	Up to Year 9.
Adverse Event Reporting Description	Safety set: participants who signed informed consent, received at least 1 dose. Data reported as per dose groups (50/100 mg) as well as for all participants. In the event, 1 participant experienced both serious and non-serious forms of same AE, individual was included in numerator (number of participants affected) of each AE table.
Arm/Group Title	Eliglustat 50 mg BID		Eliglustat 100 mg BID		Eliglustat
Arm/Group Description	Participants who received eliglustat capsule as single 50 mg dose on Day 1 followed by eliglustat 50 mg BID from Day 2 to Year 9.		Participants who received eliglustat capsule as single 50 mg dose on Day 1 followed by eliglustat 50 mg capsule BID from Day 2 to Day 19 and then eliglustat 100 mg capsule BID from Day 20 to Year 9.		Participants who received eliglustat capsule as a single 50 mg dose on Day 1 then eliglustat 50 mg BID from Day 2 to Day 19, and then either eliglustat 50 mg BID or eliglustat 100 mg BID from Day 20 to Year 9. Participants who discontinued prior to Day 20 dose had their dose group set to missing and are only included in the all participants group. The Eliglustat group contains all participants who were treated with Eliglustat, including 2 participants dosed with 50 mg QD and 1 participant dosed with 150 mg BID for majority of study. Participants who had dose adjustment will be presented in dose group they received for majority of study.
All Cause Mortality
	Eliglustat 50 mg BID		Eliglustat 100 mg BID		Eliglustat
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Eliglustat 50 mg BID		Eliglustat 100 mg BID		Eliglustat
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		3/18 (16.7%)		5/26 (19.2%)
Cardiac disorders
Ventricular tachycardia	0/5 (0%)		0/18 (0%)		1/26 (3.8%)
Gastrointestinal disorders
Inguinal hernia	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Hepatobiliary disorders
Cholecystitis	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Injury, poisoning and procedural complications
Exposure during pregnancy	0/5 (0%)		2/18 (11.1%)		2/26 (7.7%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Reproductive system and breast disorders
Ovarian cyst ruptured	0/5 (0%)		0/18 (0%)		1/26 (3.8%)
Other (Not Including Serious) Adverse Events
	Eliglustat 50 mg BID		Eliglustat 100 mg BID		Eliglustat
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/5 (100%)		18/18 (100%)		23/26 (88.5%)
Blood and lymphatic system disorders
Anaemia	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Bone marrow disorder	2/5 (40%)		6/18 (33.3%)		8/26 (30.8%)
Lymphadenopathy	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Splenomegaly	0/5 (0%)		2/18 (11.1%)		2/26 (7.7%)
Thrombocytopenia	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Cardiac disorders
Diastolic dysfunction	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Left atrial dilatation	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Palpitations	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Ear and labyrinth disorders
Ear haemorrhage	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Tinnitus	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Endocrine disorders
Autoimmune thyroiditis	1/5 (20%)		0/18 (0%)		1/26 (3.8%)
Gastrointestinal disorders
Abdominal pain	1/5 (20%)		2/18 (11.1%)		3/26 (11.5%)
Abdominal pain upper	0/5 (0%)		2/18 (11.1%)		2/26 (7.7%)
Constipation	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Dental caries	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Diarrhoea	2/5 (40%)		2/18 (11.1%)		4/26 (15.4%)
Dyspepsia	0/5 (0%)		3/18 (16.7%)		3/26 (11.5%)
Food poisoning	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Haemorrhoids	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Hiatus hernia	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Nausea	0/5 (0%)		3/18 (16.7%)		3/26 (11.5%)
Odynophagia	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Oesophagitis	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Rectal haemorrhage	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Regurgitation	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Toothache	1/5 (20%)		1/18 (5.6%)		2/26 (7.7%)
Vomiting	1/5 (20%)		0/18 (0%)		1/26 (3.8%)
General disorders
Asthenia	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Chest pain	0/5 (0%)		2/18 (11.1%)		2/26 (7.7%)
Chills	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Fatigue	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Influenza like illness	1/5 (20%)		0/18 (0%)		1/26 (3.8%)
Oedema peripheral	0/5 (0%)		3/18 (16.7%)		3/26 (11.5%)
Pain	1/5 (20%)		0/18 (0%)		1/26 (3.8%)
Peripheral swelling	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Pyrexia	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Vessel puncture site swelling	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Hepatobiliary disorders
Biliary dyskinesia	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Cholelithiasis	1/5 (20%)		1/18 (5.6%)		2/26 (7.7%)
Infections and infestations
Abscess	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Bacteriuria	1/5 (20%)		0/18 (0%)		1/26 (3.8%)
Bronchitis	0/5 (0%)		3/18 (16.7%)		3/26 (11.5%)
Conjunctivitis	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Cystitis	0/5 (0%)		2/18 (11.1%)		2/26 (7.7%)
Infected dermal cyst	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Influenza	1/5 (20%)		2/18 (11.1%)		3/26 (11.5%)
Nasopharyngitis	1/5 (20%)		3/18 (16.7%)		4/26 (15.4%)
Onychomycosis	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Otitis media	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Pharyngitis	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Respiratory tract infection	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Respiratory tract infection viral	0/5 (0%)		2/18 (11.1%)		2/26 (7.7%)
Sinusitis	1/5 (20%)		2/18 (11.1%)		3/26 (11.5%)
Tooth infection	1/5 (20%)		0/18 (0%)		1/26 (3.8%)
Upper respiratory tract infection	0/5 (0%)		4/18 (22.2%)		4/26 (15.4%)
Urinary tract infection	1/5 (20%)		5/18 (27.8%)		6/26 (23.1%)
Viral infection	2/5 (40%)		5/18 (27.8%)		7/26 (26.9%)
Injury, poisoning and procedural complications
Chest injury	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Epicondylitis	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Joint dislocation	1/5 (20%)		0/18 (0%)		1/26 (3.8%)
Limb injury	0/5 (0%)		2/18 (11.1%)		2/26 (7.7%)
Post-traumatic pain	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Radius fracture	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Road traffic accident	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Scar	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Tibia fracture	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Investigations
Bacterial test positive	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Blood folate decreased	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Blood pressure increased	0/5 (0%)		2/18 (11.1%)		2/26 (7.7%)
Body temperature increased	0/5 (0%)		2/18 (11.1%)		2/26 (7.7%)
Bone density decreased	1/5 (20%)		0/18 (0%)		1/26 (3.8%)
Gamma-glutamyltransferase increased	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Nerve conduction studies abnormal	1/5 (20%)		2/18 (11.1%)		3/26 (11.5%)
Urinary sediment present	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Vitamin B12 decreased	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Weight decreased	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Metabolism and nutrition disorders
Iron deficiency	1/5 (20%)		0/18 (0%)		1/26 (3.8%)
Obesity	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Type 2 diabetes mellitus	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Vitamin B12 deficiency	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/5 (20%)		5/18 (27.8%)		6/26 (23.1%)
Arthritis	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Back pain	0/5 (0%)		3/18 (16.7%)		3/26 (11.5%)
Bone pain	1/5 (20%)		0/18 (0%)		1/26 (3.8%)
Muscular weakness	0/5 (0%)		2/18 (11.1%)		2/26 (7.7%)
Musculoskeletal chest pain	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Musculoskeletal discomfort	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Musculoskeletal pain	0/5 (0%)		4/18 (22.2%)		4/26 (15.4%)
Osteoarthritis	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Osteochondrosis	0/5 (0%)		2/18 (11.1%)		2/26 (7.7%)
Osteonecrosis	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Osteoporosis	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Pain in extremity	1/5 (20%)		5/18 (27.8%)		6/26 (23.1%)
Spinal osteoarthritis	1/5 (20%)		1/18 (5.6%)		2/26 (7.7%)
Tendonitis	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Haemangioma of bone	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Skin papilloma	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Nervous system disorders
Carpal tunnel syndrome	0/5 (0%)		2/18 (11.1%)		2/26 (7.7%)
Cervical radiculopathy	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Dizziness	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Dizziness postural	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Dysaesthesia	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Headache	0/5 (0%)		4/18 (22.2%)		4/26 (15.4%)
Hyperreflexia	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Lumbar radiculopathy	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Neuropathy peripheral	0/5 (0%)		2/18 (11.1%)		2/26 (7.7%)
Paraesthesia	1/5 (20%)		0/18 (0%)		1/26 (3.8%)
Peripheral sensory neuropathy	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Presyncope	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Psychiatric disorders
Anxiety	0/5 (0%)		2/18 (11.1%)		2/26 (7.7%)
Insomnia	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Sleep disorder	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Renal and urinary disorders
Calculus urinary	0/5 (0%)		2/18 (11.1%)		2/26 (7.7%)
Dysuria	1/5 (20%)		1/18 (5.6%)		2/26 (7.7%)
Haematuria	2/5 (40%)		2/18 (11.1%)		4/26 (15.4%)
Leukocyturia	1/5 (20%)		0/18 (0%)		1/26 (3.8%)
Nocturia	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Renal cyst	1/5 (20%)		0/18 (0%)		1/26 (3.8%)
Reproductive system and breast disorders
Atrophic vulvovaginitis	1/5 (20%)		0/18 (0%)		1/26 (3.8%)
Benign prostatic hyperplasia	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Cervical dysplasia	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Cervical polyp	1/5 (20%)		0/18 (0%)		1/26 (3.8%)
Erectile dysfunction	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Genital pain	1/5 (20%)		0/18 (0%)		1/26 (3.8%)
Metrorrhagia	1/5 (20%)		1/18 (5.6%)		2/26 (7.7%)
Respiratory, thoracic and mediastinal disorders
Cough	0/5 (0%)		2/18 (11.1%)		2/26 (7.7%)
Epistaxis	0/5 (0%)		2/18 (11.1%)		2/26 (7.7%)
Nasal congestion	0/5 (0%)		2/18 (11.1%)		2/26 (7.7%)
Oropharyngeal pain	0/5 (0%)		3/18 (16.7%)		3/26 (11.5%)
Paranasal sinus discomfort	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Rhinorrhoea	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Skin and subcutaneous tissue disorders
Alopecia	1/5 (20%)		0/18 (0%)		1/26 (3.8%)
Dermal cyst	0/5 (0%)		2/18 (11.1%)		2/26 (7.7%)
Dermatitis allergic	1/5 (20%)		0/18 (0%)		1/26 (3.8%)
Dry skin	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Ecchymosis	1/5 (20%)		1/18 (5.6%)		2/26 (7.7%)
Erythema	0/5 (0%)		3/18 (16.7%)		3/26 (11.5%)
Prurigo	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Pruritus	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Purpura	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Rash	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Rosacea	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Telangiectasia	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Surgical and medical procedures
Tooth extraction	1/5 (20%)		1/18 (5.6%)		2/26 (7.7%)
Vascular disorders
Haematoma	0/5 (0%)		1/18 (5.6%)		1/26 (3.8%)
Hypertension	0/5 (0%)		2/18 (11.1%)		2/26 (7.7%)

Limitations/Caveats

Due to the very small number of participants at Year 9, the point estimates of mean and standard deviation are not reliable.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.