A Study of the Efficacy and Safety of Eliglustat Tartrate... | NCT00358150

ID	Type	Description	Link
2005-004732-42	EudraCT Number
DRI12816	Other Identifier	Sanofi

Label	Type	Description	Intervention Names
Eliglustat tartrate	Experimental		Drug: Eliglustat tartrate

Name	Type	Description	Arm Group Labels	Other Names
Eliglustat tartrate	Drug	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).

Measure	Description	Time Frame
Percentage of Participants Demonstrating A Meaningful Clinical Response	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.	Baseline, Year 1

Measure	Description	Time Frame
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	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.	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)

Name	Affiliation	Role
Medical Monitor	Genzyme, a Sanofi Company	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
New York University		New York	New York		United States

PubMed Identifier	Type	Citation	Retractions
17509920	Background	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. doi: 10.1016/j.ymgme.2007.04.001. Epub 2007 May 16.
20864621

ID	Title	Description
FG000	Eliglustat	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).

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants Demonstrating A Meaningful Clinical Response

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.

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

Posted

Number

percentage of participants

Baseline, Year 1

ID	Title	Description
OG000	Eliglustat	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).

Units	Counts
Participants	OG00026

Title

Denominators

Categories

Title	Measurements
	OG00077

Secondary

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

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.

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.

Posted

Mean

Standard Deviation

percent change

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)

ID	Title	Description
OG000	Eliglustat	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).

Secondary

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

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.

Posted

Mean

Standard Deviation

percent change

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)

ID	Title	Description
OG000	Eliglustat	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).

Secondary

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

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

Posted

Mean

Standard Deviation

g/dL

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)

ID	Title	Description
OG000	Eliglustat	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).

Secondary

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

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.

Posted

Mean

Standard Deviation

percent change

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)

ID	Title	Description
OG000	Eliglustat	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).

Secondary

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

Posted

Mean

Standard Deviation

percent change

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)

ID	Title	Description
OG000	Eliglustat	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).

Secondary

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

Posted

Mean

Standard Deviation

percent change

Baseline, Year 1, Year 2

ID	Title	Description
OG000	Eliglustat	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).

Units	Counts

Secondary

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

Posted

Mean

Standard Deviation

percent change

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)

ID	Title	Description
OG000	Eliglustat	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).

Secondary

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

Posted

Mean

Standard Deviation

percent change

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)

ID	Title	Description
OG000	Eliglustat	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).

Units

Secondary

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

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.

Posted

Mean

Standard Deviation

units on a scale

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)

ID	Title	Description
OG000	Eliglustat	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).

Secondary

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

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.

Posted

Mean

Standard Deviation

units on a scale

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)

ID	Title	Description
OG000	Eliglustat	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).

Secondary

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

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.

Posted

Number

participants

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)

ID	Title	Description
OG000	Eliglustat	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).

Secondary

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

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.

Posted

Number

participants

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)

ID	Title	Description
OG000	Eliglustat	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).

Secondary

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

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.

Posted

Number

participants

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)

ID	Title	Description
OG000	Eliglustat	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).

Secondary

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)

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.

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.

Posted

Count of Participants

Participants

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)

ID	Title	Description
OG000	Eliglustat	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).

Secondary

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

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).

Posted

Mean

Standard Deviation

T-Score

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)

ID	Title	Description
OG000	Eliglustat	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).

Secondary

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

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).

Posted

Mean

Standard Deviation

Z-Score

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)

ID	Title	Description
OG000	Eliglustat	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).

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Bone marrow disorder	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected5 at risk EG0016 affected18 at risk EG0028 affected26 at risk
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Splenomegaly	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0012 affected18 at risk EG0022 affected26 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Diastolic dysfunction	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Left atrial dilatation	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Palpitations	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Ear haemorrhage	Ear and labyrinth disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Tinnitus	Ear and labyrinth disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Autoimmune thyroiditis	Endocrine disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected5 at risk EG0010 affected18 at risk EG0021 affected26 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected5 at risk EG0012 affected18 at risk EG0023 affected26 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0012 affected18 at risk EG0022 affected26 at risk
Constipation	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Dental caries	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected5 at risk EG0012 affected18 at risk EG0024 affected26 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0013 affected18 at risk EG0023 affected26 at risk
Food poisoning	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Hiatus hernia	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Nausea	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0013 affected18 at risk EG0023 affected26 at risk
Odynophagia	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Oesophagitis	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Regurgitation	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Toothache	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected5 at risk EG0011 affected18 at risk EG0022 affected26 at risk
Vomiting	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected5 at risk EG0010 affected18 at risk EG0021 affected26 at risk
Asthenia	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Chest pain	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0012 affected18 at risk EG0022 affected26 at risk
Chills	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Fatigue	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Influenza like illness	General disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected5 at risk EG0010 affected18 at risk EG0021 affected26 at risk
Oedema peripheral	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0013 affected18 at risk EG0023 affected26 at risk
Pain	General disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected5 at risk EG0010 affected18 at risk EG0021 affected26 at risk
Peripheral swelling	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Pyrexia	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Vessel puncture site swelling	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Biliary dyskinesia	Hepatobiliary disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected5 at risk EG0011 affected18 at risk EG0022 affected26 at risk
Abscess	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Bacteriuria	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected5 at risk EG0010 affected18 at risk EG0021 affected26 at risk
Bronchitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0013 affected18 at risk EG0023 affected26 at risk
Conjunctivitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Cystitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0012 affected18 at risk EG0022 affected26 at risk
Infected dermal cyst	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Influenza	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected5 at risk EG0012 affected18 at risk EG0023 affected26 at risk
Nasopharyngitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected5 at risk EG0013 affected18 at risk EG0024 affected26 at risk
Onychomycosis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Otitis media	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Pharyngitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Respiratory tract infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Respiratory tract infection viral	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0012 affected18 at risk EG0022 affected26 at risk
Sinusitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected5 at risk EG0012 affected18 at risk EG0023 affected26 at risk
Tooth infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected5 at risk EG0010 affected18 at risk EG0021 affected26 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0014 affected18 at risk EG0024 affected26 at risk
Urinary tract infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 affected5 at risk EG0015 affected18 at risk EG0026 affected26 at risk
Viral infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0002 affected5 at risk EG0015 affected18 at risk EG0027 affected26 at risk
Chest injury	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Epicondylitis	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Joint dislocation	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0001 affected5 at risk EG0010 affected18 at risk EG0021 affected26 at risk
Limb injury	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0012 affected18 at risk EG0022 affected26 at risk
Post-traumatic pain	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Radius fracture	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Scar	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Tibia fracture	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Bacterial test positive	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Blood folate decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Blood pressure increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0012 affected18 at risk EG0022 affected26 at risk
Body temperature increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0012 affected18 at risk EG0022 affected26 at risk
Bone density decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0001 affected5 at risk EG0010 affected18 at risk EG0021 affected26 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Nerve conduction studies abnormal	Investigations	MedDRA 18.0	Systematic Assessment	EG0001 affected5 at risk EG0012 affected18 at risk EG0023 affected26 at risk
Urinary sediment present	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Vitamin B12 decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Weight decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Iron deficiency	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected5 at risk EG0010 affected18 at risk EG0021 affected26 at risk
Obesity	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Type 2 diabetes mellitus	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Vitamin B12 deficiency	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected5 at risk EG0015 affected18 at risk EG0026 affected26 at risk
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0013 affected18 at risk EG0023 affected26 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected5 at risk EG0010 affected18 at risk EG0021 affected26 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0012 affected18 at risk EG0022 affected26 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Musculoskeletal discomfort	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0014 affected18 at risk EG0024 affected26 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Osteochondrosis	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0012 affected18 at risk EG0022 affected26 at risk
Osteonecrosis	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Osteoporosis	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected5 at risk EG0015 affected18 at risk EG0026 affected26 at risk
Spinal osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected5 at risk EG0011 affected18 at risk EG0022 affected26 at risk
Tendonitis	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Haemangioma of bone	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Skin papilloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Carpal tunnel syndrome	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0012 affected18 at risk EG0022 affected26 at risk
Cervical radiculopathy	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Dizziness	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Dizziness postural	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Dysaesthesia	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Headache	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0014 affected18 at risk EG0024 affected26 at risk
Hyperreflexia	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Lumbar radiculopathy	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0012 affected18 at risk EG0022 affected26 at risk
Paraesthesia	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected5 at risk EG0010 affected18 at risk EG0021 affected26 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Presyncope	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Anxiety	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0012 affected18 at risk EG0022 affected26 at risk
Insomnia	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Sleep disorder	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Calculus urinary	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0012 affected18 at risk EG0022 affected26 at risk
Dysuria	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected5 at risk EG0011 affected18 at risk EG0022 affected26 at risk
Haematuria	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0002 affected5 at risk EG0012 affected18 at risk EG0024 affected26 at risk
Leukocyturia	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected5 at risk EG0010 affected18 at risk EG0021 affected26 at risk
Nocturia	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Renal cyst	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected5 at risk EG0010 affected18 at risk EG0021 affected26 at risk
Atrophic vulvovaginitis	Reproductive system and breast disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected5 at risk EG0010 affected18 at risk EG0021 affected26 at risk
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Cervical dysplasia	Reproductive system and breast disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Cervical polyp	Reproductive system and breast disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected5 at risk EG0010 affected18 at risk EG0021 affected26 at risk
Erectile dysfunction	Reproductive system and breast disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Genital pain	Reproductive system and breast disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected5 at risk EG0010 affected18 at risk EG0021 affected26 at risk
Metrorrhagia	Reproductive system and breast disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected5 at risk EG0011 affected18 at risk EG0022 affected26 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0012 affected18 at risk EG0022 affected26 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0012 affected18 at risk EG0022 affected26 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0012 affected18 at risk EG0022 affected26 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0013 affected18 at risk EG0023 affected26 at risk
Paranasal sinus discomfort	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected5 at risk EG0010 affected18 at risk EG0021 affected26 at risk
Dermal cyst	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0012 affected18 at risk EG0022 affected26 at risk
Dermatitis allergic	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected5 at risk EG0010 affected18 at risk EG0021 affected26 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Ecchymosis	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 affected5 at risk EG0011 affected18 at risk EG0022 affected26 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0013 affected18 at risk EG0023 affected26 at risk
Prurigo	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Purpura	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Rosacea	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Telangiectasia	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Tooth extraction	Surgical and medical procedures	MedDRA 18.0	Systematic Assessment	EG0001 affected5 at risk EG0011 affected18 at risk EG0022 affected26 at risk
Haematoma	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Hypertension	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0012 affected18 at risk EG0022 affected26 at risk

ID	Term
D013106	Sphingolipidoses
D020140	Lysosomal Storage Diseases, Nervous System
D020739	Brain Diseases, Metabolic, Inborn
D001928	Brain Diseases, Metabolic
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D008661	Metabolism, Inborn Errors
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D008064	Lipidoses
D008052	Lipid Metabolism, Inborn Errors
D016464	Lysosomal Storage Diseases
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D052439	Lipid Metabolism Disorders

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Eliglustat 50 mg BID	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.	0	5	5	5
EG001	Eliglustat 100 mg BID	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.	3	18	18	18
EG002	Eliglustat	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.	5	26	23	26

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Ventricular tachycardia	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0010 affected18 at risk EG0021 affected26 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Exposure during pregnancy	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0012 affected18 at risk EG0022 affected26 at risk
Abortion spontaneous	Pregnancy, puerperium and perinatal conditions	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0011 affected18 at risk EG0021 affected26 at risk
Ovarian cyst ruptured	Reproductive system and breast disorders	MedDRA 18.0	Systematic Assessment	EG0000 affected5 at risk EG0010 affected18 at risk EG0021 affected26 at risk