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Clinical Trial Results:
A Phase 3, Randomized, MultiCenter, MultiNational, DoubleBlind Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Once Daily Versus Twice Daily Dosing of Genz112638 in Patients With Gaucher Disease Type 1 Who Have Demonstrated Clinical Stability on a Twice Daily Dose of Genz112638

Summary
EudraCT number	2009-015811-42
Trial protocol	SE PT AT GR
Global end of trial date	06 Oct 2015

Results information
Results version number	v1(current)
This version publication date	04 Nov 2016
First version publication date	04 Nov 2016
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

GZGD03109

ISRCTN number

US NCT number

NCT01074944

WHO universal trial number (UTN)

Sponsor organisation name

Genzyme, a Sanofi Company

Sponsor organisation address

500 Kendall Street, Cambridge MA, United States, 02142

Public contact

Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com

Scientific contact

Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.co

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

10 Sep 2016

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

06 Oct 2015

Was the trial ended prematurely?

Main objective of the trial

To evaluate the efficacy and safety of once daily (QD) versus twice daily (BID) dosing of eliglustat in subjects with Gaucher disease type 1 (GD1) who had previously demonstrated clinical stability on BID dosing of eliglustat.

Protection of trial subjects

Subjects were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time in language and terms appropriate for the subject and considering the local culture. During the course of the trial, subjects were provided with individual subject cards indicating the nature of the trial the subject is participating, contact details and any information needed in the event of a medical emergency. Collected personal data and human biological samples were processed in compliance with the Sanofi Aventis Group Personal Data Protection Charter ensuring that the Group abides by the laws governing personal data protection in force in all countries in which it operates.

Background therapy

Evidence for comparator

Actual start date of recruitment

01 Jun 2010

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 5

Country: Number of subjects enrolled

Austria: 4

Country: Number of subjects enrolled

Brazil: 40

Country: Number of subjects enrolled

Canada: 5

Country: Number of subjects enrolled

China: 25

Country: Number of subjects enrolled

France: 5

Country: Number of subjects enrolled

Greece: 3

Country: Number of subjects enrolled

Croatia: 5

Country: Number of subjects enrolled

India: 4

Country: Number of subjects enrolled

Japan: 10

Country: Number of subjects enrolled

Netherlands: 6

Country: Number of subjects enrolled

Portugal: 6

Country: Number of subjects enrolled

Romania: 2

Country: Number of subjects enrolled

Russian Federation: 12

Country: Number of subjects enrolled

Serbia: 7

Country: Number of subjects enrolled

Sweden: 3

Country: Number of subjects enrolled

United States: 28

Worldwide total number of subjects

170

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

162

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

The study was conducted at 45 centers in 17 countries between 1 June 2010 and 6 October 2015. A total of 219 subjects were screened, out of which 170 entered into the lead in period. Remaining 48 subjects were screen failures and 1 subject withdrew before entering into the lead in period.

Screening details

Subject disposition divided in 4 periods. Lead in Period (LIP):to assess randomization criteria.Primary analysis period(PAP):assess therapeutic efficacy at 2 dosing regimen in randomized subjects. Long-term treatment period (LTTP):assess long term efficacy. Extended treatment period(ETP):who were non-randomized after LIP continued in this period

Period 1 title

LIP (up to 78 weeks)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

LIP, Eliglustat

Arm description

All subjects (except in Japan) received eliglustat 50 mg, BID on Day 1 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual pharmacokinetics data for up to 78 weeks. All subjects in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual pharmacokinetics data for up to 78 weeks.

Arm type

Experimental

Investigational medicinal product name

Eliglustat

Investigational medicinal product code

Genz-112638

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

All subjects (except in Japan) received eliglustat 50 mg BID on Day 1 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual pharmacokinetics data for up to 78 weeks. All subjects in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual pharmacokinetics data for up to 78 weeks.

Number of subjects in period 1	LIP, Eliglustat
Started	170
Completed	131
Not completed	39
Consent withdrawn by subject	7
Failed to Meet Randomization Criteria	25
Adverse event, non-fatal	2
Pregnancy	4
Non-Compliance With Protocol	1

Period 2 title

PAP (up to 52 weeks)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

PAP, Eliglustat: QD

Arm description

All subjects who were randomized after meeting all randomization criteria (defined as: no more than 1 bone crisis and was free of other clinically symptomatic bone disease [such as bone pain attributable to osteonecrosis and/or pathological fractures) during the first 6 months of the LIP; mean hemoglobin level of ≥11 g/ dL [if female] and ≥12 g/dL [if male]; mean platelet count ≥100,000/mm^3; spleen volume ≤10 times of normal; liver volume ≤1.5 times of normal; had a dose of 50 mg BID or 100 mg BID of eliglustat for at least 4 months and a peak (2-hour) Genz-99067 plasma concentration of <50 ng/mL) after either 26, 52 or 78 weeks of LIP received eliglustat capsules at the total daily dose (TDD) of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).

Arm type

Experimental

Investigational medicinal product name

Eliglustat

Investigational medicinal product code

Genz-112638

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Eliglustat at the TDD of 100 mg or 200 mg QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).

PAP, Eliglustat: BID

Arm description

All subjects who were randomized after meeting all randomization criteria (defined as: no more than 1 bone crisis and was free of other clinically symptomatic bone disease [such as bone pain attributable to osteonecrosis and/or pathological fractures) during the first 6 months of the LIP; mean hemoglobin level of ≥11 g/ dL [if female] and ≥12 g/dL [if male]; mean platelet count ≥100,000/mm^3; spleen volume ≤10 times of normal; liver volume ≤1.5 times of normal; had a dose of 50 mg BID or 100 mg BID of eliglustat for at least 4 months and a peak (2-hour) Genz-99067 plasma concentration of <50 ng/mL) after either 26, 52 or 78 weeks of LIP, received eliglustat at the TDD of 100 or 200 mg (the TDD they were on before randomization) given BID from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).

Arm type

Experimental

Investigational medicinal product name

Eliglustat

Investigational medicinal product code

Genz-112638

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Eliglustat at the TDD of 100 mg or 200 mg administered as 50 mg or 100 mg capsule BID from Day 1 up to Week 52 in PAP.

Number of subjects in period 2	PAP, Eliglustat: QD	PAP, Eliglustat: BID
Started	65	66
Completed Successfully the PAP	54 ^[1]	60 ^[2]
Completed	60	61
Not completed	5	5
Consent withdrawn by subject	1	1
Pregnancy	1	-
Adverse event	2	3
Non-Compliant to Protocol	1	1

Notes
[1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Six subjects in the QD arm completed the PAP, but failed (did not maintain their therapeutic goals; see Period 3, LTTP arm description) below.
[2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: One subject in the BID arm completed the PAP, but failed (did not maintain their therapeutic goals; see Period 3, LTTP, arm description) below.

Period 3 title

LTTP

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

LTTP, Eliglustat

Arm description

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

Arm type

Experimental

Investigational medicinal product name

Eliglustat

Investigational medicinal product code

Genz-112638

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Eliglustat at the TDD of 100 mg or 200 mg QD till the end of study. Subjects who did not maintain their therapeutic goals continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) BID till the end of the study.

Number of subjects in period 3	LTTP, Eliglustat
Started	121
Completed	95
Not completed	26
Consent withdrawn by subject	2
Transitioned to Commercial Eliglustat	18
Entered in Period, But Not Treated	1
Adverse event	3
Lost to follow-up	2

Period 4 title

ETP

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Extended Treatment Period (ETP), Eliglustat

Arm description

All subjects who did not meet all the randomization criteria at Week 78 of the LIP continued in the ETP and received eliglustat capsules at the same dose as they were receiving at the end of LIP till the end of the study.

Arm type

Experimental

Investigational medicinal product name

Eliglustat

Investigational medicinal product code

Genz-112638

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Eliglustat at the dose the subjects received at the end of LIP (50 mg QD, 50 mg BID or 100 mg BID).

Number of subjects in period 4 ^[3]	Extended Treatment Period (ETP), Eliglustat
Started	25
Completed	20
Not completed	5
Transitioned to Commercial Eliglustat	3
Pregnancy	2

Notes
[3] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Started number includes only those subjects who failed to meet the randomization criteria during the lead in period.

Baseline characteristics

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Reporting group title

LIP, Eliglustat

Reporting group description

Reporting group values	LIP, Eliglustat	Total
Number of subjects	170	170
Age categorical
Units: Subjects
Age Continuous
Units: years
arithmetic mean (standard deviation)	37.7 ( 15.1 )	-
Gender, Male/Female
Units: subjects
Female	81	81
Male	89	89

End points

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Reporting group title

LIP, Eliglustat

Reporting group description

Reporting group title

PAP, Eliglustat: QD

Reporting group description

Reporting group title

PAP, Eliglustat: BID

Reporting group description

All subjects who were randomized after meeting all randomization criteria (defined as: no more than 1 bone crisis and was free of other clinically symptomatic bone disease [such as bone pain attributable to osteonecrosis and/or pathological fractures) during the first 6 months of the LIP; mean hemoglobin level of ≥11 g/ dL [if female] and ≥12 g/dL [if male]; mean platelet count ≥100,000/mm^3; spleen volume ≤10 times of normal; liver volume ≤1.5 times of normal; had a dose of 50 mg BID or 100 mg BID of eliglustat for at least 4 months and a peak (2-hour) Genz-99067 plasma concentration of <50 ng/mL) after either 26, 52 or 78 weeks of LIP, received eliglustat at the TDD of 100 or 200 mg (the TDD they were on before randomization) given BID from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).

Reporting group title

LTTP, Eliglustat

Reporting group description

Reporting group title

Extended Treatment Period (ETP), Eliglustat

Reporting group description

Primary: PAP: Percentage of Subjects Who Remained Stable for 52 Weeks During the PAP

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End point title

PAP: Percentage of Subjects Who Remained Stable for 52 Weeks During the PAP

End point description

Subject were considered as stable if they met the following criteria: hemoglobin level did not decrease >1.5 g/dL from baseline for PAP, platelet count does not decrease >25% below Baseline for PAP, liver volume does not increase >20% above Baseline for PAP, spleen volume does not increase >25% above Baseline for PAP. Baseline for PAP was defined as last available assessment prior to randomization. Analysis was performed on per protocol (PP) population which included all subjects who were at least 80% compliant with investigational medicinal product (IMP) dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations.

End point type

Primary

End point timeframe

PAP Baseline up to the end of PAP (Week 52)

End point values	PAP, Eliglustat: QD	PAP, Eliglustat: BID
Number of subjects analysed	56	59
Units: percentage of subjects
number (confidence interval 95%)	80.4 (67.6 to 89.8)	83.1 (71 to 91.6)

Statistical Analysis 1

Comparison groups

PAP, Eliglustat: QD v PAP, Eliglustat: BID

Number of subjects included in analysis

115

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[1]

Method

Parameter type

Difference in Percentage Stable

Point estimate

-2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-17.7

upper limit

11.9

Notes
[1] - Eliglustat QD treatment was declared non-inferior to BID treatment if the lower bound of the 95% confidence interval (CI) for the difference was within the non-inferiority margin of -0.15 (or -15%).

Secondary: PAP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26, 52

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End point title

PAP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26, 52

End point description

PP population included all subjects who were at least 80% compliant with dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. Here 'n' signifies number of subjects with available data at specified time points for each arm respectively.

End point type

Secondary

End point timeframe

Baseline, Week 26 and Week 52

End point values	PAP, Eliglustat: QD	PAP, Eliglustat: BID
Number of subjects analysed	56	59
Units: g/dL
arithmetic mean (standard deviation)
Baseline (n=56, 59)	13.641 ( 1.214 )	13.691 ( 1.273 )
Week 26 (n=56, 57)	13.677 ( 1.377 )	13.946 ( 1.509 )
Week 52 (n=56, 59)	13.605 ( 1.432 )	13.824 ( 1.442 )

No statistical analyses for this end point

Secondary: PAP: Mean Platelet Count at Baseline, Weeks 26, 52

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End point title

PAP: Mean Platelet Count at Baseline, Weeks 26, 52

End point description

End point type

Secondary

End point timeframe

Baseline, Week 26 and Week 52

End point values	PAP, Eliglustat: QD	PAP, Eliglustat: BID
Number of subjects analysed	56	59
Units: platelets*10^9 /L
arithmetic mean (standard deviation)
Baseline (n=56, 59)	204.01 ( 81.49 )	171.09 ( 63.5 )
Week 26 (n=56, 57)	195.75 ( 66.65 )	173.94 ( 65.61 )
Week 52 (n=56, 59)	207.2 ( 80.62 )	176.1 ( 62.01 )

No statistical analyses for this end point

Secondary: PAP: Mean Spleen Volume at Baseline, Weeks 26, 52

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End point title

PAP: Mean Spleen Volume at Baseline, Weeks 26, 52

End point description

PP population included all subjects who were at least 80% compliant with dosing during PAP, had all of the necessary baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. Here 'n' signifies number of subjects with available data for specified category for each arm respectively.

End point type

Secondary

End point timeframe

Baseline, Week 26, Week 52

End point values	PAP, Eliglustat: QD	PAP, Eliglustat: BID
Number of subjects analysed	56	59
Units: MN
arithmetic mean (standard deviation)
Baseline (n= 39, 45)	3.309 ( 1.465 )	3.787 ( 1.623 )
Week 26 (n= 39, 45)	3.066 ( 1.299 )	3.504 ( 1.365 )
Week 52 (n= 39, 45)	3.017 ( 1.381 )	3.394 ( 1.305 )

No statistical analyses for this end point

Secondary: PAP: Mean Liver Volume at Baseline, Weeks 26, 52

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End point title

PAP: Mean Liver Volume at Baseline, Weeks 26, 52

End point description

PP population included all subjects who were at least 80% compliant with dosing during PAP, had all of the necessary baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. Here, 'n' signifies number of subjects with available data for specified category for each arm respectively.

End point type

Secondary

End point timeframe

Baseline, Week 26 and Week 52

End point values	PAP, Eliglustat: QD	PAP, Eliglustat: BID
Number of subjects analysed	56	59
Units: MN
arithmetic mean (standard deviation)
Baseline (n=56, 59)	0.981 ( 0.187 )	1.04 ( 0.198 )
Week 26 (n=56, 59)	0.987 ( 0.19 )	1.024 ( 0.179 )
Week 52 (n=56, 59)	0.97 ( 0.17 )	1.009 ( 0.196 )

No statistical analyses for this end point

Secondary: PAP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26 and Week 52

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End point title

PAP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26 and Week 52

End point description

Chitotriosidase biomarker was assayed from plasma. PP population which all subjects who were at least 80% compliant with dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. Here, 'n' signifies number of subjects with available data for specified category for each arm respectively.

End point type

Secondary

End point timeframe

Baseline, Week 26, Week 52

End point values	PAP, Eliglustat: QD	PAP, Eliglustat: BID
Number of subjects analysed	56	59
Units: nmol/hr/mL
arithmetic mean (standard deviation)
Baseline (n=55, 59)	1523.7 ( 2556.6 )	1554.9 ( 1895 )
Week 26 (n=52, 54)	1279.6 ( 2328.1 )	1242 ( 2012.6 )
Week 52 (n=54, 55)	1076.6 ( 1855.8 )	1170.1 ( 1683.3 )

No statistical analyses for this end point

Secondary: PAP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26, and Week 52

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End point title

PAP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26, and Week 52

End point description

GL-1 on DBS biomarker was assayed from dried blood spot (DBS). PP population included all subjects who were at least 80% compliant with dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. Here 'n' signifies number of subjects with available data at specified time points for each arm respectively.

End point type

Secondary

End point timeframe

Baseline, Week 26, and Week 52

End point values	PAP, Eliglustat: QD	PAP, Eliglustat: BID
Number of subjects analysed	56	59
Units: mcg/mL
arithmetic mean (standard deviation)
GL-1 on DBS: Baseline (n=54, 55)	2.257 ( 0.835 )	2.425 ( 1.378 )
GL-1 on DBS: week 26 (n=54, 54)	2.481 ( 1.037 )	2.563 ( 1.1 )
GL-1 on DBS: week 52 (n=53, 55)	2.853 ( 1.383 )	2.707 ( 1.443 )

No statistical analyses for this end point

Secondary: PAP: Mean Biomarker Macrophage Inflammatory Protein-1 Beta (MIP1-beta) Value at Baseline, Weeks 26, 52

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End point title

PAP: Mean Biomarker Macrophage Inflammatory Protein-1 Beta (MIP1-beta) Value at Baseline, Weeks 26, 52

End point description

MIP1-beta biomarker was assayed from plasma. PP population included all subjects who were at least 80% compliant with dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. Here, 'n' signifies number of subjects with available data for specified category for each arm respectively.

End point type

Secondary

End point timeframe

Baseline, Week 26, Week 52

End point values	PAP, Eliglustat: QD	PAP, Eliglustat: BID
Number of subjects analysed	56	59
Units: pg/mL
arithmetic mean (standard deviation)
Baseline (n=54, 58)	77.7 ( 74.4 )	118.8 ( 156.3 )
Week 26 (n=52, 54)	74.5 ( 68 )	121 ( 204.4 )
Week 52 (n=54, 55)	81.3 ( 82.8 )	117.9 ( 165.3 )

No statistical analyses for this end point

Secondary: PAP: Bone Mineral Density (BMD) at Baseline and Week 52: PP Population

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End point title

PAP: Bone Mineral Density (BMD) at Baseline and Week 52: PP Population

End point description

BMD measurements of the spine and bilateral femur were acquired by dual-energy x-ray absorptiometry (DXA) scan. PP population included all subjects who were at least 80% compliant with dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. Here, 'n' signifies number of subjects with available data at specified time points for each arm respectively.

End point type

Secondary

End point timeframe

Baseline, Week 52

End point values	PAP, Eliglustat: QD	PAP, Eliglustat: BID
Number of subjects analysed	56	59
Units: g/cm^2
arithmetic mean (standard deviation)
Lumbar Spine: Baseline (n=51, 55)	1.073 ( 0.177 )	1.081 ( 0.172 )
Lumbar Spine: Week 52 (n=51, 55)	1.089 ( 0.183 )	1.086 ( 0.177 )
Left Femur: Baseline (n=48, 47)	0.979 ( 0.219 )	1 ( 0.199 )
Left Femur: Week 52 (n=48, 47)	0.972 ( 0.211 )	0.99 ( 0.196 )
Right Femur: Baseline (n=48, 47)	0.971 ( 0.217 )	0.996 ( 0.184 )
Right Femur: Week 52 (n=48, 47)	0.967 ( 0.213 )	0.981 ( 0.177 )

No statistical analyses for this end point

Secondary: PAP: Total T-Scores for BMD at Baseline and Week 52

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End point title

PAP: Total T-Scores for BMD at Baseline and Week 52

End point description

Images of the spine and bilateral femur were obtained by DXA to determine T-score for each bone area and total bone mineral density. The T-score bone density categories were: normal (score >-1), osteopenia (score -2.5 to <=-1), and osteoporosis (score <= -2.5). PP population included all subjects who were at least 80% compliant with dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. Here 'n' signifies number of subjects with available data at specified time points for each arm respectively.

End point type

Secondary

End point timeframe

Baseline, Week 52

End point values	PAP, Eliglustat: QD	PAP, Eliglustat: BID
Number of subjects analysed	56	59
Units: T-score
arithmetic mean (standard deviation)
Lumbar Spine T-Score: Baseline (n=49, 52)	-0.722 ( 1.415 )	-0.771 ( 1.217 )
Lumbar Spine T-Score: Week 52 (n=49, 52)	-0.58 ( 1.476 )	-0.717 ( 1.271 )
Left Femur T-Score: Baseline (n=46, 44)	-0.459 ( 1.385 )	-0.368 ( 1.347 )
Left Femur T-Score: Week 52 (n=46, 44)	-0.509 ( 1.342 )	-0.441 ( 1.326 )
Right Femur T-score: Baseline (n=46, 44)	-0.574 ( 1.327 )	-0.382 ( 1.282 )
Right Femur T-score: Week 52 (n=46, 44)	-0.607 ( 1.308 )	-0.53 ( 1.236 )

No statistical analyses for this end point

Secondary: PAP: Total Z-scores for BMD at Baseline and Week 52

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End point title

PAP: Total Z-scores for BMD at Baseline and Week 52

End point description

Images of the spine and bilateral femur were obtained by DXA to determine Z-score for each bone area and total bone mineral density. The Z-score bone density categories are: normal (score >-2) and below normal (score <=-2). PP population included all subjects who were at least 80% compliant with dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. Here 'n' signifies number of subjects with available data for specified category for each arm respectively.

End point type

Secondary

End point timeframe

Baseline, Week 52

End point values	PAP, Eliglustat: QD	PAP, Eliglustat: BID
Number of subjects analysed	56	59
Units: Z-score
arithmetic mean (standard deviation)
Lumbar Spine Z-scores: Baseline (n=51, 55)	-0.492 ( 1.517 )	-0.609 ( 1.166 )
Lumbar Spine Z-scores: Week 52 (n=51, 55)	-0.324 ( 1.559 )	-0.555 ( 1.202 )
Left Femur Z-scores: Baseline (n= 48, 47)	-0.171 ( 1.316 )	-0.115 ( 1.294 )
Left Femur Z-scores: Week 52 (n= 48, 47)	-0.202 ( 1.25 )	-0.183 ( 1.274 )
Right Femur Z-scores: Baseline (n= 48, 47)	-0.235 ( 1.251 )	-0.14 ( 1.194 )
Right Femur Z-scores: Week 52 (n= 48, 47)	-0.248 ( 1.214 )	-0.26 ( 1.141 )

No statistical analyses for this end point

Secondary: PAP: Number of Subjects With Mobility Status (MS) at Baseline, Weeks 26, and 52

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End point title

PAP: Number of Subjects With Mobility Status (MS) at Baseline, Weeks 26, and 52

End point description

Mobility, i.e., ability to walk was assessed as a part of gaucher disease assessment in subjects. In this endpoint, number of subjects with their different mobility status along with the use of mobility aids (unrestricted mobility, walks with difficulty, walks with orthopaedic aid, requires wheelchair, bedridden) at specified time points were reported. PP population included all subjects who were at least 80% compliant with dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. Here 'n' signifies number of subjects with available data at specified time points for each arm respectively.

End point type

Secondary

End point timeframe

Baseline, Week 26 and Week 52

End point values	PAP, Eliglustat: QD	PAP, Eliglustat: BID
Number of subjects analysed	56	59
Units: subjects
number (not applicable)
MS, Unrestricted: Baseline (n=56, 59)	49	59
MS, Unrestricted: Week 26 (n=55, 57)	46	56
MS, Unrestricted: Week 52 (n=51, 58)	50	57
MS, Walks with Difficulty: Baseline (n=56, 59)	6	0
MS, Walks with Difficulty: Week 26 (n=55, 57)	8	1
MS, Walks with Difficulty: Week 52 (n=51, 58)	5	1
MS, Walks with Orthopedic Aid: Baseline (n=56, 59)	1	0
MS, Walks with Orthopedic Aid: Week 26 (n=55,	1	0
MS, Walks with Orthopedic Aid: Week 52 (n=51, 58)	0	0
MS, Required Wheelchair: Baseline (n=56, 59)	0	0
MS, Required Wheelchair: Week 26 (n=55, 57)	0	0
MS, Required Wheelchair: Week 52 (n=51, 58)	1	0
MS, Bedridden: Baseline (n=56, 59)	0	0
MS, Bedridden: Week 26 (n=55, 57)	0	0
MS, Bedridden: Week 52 (n=51, 58)	0	0

No statistical analyses for this end point

Secondary: PAP: Number of Subjects With Bone Crises Assessment at Baseline, Weeks 26, and 52

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End point title

PAP: Number of Subjects With Bone Crises Assessment at Baseline, Weeks 26, and 52

End point description

Bone crises was assessed as a part of gaucher disease assessment in subjects. Acute, excruciating episodic bone pain is characteristic of Gaucher bone crises, which typically causes debilitation lasting several days or longer and requires treatment with immobilization, hydration, and opioid analgesics. Subjects were categorized as 0= no bone crises, 1= 1 bone crises, 2= 2 bone crises during the assessment period. In this endpoint, number of subjects with different bone crises levels at specified time points were reported. PP population included all subjects who were at least 80% compliant with dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. Here 'n' signifies number of subjects with available data at specified time points for each arm respectively.

End point type

Secondary

End point timeframe

Baseline, Week 26, and Week 52

End point values	PAP, Eliglustat: QD	PAP, Eliglustat: BID
Number of subjects analysed	56	59
Units: subjects
number (not applicable)
Bone Crisis (0): Baseline (n=56, 59)	55	57
Bone Crisis (0): Week 26 (n=55,57)	54	56
Bone Crisis (0): Week 52 (n=56, 58)	56	57
Bone Crisis (1): Baseline (n=56, 59)	1	2
Bone Crisis (1): Week 26 (n=55, 57)	0	1
Bone Crisis (1): Week 52 (n=56, 58)	0	1
Bone Crisis (2): Baseline (n=56, 59)	0	0
Bone Crisis (2): week 26 (n=55, 57)	1	0
Bone Crisis (2): week 52 (n=56, 58)	0	0

No statistical analyses for this end point

Secondary: PAP: Number of Subjects With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and Week 52

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End point title

PAP: Number of Subjects With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and Week 52

End point description

Bone pain was assessed as a part of gaucher disease assessment in subjects. Subjects were categorized as none (no bone pain), very mild bone pain, mild bone pain, moderate bone pain, severe bone pain and extreme bone pain. In this endpoint, number of subjects with different level of bone pain during the past 4 weeks at specified time points were reported. PP population included all subjects who were at least 80% compliant with dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. Here 'n' signifies number of subjects with available data at specified time points for each arm respectively.

End point type

Secondary

End point timeframe

Baseline, Week 26, and Week 52

End point values	PAP, Eliglustat: QD	PAP, Eliglustat: BID
Number of subjects analysed	56	59
Units: subjects
number (not applicable)
None: Baseline (n=56, 59)	42	49
None: Week 26 (n=55, 57)	42	49
None: Week 52 (n=56, 58)	41	45
Very Mild: Baseline (n=56, 59)	2	1
Very Mild: Week 26 (n=55, 57)	3	4
Very Mild: Week 52 (n=56, 58)	3	7
Mild: Baseline (n=56, 59)	7	3
Mild: Week 26 (n=55, 57)	5	3
Mild: Week 52 (n=56, 58)	6	2
Moderate: Baseline (n=56, 59)	4	5
Moderate: Week 26 (n=55, 57)	5	1
Moderate: Week 52 (56, 58)	6	2
Severe: Baseline (n=56, 59)	1	1
Severe: Week 26 (n=55, 57)	0	0
Severe: Week 52 (n=56, 58)	0	2
Extreme: Baseline (n=56, 59)	0	0
Extreme: Week 26 (n=55, 57)	0	0
Extreme: Week 52 (n=56, 58)	0	0

No statistical analyses for this end point

Secondary: PAP: Total Bone Marrow Burden Score (BMB) at Baseline and 52 weeks

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End point title

PAP: Total Bone Marrow Burden Score (BMB) at Baseline and 52 weeks

End point description

BMB Score was measured using magnetic resonance imaging (MRI), range from 0 (no abnormalities) to 8 points (severe disease) for the lumbar spine and from 0 (no abnormalities) to 8 points (severe disease) for the femurs. The total score was calculated as the sum of scores for femur and lumbar spine regions which ranged from 0 (no abnormalities) -16 (severe disease) points. A higher BMB score signified more severe bone marrow involvement. A higher BMB score signified more severe bone marrow involvement. PP population included all subjects who were at least 80% compliant with dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. Here, 'n' signifies number of subjects with available data at specified time points for each arm respectively.

End point type

Secondary

End point timeframe

Baseline, Week 52

End point values	PAP, Eliglustat: QD	PAP, Eliglustat: BID
Number of subjects analysed	56	59
Units: BMB Score
arithmetic mean (standard deviation)
BMB Score: Baseline (n=52, 49)	8.276 ( 2.891 )	9.136 ( 2.784 )
BMB Score: week 52 (n=51, 48)	7.971 ( 2.689 )	8.705 ( 2.633 )

No statistical analyses for this end point

Secondary: LIP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26, 52 and 78

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End point title

LIP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26, 52 and 78

End point description

Analysis was performed on all treated (AT) analysis set which included all subjects who received at least 1 dose of eliglustat during lead in period. Here 'n' signifies number of subjects with available data at specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 26, Week, 52, and Week 78

End point values	LIP, Eliglustat
Number of subjects analysed	170
Units: g/dL
arithmetic mean (standard deviation)
Baseline (n=170)	13.435 ( 1.56 )
Week 26 (n=163)	13.443 ( 1.382 )
Week 52 (n=74)	13.434 ( 1.497 )
Week 78 (n=41)	13.329 ( 1.528 )

No statistical analyses for this end point

Secondary: LIP: Mean Platelet Count at Baseline, Weeks 26, 52 and 78

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End point title

LIP: Mean Platelet Count at Baseline, Weeks 26, 52 and 78

End point description

Analysis was performed on AT analysis set which included all subjects who received at least 1 dose of eliglustat during LIP. Here ‘n’ signifies number of subjects with available data at specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 26, Week 52, Week 78

End point values	LIP, Eliglustat
Number of subjects analysed	170
Units: platelets*10^9 /L
arithmetic mean (standard deviation)
Baseline (n=170)	178.653 ( 92.732 )
Week 26 (n=163)	180.021 ( 85.426 )
Week 52 (n=74)	176.378 ( 79.88 )
Week 78 (n=41)	168.72 ( 74.117 )

No statistical analyses for this end point

Secondary: LIP: Mean Liver Volume at Baseline, Weeks 26, 52 and 78

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End point title

LIP: Mean Liver Volume at Baseline, Weeks 26, 52 and 78

End point description

Analysis was performed on AT subjects which included all subjects who received at least 1 dose of eliglustat during lead in period. Here, 'n' signifies number of subjects with available data at specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 26, Week 52, Week 78

End point values	LIP, Eliglustat
Number of subjects analysed	170
Units: MN
arithmetic mean (standard deviation)
Baseline (n=170)	1.044 ( 0.243 )
Week 26 (n=149)	1.04 ( 0.229 )
Week 52 (n=68)	1.059 ( 0.242 )
Week 78 (n=39)	1.062 ( 0.236 )

No statistical analyses for this end point

Secondary: LIP: Mean Spleen Volume at Baseline, Weeks 26, 52 and 78

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End point title

LIP: Mean Spleen Volume at Baseline, Weeks 26, 52 and 78

End point description

Analysis was performed on AT subjects which included all subjects who received at least 1 dose of eliglustat during lead in period. Here 'n' signifies number of subjects with available data at specified time points for each arm respectively.

End point type

Secondary

End point timeframe

Baseline, Week 26, Week 52, Week 78

End point values	LIP, Eliglustat
Number of subjects analysed	170
Units: multiples of normal (MN)
arithmetic mean (standard deviation)
Baseline (n=119)	4.448 ( 2.314 )
Week 26 (n=106)	3.84 ( 1.801 )
Week 52 (n=52)	4.094 ( 1.767 )
Week 78 (n=30)	4.088 ( 2.089 )

No statistical analyses for this end point

Secondary: LIP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26, 52, and 78

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End point title

LIP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26, 52, and 78

End point description

Chitotriosidase biomarker was assayed from plasma. Analysis was performed on AT analysis set which included all subjects who received at least 1 dose of eliglustat during LIP. Here ‘n’ signifies number of subjects with available data at specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 26, Week 52, and Week 78

End point values	LIP, Eliglustat
Number of subjects analysed	170
Units: nmol/hr/mL
arithmetic mean (standard deviation)
Chitotriosidase: Baseline (n=170)	2437.92 ( 3291.25 )
Chitotriosidase: week 26 (n=157)	1802.93 ( 2529.29 )
Chitotriosidase: week 52 (n=72)	1755.7 ( 2649.14 )
Chitotriosidase: week 78 (n=41)	1677.02 ( 2718.75 )

No statistical analyses for this end point

Secondary: LIP: Mean Biomarker (GL-1 on DBS) Value at Baseline, week 26, week 52, and week 78

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End point title

LIP: Mean Biomarker (GL-1 on DBS) Value at Baseline, week 26, week 52, and week 78

End point description

GL-1 on DBS biomarker was assayed from dried blood spot. Analysis was performed on AT analysis set which included all subjects who received at least 1 dose of eliglustat during LIP. Here ‘n’ signifies number of subjects with available data at specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 26, Week 52, and Week 78

End point values	LIP, Eliglustat
Number of subjects analysed	170
Units: mcg/mL
arithmetic mean (standard deviation)
GL-1 on DBS: Baseline (n=159)	4.358 ( 2.155 )
GL-1 on DBS: week 26 (n=144)	2.34 ( 0.868 )
GL-1 on DBS: week 52 (n=68)	2.279 ( 0.73 )
GL-1 on DBS: week 78 (n=39)	2.495 ( 1.5 )

No statistical analyses for this end point

Secondary: LIP: Mean Biomarker (MIP1-beta) Value at Baseline, Week 78

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End point title

LIP: Mean Biomarker (MIP1-beta) Value at Baseline, Week 78

End point description

MIP1-beta biomarker was assayed from plasma. Analysis was performed on AT analysis set which included all subjects who received at least 1 dose of eliglustat during LIP. Here ‘n’ signifies number of subjects with available data at specified time points.

End point type

Secondary

End point timeframe

Baseline, and week 78

End point values	LIP, Eliglustat
Number of subjects analysed	170
Units: pg/mL
arithmetic mean (standard deviation)
MIP-1beta: Baseline (n=170)	142.433 ( 125.961 )
MIP-1beta: 78 weeks (n=41)	132.18 ( 189.454 )

No statistical analyses for this end point

Secondary: LIP: Number of Subjects With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78

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End point title

LIP: Number of Subjects With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78

End point description

Mobility, i.e., ability to walk was assessed as a part of gaucher disease assessment in subjects. In this endpoint, number of subjects with their different mobility status along with the use of mobility aids (unrestricted mobility, walks with difficulty, walks with orthopaedic aid, requires wheelchair, bedridden) at specified time points were reported. Analysis was performed on AT analysis set which included all subjects who received at least 1 dose of eliglustat during LIP. Here, 'n' signifies number of subjects with available data at specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 26, Week 52, Week 78

End point values	LIP, Eliglustat
Number of subjects analysed	170
Units: subjects
number (not applicable)
MS,Unrestricted: Baseline (n=163)	146
MS,Unrestricted: Week 26 (n=161)	153
MS,Unrestricted: Week 52 (n=72)	70
MS,Unrestricted: Week 78 (n= 41)	39
MS, Walks With Difficulty: Baseline (n=163)	12
MS, Walks With Difficulty: Week 26 (n=161)	6
MS, Walks With Difficulty: Week 52 (n=72)	1
MS, Walks With Difficulty: Week 78 (n=41)	2
MS, Walks With Orthopedic Aid: Baseline (n=163)	3
MS, Walks With Orthopedic Aid: Week 26 (n=161)	1
MS, Walks With Orthopedic Aid: Week 52 (n=72)	0
MS, Walks With Orthopedic Aid: Week 78 (n=41)	0
MS, Required wheelchair: Baseline (n=163)	2
MS, Required wheelchair: Week 26 (n=161)	1
MS, Required wheelchair: Week 52 (n=72)	1
MS, Required wheelchair: Week 78 (n=41)	0
MS, Bedridden: Baseline (n=163)	0
MS, Bedridden: Week 26 (n=161)	0
MS, Bedridden: Week 52 (n=72)	0
MS, Bedridden: Week 78 (n=41)	0

No statistical analyses for this end point

Secondary: LIP: Number of Subjects With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78

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End point title

LIP: Number of Subjects With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78

End point description

Bone crises was assessed as a part of gaucher disease assessment in subjects. Acute, excruciating episodic bone pain is characteristic of Gaucher bone crises, which typically causes debilitation lasting several days or longer and requires treatment with immobilization, hydration, and opioid analgesics. Subjects were categorized as 0= no bone crises, 1= 1 bone crises, 2= 2 bone crises, 6= 6 bone crises, 24= 24 bone crises during the assessment period. In this endpoint, number of subjects with different bone crises levels at specified time points were reported. Analysis was performed on AT analysis set which included all subjects who received at least 1 dose of eliglustat during LIP. Here, 'n' signifies number of subjects with available data at specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 26, Week 52, Week 78

End point values	LIP, Eliglustat
Number of subjects analysed	170
Units: subjects
number (not applicable)
Bone Crisis (0): Baseline (n=162)	151
Bone Crisis (0): Week 26 (n=162)	159
Bone Crisis (0): Week 52 (n=72)	72
Bone Crisis (0): Week 78 (n=41)	41
Bone Crisis (1): Baseline (n=162)	8
Bone Crisis (1): Week 26 (n=162)	3
Bone Crisis (1): Week 52 (n=72)	0
Bone Crisis (1): Week 78 (n=41)	0
Bone Crisis (2): Baseline (n=162)	1
Bone Crisis (2): Week 26 (n=162)	0
Bone Crisis (2): Week 52 (n=72)	0
Bone Crisis (2): Week 78 (n=41)	0
Bone Crisis (6): Baseline (n=162)	1
Bone Crisis (6): Week 26 (n=162)	0
Bone Crisis (6): Week 52 (n=72)	0
Bone Crisis (6): Week 78 (n=41)	0
Bone Crisis (24): Baseline (n=162)	1
Bone Crisis (24): Week 26 (n=162)	0
Bone Crisis (24): Week 52 (n=72)	0
Bone Crisis (24): Week 78 (n=41)	0

No statistical analyses for this end point

Secondary: LIP: Number of Subjects With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78

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End point title

LIP: Number of Subjects With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78

End point description

Bone pain was assessed as a part of gaucher disease assessment in subjects. Subjects were categorized as none (no bone pain), very mild bone pain, mild bone pain, moderate bone pain, severe bone pain and extreme bone pain. In this endpoint, number of subjects with different type of bone pain during the past 4 weeks at specified time points were reported. Analysis was performed on AT analysis set which included all subjects who received at least 1 dose of eliglustat during LIP. Here, 'n' signifies number of subjects with available data at specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 26, Week 52, Week 78

End point values	LIP, Eliglustat
Number of subjects analysed	170
Units: subjects
number (not applicable)
None: Baseline (n=163)	112
None: Week 26 (n=161)	125
None: Week 52 (n=72)	62
None: Week 78 (n=41)	39
Very Mild: Baseline (n=163)	17
Very Mild: Week 26 (n=161)	14
Very Mild: Week 52 (n=72)	4
Very Mild: Week 78 (n=41)	1
Mild: Baseline (n=163)	22
Mild: Week 26 (n=161)	10
Mild: Week 52 (n=72)	3
Mild: Week 78 (n=41)	0
Moderate: Baseline (n=163)	8
Moderate: Week 26 (n=161)	10
Moderate: Week 52 (n=72)	3
Moderate: Week 78 (n=41)	1
Severe: Baseline (n=163)	4
Severe: Week 26 (n=161)	2
Severe: Week 52 (n=72)	0
Severe: Week 78 (n=41)	0
Extreme: Baseline (n=163)	0
Extreme: Week 26 (n=161)	0
Extreme: Week 52 (n=72)	0
Extreme: Week 78 (n=41)	0

No statistical analyses for this end point

Secondary: LTTP: Percentage of Subjects who Maintained a Stable Bone Criterion, Hemoglobin Level, Platelet Count, Liver Volume and Spleen Volume at 1 Year and 2 Years

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End point title

LTTP: Percentage of Subjects who Maintained a Stable Bone Criterion, Hemoglobin Level, Platelet Count, Liver Volume and Spleen Volume at 1 Year and 2 Years

End point description

Subjects were considered as stable if they met the following criteria: hemoglobin level did not decrease >1.5 g/dL from baseline for PAP, platelet count does not decrease >25% below Baseline for PAP, liver volume does not increase >20% above Baseline for PAP, spleen volume does not increase >25% above Baseline for PAP. Baseline for PAP was defined as last available assessment prior to randomization. Analysis was performed on ITT population which included all subjects who received at least 1 dose of eliglustat after randomization. Here ‘n’ signifies number of subjects with available data at specified time points.

End point type

Secondary

End point timeframe

1 Year, 2 Years

End point values	LTTP, Eliglustat
Number of subjects analysed	121
Units: percentage of subjects
number (confidence interval 95%)
Bone Criterion Stable at 1 year (n=104)	92.3 (85.4 to 96.6)
Bone Criterion Stable at 2 years (n=32)	84.4 (67.2 to 94.7)
Hemoglobin Level Stable at 1 year (n=104)	92.3 (85.4 to 96.6)
Hemoglobin Level Stable at 2 years (n=32)	81.3 (63.6 to 92.8)
Platelet Count Stable at 1 year (n=104)	93.3 (86.6 to 97.3)
Platelet Count Stable at 2 years (n=32)	84.4 (67.2 to 94.7)
Liver Volume Stable at 1 year (n=103)	93.2 (86.5 to 97.2)
Liver Volume Stable at 2 years (n=31)	83.9 (66.3 to 94.5)
Spleen Volume Stable at 1 year (n=72)	95.8 (88.3 to 99.1)
Spleen Volume Stable at 2 years (n=20)	95 (75.1 to 99.9)

No statistical analyses for this end point

Secondary: LTTP: Number of Subjects With Mobility Status (MS) at Baseline, 1 year, and 2 years

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End point title

LTTP: Number of Subjects With Mobility Status (MS) at Baseline, 1 year, and 2 years

End point description

Mobility, i.e., ability to walk was assessed as a part of gaucher disease assessment in subjects. In this endpoint, number of subjects with their different mobility status along with the use of mobility aids (unrestricted mobility, walks with difficulty, walks with orthopaedic aid, requires wheelchair, bedridden) at specified time points were reported. Analysis was performed on all subjects who received at least one dose of eliglustat during the LTTP. Here, "n" signifies number of subjects with available data at specified time points.

End point type

Secondary

End point timeframe

Baseline, 1 year, and 2 years

End point values	LTTP, Eliglustat
Number of subjects analysed	121
Units: subjects
number (not applicable)
MS, Unrestricted: Baseline (n=120)	111
MS, Unrestricted: 1 year (n=104)	97
MS, Unrestricted: 2 years (n=32)	28
MS, Walks with Difficulty: Baseline (n=120)	7
MS, Walks with Difficulty: 1 year (n=104)	4
MS, Walks with Difficulty: 2 years (n=32)	2
MS, Walks with Orthopedic Aid: Baseline (n=120)	0
MS, Walks with Orthopedic Aid: 1 year (n=104)	1
MS, Walks with Orthopedic Aid: 2 years (n=32)	0
MS, Required Wheelchair: Baseline (n=120)	2
MS, Required Wheelchair: 1 year (n=104)	2
MS, Required Wheelchair: 2 years (n=32)	2
MS, Bedridden: Baseline (n=120)	0
MS, Bedridden: 1 year (n=104)	0
MS, Bedridden: 2 years (n=32)	0

No statistical analyses for this end point

Secondary: LTTP: Number of Subjects With Bone Crises Assessment at Baseline, 1 year, and 2 years

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End point title

LTTP: Number of Subjects With Bone Crises Assessment at Baseline, 1 year, and 2 years

End point description

Bone crises was assessed as a part of gaucher disease assessment in subjects. Acute, excruciating episodic bone pain is characteristic of Gaucher bone crises, which typically causes debilitation lasting several days or longer and requires treatment with immobilization, hydration, and opioid analgesics. Subjects were categorized as 0= no bone crises, 1= 1 bone crises during the assessment period. In this endpoint, number of subjects with different bone crises levels at specified time points were reported. Analysis was performed on all subjects who received at least one dose of eliglustat during the LTTP. Here, "n" signifies number of subjects with available data at specified time points.

End point type

Secondary

End point timeframe

Baseline, 1 year, and 2 years

End point values	LTTP, Eliglustat
Number of subjects analysed	121
Units: subjects
number (not applicable)
Bone Crisis (0): Baseline (n=120)	119
Bone Crisis (0): 1 year (n=104)	104
Bone Crisis (0): 2 years (n=32)	32
Bone Crisis (1): Baseline (n=120)	1
Bone Crisis (1): 1 year (n=104)	0
Bone Crisis (1): 2 years (n=32)	0

No statistical analyses for this end point

Secondary: LTTP: Number of Subjects With Bone Pain Levels During the Past 4 Weeks at Baseline, 1 year, and 2 years

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End point title

LTTP: Number of Subjects With Bone Pain Levels During the Past 4 Weeks at Baseline, 1 year, and 2 years

End point description

Bone pain was assessed as a part of gaucher disease assessment in subjects. Subjects were categorized as none (no bone pain), very mild bone pain, mild bone pain, moderate bone pain, severe bone pain and extreme bone pain. In this endpoint, number of subjects with different type of bone pain during the past 4 weeks at specified time points were reported. Analysis was performed on all subjects who received at least one dose of eliglustat during the LTTP. Here, "n" signifies number of subjects with available data at specified time points.

End point type

Secondary

End point timeframe

Baseline, 1 year, and 2 years

End point values	LTTP, Eliglustat
Number of subjects analysed	121
Units: subjects
number (not applicable)
None: Baseline (n=120)	91
None: 1 year (n=104)	83
None: 2 years (n=32)	32
Very Mild: Baseline (n=120)	12
Very Mild: 1 year (n=104)	9
Very Mild: 2 years (n=32)	0
Mild: Baseline (n=120)	8
Mild: 1 year (n=104)	10
Mild: 2 years (n=32)	0
Moderate: Baseline (n=120)	7
Moderate: 1 year (n=104)	1
Moderate: 2 years (n=32)	0
Severe: Baseline (n=120)	2
Severe: 1 year (n=104)	0
Severe: 2 years (n=32)	0
Extreme: Baseline (n=120)	0
Extreme: 1 year (n=104)	1
Extreme: 2 years (n=32)	0

No statistical analyses for this end point

Secondary: LTTP: Bone Mineral Density (BMD) at Baseline, 1 year, and 2 years

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End point title

LTTP: Bone Mineral Density (BMD) at Baseline, 1 year, and 2 years

End point description

BMD measurements of the spine and bilateral femur were acquired by dual-energy x-ray absorptiometry (DXA) scan. Analysis was performed on all subjects who received at least one dose of eliglustat during the LTTP. Here, "n" signifies number of subjects with available data at specified time points.

End point type

Secondary

End point timeframe

Baseline, 1 year, and 2 years

End point values	LTTP, Eliglustat
Number of subjects analysed	121
Units: g/cm^2
arithmetic mean (standard deviation)
Lumbar Spine: Baseline (n=113)	1.087 ( 0.182 )
Lumbar Spine: 1 year (n=101)	1.083 ( 0.183 )
Lumbar Spine: 2 years (n=26)	1.082 ( 0.19 )
Left Femur: Baseline (n=107)	0.986 ( 0.205 )
Left Femur: 1 year (n=95)	0.994 ( 0.226 )
Left Femur: 2 years (n=22)	0.95 ( 0.22 )
Right Femur: Baseline (n=103)	0.983 ( 0.201 )
Right Femur: 1 year (n=91)	0.979 ( 0.202 )
Right Femur: 2 years (n=21)	0.908 ( 0.131 )

No statistical analyses for this end point

Secondary: LTTP: Total T-Scores for BMD at Baseline, 1 year, and 2 years

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End point title

LTTP: Total T-Scores for BMD at Baseline, 1 year, and 2 years

End point description

Images of the spine and bilateral femur were obtained by DXA to determine T-score for each bone area and total bone mineral density. The T-score bone density categories were: normal (score >-1), osteopenia (score -2.5 to <=-1), and osteoporosis (score <= -2.5). Analysis was performed on all subjects who received at least one dose of eliglustat during the LTTP. Here, "n" signifies number of subjects with available data at specified time points.

End point type

Secondary

End point timeframe

Baseline, 1 year, and 2 years

End point values	LTTP, Eliglustat
Number of subjects analysed	121
Units: T-score
arithmetic mean (standard deviation)
Lumbar Spine T-Score: Baseline (n=110)	-0.674 ( 1.383 )
Lumbar Spine T-Score: 1 year (n=98)	-0.718 ( 1.394 )
Lumbar Spine T-Score: 2 years (n=26)	-0.75 ( 1.37 )
Left Femur T-Score: Baseline (n=103)	-0.421 ( 1.377 )
Left Femur T-Score: 1 year (n=91)	-0.382 ( 1.551 )
Left Femur T-Score: 2 years (n=22)	-0.682 ( 1.532 )
Right Femur T-Score: Baseline (n=99)	-0.461 ( 1.36 )
Right Femur T-Score: 1 year (n=87)	-0.5 ( 1.381 )
Right Femur T-Score: 2 years (n=21)	-1.005 ( 0.931 )

No statistical analyses for this end point

Secondary: LTTP: Total Z-scores for BMD at Baseline, 1 year, and 2 years

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End point title

LTTP: Total Z-scores for BMD at Baseline, 1 year, and 2 years

End point description

Images of the spine and bilateral femur were obtained by DXA to determine Z-score for each bone area and total bone mineral density. The Z-score bone density categories are: normal (score >-2) and below normal (score <=-2). Analysis was performed on all subjects who received at least one dose of eliglustat during the LTTP. Here, "n" signifies number of subjects with available data at specified time points.

End point type

Secondary

End point timeframe

Baseline, 1 year, and 2 years

End point values	LTTP, Eliglustat
Number of subjects analysed	121
Units: Z-score
arithmetic mean (standard deviation)
Lumbar Spine Z-Score: Baseline (n=113)	0.46 ( 1.376 )
Lumbar Spine Z-Score: 1 year (n=101)	0.512 ( 1.368 )
Lumbar Spine Z-Score: 2 years (n=26)	0.385 ( 1.316 )
Left Femur Z-Score: Baseline (n=107)	0.164 ( 1.277 )
Left Femur Z-Score: 1 year (n=95)	0.132 ( 1.459 )
Left Femur Z-Score: 2 years (n=22)	0.264 ( 1.525 )
Right Femur Z-Score: Baseline (n=103)	0.214 ( 1.227 )
Right Femur Z-Score: 1 year (n=91)	0.262 ( 1.27 )
Right Femur Z-Score: 2 years (n=21)	0.605 ( 0.957 )

No statistical analyses for this end point

Secondary: LTTP: Total Bone Marrow Burden Score (BMB) at Baseline, 1 year, and 2 years

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End point title

LTTP: Total Bone Marrow Burden Score (BMB) at Baseline, 1 year, and 2 years

End point description

BMB Score was measured using MRI, range from 0 (no abnormalities) to 8 points (severe disease) for the lumbar spine and from 0 (no abnormalities) to 8 points (severe disease) for the femurs. The total score was calculated as the sum of scores for femur and lumbar spine regions which ranged from 0-16 points. A higher BMB score signified more severe bone marrow involvement. Analysis was performed on all subjects who received at least one dose of eliglustat during the LTTP. Here, "n" signifies number of subjects with available data at specified time points.

End point type

Secondary

End point timeframe

Baseline, 1 year, and 2 years

End point values	LTTP, Eliglustat
Number of subjects analysed	121
Units: BMB Score
arithmetic mean (standard deviation)
BMB Score: Baseline (n=115)	8.164 ( 2.646 )
BMB Score: 1 year (n=26)	7.853 ( 2.497 )
BMB Score: 2 years (n=17)	8.059 ( 1.918 )

No statistical analyses for this end point

Secondary: LTTP: Mean Biomarker (Chitotriosidase) Value at Baseline, 1 year, and 2 years

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End point title

LTTP: Mean Biomarker (Chitotriosidase) Value at Baseline, 1 year, and 2 years

End point description

Chitotriosidase biomarker was assayed from plasma. Analysis was performed on all subjects who received at least one dose of eliglustat during the LTTP. Here, "n" signifies number of subjects with available data at specified time points.

End point type

Secondary

End point timeframe

Baseline, 1 year, and 2 years

End point values	LTTP, Eliglustat
Number of subjects analysed	121
Units: nmol/hr/mL
arithmetic mean (standard deviation)
Chitotriosidase: Baseline (n=118)	1188.983 ( 1857.521 )
Chitotriosidase: 1 year (n=97)	1221.753 ( 2072.446 )
Chitotriosidase: 2 years (n=31)	598.161 ( 1463.603 )

No statistical analyses for this end point

Secondary: LTTP: Mean Biomarker (GL-1 on DBS) Value at Baseline, 1 Year, and 2 Years

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End point title

LTTP: Mean Biomarker (GL-1 on DBS) Value at Baseline, 1 Year, and 2 Years

End point description

GL-1 on DBS biomarker was assayed from dried blood spot. Anaysis was performed on all subjects who received at least one dose of eliglustat during the LTTP. Here 'n' signifies number of subjects with available data at specified time points.

End point type

Secondary

End point timeframe

Baseline, 1 year, and 2 years

End point values	LTTP, Eliglustat
Number of subjects analysed	121
Units: mcg/mL
arithmetic mean (standard deviation)
GL-1 on DBS: Baseline (n=114)	2.725 ( 1.35 )
GL-1 on DBS: 1 year (n=98)	2.5 ( 1.031 )
GL-1 on DBS: 2 years (n=29)	2.238 ( 0.658 )

No statistical analyses for this end point

Secondary: LTTP: Mean Biomarker (MIP1-beta) Value at Baseline, 1 year, and 2 years

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End point title

LTTP: Mean Biomarker (MIP1-beta) Value at Baseline, 1 year, and 2 years

End point description

MIP1-beta biomarker was assayed from plasma. Analysis was performed on all subjects who received at least one dose of eliglustat during the LTTP. Here, "n" signifies number of subjects with available data at specified time points.

End point type

Secondary

End point timeframe

Baseline, 1 year, and 2 years

End point values	LTTP, Eliglustat
Number of subjects analysed	121
Units: pg/mL
arithmetic mean (standard deviation)
MIP-1beta: Baseline (n=114)	97.857 ( 125.857 )
MIP-1beta: 1 year (n=94)	90.398 ( 90.549 )
MIP-1beta: 2 years (n=31)	68.445 ( 64.774 )

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit regardless of seriousness or relationship to investigational product.

Adverse event reporting additional description

Reported AEs and deaths are treatment emergent that is AEs that developed/worsened and deaths that is occurred during 'the treatment emergent period’ (from the first dose of study drug up to the last dose of study drug + 37 days). Analysis was performed on safety population. Adverse events data was planned to be reported for overall population.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

18.0

Reporting group title

Eliglustat

Reporting group description

Serious adverse events	Eliglustat
Total subjects affected by serious adverse events
subjects affected / exposed	40 / 170 (23.53%)
number of deaths (all causes)	2
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lipoma
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Papillary Thyroid Cancer
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Vascular disorders
Aortic Aneurysm
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Hypertension
subjects affected / exposed	2 / 170 (1.18%)
occurrences causally related to treatment / all	0 / 2
deaths causally related to treatment / all	0 / 0
Haemorrhage
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 1
Pregnancy, puerperium and perinatal conditions
Ectopic Pregnancy
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
General disorders and administration site conditions
Disuse Syndrome
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Device Dislocation
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Impaired Healing
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Medical Device Pain
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Hernia
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Reproductive system and breast disorders
Uterine Polyp
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Psychiatric disorders
Conversion Disorder
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Major Depression
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Investigations
Hepatic Enzyme Increased
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Femoral Neck Fracture
subjects affected / exposed	2 / 170 (1.18%)
occurrences causally related to treatment / all	0 / 2
deaths causally related to treatment / all	0 / 0
Femur Fracture
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	0 / 2
deaths causally related to treatment / all	0 / 0
Incisional Hernia
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Forearm Fracture
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Radius Fracture
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Spinal Fracture
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Injury
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 1
Cardiac disorders
Arrhythmia
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Angina Pectoris
subjects affected / exposed	2 / 170 (1.18%)
occurrences causally related to treatment / all	0 / 2
deaths causally related to treatment / all	0 / 0
Cardiac Arrest
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 1
Nervous system disorders
Epilepsy
subjects affected / exposed	2 / 170 (1.18%)
occurrences causally related to treatment / all	0 / 2
deaths causally related to treatment / all	0 / 0
Dizziness
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Presyncope
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Ischaemic Stroke
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	0 / 2
deaths causally related to treatment / all	0 / 0
Seizure
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	0 / 2
deaths causally related to treatment / all	0 / 0
Syncope
subjects affected / exposed	3 / 170 (1.76%)
occurrences causally related to treatment / all	3 / 3
deaths causally related to treatment / all	0 / 0
Gastrointestinal disorders
Mallory-Weiss Syndrome
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Abdominal Wall Haematoma
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Hepatobiliary disorders
Cholecystitis
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Cholecystitis Chronic
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Renal and urinary disorders
Calculus Urinary
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	0 / 2
deaths causally related to treatment / all	0 / 0
Musculoskeletal and connective tissue disorders
Arthritis
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Arthralgia
subjects affected / exposed	2 / 170 (1.18%)
occurrences causally related to treatment / all	0 / 2
deaths causally related to treatment / all	0 / 0
Muscular Weakness
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	1 / 1
deaths causally related to treatment / all	0 / 0
Joint Range Of Motion Decreased
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Osteonecrosis
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Osteoarthritis
subjects affected / exposed	3 / 170 (1.76%)
occurrences causally related to treatment / all	0 / 3
deaths causally related to treatment / all	0 / 0
Infections and infestations
Acute Hepatitis B
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Appendicitis
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Hepatitis A
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0
Staphylococcal Sepsis
subjects affected / exposed	1 / 170 (0.59%)
occurrences causally related to treatment / all	0 / 1
deaths causally related to treatment / all	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Eliglustat
Total subjects affected by non serious adverse events
subjects affected / exposed	144 / 170 (84.71%)
Vascular disorders
Hypertension
subjects affected / exposed	9 / 170 (5.29%)
occurrences all number	11
Cardiac disorders
Palpitations
subjects affected / exposed	11 / 170 (6.47%)
occurrences all number	14
Nervous system disorders
Headache
subjects affected / exposed	37 / 170 (21.76%)
occurrences all number	99
Dizziness
subjects affected / exposed	28 / 170 (16.47%)
occurrences all number	33
Blood and lymphatic system disorders
Thrombocytopenia
subjects affected / exposed	9 / 170 (5.29%)
occurrences all number	12
General disorders and administration site conditions
Fatigue
subjects affected / exposed	17 / 170 (10.00%)
occurrences all number	18
Pyrexia
subjects affected / exposed	16 / 170 (9.41%)
occurrences all number	19
Gastrointestinal disorders
Abdominal Distension
subjects affected / exposed	9 / 170 (5.29%)
occurrences all number	9
Abdominal Pain
subjects affected / exposed	15 / 170 (8.82%)
occurrences all number	20
Abdominal Pain Upper
subjects affected / exposed	26 / 170 (15.29%)
occurrences all number	36
Constipation
subjects affected / exposed	16 / 170 (9.41%)
occurrences all number	17
Gastrooesophageal Reflux Disease
subjects affected / exposed	9 / 170 (5.29%)
occurrences all number	11
Diarrhoea
subjects affected / exposed	24 / 170 (14.12%)
occurrences all number	29
Dyspepsia
subjects affected / exposed	19 / 170 (11.18%)
occurrences all number	29
Nausea
subjects affected / exposed	18 / 170 (10.59%)
occurrences all number	21
Vomiting
subjects affected / exposed	14 / 170 (8.24%)
occurrences all number	18
Hepatobiliary disorders
Hepatomegaly
subjects affected / exposed	9 / 170 (5.29%)
occurrences all number	10
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	21 / 170 (12.35%)
occurrences all number	23
Epistaxis
subjects affected / exposed	13 / 170 (7.65%)
occurrences all number	16
Oropharyngeal Pain
subjects affected / exposed	18 / 170 (10.59%)
occurrences all number	23
Psychiatric disorders
Depression
subjects affected / exposed	10 / 170 (5.88%)
occurrences all number	14
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	30 / 170 (17.65%)
occurrences all number	49
Back Pain
subjects affected / exposed	29 / 170 (17.06%)
occurrences all number	40
Musculoskeletal Pain
subjects affected / exposed	10 / 170 (5.88%)
occurrences all number	12
Myalgia
subjects affected / exposed	11 / 170 (6.47%)
occurrences all number	13
Pain In Extremity
subjects affected / exposed	24 / 170 (14.12%)
occurrences all number	35
Infections and infestations
Nasopharyngitis
subjects affected / exposed	52 / 170 (30.59%)
occurrences all number	94
Urinary Tract Infection
subjects affected / exposed	14 / 170 (8.24%)
occurrences all number	22
Gastroenteritis
subjects affected / exposed	15 / 170 (8.82%)
occurrences all number	24
Viral Infection
subjects affected / exposed	10 / 170 (5.88%)
occurrences all number	12
Influenza
subjects affected / exposed	23 / 170 (13.53%)
occurrences all number	28
Upper Respiratory Tract Infection
subjects affected / exposed	22 / 170 (12.94%)
occurrences all number	38

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

27 Jun 2011

•Amendment was prepared in response to observed high variability in Genz99067 plasma concentrations in the Phase 3 studies (GZGD02507 [ENGAGE] and GZGD02607 [ENCORE]) compared to those in the Phase 2 study (GZGD00304). The principal change was the implementation of additional safety monitoring in subjects with a peak Genz99067 plasma concentration ≥150 ng/mL. It provided details on the management of subjects with peak plasma concentrations ≥150 ng/mL. •Addressed ongoing challenges with recruitment of the target population. It also prepared in response to emerging nonclinical and clinical data for eliglustat, and included the following key changes: •Planned enrollment was reduced from 234 subjects to 131 subjects. •Added additional criteria to be entered into the PAP of the study. •Eliminated the 150 mg BID vs 300 mg QD dosegroup pair in the PAP. •Updated guidance on prohibited prior and concomitant medications. •Modified PK sampling and analysis to add peak Genz-99067 plasma concentrations. •Adjusted statistical methodology based on change in sample size, elimination of the 150 mg BID vs. 300 mg QD pair, and change in approach for analyzing organ volumes. •Allowed subjects who had not reached therapeutic goals by NMonth 18 to receive 150 mg BID in the ETP. •Harmonized Japan and outside Japan protocol versions into a single version. •Updated the risk/benefit and dose rationale information.

23 Jul 2012

Addressed changes in conduct of the study, including increased enrollment of subjects. Planned enrollment was recalculated from 131 subjects to 170 subjects. The underlying sample size assumptions were unchanged, and the study remained adequately powered for the primary efficacy endpoint. Other key change included: •Extended the maximum duration of a subject’s participation in the study to 60 months. •Provided a minimum schedule of assessments for subjects who remained in the study beyond 42 months. •Provided a simplified presentation of concomitant medication guidance. •Clarification that subjects on a dose of 150 mg BID are not eligible for randomization, but will remain in the LIP for the entire 18 months. •Updated benefit/risk summary.

06 Feb 2013

It provided updated concomitant medication guidelines based on information from Phase 1 drug drug interaction studies.

31 Jan 2014

It provided clarification that the assay for GL1 be performed on plasma samples or DBS.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: PAP: Percentage of Subjects Who Remained Stable for 52 Weeks During the PAP

Primary: PAP: Percentage of Subjects Who Remained Stable for 52 Weeks During the PAP

Secondary: PAP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26, 52

Secondary: PAP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26, 52

Secondary: PAP: Mean Platelet Count at Baseline, Weeks 26, 52

Secondary: PAP: Mean Platelet Count at Baseline, Weeks 26, 52

Secondary: PAP: Mean Spleen Volume at Baseline, Weeks 26, 52

Secondary: PAP: Mean Spleen Volume at Baseline, Weeks 26, 52

Secondary: PAP: Mean Liver Volume at Baseline, Weeks 26, 52

Secondary: PAP: Mean Liver Volume at Baseline, Weeks 26, 52

Secondary: PAP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26 and Week 52

Secondary: PAP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26 and Week 52

Secondary: PAP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26, and Week 52

Secondary: PAP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26, and Week 52

Secondary: PAP: Mean Biomarker Macrophage Inflammatory Protein-1 Beta (MIP1-beta) Value at Baseline, Weeks 26, 52

Secondary: PAP: Mean Biomarker Macrophage Inflammatory Protein-1 Beta (MIP1-beta) Value at Baseline, Weeks 26, 52

Secondary: PAP: Bone Mineral Density (BMD) at Baseline and Week 52: PP Population

Secondary: PAP: Bone Mineral Density (BMD) at Baseline and Week 52: PP Population

Secondary: PAP: Total T-Scores for BMD at Baseline and Week 52

Secondary: PAP: Total T-Scores for BMD at Baseline and Week 52

Secondary: PAP: Total Z-scores for BMD at Baseline and Week 52

Secondary: PAP: Total Z-scores for BMD at Baseline and Week 52

Secondary: PAP: Number of Subjects With Mobility Status (MS) at Baseline, Weeks 26, and 52

Secondary: PAP: Number of Subjects With Mobility Status (MS) at Baseline, Weeks 26, and 52

Secondary: PAP: Number of Subjects With Bone Crises Assessment at Baseline, Weeks 26, and 52

Secondary: PAP: Number of Subjects With Bone Crises Assessment at Baseline, Weeks 26, and 52

Secondary: PAP: Number of Subjects With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and Week 52

Secondary: PAP: Number of Subjects With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and Week 52

Secondary: PAP: Total Bone Marrow Burden Score (BMB) at Baseline and 52 weeks

Secondary: PAP: Total Bone Marrow Burden Score (BMB) at Baseline and 52 weeks

Secondary: LIP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26, 52 and 78

Secondary: LIP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26, 52 and 78

Secondary: LIP: Mean Platelet Count at Baseline, Weeks 26, 52 and 78

Secondary: LIP: Mean Platelet Count at Baseline, Weeks 26, 52 and 78

Secondary: LIP: Mean Liver Volume at Baseline, Weeks 26, 52 and 78

Secondary: LIP: Mean Liver Volume at Baseline, Weeks 26, 52 and 78

Secondary: LIP: Mean Spleen Volume at Baseline, Weeks 26, 52 and 78

Secondary: LIP: Mean Spleen Volume at Baseline, Weeks 26, 52 and 78

Secondary: LIP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26, 52, and 78

Secondary: LIP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26, 52, and 78

Secondary: LIP: Mean Biomarker (GL-1 on DBS) Value at Baseline, week 26, week 52, and week 78

Secondary: LIP: Mean Biomarker (GL-1 on DBS) Value at Baseline, week 26, week 52, and week 78

Secondary: LIP: Mean Biomarker (MIP1-beta) Value at Baseline, Week 78

Secondary: LIP: Mean Biomarker (MIP1-beta) Value at Baseline, Week 78

Secondary: LIP: Number of Subjects With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78

Secondary: LIP: Number of Subjects With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78

Secondary: LIP: Number of Subjects With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78

Secondary: LIP: Number of Subjects With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78

Secondary: LIP: Number of Subjects With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78

Secondary: LIP: Number of Subjects With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78

Secondary: LTTP: Percentage of Subjects who Maintained a Stable Bone Criterion, Hemoglobin Level, Platelet Count, Liver Volume and Spleen Volume at 1 Year and 2 Years

Secondary: LTTP: Percentage of Subjects who Maintained a Stable Bone Criterion, Hemoglobin Level, Platelet Count, Liver Volume and Spleen Volume at 1 Year and 2 Years

Secondary: LTTP: Number of Subjects With Mobility Status (MS) at Baseline, 1 year, and 2 years

Secondary: LTTP: Number of Subjects With Mobility Status (MS) at Baseline, 1 year, and 2 years

Secondary: LTTP: Number of Subjects With Bone Crises Assessment at Baseline, 1 year, and 2 years

Secondary: LTTP: Number of Subjects With Bone Crises Assessment at Baseline, 1 year, and 2 years

Secondary: LTTP: Number of Subjects With Bone Pain Levels During the Past 4 Weeks at Baseline, 1 year, and 2 years

Secondary: LTTP: Number of Subjects With Bone Pain Levels During the Past 4 Weeks at Baseline, 1 year, and 2 years

Secondary: LTTP: Bone Mineral Density (BMD) at Baseline, 1 year, and 2 years

Secondary: LTTP: Bone Mineral Density (BMD) at Baseline, 1 year, and 2 years

Secondary: LTTP: Total T-Scores for BMD at Baseline, 1 year, and 2 years

Secondary: LTTP: Total T-Scores for BMD at Baseline, 1 year, and 2 years

Secondary: LTTP: Total Z-scores for BMD at Baseline, 1 year, and 2 years

Secondary: LTTP: Total Z-scores for BMD at Baseline, 1 year, and 2 years

Secondary: LTTP: Total Bone Marrow Burden Score (BMB) at Baseline, 1 year, and 2 years

Secondary: LTTP: Total Bone Marrow Burden Score (BMB) at Baseline, 1 year, and 2 years

Secondary: LTTP: Mean Biomarker (Chitotriosidase) Value at Baseline, 1 year, and 2 years

Secondary: LTTP: Mean Biomarker (Chitotriosidase) Value at Baseline, 1 year, and 2 years

Secondary: LTTP: Mean Biomarker (GL-1 on DBS) Value at Baseline, 1 Year, and 2 Years

Secondary: LTTP: Mean Biomarker (GL-1 on DBS) Value at Baseline, 1 Year, and 2 Years

Secondary: LTTP: Mean Biomarker (MIP1-beta) Value at Baseline, 1 year, and 2 years