A Study of Eliglustat Tartrate (Genz-112638) in Patients... | NCT01074944

ID	Type	Description	Link
2009-015811-42	EudraCT Number
EFC12818	Other Identifier	Sanofi

Label	Type	Description	Intervention Names
Twice Daily (BID) Dose Regimen	Experimental	Patients will receive either 50 mg BID or 100 mg BID	Drug: Eliglustat tartrate
Once Daily (QD) Dose Regimen	Experimental	Patients will receive either 100 mg QD or 200 mg QD	Drug: Eliglustat tartrate

Name	Type	Description	Arm Group Labels	Other Names
Eliglustat tartrate	Drug	Oral Capsule in 50 mg or 100 mg dosages	Once Daily (QD) Dose Regimen Twice Daily (BID) Dose Regimen

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

Measure	Description	Time Frame
PAP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26 and 52		Baseline, Week 26, Week 52
PAP: Mean Platelet Count at Baseline, Weeks 26, 52		Baseline, Week 26, Week 52

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

The participant who was willing and provided signed informed consent prior to any study-related procedures.
The participant was ≥18 years of age.
The participant diagnosed with GD 1 confirmed by a documented deficiency of acid β-glucosidase activity by enzyme assay.
Female participants of childbearing potential had a documented negative pregnancy test prior to administration of the first dose of eliglustat tartrate (Genz-112638) in this study. In addition, all female participants of childbearing potential used a medically accepted form of contraception throughout the study, i.e., either a barrier method or hormonal contraceptive with norethindrone and ethinyl estradiol or similar active components
The participant met all of the following criteria at the time of screening: hemoglobin level ≥9 g/dL (mean of 2 measurements); platelet count ≥70,000/mm^3 (mean of 2 measurements); spleen volume ≤25 multiples of normal (MN); liver volume ≤2.0 MN.
The participant consented to provide a blood sample for genotyping for Gaucher disease and for CYP2D6 to categorize the participant's predicted rate of metabolism, if these genotyping results were not already available for the participant.
The participant was willing to abstain from consumption of grapefruit, grapefruit juice, or grapefruit products for 72 hours prior to administration of the first dose of Genz-112638 and throughout the duration of the study.

Exclusion Criteria:

The participant was participating in GZGD02607 study, "A Phase 3, Randomized, Multi-Center, Multi-National, Open-Label, Active Comparator Study to Evaluate the Efficacy and Safety of Genz-112638 in Participants with GD1 who have been Stabilized with Cerezyme ® ," or was eligible for inclusion in GZGD02607 (while enrollment was ongoing) and had access to a physician participating in GZGD02607, or the participant was participating in GZGD02507 study, "A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study Confirming the Efficacy and Safety of Genz-112638 in Participants with GD1," or was eligible for inclusion in GZGD02507 (while enrollment was ongoing) and had access to a physician participating in GZGD02507.
The participant received miglustat within 6 months prior to administration of the first dose of Genz-112638 in this study.
The participant had a partial or total splenectomy within 3 years prior to randomization.
The participant received pharmacological chaperones or miglustat within 6 months prior to administration of the first dose of eliglustat tartrate (Genz-112638) in this study.
The participant had any evidence of neurologic disorder (e.g., peripheral neuropathy, tremor, seizures, Parkinsonism or cognitive impairment) or pulmonary involvement (e.g., pulmonary hypertension) as related to Gaucher disease.
The participant was transfusion-dependent.
The participant had a documented deficiency of iron, vitamin B-12, or folate that requires treatment not yet initiated or, if initiated, the participant had not been stable under treatment for at least 3 months prior to administration of the first dose of Genz-112638 in this study.
The participant had documented prior esophageal varices or clinically significant liver infarction or current liver enzymes (alanine transaminase [ALT]/aspartate aminotransferase [AST]) or total bilirubin >2 times the upper limit of normal (ULN), unless the participant had a diagnosis of Gilbert Syndrome.
The participant had any clinically significant disease, other than Gaucher disease, including cardiovascular, renal, hepatic, gastrointestinal, pulmonary, neurologic, endocrine, metabolic (including hypokalaemia or hypomagnesemia), or psychiatric disease, other medical conditions, or serious intercurrent illnesses that, in the opinion of the Investigator, precluded participation in the study.
The participant was known to have any of the following: Clinically significant coronary artery disease including history of myocardial infarction [MI] or ongoing signs or symptoms consistent with cardiac ischemia or heart failure; or clinically significant arrhythmias or conduction defect such as 2nd or 3rd degree AV block, complete bundle branch block, prolonged QTc interval, or sustained ventricular tachycardia (VT).
The participant who tested positive for the human immunodeficiency virus (HIV) antibody, Hepatitis C antibody, or Hepatitis B surface antigen.
The participant received an investigational product (other than eliglustat tartrate (Genz-112638)) within 30 days prior to administration of the first dose of eliglustat tartrate (Genz-112638) in this study.
The participant was scheduled for in-participant hospitalization, including elective surgery, during the study.
The participant had a history of cancer, with the exception of basal cell carcinoma, within 5 years prior to administration of the first dose of Genz-112638 in this study.
The participant was pregnant or lactating.
The participant had received any medication that may cause QTc interval prolongation within 30 days prior to the first dose of Genz-112638. Exception: Diphenhydramine (Benadryl) or other medications used as premedication for ERT infusions were allowed up to 7 days prior to the first dose of Genz-112638.
The participant had received for the first time (i.e., the participant was not already chronically using) any of the following medications within 30 days prior to the first dose of Genz-112638:
- Strong inhibitors of CYP2D6 or CYP3A4;
- Inducers of CYP3A4. Exception: Premedications for ERT infusions were allowed up to 7 days prior to the first dose of Genz-112638.
The participant was a CYP2D6 non-poor metabolizer or an indeterminate metabolizer with one allele identified as active who was chronically receiving both a strong competitive inhibitor of CYP2D6 and a strong competitive inhibitor of CYP3A4 and for whom no reasonable alternative medication exists. or
The participant was a CYP2D6 poor metabolizer or an indeterminate metabolizer with neither allele known to be active who was chronically receiving a strong competitive inhibitor of CYP3A4 and for whom no reasonable alternative medication exists.

Exception for both cases: Premedications for ERT infusions were allowed up to 7 days prior to the first dose of Genz-112638.

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

Facility	Status	City	State	ZIP	Country	Contacts
University of California, San Diego Medical Center		San Diego	California		United States
Yale University School of Medicine

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.
20439622

Label	URL
GZGD02507 (NCT00891202) eliglustat tartrate (Genz-112638) Phase 3 Clinical Study in untreated patients with Gaucher disease type 1	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	LIP, Eliglustat	All participants (except in Japan) received eliglustat 50 mg, twice daily (BID) on Day 1 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual pharmacokinetics (PK) data for up to 78 weeks. All participants in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

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

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

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

Analysis was performed on per protocol (PP) population which included all participants who were at least 80% compliant with investigational medicinal product (IMP) dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations.

Posted

Number

95% Confidence Interval

percentage of participants

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

ID	Title	Description
OG000	PAP, Eliglustat: Once Daily	All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
OG001	PAP, Eliglustat: Twice Daily	All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).

Units	Counts
Participants	OG00056 OG00159

Title

Denominators

Categories

Title	Measurements
	OG00080.4(67.6 to 89.8) OG00183.1(71.0 to 91.6)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001						Difference in Percentage Stable	-2.7			2-Sided	95	-17.7	11.9				Yes	Non-Inferiority or Equivalence	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 and 52

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

Posted

Mean

Standard Deviation

g/dL

Baseline, Week 26, Week 52

ID	Title	Description
OG000	PAP, Eliglustat: Once Daily	All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
OG001	PAP, Eliglustat: Twice Daily	All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).

Units	Counts
Participants

Secondary

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

Posted

Mean

Standard Deviation

platelets*10^9 /L

Baseline, Week 26, Week 52

ID	Title	Description
OG000	PAP, Eliglustat: Once Daily	All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
OG001	PAP, Eliglustat: Twice Daily	All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).

Units	Counts
Participants

Secondary

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

Posted

Mean

Standard Deviation

Baseline, Week 26, Week 52

ID	Title	Description
OG000	PAP, Eliglustat: Once Daily	All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
OG001	PAP, Eliglustat: Twice Daily	All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).

Units	Counts
Participants

Secondary

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

Posted

Mean

Standard Deviation

Baseline, Week 26 and Week 52

ID	Title	Description
OG000	PAP, Eliglustat: Once Daily	All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
OG001	PAP, Eliglustat: Twice Daily	All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).

Units	Counts
Participants	OG000

Secondary

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

Chitotriosidase biomarker was assayed from plasma.

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

Posted

Mean

Standard Deviation

nmol/hr/mL

Baseline, Week 26, Week 52

ID	Title	Description
OG000	PAP, Eliglustat: Once Daily	All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
OG001	PAP, Eliglustat: Twice Daily	All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).

Units	Counts
Participants

Secondary

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

GL-1 on DBS biomarker was assayed from dried blood spot (DBS).

Posted

Mean

Standard Deviation

mcg/mL

Baseline, Week 26 and week 52

ID	Title	Description
OG000	PAP, Eliglustat: Once Daily	All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
OG001	PAP, Eliglustat: Twice Daily	All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).

Units	Counts

Secondary

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

MIP1-beta biomarker was assayed from plasma.

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

Posted

Mean

Standard Deviation

pg/mL

Baseline, Week 26, Week 52

ID	Title	Description
OG000	PAP, Eliglustat: Once Daily	All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
OG001	PAP, Eliglustat: Twice Daily	All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).

Units	Counts

Secondary

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

BMD measurements of the spine and bilateral femur were acquired by dual-energy x-ray absorptiometry (DXA) scan.

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

Posted

Mean

Standard Deviation

g/cm^2

Baseline, Week 52

ID	Title	Description
OG000	PAP, Eliglustat: Once Daily	All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
OG001	PAP, Eliglustat: Twice Daily	All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).

Units	Counts

Secondary

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

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).

Posted

Mean

Standard Deviation

T-score

Baseline, Week 52

ID	Title	Description
OG000	PAP, Eliglustat: Once Daily	All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
OG001	PAP, Eliglustat: Twice Daily	All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).

Secondary

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

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).

Posted

Mean

Standard Deviation

Z-score

Baseline, Week 52

ID	Title	Description
OG000	PAP, Eliglustat: Once Daily	All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
OG001	PAP, Eliglustat: Twice Daily	All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).

Secondary

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

Mobility, i.e., ability to walk was assessed as a part of Gaucher disease assessment in participants. In this outcome, number of participants with their different mobility status along with the use of mobility aids (unrestricted mobility, walks with difficulty, walks with orthopaedic aid, requires wheelchair, bedridden) at specified time points were reported.

Posted

Number

participants

Baseline, Week 26 and Week 52

ID	Title	Description
OG000	PAP, Eliglustat: Once Daily	All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
OG001	PAP, Eliglustat: Twice Daily	All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).

Secondary

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

Bone crisis was assessed as a part of Gaucher disease assessment in participants. Acute, excruciating episodic bone pain is characteristic of Gaucher bone crisis, which typically causes debilitation lasting several days or longer and requires treatment with immobilization, hydration, and opioid analgesics. Participants were categorized as 0= no bone crisis, 1= 1 bone crisis, and 2= 2 bone crises during the assessment period. In this outcome, number of participants with different bone crises levels at specified time points were reported.

Posted

Number

participants

Baseline, Week 26, and Week 52

ID	Title	Description
OG000	PAP, Eliglustat: Once Daily	All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
OG001	PAP, Eliglustat: Twice Daily	All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).

Secondary

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

Bone pain was assessed as a part of Gaucher disease assessment in participants. Participants were categorized as none (no bone pain), very mild bone pain, mild bone pain, moderate bone pain, severe bone pain and extreme bone pain during the past 4 weeks. In this outcome, number of participants with different level of bone pain during the past 4 weeks at specified time points were reported.

Posted

Number

participants

Baseline, Week 26, and Week 52

ID	Title	Description
OG000	PAP, Eliglustat: Once Daily	All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
OG001	PAP, Eliglustat: Twice Daily	All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).

Secondary

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

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.

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

Posted

Mean

Standard Deviation

BMB Score

Baseline, Week 52

ID	Title	Description
OG000	PAP, Eliglustat: Once Daily	All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
OG001	PAP, Eliglustat: Twice Daily	All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).

Secondary

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

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

Posted

Mean

Standard Deviation

g/dL

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

ID	Title	Description
OG000	LIP: Eliglustat	All participants (except in Japan) received eliglustat 50 mg BID on Day 1 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. All participants in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks.

Units	Counts
Participants	OG000

Secondary

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

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

Posted

Mean

Standard Deviation

platelets*10^9 /L

Baseline, Week 26, Week 52, Week 78

ID	Title	Description
OG000	LIP: Eliglustat	All participants (except in Japan) received eliglustat 50 mg BID on Day 1 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. All participants in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks.

Units	Counts
Participants	OG000

Secondary

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

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

Posted

Mean

Standard Deviation

Baseline, Week 26, Week 52, Week 78

ID	Title	Description
OG000	LIP: Eliglustat	All participants (except in Japan) received eliglustat 50 mg BID on Day 1 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. All participants in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks.

Units	Counts
Participants	OG000

Secondary

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

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

Posted

Mean

Standard Deviation

Baseline, Week 26, Week 52, Week 78

ID	Title	Description
OG000	LIP: Eliglustat	All participants (except in Japan) received eliglustat 50 mg BID on Day 1 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. All participants in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks.

Units	Counts
Participants	OG000

Secondary

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

Chitotriosidase biomarker was assayed from plasma.

Posted

Mean

Standard Deviation

nmol/hr/mL

Baseline, Week 26, Week 52 and Week 78

ID	Title	Description
OG000	LIP: Eliglustat	All participants (except in Japan) received eliglustat 50 mg, twice daily (BID) on Day 1 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. All participants in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks.

Units	Counts
Participants	OG000

Secondary

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

GL-1 on DBS biomarker was assayed from dried blood spot.

Posted

Mean

Standard Deviation

mcg/mL

Baseline, Week 26, Week 52 and Week 78

ID	Title	Description
OG000	LIP: Eliglustat	All participants (except in Japan) received eliglustat 50 mg, twice daily (BID) on Day 1 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. All participants in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks.

Units	Counts
Participants	OG000

Secondary

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

MIP1-beta biomarker was assayed from plasma.

Posted

Mean

Standard Deviation

pg/mL

Baseline and Week 78

ID	Title	Description
OG000	LIP: Eliglustat	All participants (except in Japan) received eliglustat 50 mg, twice daily (BID) on Day 1 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. All participants in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks.

Units	Counts
Participants	OG000

Secondary

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

Analysis was performed on AT analysis set which included all participants who received at least 1 dose of eliglustat during LIP.

Posted

Number

participants

Baseline, Week 26, Week 52, Week 78

ID	Title	Description
OG000	LIP: Eliglustat	All participants (except in Japan) received eliglustat 50 mg, twice daily (BID) on Day 1 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. All participants in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks.

Units	Counts
Participants	OG000

Secondary

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

Bone crises was assessed as a part of Gaucher disease assessment in participants. Acute, excruciating episodic bone pain is characteristic of Gaucher bone crises, which typically causes debilitation lasting several days or longer and requires treatment with immobilization, hydration, and opioid analgesics. Participants were categorized as 0= no bone crisis, 1= 1 bone crisis, 2= 2 bone crises, 6= 6 bone crises, and 24= 24 bone crises during the assessment period. In this outcome, number of participants with different bone crises levels at specified time points were reported.

Analysis was performed on AT analysis set which included all participants who received at least 1 dose of eliglustat during LIP.

Posted

Number

participants

Baseline, Week 26, Week 52, Week 78

ID	Title	Description
OG000	LIP: Eliglustat	All participants (except in Japan) received eliglustat 50 mg, twice daily (BID) on Day 1 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. All participants in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks.

Units	Counts
Participants

Secondary

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

Bone pain was assessed as a part of Gaucher disease assessment in participants. Participants were categorized as none (no bone pain), very mild bone pain, mild bone pain, moderate bone pain, severe bone pain and extreme bone pain. In this outcome, number of participants with different type of bone pain during the past 4 weeks at specified time points were reported.

Analysis was performed on AT analysis set which included all participants who received at least 1 dose of eliglustat during LIP.

Posted

Number

participants

Baseline, Week 26, Week 52, Week 78

ID	Title	Description
OG000	LIP: Eliglustat	All participants (except in Japan) received eliglustat 50 mg, twice daily (BID) on Day 1 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. All participants in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks.

Units	Counts
Participants	OG000

Secondary

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

Participant were considered as stable if they met the following criteria: hemoglobin level did not decrease >1.5 g/dL from baseline for PAP, platelet count does not decrease >25% below Baseline for PAP, liver volume does not increase >20% above Baseline for PAP, spleen volume does not increase >25% above Baseline for PAP. Baseline for PAP was defined as last available assessment prior to randomization.

Analysis was performed on intent to treat (ITT) population which included all participants who received at least 1 dose of eliglustat after randomization. Here 'n' signifies number of participants with available data at specified time points.

Posted

Number

95% Confidence Interval

percentage of participants

1 Year, 2 Years

ID	Title	Description
OG000	LTTP: Eliglustat	All participants who entered PAP continued their blinded randomized treatment for first 4 weeks. Participants who at Week 52 of PAP maintained their therapeutic goals (defined as: no more than 2 bone crisis during PAP [with no more than 1 bone crisis during either first 6 months or later 6 months of PAP] and is free of other clinically symptomatic bone disease during PAP; hemoglobin level not decreased by >1.5 g/dL from Baseline for PAP [defined as last available assessment prior to randomization]; platelet count not decreased by >25% from Baseline for PAP; spleen volume not increased by 25% from Baseline for PAP; liver volume not increased by >20% from Baseline for PAP), continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) QD till the end of the study. The participants who did not maintain all their therapeutic goals continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) BID till the end of the study.

Secondary

LTTP: Number of Participants With Mobility Status (MS) at Baseline, 1 Year and 2 Years

All participants who received at least one dose of eliglustat during the LTTP.

Posted

Number

participants

Baseline, 1 year, and 2 years

ID	Title	Description
OG000	LTTP: Eliglustat	All participants who entered PAP continued their blinded randomized treatment for first 4 weeks. Participants who at Week 52 of PAP maintained their therapeutic goals (defined as: no more than 2 bone crisis during PAP [with no more than 1 bone crisis during either first 6 months or later 6 months of PAP] and is free of other clinically symptomatic bone disease during PAP; hemoglobin level not decreased by >1.5 g/dL from Baseline for PAP [defined as last available assessment prior to randomization]; platelet count not decreased by >25% from Baseline for PAP; spleen volume not increased by 25% from Baseline for PAP; liver volume not increased by >20% from Baseline for PAP), continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) QD till the end of the study. The participants who did not maintain all their therapeutic goals continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) BID till the end of the study.

Secondary

LTTP: Number of Participants With Bone Crises Assessment at Baseline, 1 Year and 2 Years

Bone crises was assessed as a part of Gaucher disease assessment in participants. Acute, excruciating episodic bone pain is characteristic of Gaucher bone crises, which typically causes debilitation lasting several days or longer and requires treatment with immobilization, hydration, and opioid analgesics. Participants were categorized as 0= no bone crises, 1= 1 bone crisis during the assessment period. In this outcome, number of participants with different bone crises levels at specified time points were reported.

All participants who received at least one dose of eliglustat during the LTTP.

Posted

Number

participants

Baseline, 1 year and 2 years

ID	Title	Description
OG000	LTTP: Eliglustat	All participants who entered PAP continued their blinded randomized treatment for first 4 weeks. Participants who at Week 52 of PAP maintained their therapeutic goals (defined as: no more than 2 bone crisis during PAP [with no more than 1 bone crisis during either first 6 months or later 6 months of PAP] and is free of other clinically symptomatic bone disease during PAP; hemoglobin level not decreased by >1.5 g/dL from Baseline for PAP [defined as last available assessment prior to randomization]; platelet count not decreased by >25% from Baseline for PAP; spleen volume not increased by 25% from Baseline for PAP; liver volume not increased by >20% from Baseline for PAP), continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) QD till the end of the study. The participants who did not maintain all their therapeutic goals continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) BID till the end of the study.

Secondary

LTTP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, 1 Year, and 2 Years

Bone pain was assessed as a part of Gaucher disease assessment in participants. Participants were categorized as none (no bone pain), very mild bone pain, mild bone pain, moderate bone pain, severe bone pain and extreme bone pain. In this outcome, number of participants with different level of bone pain during the past 4 weeks at specified time points were reported.

All participants who received at least one dose of eliglustat during the LTTP.

Posted

Number

participants

Baseline, 1 year and 2 years

ID	Title	Description
OG000	LTTP: Eliglustat	All participants who entered PAP continued their blinded randomized treatment for first 4 weeks. Participants who at Week 52 of PAP maintained their therapeutic goals (defined as: no more than 2 bone crisis during PAP [with no more than 1 bone crisis during either first 6 months or later 6 months of PAP] and is free of other clinically symptomatic bone disease during PAP; hemoglobin level not decreased by >1.5 g/dL from Baseline for PAP [defined as last available assessment prior to randomization]; platelet count not decreased by >25% from Baseline for PAP; spleen volume not increased by 25% from Baseline for PAP; liver volume not increased by >20% from Baseline for PAP), continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) QD till the end of the study. The participants who did not maintain all their therapeutic goals continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) BID till the end of the study.

Secondary

LTTP: Bone Mineral Density (BMD) at Baseline, 1 Year, and 2 Years

BMD measurements of the spine and bilateral femur were acquired by DXA scan.

All participants who received at least one dose of eliglustat during the LTTP.

Posted

Mean

Standard Deviation

g/cm^2

Baseline, 1 year, and 2 years

ID	Title	Description
OG000	LTTP: Eliglustat	All participants who entered PAP continued their blinded randomized treatment for first 4 weeks. Participants who at Week 52 of PAP maintained their therapeutic goals (defined as: no more than 2 bone crisis during PAP [with no more than 1 bone crisis during either first 6 months or later 6 months of PAP] and is free of other clinically symptomatic bone disease during PAP; hemoglobin level not decreased by >1.5 g/dL from Baseline for PAP [defined as last available assessment prior to randomization]; platelet count not decreased by >25% from Baseline for PAP; spleen volume not increased by 25% from Baseline for PAP; liver volume not increased by >20% from Baseline for PAP), continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) QD till the end of the study. The participants who did not maintain all their therapeutic goals continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) BID till the end of the study.

Units	Counts
Participants

Secondary

LTTP: Total T-Scores for BMD at Baseline, 1 Year, and 2 Years

All participants who received at least one dose of eliglustat during the LTTP.

Posted

Mean

Standard Deviation

T-score

Baseline, 1 year, and 2 years

ID	Title	Description
OG000	LTTP: Eliglustat	All participants who entered PAP continued their blinded randomized treatment for first 4 weeks. Participants who at Week 52 of PAP maintained their therapeutic goals (defined as: no more than 2 bone crisis during PAP [with no more than 1 bone crisis during either first 6 months or later 6 months of PAP] and is free of other clinically symptomatic bone disease during PAP; hemoglobin level not decreased by >1.5 g/dL from Baseline for PAP [defined as last available assessment prior to randomization]; platelet count not decreased by >25% from Baseline for PAP; spleen volume not increased by 25% from Baseline for PAP; liver volume not increased by >20% from Baseline for PAP), continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) QD till the end of the study. The participants who did not maintain all their therapeutic goals continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) BID till the end of the study.

Secondary

LTTP: Total Z-scores for BMD at Baseline, 1 Year, and 2 Years

All participants who received at least one dose of eliglustat during the LTTP.

Posted

Mean

Standard Deviation

Z-score

Baseline, 1 year, and 2 years

ID	Title	Description
OG000	LTTP: Eliglustat	All participants who entered PAP continued their blinded randomized treatment for first 4 weeks. Participants who at Week 52 of PAP maintained their therapeutic goals (defined as: no more than 2 bone crisis during PAP [with no more than 1 bone crisis during either first 6 months or later 6 months of PAP] and is free of other clinically symptomatic bone disease during PAP; hemoglobin level not decreased by >1.5 g/dL from Baseline for PAP [defined as last available assessment prior to randomization]; platelet count not decreased by >25% from Baseline for PAP; spleen volume not increased by 25% from Baseline for PAP; liver volume not increased by >20% from Baseline for PAP), continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) QD till the end of the study. The participants who did not maintain all their therapeutic goals continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) BID till the end of the study.

Secondary

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

BMB Score was measured using MRI, range from 0 (no abnormalities) to 8 points (severe disease) for the lumbar spine and from 0 (no abnormalities) to 8 points (severe disease) for the femurs. The total score was calculated as the sum of scores for femur and lumbar spine regions which ranged from 0 (no abnormalities) -16 (severe disease) points. A higher BMB score signified more severe bone marrow involvement.

All participants who received at least one dose of eliglustat during the LTTP.

Posted

Mean

Standard Deviation

BMB Score

Baseline, 1 year, and 2 years

ID	Title	Description
OG000	LTTP: Eliglustat	All participants who entered PAP continued their blinded randomized treatment for first 4 weeks. Participants who at Week 52 of PAP maintained their therapeutic goals (defined as: no more than 2 bone crisis during PAP [with no more than 1 bone crisis during either first 6 months or later 6 months of PAP] and is free of other clinically symptomatic bone disease during PAP; hemoglobin level not decreased by >1.5 g/dL from Baseline for PAP [defined as last available assessment prior to randomization]; platelet count not decreased by >25% from Baseline for PAP; spleen volume not increased by 25% from Baseline for PAP; liver volume not increased by >20% from Baseline for PAP), continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) QD till the end of the study. The participants who did not maintain all their therapeutic goals continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) BID till the end of the study.

Secondary

LTTP: Mean Biomarker (Chitotriosidase) Value at Baseline, 1 Year, and 2 Years

Chitotriosidase biomarker was assayed from plasma.

All participants who received at least one dose of eliglustat during the LTTP.

Posted

Mean

Standard Deviation

nmol/hr/mL

Baseline, 1 year, and 2 years

ID	Title	Description
OG000	LTTP: Eliglustat	All participants who entered PAP continued their blinded randomized treatment for first 4 weeks. Participants who at Week 52 of PAP maintained their therapeutic goals (defined as: no more than 2 bone crisis during PAP [with no more than 1 bone crisis during either first 6 months or later 6 months of PAP] and is free of other clinically symptomatic bone disease during PAP; hemoglobin level not decreased by >1.5 g/dL from Baseline for PAP [defined as last available assessment prior to randomization]; platelet count not decreased by >25% from Baseline for PAP; spleen volume not increased by 25% from Baseline for PAP; liver volume not increased by >20% from Baseline for PAP), continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) QD till the end of the study. The participants who did not maintain all their therapeutic goals continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) BID till the end of the study.

Units	Counts
Participants

Secondary

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

GL-1 on DBS biomarker was assayed from dried blood spot.

All participants who received at least one dose of eliglustat during the LTTP.

Posted

Mean

Standard Deviation

mcg/mL

Baseline, 1 year, and 2 years

ID	Title	Description
OG000	LTTP: Eliglustat	All participants who entered PAP continued their blinded randomized treatment for first 4 weeks. Participants who at Week 52 of PAP maintained their therapeutic goals (defined as: no more than 2 bone crisis during PAP [with no more than 1 bone crisis during either first 6 months or later 6 months of PAP] and is free of other clinically symptomatic bone disease during PAP; hemoglobin level not decreased by >1.5 g/dL from Baseline for PAP [defined as last available assessment prior to randomization]; platelet count not decreased by >25% from Baseline for PAP; spleen volume not increased by 25% from Baseline for PAP; liver volume not increased by >20% from Baseline for PAP), continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) QD till the end of the study. The participants who did not maintain all their therapeutic goals continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) BID till the end of the study.

Units	Counts
Participants

Secondary

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

MIP1-beta biomarker was assayed from plasma.

All participants who received at least one dose of eliglustat during the LTTP.

Posted

Mean

Standard Deviation

pg/mL

Baseline, 1 year, and 2 years

ID	Title	Description
OG000	LTTP: Eliglustat	All participants who entered PAP continued their blinded randomized treatment for first 4 weeks. Participants who at Week 52 of PAP maintained their therapeutic goals (defined as: no more than 2 bone crisis during PAP [with no more than 1 bone crisis during either first 6 months or later 6 months of PAP] and is free of other clinically symptomatic bone disease during PAP; hemoglobin level not decreased by >1.5 g/dL from Baseline for PAP [defined as last available assessment prior to randomization]; platelet count not decreased by >25% from Baseline for PAP; spleen volume not increased by 25% from Baseline for PAP; liver volume not increased by >20% from Baseline for PAP), continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) QD till the end of the study. The participants who did not maintain all their therapeutic goals continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) BID till the end of the study.

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Angina pectoris	Cardiac disorders	MedDra 18.0	Systematic Assessment	EG0002 affected170 at risk
Arrhythmia	Cardiac disorders	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Cardiac arrest	Cardiac disorders	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Abdominal wall haematoma	Gastrointestinal disorders	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Mallory-Weiss syndrome	Gastrointestinal disorders	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Device dislocation	General disorders	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Disuse syndrome	General disorders	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Hernia	General disorders	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Impaired healing	General disorders	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Medical device pain	General disorders	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Cholecystitis	Hepatobiliary disorders	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Cholecystitis chronic	Hepatobiliary disorders	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Acute hepatitis B	Infections and infestations	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Appendicitis	Infections and infestations	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Hepatitis A	Infections and infestations	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Staphylococcal sepsis	Infections and infestations	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Fall	Injury, poisoning and procedural complications	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	MedDra 18.0	Systematic Assessment	EG0002 affected170 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Forearm fracture	Injury, poisoning and procedural complications	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Incisional hernia	Injury, poisoning and procedural complications	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Injury	Injury, poisoning and procedural complications	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Radius fracture	Injury, poisoning and procedural complications	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Spinal fracture	Injury, poisoning and procedural complications	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Hepatic enzyme increased	Investigations	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDra 18.0	Systematic Assessment	EG0002 affected170 at risk
Arthritis	Musculoskeletal and connective tissue disorders	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Joint range of motion decreased	Musculoskeletal and connective tissue disorders	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDra 18.0	Systematic Assessment	EG0003 affected170 at risk
Osteonecrosis	Musculoskeletal and connective tissue disorders	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Lipoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Papillary thyroid cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Dizziness	Nervous system disorders	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Epilepsy	Nervous system disorders	MedDra 18.0	Systematic Assessment	EG0002 affected170 at risk
Ischaemic stroke	Nervous system disorders	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Presyncope	Nervous system disorders	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Seizure	Nervous system disorders	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Syncope	Nervous system disorders	MedDra 18.0	Systematic Assessment	EG0003 affected170 at risk
Ectopic pregnancy	Pregnancy, puerperium and perinatal conditions	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Conversion disorder	Psychiatric disorders	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Major depression	Psychiatric disorders	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Calculus urinary	Renal and urinary disorders	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Uterine polyp	Reproductive system and breast disorders	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Aortic aneurysm	Vascular disorders	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Haemorrhage	Vascular disorders	MedDra 18.0	Systematic Assessment	EG0001 affected170 at risk
Hypertension	Vascular disorders	MedDra 18.0	Systematic Assessment	EG0002 affected170 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Thrombocytopenia	Blood and lymphatic system disorders	MedDra 18.0	Systematic Assessment	EG0009 affected170 at risk
Palpitations	Cardiac disorders	MedDra 18.0	Systematic Assessment	EG00011 affected170 at risk
Abdominal distension	Gastrointestinal disorders	MedDra 18.0	Systematic Assessment	EG0009 affected170 at risk
Abdominal pain	Gastrointestinal disorders	MedDra 18.0	Systematic Assessment	EG00015 affected170 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDra 18.0	Systematic Assessment	EG00026 affected170 at risk
Constipation	Gastrointestinal disorders	MedDra 18.0	Systematic Assessment	EG00016 affected170 at risk
Diarrhoea	Gastrointestinal disorders	MedDra 18.0	Systematic Assessment	EG00024 affected170 at risk
Dyspepsia	Gastrointestinal disorders	MedDra 18.0	Systematic Assessment	EG00019 affected170 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDra 18.0	Systematic Assessment	EG0009 affected170 at risk
Nausea	Gastrointestinal disorders	MedDra 18.0	Systematic Assessment	EG00018 affected170 at risk
Vomiting	Gastrointestinal disorders	MedDra 18.0	Systematic Assessment	EG00014 affected170 at risk
Fatigue	General disorders	MedDra 18.0	Systematic Assessment	EG00017 affected170 at risk
Pyrexia	General disorders	MedDra 18.0	Systematic Assessment	EG00016 affected170 at risk
Hepatomegaly	Hepatobiliary disorders	MedDra 18.0	Systematic Assessment	EG0009 affected170 at risk
Gastroenteritis	Infections and infestations	MedDra 18.0	Systematic Assessment	EG00015 affected170 at risk
Influenza	Infections and infestations	MedDra 18.0	Systematic Assessment	EG00023 affected170 at risk
Nasopharyngitis	Infections and infestations	MedDra 18.0	Systematic Assessment	EG00052 affected170 at risk
Upper respiratory tract infection	Infections and infestations	MedDra 18.0	Systematic Assessment	EG00022 affected170 at risk
Urinary tract infection	Infections and infestations	MedDra 18.0	Systematic Assessment	EG00014 affected170 at risk
Viral infection	Infections and infestations	MedDra 18.0	Systematic Assessment	EG00010 affected170 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDra 18.0	Systematic Assessment	EG00030 affected170 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDra 18.0	Systematic Assessment	EG00029 affected170 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDra 18.0	Systematic Assessment	EG00010 affected170 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDra 18.0	Systematic Assessment	EG00011 affected170 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDra 18.0	Systematic Assessment	EG00024 affected170 at risk
Dizziness	Nervous system disorders	MedDra 18.0	Systematic Assessment	EG00028 affected170 at risk
Headache	Nervous system disorders	MedDra 18.0	Systematic Assessment	EG00037 affected170 at risk
Depression	Psychiatric disorders	MedDra 18.0	Systematic Assessment	EG00010 affected170 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDra 18.0	Systematic Assessment	EG00021 affected170 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDra 18.0	Systematic Assessment	EG00013 affected170 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDra 18.0	Systematic Assessment	EG00018 affected170 at risk
Hypertension	Vascular disorders	MedDra 18.0	Systematic Assessment	EG0009 affected170 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