Gaucher Disease
Conditions
Keywords
Gaucher disease, Genz-112638, beta-glucosidase, acid β-glucosidase, glucocerebrosidase, glucosylceramide, D-glucosyl-N-acylsphingosine glucohydrolase, substrate reduction therapy
Brief summary
The primary objective of this study was to evaluate the efficacy and safety of once daily (QD) versus twice daily (BID) dosing of eliglustat tartrate (Genz-112638) in participants with Gaucher disease type 1 who had demonstrated clinical stability on BID dosing of eliglustat tartrate (Genz-112638). The secondary objective was to evaluate the pharmacokinetics (PK) of Genz-99067 when eliglustat tartrate (Genz-112638) was administered QD and BID in participants with Gaucher disease type 1 who had demonstrated clinical stability on BID dosing of eliglustat tartrate (Genz-112638).
Detailed description
NOTE: Other Phase 3 studies being conducted with eliglustat tartrate (Genz-112638) are GZGD02507 (ENGAGE): NCT00891202 and GZGD02607 (ENCORE): NCT00943111
Interventions
Oral Capsule in 50 mg or 100 mg dosages
Sponsors
Genzyme, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PAP: Percentage of Participants Who Remained Stable for 52 Weeks During the PAP | PAP Baseline up to the end of PAP (Week 52) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PAP: Mean Platelet Count at Baseline, Weeks 26, 52 | Baseline, Week 26, Week 52 | — |
| PAP: Mean Spleen Volume at Baseline, Weeks 26, 52 | Baseline, Week 26, Week 52 | — |
| PAP: Mean Liver Volume at Baseline, Weeks 26, 52 | Baseline, Week 26 and Week 52 | — |
| PAP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26 and Week 52 | Baseline, Week 26, Week 52 | Chitotriosidase biomarker was assayed from plasma. |
| PAP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26 and Week 52 | Baseline, Week 26 and week 52 | GL-1 on DBS biomarker was assayed from dried blood spot (DBS). |
| PAP: Mean Biomarker Macrophage Inflammatory Protein-1 Beta (MIP1-beta) Value at Baseline, Weeks 26, 52 | Baseline, Week 26, Week 52 | MIP1-beta biomarker was assayed from plasma. |
| PAP: Bone Mineral Density (BMD) at Baseline and Week 52 | Baseline, Week 52 | BMD measurements of the spine and bilateral femur were acquired by dual-energy x-ray absorptiometry (DXA) scan. |
| PAP: Total T-Scores for BMD at Baseline and Week 52 | Baseline, 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). |
| PAP: Total Z-scores for BMD at Baseline and Week 52 | Baseline, 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). |
| PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52. | Baseline, Week 26 and Week 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. |
| LTTP: Total Z-scores for BMD at Baseline, 1 Year, and 2 Years | Baseline, 1 year, and 2 years | 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). |
| PAP: Number of Participants With Bone Crises at Baseline, Weeks 26 and 52 | Baseline, Week 26, and Week 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. |
| PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 | Baseline, Week 26, and Week 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. |
| PAP: Total Bone Marrow Burden Score (BMB) at Baseline and Week 52 | Baseline, 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. |
| LIP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26, 52 and 78 | Baseline, Week 26, Week, 52, and Week 78 | — |
| LIP: Mean Platelet Count at Baseline, Weeks 26, 52 and 78 | Baseline, Week 26, Week 52, Week 78 | — |
| LIP: Mean Liver Volume at Baseline, Weeks 26, 52 and 78 | Baseline, Week 26, Week 52, Week 78 | — |
| PAP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26 and 52 | Baseline, Week 26, Week 52 | — |
| LIP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26, 52, and 78 | Baseline, Week 26, Week 52 and Week 78 | Chitotriosidase biomarker was assayed from plasma. |
| LIP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26, Week 52, and Week 78 | Baseline, Week 26, Week 52 and Week 78 | GL-1 on DBS biomarker was assayed from dried blood spot. |
| LIP: Mean Biomarker (MIP1-beta) Value at Baseline, Week 78 | Baseline and Week 78 | MIP1-beta biomarker was assayed from plasma. |
| LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78 | Baseline, Week 26, Week 52, Week 78 | 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. |
| LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78 | Baseline, Week 26, Week 52, Week 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. |
| LIP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78 | Baseline, Week 26, Week 52, Week 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. |
| 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 | 1 Year, 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. |
| LTTP: Number of Participants With Mobility Status (MS) at Baseline, 1 Year and 2 Years | Baseline, 1 year, and 2 years | 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. |
| LTTP: Number of Participants With Bone Crises Assessment at Baseline, 1 Year and 2 Years | 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. |
| LTTP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, 1 Year, and 2 Years | 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. |
| LTTP: Bone Mineral Density (BMD) at Baseline, 1 Year, and 2 Years | Baseline, 1 year, and 2 years | BMD measurements of the spine and bilateral femur were acquired by DXA scan. |
| LTTP: Total T-Scores for BMD at Baseline, 1 Year, and 2 Years | Baseline, 1 year, and 2 years | 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). |
| LTTP: Total Bone Marrow Burden Score (BMB) at Baseline, 1 Year, and 2 Years | 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. |
| LTTP: Mean Biomarker (Chitotriosidase) Value at Baseline, 1 Year, and 2 Years | Baseline, 1 year, and 2 years | Chitotriosidase biomarker was assayed from plasma. |
| LTTP: Mean Biomarker (GL-1 on DBS) Value at Baseline, 1 Year, and 2 Years | Baseline, 1 year, and 2 years | GL-1 on DBS biomarker was assayed from dried blood spot. |
| LTTP: Mean Biomarker (MIP1-beta) Value at Baseline, 1 Year, and 2 Years | Baseline, 1 year, and 2 years | MIP1-beta biomarker was assayed from plasma. |
| LIP: Mean Spleen Volume at Baseline, Weeks 26, 52 and 78 | Baseline, Week 26, Week 52, Week 78 | — |
Countries
Australia, Austria, Brazil, Canada, China, Croatia, France, Greece, India, Japan, Netherlands, Portugal, Romania, Russia, Serbia, Sweden, United States
Participant flow
Recruitment details
The study was conducted at 45 centers in 17 countries between 1 June 2010 and 6 October 2015. A total of 219 participants were screened, out of which 170 entered into the lead in period (LIP). Remaining 48 participants were screen failures and 1 participant withdrew before entering into the LIP.
Pre-assignment details
Participant flow divided into 4 periods: LIP:to assess randomization criteria. Primary analysis period (PAP):to assess therapeutic efficacy at 2 dosing regimen in randomized participants. Long-term treatment period (LTTP): to assess long term efficacy. Extended treatment period (ETP):those who were non-randomized after LIP continued in this period.
Participants by arm
| Arm | Count |
|---|---|
| All Participants All participants who received treatment in LIP (eliglustat 50 mg BID on Day 1 titrated up to 100 mg BID \[50 or 100 mg capsules\] based on their individual PK data for up to 78 weeks \[except for the participants in Japan\]. Participants in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID \[50 or 100 mg capsules\] based on their individual PK data for up to 78 weeks) and assessed for randomization. | 170 |
| Total | 170 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Extended Treatment (up to 42 Months) | Pregnancy | 0 | 0 | 0 | 0 | 2 |
| Extended Treatment (up to 42 Months) | Transitioned to Commercial Eliglustat | 0 | 0 | 0 | 0 | 3 |
| Lead-in Period (up to 78 Weeks) | Adverse Event | 2 | 0 | 0 | 0 | 0 |
| Lead-in Period (up to 78 Weeks) | Non-Compliance With Protocol | 1 | 0 | 0 | 0 | 0 |
| Lead-in Period (up to 78 Weeks) | Pregnancy | 4 | 0 | 0 | 0 | 0 |
| Lead-in Period (up to 78 Weeks) | Withdrawal by Subject | 6 | 0 | 0 | 0 | 0 |
| Long Term Treatment | Adverse Event | 0 | 0 | 0 | 3 | 0 |
| Long Term Treatment | Entered in Period, But Not Treated | 0 | 0 | 0 | 1 | 0 |
| Long Term Treatment | Lost to Follow-up | 0 | 0 | 0 | 2 | 0 |
| Long Term Treatment | Transitioned to Commercial Eliglustat | 0 | 0 | 0 | 18 | 0 |
| Long Term Treatment | Withdrawal by Subject | 0 | 0 | 0 | 2 | 0 |
| Primary Analysis Period (up to 52 Weeks) | Adverse Event | 0 | 2 | 3 | 0 | 0 |
| Primary Analysis Period (up to 52 Weeks) | Non-Compliant to Protocol | 0 | 1 | 1 | 0 | 0 |
| Primary Analysis Period (up to 52 Weeks) | Pregnancy | 0 | 1 | 0 | 0 | 0 |
| Primary Analysis Period (up to 52 Weeks) | Treatment Failure | 0 | 6 | 1 | 0 | 0 |
| Primary Analysis Period (up to 52 Weeks) | Withdrawal by Subject | 0 | 1 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 37.7 years STANDARD_DEVIATION 15.1 |
| Gender Female | 81 Participants |
| Gender Male | 89 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 144 / 170 |
| serious Total, serious adverse events | 40 / 170 |
Outcome results
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.
Time frame: PAP Baseline up to the end of PAP (Week 52)
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PAP, Eliglustat: Once Daily | PAP: Percentage of Participants Who Remained Stable for 52 Weeks During the PAP | 80.4 percentage of participants |
| PAP, Eliglustat: Twice Daily | PAP: Percentage of Participants Who Remained Stable for 52 Weeks During the PAP | 83.1 percentage of participants |
95% CI: [-17.7, 11.9]
Secondary
LIP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26, 52, and 78
Chitotriosidase biomarker was assayed from plasma.
Time frame: Baseline, Week 26, Week 52 and Week 78
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAP, Eliglustat: Once Daily | LIP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26, 52, and 78 | Chitotriosidase: Baseline (n=170) | 2437.92 nmol/hr/mL | Standard Deviation 3291.25 |
| PAP, Eliglustat: Once Daily | LIP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26, 52, and 78 | Chitotriosidase: week 26 (n=157) | 1802.93 nmol/hr/mL | Standard Deviation 2529.29 |
| PAP, Eliglustat: Once Daily | LIP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26, 52, and 78 | Chitotriosidase: week 52 (n=72) | 1755.70 nmol/hr/mL | Standard Deviation 2649.14 |
| PAP, Eliglustat: Once Daily | LIP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26, 52, and 78 | Chitotriosidase: week 78 (n=41) | 1677.02 nmol/hr/mL | Standard Deviation 2718.75 |
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.
Time frame: Baseline, Week 26, Week 52 and Week 78
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAP, Eliglustat: Once Daily | LIP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26, Week 52, and Week 78 | GL-1 on DBS: Baseline (n=159) | 4.358 mcg/mL | Standard Deviation 2.155 |
| PAP, Eliglustat: Once Daily | LIP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26, Week 52, and Week 78 | GL-1 on DBS: Week 26 (n=144) | 2.340 mcg/mL | Standard Deviation 0.868 |
| PAP, Eliglustat: Once Daily | LIP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26, Week 52, and Week 78 | GL-1 on DBS: Week 52 (n=68) | 2.279 mcg/mL | Standard Deviation 0.73 |
| PAP, Eliglustat: Once Daily | LIP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26, Week 52, and Week 78 | GL-1 on DBS: Week 78 (n=39) | 2.495 mcg/mL | Standard Deviation 1.5 |
Secondary
LIP: Mean Biomarker (MIP1-beta) Value at Baseline, Week 78
MIP1-beta biomarker was assayed from plasma.
Time frame: Baseline and Week 78
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAP, Eliglustat: Once Daily | LIP: Mean Biomarker (MIP1-beta) Value at Baseline, Week 78 | MIP-1beta: Baseline (n=170) | 142.433 pg/mL | Standard Deviation 125.961 |
| PAP, Eliglustat: Once Daily | LIP: Mean Biomarker (MIP1-beta) Value at Baseline, Week 78 | MIP-1beta: Week 78 (n=41) | 132.180 pg/mL | Standard Deviation 189.454 |
Secondary
LIP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26, 52 and 78
Time frame: Baseline, Week 26, Week, 52, and Week 78
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAP, Eliglustat: Once Daily | LIP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26, 52 and 78 | Baseline (n=170) | 13.435 g/dL | Standard Deviation 1.56 |
| PAP, Eliglustat: Once Daily | LIP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26, 52 and 78 | Week 26 (n=163) | 13.443 g/dL | Standard Deviation 1.382 |
| PAP, Eliglustat: Once Daily | LIP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26, 52 and 78 | Week 52 (n=74) | 13.434 g/dL | Standard Deviation 1.497 |
| PAP, Eliglustat: Once Daily | LIP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26, 52 and 78 | Week 78 (n=41) | 13.329 g/dL | Standard Deviation 1.528 |
Secondary
LIP: Mean Liver Volume at Baseline, Weeks 26, 52 and 78
Time frame: Baseline, Week 26, Week 52, Week 78
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAP, Eliglustat: Once Daily | LIP: Mean Liver Volume at Baseline, Weeks 26, 52 and 78 | Baseline (n=170) | 1.044 MN | Standard Deviation 0.243 |
| PAP, Eliglustat: Once Daily | LIP: Mean Liver Volume at Baseline, Weeks 26, 52 and 78 | Week 26 (n=149) | 1.040 MN | Standard Deviation 0.229 |
| PAP, Eliglustat: Once Daily | LIP: Mean Liver Volume at Baseline, Weeks 26, 52 and 78 | Week 52 (n=68) | 1.059 MN | Standard Deviation 0.242 |
| PAP, Eliglustat: Once Daily | LIP: Mean Liver Volume at Baseline, Weeks 26, 52 and 78 | Week 78 (n=39) | 1.062 MN | Standard Deviation 0.236 |
Secondary
LIP: Mean Platelet Count at Baseline, Weeks 26, 52 and 78
Time frame: Baseline, Week 26, Week 52, Week 78
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAP, Eliglustat: Once Daily | LIP: Mean Platelet Count at Baseline, Weeks 26, 52 and 78 | Baseline (n=170) | 178.653 platelets*10^9 /L | Standard Deviation 92.732 |
| PAP, Eliglustat: Once Daily | LIP: Mean Platelet Count at Baseline, Weeks 26, 52 and 78 | Week 26 (n=163) | 180.021 platelets*10^9 /L | Standard Deviation 85.426 |
| PAP, Eliglustat: Once Daily | LIP: Mean Platelet Count at Baseline, Weeks 26, 52 and 78 | Week 52 (n=74) | 176.378 platelets*10^9 /L | Standard Deviation 79.88 |
| PAP, Eliglustat: Once Daily | LIP: Mean Platelet Count at Baseline, Weeks 26, 52 and 78 | Week 78 (n=41) | 168.720 platelets*10^9 /L | Standard Deviation 74.117 |
Secondary
LIP: Mean Spleen Volume at Baseline, Weeks 26, 52 and 78
Time frame: Baseline, Week 26, Week 52, Week 78
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAP, Eliglustat: Once Daily | LIP: Mean Spleen Volume at Baseline, Weeks 26, 52 and 78 | Baseline (n=119) | 4.448 MN | Standard Deviation 2.314 |
| PAP, Eliglustat: Once Daily | LIP: Mean Spleen Volume at Baseline, Weeks 26, 52 and 78 | Week 26 (n=106) | 3.840 MN | Standard Deviation 1.801 |
| PAP, Eliglustat: Once Daily | LIP: Mean Spleen Volume at Baseline, Weeks 26, 52 and 78 | Week 52 (n=52) | 4.094 MN | Standard Deviation 1.767 |
| PAP, Eliglustat: Once Daily | LIP: Mean Spleen Volume at Baseline, Weeks 26, 52 and 78 | Week 78 (n=30) | 4.088 MN | Standard Deviation 2.089 |
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.
Time frame: Baseline, Week 26, Week 52, Week 78
Population: Analysis was performed on AT analysis set which included all participants who received at least 1 dose of eliglustat during LIP.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78 | Bone Crisis (0): Baseline (n=162) | 151 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78 | Bone Crisis (0): Week 26 (n=162) | 159 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78 | Bone Crisis (0): Week 52 (n=72) | 72 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78 | Bone Crisis (0): Week 78 (n=41) | 41 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78 | Bone Crisis (1): Baseline (n=162) | 8 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78 | Bone Crisis (1): Week 26 (n=162) | 3 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78 | Bone Crisis (1): Week 52 (n=72) | 0 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78 | Bone Crisis (1): Week 78 (n=41) | 0 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78 | Bone Crisis (2): Baseline (n=162) | 1 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78 | Bone Crisis (2): Week 26 (n=162) | 0 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78 | Bone Crisis (2): Week 52 (n=72) | 0 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78 | Bone Crisis (2): Week 78 (n=41) | 0 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78 | Bone Crisis (6): Baseline (n=162) | 1 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78 | Bone Crisis (6): Week 26 (n=162) | 0 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78 | Bone Crisis (6): Week 52 (n=72) | 0 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78 | Bone Crisis (6): Week 78 (n=41) | 0 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78 | Bone Crisis (24): Baseline (n=162) | 1 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78 | Bone Crisis (24): Week 26 (n=162) | 0 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78 | Bone Crisis (24): Week 52 (n=72) | 0 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78 | Bone Crisis (24): Week 78 (n=41) | 0 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.
Time frame: Baseline, Week 26, Week 52, Week 78
Population: Analysis was performed on AT analysis set which included all participants who received at least 1 dose of eliglustat during LIP.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78 | None: Baseline (n=163) | 112 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78 | None: Week 26 (n=161) | 125 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78 | None: Week 52 (n=72) | 62 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78 | None: Week 78 (n=41) | 39 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78 | Very Mild: Baseline (n=163) | 17 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78 | Very Mild: Week 26 (n=161) | 14 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78 | Very Mild: Week 52 (n=72) | 4 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78 | Very Mild: Week 78 (n=41) | 1 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78 | Mild: Baseline (n=163) | 22 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78 | Mild: Week 26 (n=161) | 10 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78 | Mild: Week 52 (n=72) | 3 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78 | Mild: Week 78 (n=41) | 0 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78 | Moderate: Baseline (n=163) | 8 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78 | Moderate: Week 26 (n=161) | 10 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78 | Moderate: Week 52 (n=72) | 3 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78 | Moderate: Week 78 (n=41) | 1 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78 | Severe: Baseline (n=163) | 4 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78 | Severe: Week 26 (n=161) | 2 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78 | Severe: Week 52 (n=72) | 0 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78 | Severe: Week 78 (n=41) | 0 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78 | Extreme: Baseline (n=163) | 0 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78 | Extreme: Week 26 (n=161) | 0 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78 | Extreme: Week 52 (n=72) | 0 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78 | Extreme: Week 78 (n=41) | 0 participants |
Secondary
LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78
Mobility, i.e., ability to walk was assessed as a part of Gaucher disease assessment in participants. In this outcome, number of participants with their different mobility status along with the use of mobility aids (unrestricted mobility, walks with difficulty, walks with orthopaedic aid, requires wheelchair, bedridden) at specified time points were reported.
Time frame: Baseline, Week 26, Week 52, Week 78
Population: Analysis was performed on AT analysis set which included all participants who received at least 1 dose of eliglustat during LIP.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78 | MS,Unrestricted: Baseline (n=163) | 146 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78 | MS,Unrestricted: Week 26 (n=161) | 153 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78 | MS,Unrestricted: Week 52 (n=72) | 70 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78 | MS,Unrestricted: Week 78 (n= 41) | 39 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78 | MS, Walks With Difficulty: Baseline (n=163) | 12 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78 | MS, Walks With Difficulty: Week 26 (n=161) | 6 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78 | MS, Walks With Difficulty: Week 52 (n=72) | 1 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78 | MS, Walks With Difficulty: Week 78 (n=41) | 2 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78 | MS, Walks With Orthopedic Aid: Baseline (n=163) | 3 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78 | MS, Walks With Orthopedic Aid: Week 26 (n=161) | 1 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78 | MS, Walks With Orthopedic Aid: Week 52 (n=72) | 0 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78 | MS, Walks With Orthopedic Aid: Week 78 (n=41) | 0 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78 | MS, Required wheelchair: Baseline (n=163) | 2 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78 | MS, Required wheelchair: Week 26 (n=161) | 1 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78 | MS, Required wheelchair: Week 52 (n=72) | 1 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78 | MS, Required wheelchair: Week 78 (n=41) | 0 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78 | MS, Bedridden: Baseline (n=163) | 0 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78 | MS, Bedridden: Week 26 (n=161) | 0 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78 | MS, Bedridden: Week 52 (n=72) | 0 participants |
| PAP, Eliglustat: Once Daily | LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78 | MS, Bedridden: Week 78 (n=41) | 0 participants |
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.
Time frame: Baseline, 1 year, and 2 years
Population: All participants who received at least one dose of eliglustat during the LTTP.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAP, Eliglustat: Once Daily | LTTP: Bone Mineral Density (BMD) at Baseline, 1 Year, and 2 Years | Lumbar Spine: Baseline (n=113) | 1.087 g/cm^2 | Standard Deviation 0.182 |
| PAP, Eliglustat: Once Daily | LTTP: Bone Mineral Density (BMD) at Baseline, 1 Year, and 2 Years | Lumbar Spine: 1 year (n=101) | 1.083 g/cm^2 | Standard Deviation 0.183 |
| PAP, Eliglustat: Once Daily | LTTP: Bone Mineral Density (BMD) at Baseline, 1 Year, and 2 Years | Lumbar Spine: 2 years (n=26) | 1.082 g/cm^2 | Standard Deviation 0.19 |
| PAP, Eliglustat: Once Daily | LTTP: Bone Mineral Density (BMD) at Baseline, 1 Year, and 2 Years | Left Femur: Baseline (n=107) | 0.986 g/cm^2 | Standard Deviation 0.205 |
| PAP, Eliglustat: Once Daily | LTTP: Bone Mineral Density (BMD) at Baseline, 1 Year, and 2 Years | Left Femur: 1 year (n=95) | 0.994 g/cm^2 | Standard Deviation 0.226 |
| PAP, Eliglustat: Once Daily | LTTP: Bone Mineral Density (BMD) at Baseline, 1 Year, and 2 Years | Left Femur: 2 years (n=22) | 0.950 g/cm^2 | Standard Deviation 0.22 |
| PAP, Eliglustat: Once Daily | LTTP: Bone Mineral Density (BMD) at Baseline, 1 Year, and 2 Years | Right Femur: Baseline (n=103) | 0.983 g/cm^2 | Standard Deviation 0.201 |
| PAP, Eliglustat: Once Daily | LTTP: Bone Mineral Density (BMD) at Baseline, 1 Year, and 2 Years | Right Femur: 1 year (n=91) | 0.979 g/cm^2 | Standard Deviation 0.202 |
| PAP, Eliglustat: Once Daily | LTTP: Bone Mineral Density (BMD) at Baseline, 1 Year, and 2 Years | Right Femur: 2 years (n=21) | 0.908 g/cm^2 | Standard Deviation 0.131 |
Secondary
LTTP: Mean Biomarker (Chitotriosidase) Value at Baseline, 1 Year, and 2 Years
Chitotriosidase biomarker was assayed from plasma.
Time frame: Baseline, 1 year, and 2 years
Population: All participants who received at least one dose of eliglustat during the LTTP.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAP, Eliglustat: Once Daily | LTTP: Mean Biomarker (Chitotriosidase) Value at Baseline, 1 Year, and 2 Years | Chitotriosidase: Baseline (n=118) | 1188.983 nmol/hr/mL | Standard Deviation 1857.521 |
| PAP, Eliglustat: Once Daily | LTTP: Mean Biomarker (Chitotriosidase) Value at Baseline, 1 Year, and 2 Years | Chitotriosidase: 1 year (n=97)) | 1221.753 nmol/hr/mL | Standard Deviation 2072.446 |
| PAP, Eliglustat: Once Daily | LTTP: Mean Biomarker (Chitotriosidase) Value at Baseline, 1 Year, and 2 Years | Chitotriosidase: 2 years (n=31) | 598.161 nmol/hr/mL | Standard Deviation 1463.603 |
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.
Time frame: Baseline, 1 year, and 2 years
Population: All participants who received at least one dose of eliglustat during the LTTP.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAP, Eliglustat: Once Daily | LTTP: Mean Biomarker (GL-1 on DBS) Value at Baseline, 1 Year, and 2 Years | GL-1 on DBS: Baseline (n=114) | 2.725 mcg/mL | Standard Deviation 1.35 |
| PAP, Eliglustat: Once Daily | LTTP: Mean Biomarker (GL-1 on DBS) Value at Baseline, 1 Year, and 2 Years | GL-1 on DBS: 1 year (n=98) | 2.500 mcg/mL | Standard Deviation 1.031 |
| PAP, Eliglustat: Once Daily | LTTP: Mean Biomarker (GL-1 on DBS) Value at Baseline, 1 Year, and 2 Years | GL-1 on DBS: 2 years (n=29) | 2.238 mcg/mL | Standard Deviation 0.658 |
Secondary
LTTP: Mean Biomarker (MIP1-beta) Value at Baseline, 1 Year, and 2 Years
MIP1-beta biomarker was assayed from plasma.
Time frame: Baseline, 1 year, and 2 years
Population: All participants who received at least one dose of eliglustat during the LTTP.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAP, Eliglustat: Once Daily | LTTP: Mean Biomarker (MIP1-beta) Value at Baseline, 1 Year, and 2 Years | MIP-1beta: 1 year (n=94) | 90.398 pg/mL | Standard Deviation 90.549 |
| PAP, Eliglustat: Once Daily | LTTP: Mean Biomarker (MIP1-beta) Value at Baseline, 1 Year, and 2 Years | MIP-1beta: Baseline (n=114) | 97.857 pg/mL | Standard Deviation 125.857 |
| PAP, Eliglustat: Once Daily | LTTP: Mean Biomarker (MIP1-beta) Value at Baseline, 1 Year, and 2 Years | MIP-1beta: 2 years (n=31) | 68.445 pg/mL | Standard Deviation 64.774 |
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.
Time frame: Baseline, 1 year and 2 years
Population: All participants who received at least one dose of eliglustat during the LTTP.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PAP, Eliglustat: Once Daily | LTTP: Number of Participants With Bone Crises Assessment at Baseline, 1 Year and 2 Years | Bone Crisis (0): Baseline (n=120) | 119 participants |
| PAP, Eliglustat: Once Daily | LTTP: Number of Participants With Bone Crises Assessment at Baseline, 1 Year and 2 Years | Bone Crisis (0): 1 year (n=104) | 104 participants |
| PAP, Eliglustat: Once Daily | LTTP: Number of Participants With Bone Crises Assessment at Baseline, 1 Year and 2 Years | Bone Crisis (0): 2 years (n=32) | 32 participants |
| PAP, Eliglustat: Once Daily | LTTP: Number of Participants With Bone Crises Assessment at Baseline, 1 Year and 2 Years | Bone Crisis (1): Baseline (n=120) | 1 participants |
| PAP, Eliglustat: Once Daily | LTTP: Number of Participants With Bone Crises Assessment at Baseline, 1 Year and 2 Years | Bone Crisis (1): 1 year (n=104) | 0 participants |
| PAP, Eliglustat: Once Daily | LTTP: Number of Participants With Bone Crises Assessment at Baseline, 1 Year and 2 Years | Bone Crisis (1): 2 years (n=32) | 0 participants |
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.
Time frame: Baseline, 1 year and 2 years
Population: All participants who received at least one dose of eliglustat during the LTTP.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PAP, Eliglustat: Once Daily | LTTP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, 1 Year, and 2 Years | None: Baseline (n=120) | 91 participants |
| PAP, Eliglustat: Once Daily | LTTP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, 1 Year, and 2 Years | None: 1 year (n=104) | 83 participants |
| PAP, Eliglustat: Once Daily | LTTP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, 1 Year, and 2 Years | None: 2 years (n=32) | 32 participants |
| PAP, Eliglustat: Once Daily | LTTP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, 1 Year, and 2 Years | Very Mild: Baseline (n=120) | 12 participants |
| PAP, Eliglustat: Once Daily | LTTP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, 1 Year, and 2 Years | Very Mild: 1 year (n=104) | 9 participants |
| PAP, Eliglustat: Once Daily | LTTP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, 1 Year, and 2 Years | Very Mild: 2 years (n=32) | 0 participants |
| PAP, Eliglustat: Once Daily | LTTP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, 1 Year, and 2 Years | Mild: Baseline (n=120) | 8 participants |
| PAP, Eliglustat: Once Daily | LTTP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, 1 Year, and 2 Years | Mild: 1 year (n=104) | 10 participants |
| PAP, Eliglustat: Once Daily | LTTP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, 1 Year, and 2 Years | Mild: 2 years (n=32) | 0 participants |
| PAP, Eliglustat: Once Daily | LTTP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, 1 Year, and 2 Years | Moderate: Baseline (n=120) | 7 participants |
| PAP, Eliglustat: Once Daily | LTTP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, 1 Year, and 2 Years | Moderate: 1 year (n=104) | 1 participants |
| PAP, Eliglustat: Once Daily | LTTP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, 1 Year, and 2 Years | Moderate: 2 years (n=32) | 0 participants |
| PAP, Eliglustat: Once Daily | LTTP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, 1 Year, and 2 Years | Severe: Baseline (n=120) | 2 participants |
| PAP, Eliglustat: Once Daily | LTTP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, 1 Year, and 2 Years | Severe: 1 year (n=104) | 0 participants |
| PAP, Eliglustat: Once Daily | LTTP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, 1 Year, and 2 Years | Severe: 2 years (n=32) | 0 participants |
| PAP, Eliglustat: Once Daily | LTTP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, 1 Year, and 2 Years | Extreme: Baseline (n=120) | 0 participants |
| PAP, Eliglustat: Once Daily | LTTP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, 1 Year, and 2 Years | Extreme: 1 year (n=104) | 1 participants |
| PAP, Eliglustat: Once Daily | LTTP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, 1 Year, and 2 Years | Extreme: 2 years (n=32) | 0 participants |
Secondary
LTTP: Number of Participants With Mobility Status (MS) at Baseline, 1 Year and 2 Years
Mobility, i.e., ability to walk was assessed as a part of Gaucher disease assessment in participants. In this outcome, number of participants with their different mobility status along with the use of mobility aids (unrestricted mobility, walks with difficulty, walks with orthopaedic aid, requires wheelchair, bedridden) at specified time points were reported.
Time frame: Baseline, 1 year, and 2 years
Population: All participants who received at least one dose of eliglustat during the LTTP.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PAP, Eliglustat: Once Daily | LTTP: Number of Participants With Mobility Status (MS) at Baseline, 1 Year and 2 Years | MS, Unrestricted: Baseline (n=120) | 111 participants |
| PAP, Eliglustat: Once Daily | LTTP: Number of Participants With Mobility Status (MS) at Baseline, 1 Year and 2 Years | MS, Unrestricted: 1 year (n=104) | 97 participants |
| PAP, Eliglustat: Once Daily | LTTP: Number of Participants With Mobility Status (MS) at Baseline, 1 Year and 2 Years | MS, Unrestricted: 2 years (n=32) | 28 participants |
| PAP, Eliglustat: Once Daily | LTTP: Number of Participants With Mobility Status (MS) at Baseline, 1 Year and 2 Years | MS, Walks with Difficulty: Baseline (n=120) | 7 participants |
| PAP, Eliglustat: Once Daily | LTTP: Number of Participants With Mobility Status (MS) at Baseline, 1 Year and 2 Years | MS, Walks with Difficulty: 1 year (n=104) | 4 participants |
| PAP, Eliglustat: Once Daily | LTTP: Number of Participants With Mobility Status (MS) at Baseline, 1 Year and 2 Years | Ms, Walks with Difficulty: 2 years (n=32) | 2 participants |
| PAP, Eliglustat: Once Daily | LTTP: Number of Participants With Mobility Status (MS) at Baseline, 1 Year and 2 Years | MS, Walks with Orthopedic Aid: Baseline (n=120) | 0 participants |
| PAP, Eliglustat: Once Daily | LTTP: Number of Participants With Mobility Status (MS) at Baseline, 1 Year and 2 Years | MS, Walks with Orthopedic Aid: 1 year (n=104) | 1 participants |
| PAP, Eliglustat: Once Daily | LTTP: Number of Participants With Mobility Status (MS) at Baseline, 1 Year and 2 Years | MS, Walks with Orthopedic Aid: 2 years (n=32) | 0 participants |
| PAP, Eliglustat: Once Daily | LTTP: Number of Participants With Mobility Status (MS) at Baseline, 1 Year and 2 Years | MS, Required Wheelchair: Baseline (n=120) | 2 participants |
| PAP, Eliglustat: Once Daily | LTTP: Number of Participants With Mobility Status (MS) at Baseline, 1 Year and 2 Years | MS, Required Wheelchair: 1 year (n=104) | 2 participants |
| PAP, Eliglustat: Once Daily | LTTP: Number of Participants With Mobility Status (MS) at Baseline, 1 Year and 2 Years | MS, Required Wheelchair: 2 years (n=32) | 2 participants |
| PAP, Eliglustat: Once Daily | LTTP: Number of Participants With Mobility Status (MS) at Baseline, 1 Year and 2 Years | MS, Bedridden: Baseline (n=120) | 0 participants |
| PAP, Eliglustat: Once Daily | LTTP: Number of Participants With Mobility Status (MS) at Baseline, 1 Year and 2 Years | MS, Bedridden: 1 year (n=104) | 0 participants |
| PAP, Eliglustat: Once Daily | LTTP: Number of Participants With Mobility Status (MS) at Baseline, 1 Year and 2 Years | MS, Bedridden: 2 years (n=32) | 0 participants |
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.
Time frame: 1 Year, 2 Years
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PAP, Eliglustat: Once Daily | 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 | Bone Criterion Stable at 1 year (n=104) | 92.3 percentage of participants |
| PAP, Eliglustat: Once Daily | 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 | Bone Criterion Stable at 2 years (n=32) | 84.4 percentage of participants |
| PAP, Eliglustat: Once Daily | 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 | Hemoglobin Level Stable at 1 year (n=104) | 92.3 percentage of participants |
| PAP, Eliglustat: Once Daily | 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 | Hemoglobin Level Stable at 2 years (n=32) | 81.3 percentage of participants |
| PAP, Eliglustat: Once Daily | 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 | Platelet Count Stable at 1 year (n=104) | 93.3 percentage of participants |
| PAP, Eliglustat: Once Daily | 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 | Platelet Count Stable at 2 years (n=32) | 84.4 percentage of participants |
| PAP, Eliglustat: Once Daily | 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 | Liver Volume Stable at 1 year (n=103) | 93.2 percentage of participants |
| PAP, Eliglustat: Once Daily | 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 | Liver Volume Stable at 2 years (n=31) | 83.9 percentage of participants |
| PAP, Eliglustat: Once Daily | 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 | Spleen Volume Stable at 1 year (n=72) | 95.8 percentage of participants |
| PAP, Eliglustat: Once Daily | 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 | Spleen Volume Stable at 2 years (n=20) | 95.0 percentage of participants |
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.
Time frame: Baseline, 1 year, and 2 years
Population: All participants who received at least one dose of eliglustat during the LTTP.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAP, Eliglustat: Once Daily | LTTP: Total Bone Marrow Burden Score (BMB) at Baseline, 1 Year, and 2 Years | BMB Score: Baseline (n=115) | 8.164 BMB Score | Standard Deviation 2.646 |
| PAP, Eliglustat: Once Daily | LTTP: Total Bone Marrow Burden Score (BMB) at Baseline, 1 Year, and 2 Years | BMB Score: 1 year (n=26) | 7.853 BMB Score | Standard Deviation 2.497 |
| PAP, Eliglustat: Once Daily | LTTP: Total Bone Marrow Burden Score (BMB) at Baseline, 1 Year, and 2 Years | BMB Score: 2 years (n=17) | 8.059 BMB Score | Standard Deviation 1.918 |
Secondary
LTTP: Total T-Scores for BMD at Baseline, 1 Year, and 2 Years
Images of the spine and bilateral femur were obtained by DXA to determine T-score for each bone area and total bone mineral density. The T-score bone density categories were: normal (score \>-1), osteopenia (score -2.5 to \<=-1), and osteoporosis (score \<= -2.5).
Time frame: Baseline, 1 year, and 2 years
Population: All participants who received at least one dose of eliglustat during the LTTP.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAP, Eliglustat: Once Daily | LTTP: Total T-Scores for BMD at Baseline, 1 Year, and 2 Years | Lumbar Spine T-Score: Baseline (n=110) | -0.674 T-score | Standard Deviation 1.383 |
| PAP, Eliglustat: Once Daily | LTTP: Total T-Scores for BMD at Baseline, 1 Year, and 2 Years | Lumbar Spine T-Score: 1 year (n=98) | -0.718 T-score | Standard Deviation 1.394 |
| PAP, Eliglustat: Once Daily | LTTP: Total T-Scores for BMD at Baseline, 1 Year, and 2 Years | Lumbar Spine T-Score: 2 years (n=26) | -0.750 T-score | Standard Deviation 1.37 |
| PAP, Eliglustat: Once Daily | LTTP: Total T-Scores for BMD at Baseline, 1 Year, and 2 Years | Left Femur T-Score: Baseline (n=103) | -0.421 T-score | Standard Deviation 1.377 |
| PAP, Eliglustat: Once Daily | LTTP: Total T-Scores for BMD at Baseline, 1 Year, and 2 Years | Left Femur T-Score: 1 year (n=91) | -0.382 T-score | Standard Deviation 1.551 |
| PAP, Eliglustat: Once Daily | LTTP: Total T-Scores for BMD at Baseline, 1 Year, and 2 Years | Left Femur T-Score: 2 years (n=22) | -0.682 T-score | Standard Deviation 1.532 |
| PAP, Eliglustat: Once Daily | LTTP: Total T-Scores for BMD at Baseline, 1 Year, and 2 Years | Right Femur T-Score: Baseline (n=99) | -0.461 T-score | Standard Deviation 1.36 |
| PAP, Eliglustat: Once Daily | LTTP: Total T-Scores for BMD at Baseline, 1 Year, and 2 Years | Right Femur T-Score: 1 year (n=87) | -0.500 T-score | Standard Deviation 1.381 |
| PAP, Eliglustat: Once Daily | LTTP: Total T-Scores for BMD at Baseline, 1 Year, and 2 Years | Right Femur T-Score: 2 years (n=21) | -1.005 T-score | Standard Deviation 0.931 |
Secondary
LTTP: Total Z-scores for BMD at Baseline, 1 Year, and 2 Years
Images of the spine and bilateral femur were obtained by DXA to determine Z-score for each bone area and total bone mineral density. The Z-score bone density categories are: normal (score \>-2) and below normal (score \<=-2).
Time frame: Baseline, 1 year, and 2 years
Population: All participants who received at least one dose of eliglustat during the LTTP.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAP, Eliglustat: Once Daily | LTTP: Total Z-scores for BMD at Baseline, 1 Year, and 2 Years | Lumbar Spine Z-Score: Baseline (n=113) | -0.460 Z-score | Standard Deviation 1.376 |
| PAP, Eliglustat: Once Daily | LTTP: Total Z-scores for BMD at Baseline, 1 Year, and 2 Years | Lumbar Spine Z-Score: 1 year (n=101) | -0.512 Z-score | Standard Deviation 1.368 |
| PAP, Eliglustat: Once Daily | LTTP: Total Z-scores for BMD at Baseline, 1 Year, and 2 Years | Lumbar Spine Z-Score: 2 years (n=26) | -0.385 Z-score | Standard Deviation 1.316 |
| PAP, Eliglustat: Once Daily | LTTP: Total Z-scores for BMD at Baseline, 1 Year, and 2 Years | Left Femur Z-Score: Baseline (n=107) | -0.164 Z-score | Standard Deviation 1.277 |
| PAP, Eliglustat: Once Daily | LTTP: Total Z-scores for BMD at Baseline, 1 Year, and 2 Years | Left Femur Z-Score: 1 year (n=95) | -0.132 Z-score | Standard Deviation 1.459 |
| PAP, Eliglustat: Once Daily | LTTP: Total Z-scores for BMD at Baseline, 1 Year, and 2 Years | Left Femur Z-Score: 2 years (n=22) | -0.264 Z-score | Standard Deviation 1.525 |
| PAP, Eliglustat: Once Daily | LTTP: Total Z-scores for BMD at Baseline, 1 Year, and 2 Years | Right Femur Z-Score: Baseline (n=103) | -0.214 Z-score | Standard Deviation 1.227 |
| PAP, Eliglustat: Once Daily | LTTP: Total Z-scores for BMD at Baseline, 1 Year, and 2 Years | Right Femur Z-Score: 1 year (n=91) | -0.262 Z-score | Standard Deviation 1.27 |
| PAP, Eliglustat: Once Daily | LTTP: Total Z-scores for BMD at Baseline, 1 Year, and 2 Years | Right Femur Z-Score: 2 years (n=21) | -0.605 Z-score | Standard Deviation 0.957 |
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.
Time frame: Baseline, Week 52
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAP, Eliglustat: Once Daily | PAP: Bone Mineral Density (BMD) at Baseline and Week 52 | Lumbar Spine: Baseline (n=51, 55) | 1.073 g/cm^2 | Standard Deviation 0.177 |
| PAP, Eliglustat: Once Daily | PAP: Bone Mineral Density (BMD) at Baseline and Week 52 | Left Femur: Week 52 (n=48, 47) | 0.972 g/cm^2 | Standard Deviation 0.211 |
| PAP, Eliglustat: Once Daily | PAP: Bone Mineral Density (BMD) at Baseline and Week 52 | Lumbar Spine: Week 52 (n=51, 55) | 1.089 g/cm^2 | Standard Deviation 0.183 |
| PAP, Eliglustat: Once Daily | PAP: Bone Mineral Density (BMD) at Baseline and Week 52 | Right Femur: Baseline (n=48, 47) | 0.971 g/cm^2 | Standard Deviation 0.217 |
| PAP, Eliglustat: Once Daily | PAP: Bone Mineral Density (BMD) at Baseline and Week 52 | Left Femur: Baseline (n=48, 47) | 0.979 g/cm^2 | Standard Deviation 0.219 |
| PAP, Eliglustat: Once Daily | PAP: Bone Mineral Density (BMD) at Baseline and Week 52 | Right Femur: Week 52 (n=48, 47) | 0.967 g/cm^2 | Standard Deviation 0.213 |
| PAP, Eliglustat: Twice Daily | PAP: Bone Mineral Density (BMD) at Baseline and Week 52 | Left Femur: Baseline (n=48, 47) | 1.000 g/cm^2 | Standard Deviation 0.199 |
| PAP, Eliglustat: Twice Daily | PAP: Bone Mineral Density (BMD) at Baseline and Week 52 | Right Femur: Week 52 (n=48, 47) | 0.981 g/cm^2 | Standard Deviation 0.177 |
| PAP, Eliglustat: Twice Daily | PAP: Bone Mineral Density (BMD) at Baseline and Week 52 | Lumbar Spine: Week 52 (n=51, 55) | 1.086 g/cm^2 | Standard Deviation 0.177 |
| PAP, Eliglustat: Twice Daily | PAP: Bone Mineral Density (BMD) at Baseline and Week 52 | Lumbar Spine: Baseline (n=51, 55) | 1.081 g/cm^2 | Standard Deviation 0.172 |
| PAP, Eliglustat: Twice Daily | PAP: Bone Mineral Density (BMD) at Baseline and Week 52 | Left Femur: Week 52 (n=48, 47) | 0.990 g/cm^2 | Standard Deviation 0.196 |
| PAP, Eliglustat: Twice Daily | PAP: Bone Mineral Density (BMD) at Baseline and Week 52 | Right Femur: Baseline (n=48, 47) | 0.996 g/cm^2 | Standard Deviation 0.184 |
Secondary
PAP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26 and Week 52
Chitotriosidase biomarker was assayed from plasma.
Time frame: Baseline, Week 26, Week 52
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAP, Eliglustat: Once Daily | PAP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26 and Week 52 | Baseline (n=55, 59) | 1523.7 nmol/hr/mL | Standard Deviation 2556.6 |
| PAP, Eliglustat: Once Daily | PAP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26 and Week 52 | Week 26 (n=52, 54) | 1279.6 nmol/hr/mL | Standard Deviation 2328.1 |
| PAP, Eliglustat: Once Daily | PAP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26 and Week 52 | Week 52 (n=54, 55) | 1076.6 nmol/hr/mL | Standard Deviation 1855.8 |
| PAP, Eliglustat: Twice Daily | PAP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26 and Week 52 | Baseline (n=55, 59) | 1554.9 nmol/hr/mL | Standard Deviation 1895 |
| PAP, Eliglustat: Twice Daily | PAP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26 and Week 52 | Week 26 (n=52, 54) | 1242.0 nmol/hr/mL | Standard Deviation 2012.6 |
| PAP, Eliglustat: Twice Daily | PAP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26 and Week 52 | Week 52 (n=54, 55) | 1170.1 nmol/hr/mL | Standard Deviation 1683.3 |
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).
Time frame: Baseline, Week 26 and week 52
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAP, Eliglustat: Once Daily | PAP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26 and Week 52 | GL-1 on DBS: Baseline (n=54, 55) | 2.257 mcg/mL | Standard Deviation 0.835 |
| PAP, Eliglustat: Once Daily | PAP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26 and Week 52 | GL-1 on DBS: week 26 (n=54, 54) | 2.481 mcg/mL | Standard Deviation 1.037 |
| PAP, Eliglustat: Once Daily | PAP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26 and Week 52 | GL-1 on DBS: week 52 (n=53, 55) | 2.853 mcg/mL | Standard Deviation 1.383 |
| PAP, Eliglustat: Twice Daily | PAP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26 and Week 52 | GL-1 on DBS: Baseline (n=54, 55) | 2.425 mcg/mL | Standard Deviation 1.378 |
| PAP, Eliglustat: Twice Daily | PAP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26 and Week 52 | GL-1 on DBS: week 26 (n=54, 54) | 2.563 mcg/mL | Standard Deviation 1.1 |
| PAP, Eliglustat: Twice Daily | PAP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26 and Week 52 | GL-1 on DBS: week 52 (n=53, 55) | 2.707 mcg/mL | Standard Deviation 1.443 |
Secondary
PAP: Mean Biomarker Macrophage Inflammatory Protein-1 Beta (MIP1-beta) Value at Baseline, Weeks 26, 52
MIP1-beta biomarker was assayed from plasma.
Time frame: Baseline, Week 26, Week 52
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAP, Eliglustat: Once Daily | PAP: Mean Biomarker Macrophage Inflammatory Protein-1 Beta (MIP1-beta) Value at Baseline, Weeks 26, 52 | Baseline (n=54, 58) | 77.7 pg/mL | Standard Deviation 74.4 |
| PAP, Eliglustat: Once Daily | PAP: Mean Biomarker Macrophage Inflammatory Protein-1 Beta (MIP1-beta) Value at Baseline, Weeks 26, 52 | Week 26 (n=52, 54) | 74.5 pg/mL | Standard Deviation 68 |
| PAP, Eliglustat: Once Daily | PAP: Mean Biomarker Macrophage Inflammatory Protein-1 Beta (MIP1-beta) Value at Baseline, Weeks 26, 52 | Week 52 (n=54, 55) | 81.3 pg/mL | Standard Deviation 82.8 |
| PAP, Eliglustat: Twice Daily | PAP: Mean Biomarker Macrophage Inflammatory Protein-1 Beta (MIP1-beta) Value at Baseline, Weeks 26, 52 | Baseline (n=54, 58) | 118.8 pg/mL | Standard Deviation 156.3 |
| PAP, Eliglustat: Twice Daily | PAP: Mean Biomarker Macrophage Inflammatory Protein-1 Beta (MIP1-beta) Value at Baseline, Weeks 26, 52 | Week 26 (n=52, 54) | 121.0 pg/mL | Standard Deviation 204.4 |
| PAP, Eliglustat: Twice Daily | PAP: Mean Biomarker Macrophage Inflammatory Protein-1 Beta (MIP1-beta) Value at Baseline, Weeks 26, 52 | Week 52 (n=54, 55) | 117.9 pg/mL | Standard Deviation 165.3 |
Secondary
PAP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26 and 52
Time frame: Baseline, Week 26, Week 52
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAP, Eliglustat: Once Daily | PAP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26 and 52 | Baseline (n=56, 59) | 13.641 g/dL | Standard Deviation 1.214 |
| PAP, Eliglustat: Once Daily | PAP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26 and 52 | Week 26 (n=56, 57) | 13.677 g/dL | Standard Deviation 1.377 |
| PAP, Eliglustat: Once Daily | PAP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26 and 52 | Week 52 (n=56, 59) | 13.605 g/dL | Standard Deviation 1.432 |
| PAP, Eliglustat: Twice Daily | PAP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26 and 52 | Baseline (n=56, 59) | 13.691 g/dL | Standard Deviation 1.273 |
| PAP, Eliglustat: Twice Daily | PAP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26 and 52 | Week 26 (n=56, 57) | 13.946 g/dL | Standard Deviation 1.509 |
| PAP, Eliglustat: Twice Daily | PAP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26 and 52 | Week 52 (n=56, 59) | 13.824 g/dL | Standard Deviation 1.442 |
Secondary
PAP: Mean Liver Volume at Baseline, Weeks 26, 52
Time frame: Baseline, Week 26 and Week 52
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAP, Eliglustat: Once Daily | PAP: Mean Liver Volume at Baseline, Weeks 26, 52 | Baseline (n=56, 59) | 0.981 MN | Standard Deviation 0.187 |
| PAP, Eliglustat: Once Daily | PAP: Mean Liver Volume at Baseline, Weeks 26, 52 | Week 26 (n=56, 59) | 0.987 MN | Standard Deviation 0.19 |
| PAP, Eliglustat: Once Daily | PAP: Mean Liver Volume at Baseline, Weeks 26, 52 | Week 52 (n=56, 59) | 0.970 MN | Standard Deviation 0.17 |
| PAP, Eliglustat: Twice Daily | PAP: Mean Liver Volume at Baseline, Weeks 26, 52 | Baseline (n=56, 59) | 1.040 MN | Standard Deviation 0.198 |
| PAP, Eliglustat: Twice Daily | PAP: Mean Liver Volume at Baseline, Weeks 26, 52 | Week 26 (n=56, 59) | 1.024 MN | Standard Deviation 0.179 |
| PAP, Eliglustat: Twice Daily | PAP: Mean Liver Volume at Baseline, Weeks 26, 52 | Week 52 (n=56, 59) | 1.009 MN | Standard Deviation 0.196 |
Secondary
PAP: Mean Platelet Count at Baseline, Weeks 26, 52
Time frame: Baseline, Week 26, Week 52
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAP, Eliglustat: Once Daily | PAP: Mean Platelet Count at Baseline, Weeks 26, 52 | Baseline (n=56, 59) | 204.01 platelets*10^9 /L | Standard Deviation 81.49 |
| PAP, Eliglustat: Once Daily | PAP: Mean Platelet Count at Baseline, Weeks 26, 52 | Week 26 (n=56, 57) | 195.75 platelets*10^9 /L | Standard Deviation 66.65 |
| PAP, Eliglustat: Once Daily | PAP: Mean Platelet Count at Baseline, Weeks 26, 52 | Week 52 (n=56, 59) | 207.20 platelets*10^9 /L | Standard Deviation 80.62 |
| PAP, Eliglustat: Twice Daily | PAP: Mean Platelet Count at Baseline, Weeks 26, 52 | Baseline (n=56, 59) | 171.09 platelets*10^9 /L | Standard Deviation 63.5 |
| PAP, Eliglustat: Twice Daily | PAP: Mean Platelet Count at Baseline, Weeks 26, 52 | Week 26 (n=56, 57) | 173.94 platelets*10^9 /L | Standard Deviation 65.61 |
| PAP, Eliglustat: Twice Daily | PAP: Mean Platelet Count at Baseline, Weeks 26, 52 | Week 52 (n=56, 59) | 176.10 platelets*10^9 /L | Standard Deviation 62.01 |
Secondary
PAP: Mean Spleen Volume at Baseline, Weeks 26, 52
Time frame: Baseline, Week 26, Week 52
Population: PP population included all participants who were at least 80% compliant with IMP dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. Here 'n' signifies number of participants with available data for specified category for each arm respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAP, Eliglustat: Once Daily | PAP: Mean Spleen Volume at Baseline, Weeks 26, 52 | Baseline (n= 39, 45) | 3.309 MN | Standard Deviation 1.465 |
| PAP, Eliglustat: Once Daily | PAP: Mean Spleen Volume at Baseline, Weeks 26, 52 | Week 26 (n= 39, 45) | 3.066 MN | Standard Deviation 1.299 |
| PAP, Eliglustat: Once Daily | PAP: Mean Spleen Volume at Baseline, Weeks 26, 52 | Week 52 (n= 39, 45) | 3.017 MN | Standard Deviation 1.381 |
| PAP, Eliglustat: Twice Daily | PAP: Mean Spleen Volume at Baseline, Weeks 26, 52 | Baseline (n= 39, 45) | 3.787 MN | Standard Deviation 1.623 |
| PAP, Eliglustat: Twice Daily | PAP: Mean Spleen Volume at Baseline, Weeks 26, 52 | Week 26 (n= 39, 45) | 3.504 MN | Standard Deviation 1.365 |
| PAP, Eliglustat: Twice Daily | PAP: Mean Spleen Volume at Baseline, Weeks 26, 52 | Week 52 (n= 39, 45) | 3.394 MN | Standard Deviation 1.305 |
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.
Time frame: Baseline, Week 26, and Week 52
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Bone Crises at Baseline, Weeks 26 and 52 | Bone Crisis (0): Week 26 (n=55,57) | 54 participants |
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Bone Crises at Baseline, Weeks 26 and 52 | Bone Crisis (1): Week 52 (n=56, 58) | 0 participants |
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Bone Crises at Baseline, Weeks 26 and 52 | Bone Crisis (1): Baseline (n=56, 59) | 1 participants |
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Bone Crises at Baseline, Weeks 26 and 52 | Bone Crisis (2): Baseline (n=56, 59) | 0 participants |
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Bone Crises at Baseline, Weeks 26 and 52 | Bone Crisis (0): Week 52 (n=56, 58) | 56 participants |
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Bone Crises at Baseline, Weeks 26 and 52 | Bone Crisis (2): week 26 (n=55, 57) | 1 participants |
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Bone Crises at Baseline, Weeks 26 and 52 | Bone Crisis (1): Week 26 (n=55, 57) | 0 participants |
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Bone Crises at Baseline, Weeks 26 and 52 | Bone Crisis (2): week 52 (n=56, 58) | 0 participants |
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Bone Crises at Baseline, Weeks 26 and 52 | Bone Crisis (0): Baseline (n=56, 59) | 55 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Bone Crises at Baseline, Weeks 26 and 52 | Bone Crisis (2): week 52 (n=56, 58) | 0 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Bone Crises at Baseline, Weeks 26 and 52 | Bone Crisis (0): Baseline (n=56, 59) | 57 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Bone Crises at Baseline, Weeks 26 and 52 | Bone Crisis (0): Week 26 (n=55,57) | 56 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Bone Crises at Baseline, Weeks 26 and 52 | Bone Crisis (0): Week 52 (n=56, 58) | 57 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Bone Crises at Baseline, Weeks 26 and 52 | Bone Crisis (1): Baseline (n=56, 59) | 2 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Bone Crises at Baseline, Weeks 26 and 52 | Bone Crisis (1): Week 26 (n=55, 57) | 1 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Bone Crises at Baseline, Weeks 26 and 52 | Bone Crisis (1): Week 52 (n=56, 58) | 1 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Bone Crises at Baseline, Weeks 26 and 52 | Bone Crisis (2): Baseline (n=56, 59) | 0 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Bone Crises at Baseline, Weeks 26 and 52 | Bone Crisis (2): week 26 (n=55, 57) | 0 participants |
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.
Time frame: Baseline, Week 26, and Week 52
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 | Mild: Baseline (n=56, 59) | 7 participants |
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 | Moderate: Week 52 (56, 58) | 6 participants |
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 | Very Mild: Week 26 (n=55, 57) | 3 participants |
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 | Severe: Baseline (n=56, 59) | 1 participants |
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 | Mild: Week 26 (n=55, 57) | 5 participants |
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 | Severe: Week 26 (n=55, 57) | 0 participants |
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 | Very Mild: Baseline (n=56, 59) | 2 participants |
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 | Severe: Week 52 (n=56, 58) | 0 participants |
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 | Mild: Week 52 (n=56, 58) | 6 participants |
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 | Extreme: Baseline (n=56, 59) | 0 participants |
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 | Very Mild: Week 52 (n=56, 58) | 3 participants |
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 | Extreme: Week 26 (n=55, 57) | 0 participants |
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 | Moderate: Baseline (n=56, 59) | 4 participants |
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 | Extreme: Week 52 (n=56, 58) | 0 participants |
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 | None: Week 52 (n=56, 58) | 41 participants |
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 | None: Baseline (n=56, 59) | 42 participants |
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 | Moderate: Week 26 (n=55, 57) | 5 participants |
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 | None: Week 26 (n=55, 57) | 42 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 | Moderate: Week 26 (n=55, 57) | 1 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 | None: Week 52 (n=56, 58) | 45 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 | Very Mild: Baseline (n=56, 59) | 1 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 | Very Mild: Week 26 (n=55, 57) | 4 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 | Very Mild: Week 52 (n=56, 58) | 7 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 | Mild: Baseline (n=56, 59) | 3 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 | Mild: Week 26 (n=55, 57) | 3 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 | Mild: Week 52 (n=56, 58) | 2 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 | Moderate: Baseline (n=56, 59) | 5 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 | None: Week 26 (n=55, 57) | 49 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 | Moderate: Week 52 (56, 58) | 2 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 | Severe: Baseline (n=56, 59) | 1 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 | Severe: Week 26 (n=55, 57) | 0 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 | Severe: Week 52 (n=56, 58) | 2 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 | Extreme: Baseline (n=56, 59) | 0 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 | Extreme: Week 26 (n=55, 57) | 0 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 | Extreme: Week 52 (n=56, 58) | 0 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 | None: Baseline (n=56, 59) | 49 participants |
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.
Time frame: Baseline, Week 26 and Week 52
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52. | MS, Walks with Difficulty: Week 26 (n=55, 57) | 8 participants |
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52. | MS, Walks with Orthopedic Aid: Week 52 (n=51, 58) | 0 participants |
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52. | MS, Unrestricted: Week 26 (n=55, 57) | 46 participants |
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52. | MS, Required Wheelchair: Baseline (n=56, 59) | 0 participants |
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52. | Ms, Walks with Difficulty: Week 52 (n=51, 58) | 5 participants |
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52. | MS, Required Wheelchair: Week 26 (n=55, 57) | 0 participants |
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52. | MS, Walks with Difficulty: Baseline (n=56, 59) | 6 participants |
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52. | MS, Required Wheelchair: Week 52 (n=51, 58) | 1 participants |
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52. | MS, Walks with Orthopedic Aid: Baseline (n=56, 59) | 1 participants |
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52. | MS, Bedridden: Baseline (n=56, 59) | 0 participants |
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52. | MS, Unrestricted: Week 52 (n=51, 58) | 50 participants |
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52. | MS, Bedridden: Week 26 (n=55, 57) | 0 participants |
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52. | MS, Walks with Orthopedic Aid: Week 26 (n=55, 57) | 1 participants |
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52. | MS, Bedridden: Week 52 (n=51, 58) | 0 participants |
| PAP, Eliglustat: Once Daily | PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52. | MS, Unrestricted: Baseline (n=56, 59) | 49 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52. | MS, Bedridden: Week 52 (n=51, 58) | 0 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52. | MS, Unrestricted: Baseline (n=56, 59) | 59 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52. | MS, Unrestricted: Week 26 (n=55, 57) | 56 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52. | MS, Unrestricted: Week 52 (n=51, 58) | 57 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52. | MS, Walks with Difficulty: Baseline (n=56, 59) | 0 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52. | MS, Walks with Difficulty: Week 26 (n=55, 57) | 1 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52. | Ms, Walks with Difficulty: Week 52 (n=51, 58) | 1 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52. | MS, Walks with Orthopedic Aid: Baseline (n=56, 59) | 0 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52. | MS, Walks with Orthopedic Aid: Week 26 (n=55, 57) | 0 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52. | MS, Walks with Orthopedic Aid: Week 52 (n=51, 58) | 0 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52. | MS, Required Wheelchair: Baseline (n=56, 59) | 0 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52. | MS, Required Wheelchair: Week 26 (n=55, 57) | 0 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52. | MS, Required Wheelchair: Week 52 (n=51, 58) | 0 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52. | MS, Bedridden: Baseline (n=56, 59) | 0 participants |
| PAP, Eliglustat: Twice Daily | PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52. | MS, Bedridden: Week 26 (n=55, 57) | 0 participants |
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.
Time frame: Baseline, Week 52
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAP, Eliglustat: Once Daily | PAP: Total Bone Marrow Burden Score (BMB) at Baseline and Week 52 | BMB Score: Baseline (n=52, 49) | 8.276 BMB Score | Standard Deviation 2.891 |
| PAP, Eliglustat: Once Daily | PAP: Total Bone Marrow Burden Score (BMB) at Baseline and Week 52 | BMB Score: Week 52 (n=51, 48) | 7.971 BMB Score | Standard Deviation 2.689 |
| PAP, Eliglustat: Twice Daily | PAP: Total Bone Marrow Burden Score (BMB) at Baseline and Week 52 | BMB Score: Baseline (n=52, 49) | 9.136 BMB Score | Standard Deviation 2.784 |
| PAP, Eliglustat: Twice Daily | PAP: Total Bone Marrow Burden Score (BMB) at Baseline and Week 52 | BMB Score: Week 52 (n=51, 48) | 8.705 BMB Score | Standard Deviation 2.633 |
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).
Time frame: Baseline, Week 52
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAP, Eliglustat: Once Daily | PAP: Total T-Scores for BMD at Baseline and Week 52 | Lumbar Spine T-Score: Baseline (n=49, 52) | -0.722 T-score | Standard Deviation 1.415 |
| PAP, Eliglustat: Once Daily | PAP: Total T-Scores for BMD at Baseline and Week 52 | Lumbar Spine T-Score: Week 52 (n=49, 52) | -0.580 T-score | Standard Deviation 1.476 |
| PAP, Eliglustat: Once Daily | PAP: Total T-Scores for BMD at Baseline and Week 52 | Left Femur T-Score: Baseline (n=46, 44) | -0.459 T-score | Standard Deviation 1.385 |
| PAP, Eliglustat: Once Daily | PAP: Total T-Scores for BMD at Baseline and Week 52 | Left Femur T-Score: Week 52 (n=46, 44) | -0.509 T-score | Standard Deviation 1.342 |
| PAP, Eliglustat: Once Daily | PAP: Total T-Scores for BMD at Baseline and Week 52 | Right Femur T-score: Baseline (n=46, 44) | -0.574 T-score | Standard Deviation 1.327 |
| PAP, Eliglustat: Once Daily | PAP: Total T-Scores for BMD at Baseline and Week 52 | Right Femur T-score: Week 52 (n=46, 44) | -0.607 T-score | Standard Deviation 1.308 |
| PAP, Eliglustat: Twice Daily | PAP: Total T-Scores for BMD at Baseline and Week 52 | Right Femur T-score: Baseline (n=46, 44) | -0.382 T-score | Standard Deviation 1.282 |
| PAP, Eliglustat: Twice Daily | PAP: Total T-Scores for BMD at Baseline and Week 52 | Lumbar Spine T-Score: Baseline (n=49, 52) | -0.771 T-score | Standard Deviation 1.217 |
| PAP, Eliglustat: Twice Daily | PAP: Total T-Scores for BMD at Baseline and Week 52 | Left Femur T-Score: Week 52 (n=46, 44) | -0.441 T-score | Standard Deviation 1.326 |
| PAP, Eliglustat: Twice Daily | PAP: Total T-Scores for BMD at Baseline and Week 52 | Lumbar Spine T-Score: Week 52 (n=49, 52) | -0.717 T-score | Standard Deviation 1.271 |
| PAP, Eliglustat: Twice Daily | PAP: Total T-Scores for BMD at Baseline and Week 52 | Right Femur T-score: Week 52 (n=46, 44) | -0.530 T-score | Standard Deviation 1.236 |
| PAP, Eliglustat: Twice Daily | PAP: Total T-Scores for BMD at Baseline and Week 52 | Left Femur T-Score: Baseline (n=46, 44) | -0.368 T-score | Standard Deviation 1.347 |
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).
Time frame: Baseline, Week 52
Population: PP population included all participants who were at least 80% compliant with IMP dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. Here 'n' signifies number of participants with available data for specified category for each arm respectively
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAP, Eliglustat: Once Daily | PAP: Total Z-scores for BMD at Baseline and Week 52 | Lumbar Spine Z-scores: Baseline (n=51, 55) | -0.492 Z-score | Standard Deviation 1.517 |
| PAP, Eliglustat: Once Daily | PAP: Total Z-scores for BMD at Baseline and Week 52 | Left Femur Z-scores: Week 52 (n= 48, 47) | -0.202 Z-score | Standard Deviation 1.25 |
| PAP, Eliglustat: Once Daily | PAP: Total Z-scores for BMD at Baseline and Week 52 | Lumbar Spine Z-scores: Week 52 (n=51, 55) | -0.324 Z-score | Standard Deviation 1.559 |
| PAP, Eliglustat: Once Daily | PAP: Total Z-scores for BMD at Baseline and Week 52 | Right Femur Z-scores: Baseline (n= 48, 47) | -0.235 Z-score | Standard Deviation 1.251 |
| PAP, Eliglustat: Once Daily | PAP: Total Z-scores for BMD at Baseline and Week 52 | Right Femur Z-scores: Week 52 (n= 48, 47) | -0.248 Z-score | Standard Deviation 1.214 |
| PAP, Eliglustat: Once Daily | PAP: Total Z-scores for BMD at Baseline and Week 52 | Left Femur Z-scores: Baseline (n= 48, 47) | -0.171 Z-score | Standard Deviation 1.316 |
| PAP, Eliglustat: Twice Daily | PAP: Total Z-scores for BMD at Baseline and Week 52 | Right Femur Z-scores: Week 52 (n= 48, 47) | -0.260 Z-score | Standard Deviation 1.141 |
| PAP, Eliglustat: Twice Daily | PAP: Total Z-scores for BMD at Baseline and Week 52 | Lumbar Spine Z-scores: Week 52 (n=51, 55) | -0.555 Z-score | Standard Deviation 1.202 |
| PAP, Eliglustat: Twice Daily | PAP: Total Z-scores for BMD at Baseline and Week 52 | Left Femur Z-scores: Baseline (n= 48, 47) | -0.115 Z-score | Standard Deviation 1.294 |
| PAP, Eliglustat: Twice Daily | PAP: Total Z-scores for BMD at Baseline and Week 52 | Left Femur Z-scores: Week 52 (n= 48, 47) | -0.183 Z-score | Standard Deviation 1.274 |
| PAP, Eliglustat: Twice Daily | PAP: Total Z-scores for BMD at Baseline and Week 52 | Right Femur Z-scores: Baseline (n= 48, 47) | -0.140 Z-score | Standard Deviation 1.194 |
| PAP, Eliglustat: Twice Daily | PAP: Total Z-scores for BMD at Baseline and Week 52 | Lumbar Spine Z-scores: Baseline (n=51, 55) | -0.609 Z-score | Standard Deviation 1.166 |