Gaucher Disease, Type 1
Conditions
Keywords
Gaucher disease,, Genz-112638,, beta-glucosidase,, acid ß-glucosidase,, glucocerebrosidase,, glucosylceramide,, D-glucosyl-N-acylsphingosine glucohydrolase,, substrate reduction therapy
Brief summary
This Phase 3 study was designed to confirm the efficacy and safety of eliglustat tartrate (Genz-112638) in participants with Gaucher disease type 1 who had reached therapeutic goals with enzyme replacement therapy (ERT).
Detailed description
Gaucher disease is characterized by lysosomal accumulation of glucosylceramide due to impaired glucosylceramide hydrolysis. Gaucher disease type 1, which is the most common form, accounts for greater than (\>) 90% of cases and does not involve the central nervous system (CNS). Typical manifestations of Gaucher disease type 1 include splenomegaly, hepatomegaly, thrombocytopenia, anemia, bone disease, and decreased quality of life. The disease manifestations are caused by the accumulation of glucosylceramide (storage material) in macrophages (called Gaucher cells) which have infiltrated the spleen and liver as well as other tissues. Eliglustat tartrate is a small molecule drug developed as an oral therapy which acts to specifically inhibit production of this storage material in Gaucher cells. This study was designed to determine the efficacy, safety, and PK of eliglustat tartrate in adult participants with Gaucher disease type 1 who had been stabilized on ERT.
Interventions
Primary analysis period (PAP): Eliglustat tartrate capsule 50 milligram (mg) twice daily (BID) orally from Day 1 to Week 4 followed by eliglustat tartrate 50 mg or 100 mg capsule BID up to Week 8, and then eliglustat tartrate 50 mg or 100 mg or 150 mg capsule BID up to Week 52. Dose adjustments after Week 4 and Week 8 were based on Genz-99067 (active moiety of eliglustat tartrate in plasma) trough plasma concentrations. If Genz-99067 trough plasma concentration was less than (\<) 5 nanogram per milliliter \[ng/mL\] next higher dose was administered whereas if Genz-99067 trough plasma concentration was greater than or equal to (\>=) 5 ng/mL same dose was continued. Pharmacokinetic (PK) assessment at Week 2 and 6 were used for dose adjustment after Week 4 and Week 8, respectively. Long-term treatment period (LTTP): Participants originally randomized to eliglustat in PAP continued to receive eliglustat dose, based on their Genz 99067 plasma trough concentration at Week 6.
DRUGImiglucerase
PAP: Imiglucerase intravenous infusion every other week (q2w) up to Week 52 in doses equivalent to participant's past ERT dose prior to any unanticipated treatment interruption, dose reduction, or regimen change. LTTP: Participants originally randomized to imiglucerase received eliglustat tartrate capsule 50 mg BID orally from Week 52+1 Day to Week 56 followed by eliglustat tartrate 50 mg or 100 mg capsule BID up to Week 60, and then eliglustat tartrate 50 mg or 100 mg or 150 mg capsule BID up to 5 years. The dose adjustments after Week 56 and Week 60 were based on Genz-99067 (active moiety of eliglustat tartrate in plasma) trough plasma concentrations. If Genz-99067 trough plasma concentration was \<5 ng/mL the next higher dose was administered whereas if the Genz-99067 trough plasma concentration was \>=5 ng/mL the same dose was continued. The PK assessment at Week 54 and Week 58 were used for dose adjustment after Week 56 and Week 60, respectively.
Sponsors
Genzyme, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* The participant (and/or their parent/legal guardian) was willing and able to provide signed informed consent prior to any study-related procedures to be performed * The participant was at least 18 years old at the time of randomization * The participant had a confirmed diagnosis of Gaucher disease type 1 * The participant had received treatment with ERT for at least 3 years. Within the 9 months prior to randomization, the participant had received a total monthly dose of 30 to 130 Units/kilogram for at least 6 months * The participant had reached Gaucher disease therapeutic goals prior to randomization * Female participants of childbearing potential must have had a documented negative pregnancy test prior to dosing. In addition, all female participants of childbearing potential must use a medically accepted form of contraception throughout the study
Exclusion criteria
* The participant had a partial or total splenectomy within 3 years prior to randomization * The participant had received substrate reduction therapies for Gaucher disease within 6 months prior to randomization * The participant had Gaucher disease type 2 or 3 or was suspected of having Gaucher disease type 3 * The participant had any clinically significant disease, other than Gaucher disease, including cardiovascular, renal, hepatic, gastrointestinal (GI), pulmonary, neurologic, endocrine, metabolic (e.g. hypokalemia, hypomagnesemia), or psychiatric disease, other medical conditions, or serious intercurrent illnesses that may confound the study results or, in the opinion of the Investigator, may preclude participation in the study * The participant had tested positive for the human immunodeficiency virus (HIV) antibody, Hepatitis C antibody, or Hepatitis B surface antigen * The participant had received an investigational product within 30 days prior to randomization * The participant was pregnant or lactating
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Remained Stable for 52 Weeks During the Primary Analysis Period | Baseline up to Week 52 | For a participant to be classified as stable, the participant must have remained stable in hematological parameters (hemoglobin levels and platelet counts) and organ volumes (spleen, when applicable, and liver volumes in multiples of normal \[MN\]). Stable hematological parameters were defined as hemoglobin level did not decrease more than (\>) 1.5 gram per deciliter (g/dL) from baseline and platelet count did not decrease \>25% from baseline. Stable organ volumes were defined as spleen volume (in MN) did not increase \>25% from baseline, if applicable, and liver volume (in MN) did not increase \>20% from baseline. |
| Percentage of Participants Who Remained Stable Annually for 4 Years During the LTTP | Week 52 up to week 208 | For a participant to be classified as stable, the participant must have remained stable in hematological parameters (hemoglobin levels and platelet counts) and organ volumes (spleen, when applicable, and liver volumes in MN). Stable hematological parameters were defined as hemoglobin level did not decrease \>1.5 g/dL from baseline and platelet count did not decrease \>25% from baseline. Stable organ volumes were defined as spleen volume (in MN) did not increase \>25% from baseline, if applicable, and liver volume did not increase \>20% from baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Z-Scores for Bone Mineral Density | Baseline | 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). |
| Absolute Change From Baseline in Total Z-Scores for Bone Mineral Density at 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). Absolute change = Z-score at Week 52 minus Z-score at baseline. |
| Hemoglobin Level | Baseline | — |
| Absolute Change From Baseline in Hemoglobin Levels at Week 52 | Baseline, Week 52 | Absolute change = hemoglobin level at Week 52 minus hemoglobin level at baseline. |
| Percent Change From Baseline in Platelet Counts at Week 52 | Baseline, Week 52 | Percent change in platelet counts = (\[platelet count at Week 52 minus platelet count at baseline\] divided by \[platelet count at baseline\]) multiplied by 100. |
| Percent Change From Baseline in Spleen Volume (MN) at Week 52 | Baseline, Week 52 | Percent change in spleen volume = (\[spleen volume at Week 52 minus spleen volume at baseline\] divided by \[spleen volume at baseline\]) multiplied by 100, where all volumes are in MN. |
| Total T-Scores for Bone Mineral Density | Baseline | Images of the spine and bilateral femur were obtained by dual energy X-Ray absorptiometry (DXA) to determine T-score for each bone area and total bone mineral density. T-score compares participant's bone density with that of healthy young participant. The T-score bone density categories are: normal (score greater than \[\>\]-1), osteopenia (score -2.5 to less than or equal to \[\<=\] -1), and osteoporosis (score \<= -2.5). |
| Absolute Change From Baseline in Total T-Scores for Bone Mineral Density at Week 208 | Baseline, Week 208 | Images of the spine and bilateral femur were obtained by DXA to determine T-score for each bone area and total bone mineral density. T-score compares participant's bone density with that of healthy young participant. The T-score bone density categories are: normal (score \>-1), osteopenia (score -2.5 to \<=-1), and osteoporosis (score \<= -2.5). Absolute change = T-score at Week 208 minus T-score at baseline. |
| Absolute Change From Baseline in Total Z-Scores for Bone Mineral Density at Week 208 | Baseline, Week 208 | 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). Absolute change = Z-score at Week 208 minus Z-score at baseline. |
| Absolute Change From Baseline in Hemoglobin Levels at Week 208 | Baseline, Week 208 | Absolute change = hemoglobin level at Week 208 minus hemoglobin level at baseline. |
| Percent Change From Baseline in Platelet Counts at Week 208 | Baseline, Week 208 | Percent change in platelet counts = (\[platelet count at Week 208 minus platelet count at baseline\] divided by \[platelet count at baseline\]) multiplied by 100. |
| Percent Change From Baseline in Spleen Volume (in MN) at Week 208 | Baseline, Week 208 | Percent change in spleen volume = (\[spleen volume at Week 208 minus spleen volume at baseline\] divided by \[spleen volume at baseline\]) multiplied by 100, where all volumes are in MN. |
| Percent Change From Baseline in Liver Volume (in MN) at Week 208 | Baseline, Week 208 | Percent change in liver volume = (\[liver volume at Week 208 minus liver volume at baseline\] divided by \[liver volume at baseline\]) multiplied by 100, where all volumes are in multiples of normal. |
| Percent Change From Baseline in Liver Volume (in MN) at Week 52 | Baseline, Week 52 | Percent change in liver volume = (\[liver volume at Week 52 minus liver volume at baseline\] divided by \[liver volume at baseline\]) multiplied by 100, where all volumes are in multiples of normal. |
| Absolute Change From Baseline in Total T-Scores for Bone Mineral Density at 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. T-score compares participant's bone density with that of healthy young participant. The T-score bone density categories are: normal (score \>-1), osteopenia (score -2.5 to \<=-1), and osteoporosis (score \<= -2.5). Absolute change = T-score at Week 52 minus T-score at baseline. |
Countries
Argentina, Australia, Brazil, Canada, Egypt, France, Germany, Italy, Russia, Spain, United Kingdom, United States
Participant flow
Recruitment details
A total of 209 participants were screened, of which 46 participants were screen failure and 3 participants withdrew prior to randomization. A total of 160 participants were enrolled in this study.
Pre-assignment details
All enrolled participants received eliglustat or imiglucerase in 52 week primary analysis period (PAP). After 52-weeks PAP, all participants who remained on-study, received eliglustat in the long-term treatment period (LTTP) for up to 5 years.
Participants by arm
| Arm | Count |
|---|---|
| Eliglustat: PAP Eliglustat tartrate 50 mg capsule BID orally from Day 1 to Week 4, followed by eliglustat tartrate 50, 100 or 150 mg capsule BID orally up to Week 52. | 106 |
| Imiglucerase: PAP Imiglucerase intravenous infusion q2w up to Week 52 in doses equivalent to participant's past ERT dose prior to any unanticipated treatment interruption, dose reduction, or regimen change. | 53 |
| Total | 159 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| 52-Weeks Primary Analysis Period | Adverse Event | 2 | 1 | 0 |
| 52-Weeks Primary Analysis Period | Non-Compliance with Study Drug | 0 | 1 | 0 |
| 5 Years Long-term Treatment Period | Adverse Event | 0 | 0 | 9 |
| 5 Years Long-term Treatment Period | Lost to Follow-up | 0 | 0 | 1 |
| 5 Years Long-term Treatment Period | Other than specified above | 0 | 0 | 2 |
| 5 Years Long-term Treatment Period | Pregnancy | 0 | 0 | 4 |
| 5 Years Long-term Treatment Period | Transition to commercial eliglustat | 0 | 0 | 51 |
| 5 Years Long-term Treatment Period | Withdrawal by Subject | 0 | 0 | 8 |
Baseline characteristics
| Characteristic | Imiglucerase: PAP | Total | Eliglustat: PAP |
|---|---|---|---|
| Age, Continuous | 37.5 years STANDARD_DEVIATION 14.92 | 37.5 years STANDARD_DEVIATION 14.37 | 37.6 years STANDARD_DEVIATION 14.17 |
| Body Mass Index (BMI) | 24.5 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 4.51 | 24.9 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 5.01 | 25.2 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 5.24 |
| Height | 166.2 centimeter (cm) STANDARD_DEVIATION 9.56 | 167.1 centimeter (cm) STANDARD_DEVIATION 9.79 | 167.6 centimeter (cm) STANDARD_DEVIATION 9.92 |
| Race/Ethnicity, Customized Ethnicity: Hispanic or Latino | 19 participants | 61 participants | 42 participants |
| Race/Ethnicity, Customized Ethnicity: Not Hispanic or Latino | 34 participants | 98 participants | 64 participants |
| Race/Ethnicity, Customized Race: Asian | 1 participants | 2 participants | 1 participants |
| Race/Ethnicity, Customized Race: Black or African American | 4 participants | 10 participants | 6 participants |
| Race/Ethnicity, Customized Race: White | 48 participants | 146 participants | 98 participants |
| Race/Ethnicity, Customized Race: White/American Indian | 0 participants | 1 participants | 1 participants |
| Sex: Female, Male Female | 28 Participants | 87 Participants | 59 Participants |
| Sex: Female, Male Male | 25 Participants | 72 Participants | 47 Participants |
| Weight | 67.8 kilogram (kg) STANDARD_DEVIATION 14.44 | 69.8 kilogram (kg) STANDARD_DEVIATION 16.08 | 70.8 kilogram (kg) STANDARD_DEVIATION 16.82 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 91 / 106 | 38 / 53 |
| serious Total, serious adverse events | 18 / 106 | 7 / 53 |
Outcome results
Primary
Percentage of Participants Who Remained Stable Annually for 4 Years During the LTTP
For a participant to be classified as stable, the participant must have remained stable in hematological parameters (hemoglobin levels and platelet counts) and organ volumes (spleen, when applicable, and liver volumes in MN). Stable hematological parameters were defined as hemoglobin level did not decrease \>1.5 g/dL from baseline and platelet count did not decrease \>25% from baseline. Stable organ volumes were defined as spleen volume (in MN) did not increase \>25% from baseline, if applicable, and liver volume did not increase \>20% from baseline.
Time frame: Week 52 up to week 208
Population: FAS population for LTTP: included all participants who received at least 1 dose of eliglustat in the extension study period. Number of participants analyzed=participants at risk at specified time-points. Here 'n' signifies number of participants with available data for specified time-points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Eliglustat: PAP | Percentage of Participants Who Remained Stable Annually for 4 Years During the LTTP | Year 1 (n=127) | 83.6 percentage of participants |
| Eliglustat: PAP | Percentage of Participants Who Remained Stable Annually for 4 Years During the LTTP | Year 2 (n= 115) | 75.65 percentage of participants |
| Eliglustat: PAP | Percentage of Participants Who Remained Stable Annually for 4 Years During the LTTP | Year 3 (n= 92) | 60.53 percentage of participants |
| Eliglustat: PAP | Percentage of Participants Who Remained Stable Annually for 4 Years During the LTTP | Year 4 (n= 41) | 26.97 percentage of participants |
Primary
Percentage of Participants Who Remained Stable for 52 Weeks During the Primary Analysis Period
For a participant to be classified as stable, the participant must have remained stable in hematological parameters (hemoglobin levels and platelet counts) and organ volumes (spleen, when applicable, and liver volumes in multiples of normal \[MN\]). Stable hematological parameters were defined as hemoglobin level did not decrease more than (\>) 1.5 gram per deciliter (g/dL) from baseline and platelet count did not decrease \>25% from baseline. Stable organ volumes were defined as spleen volume (in MN) did not increase \>25% from baseline, if applicable, and liver volume (in MN) did not increase \>20% from baseline.
Time frame: Baseline up to Week 52
Population: Per protocol population for PAP included participants who were at least 80% compliant with treatment during PAP, had no major protocol deviations, and did not exhibit hematological decline as a result of medically determined etiologies other than Gaucher disease.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eliglustat: PAP | Percentage of Participants Who Remained Stable for 52 Weeks During the Primary Analysis Period | 84.8 percentage of participants |
| Imiglucerase: PAP | Percentage of Participants Who Remained Stable for 52 Weeks During the Primary Analysis Period | 93.6 percentage of participants |
95% CI: [-17.6, 4.2]
Secondary
Absolute Change From Baseline in Hemoglobin Levels at Week 208
Absolute change = hemoglobin level at Week 208 minus hemoglobin level at baseline.
Time frame: Baseline, Week 208
Population: FAS population for LTTP. Number of participants analyzed = participants with both baseline and Week 208 hemoglobin assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eliglustat: PAP | Absolute Change From Baseline in Hemoglobin Levels at Week 208 | 0.297 g/dL | Standard Deviation 0.7472 |
Secondary
Absolute Change From Baseline in Hemoglobin Levels at Week 52
Absolute change = hemoglobin level at Week 52 minus hemoglobin level at baseline.
Time frame: Baseline, Week 52
Population: Per protocol population for PAP. Number of participants analyzed = participants with both baseline and Week 52 hemoglobin assessment. Eliglustat participants switching to imiglucerase were excluded.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Eliglustat: PAP | Absolute Change From Baseline in Hemoglobin Levels at Week 52 | -0.22 g/dL | Standard Error 0.07 |
| Imiglucerase: PAP | Absolute Change From Baseline in Hemoglobin Levels at Week 52 | 0.05 g/dL | Standard Error 0.1 |
Secondary
Absolute Change From Baseline in Total T-Scores for Bone Mineral Density at Week 208
Images of the spine and bilateral femur were obtained by DXA to determine T-score for each bone area and total bone mineral density. T-score compares participant's bone density with that of healthy young participant. The T-score bone density categories are: normal (score \>-1), osteopenia (score -2.5 to \<=-1), and osteoporosis (score \<= -2.5). Absolute change = T-score at Week 208 minus T-score at baseline.
Time frame: Baseline, Week 208
Population: Number of participants analyzed = participants with both baseline and Week 208 T-score assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eliglustat: PAP | Absolute Change From Baseline in Total T-Scores for Bone Mineral Density at Week 208 | Total Spine | 0.22 T-Score | Standard Deviation 0.405 |
| Eliglustat: PAP | Absolute Change From Baseline in Total T-Scores for Bone Mineral Density at Week 208 | Total Femur | -0.03 T-Score | Standard Deviation 0.345 |
Secondary
Absolute Change From Baseline in Total T-Scores for Bone Mineral Density at 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. T-score compares participant's bone density with that of healthy young participant. The T-score bone density categories are: normal (score \>-1), osteopenia (score -2.5 to \<=-1), and osteoporosis (score \<= -2.5). Absolute change = T-score at Week 52 minus T-score at baseline.
Time frame: Baseline, Week 52
Population: Per protocol population for PAP. Number of participants analyzed = participants with both baseline and Week 52 T-score assessment. Here, 'n' signifies participants with both baseline and Week 52 T-score assessment for specified bone area. Eliglustat participants switching to imiglucerase were excluded.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Eliglustat: PAP | Absolute Change From Baseline in Total T-Scores for Bone Mineral Density at Week 52 | Change in Femur T-Score (n=80, 37) | 0.00 T-score | Standard Error 0.02 |
| Eliglustat: PAP | Absolute Change From Baseline in Total T-Scores for Bone Mineral Density at Week 52 | Change in Lumbar Spine T-Score (n=81, 38) | 0.04 T-score | Standard Error 0.03 |
| Imiglucerase: PAP | Absolute Change From Baseline in Total T-Scores for Bone Mineral Density at Week 52 | Change in Lumbar Spine T-Score (n=81, 38) | 0.03 T-score | Standard Error 0.05 |
| Imiglucerase: PAP | Absolute Change From Baseline in Total T-Scores for Bone Mineral Density at Week 52 | Change in Femur T-Score (n=80, 37) | -0.03 T-score | Standard Error 0.03 |
Secondary
Absolute Change From Baseline in Total Z-Scores for Bone Mineral Density at Week 208
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). Absolute change = Z-score at Week 208 minus Z-score at baseline.
Time frame: Baseline, Week 208
Population: FAS population for LTTP. Number of participants analyzed = participants with both baseline and Week 208 Z-score assessment. Here, 'n' signifies participants with both baseline and Week 208 Z-score assessment for specified bone area.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eliglustat: PAP | Absolute Change From Baseline in Total Z-Scores for Bone Mineral Density at Week 208 | Total Spine | 0.29 Z-score | Standard Deviation 0.358 |
| Eliglustat: PAP | Absolute Change From Baseline in Total Z-Scores for Bone Mineral Density at Week 208 | Total Femur | 0.03 Z-score | Standard Deviation 0.381 |
Secondary
Absolute Change From Baseline in Total Z-Scores for Bone Mineral Density at 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). Absolute change = Z-score at Week 52 minus Z-score at baseline.
Time frame: Baseline, Week 52
Population: Per protocol population for PAP. Number of participants analyzed = participants with both baseline and Week 52 Z-score assessment. Here, 'n' signifies participants with both baseline and Week 52 Z-score assessment for specified bone area. Eliglustat participants switching to imiglucerase were excluded.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Eliglustat: PAP | Absolute Change From Baseline in Total Z-Scores for Bone Mineral Density at Week 52 | Change in Lumbar Spine Z-Score (n=94, 45) | 0.06 Z-score | Standard Error 0.03 |
| Eliglustat: PAP | Absolute Change From Baseline in Total Z-Scores for Bone Mineral Density at Week 52 | Change in Femur Z-Score (n=93, 44) | 0.03 Z-score | Standard Error 0.02 |
| Imiglucerase: PAP | Absolute Change From Baseline in Total Z-Scores for Bone Mineral Density at Week 52 | Change in Lumbar Spine Z-Score (n=94, 45) | 0.06 Z-score | Standard Error 0.04 |
| Imiglucerase: PAP | Absolute Change From Baseline in Total Z-Scores for Bone Mineral Density at Week 52 | Change in Femur Z-Score (n=93, 44) | 0.02 Z-score | Standard Error 0.02 |
Secondary
Hemoglobin Level
Time frame: Baseline
Population: Per protocol population for PAP. Number of participants analyzed = participants with baseline hemoglobin assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eliglustat: PAP | Hemoglobin Level | 13.592 gram per deciliter (g/dL) | Standard Deviation 1.2467 |
| Imiglucerase: PAP | Hemoglobin Level | 13.797 gram per deciliter (g/dL) | Standard Deviation 1.2234 |
Secondary
Percent Change From Baseline in Liver Volume (in MN) at Week 208
Percent change in liver volume = (\[liver volume at Week 208 minus liver volume at baseline\] divided by \[liver volume at baseline\]) multiplied by 100, where all volumes are in multiples of normal.
Time frame: Baseline, Week 208
Population: FAS population for LTTP. Number of participants analyzed = participants with both baseline and Week 208 liver volume assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eliglustat: PAP | Percent Change From Baseline in Liver Volume (in MN) at Week 208 | -2.345 percent change | Standard Deviation 12.8795 |
Secondary
Percent Change From Baseline in Liver Volume (in MN) at Week 52
Percent change in liver volume = (\[liver volume at Week 52 minus liver volume at baseline\] divided by \[liver volume at baseline\]) multiplied by 100, where all volumes are in multiples of normal.
Time frame: Baseline, Week 52
Population: Per protocol population for PAP. Number of participants analyzed = participants with both baseline and Week 52 liver volume assessment. Eliglustat participants switching to imiglucerase were excluded.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Eliglustat: PAP | Percent Change From Baseline in Liver Volume (in MN) at Week 52 | 1.99 percent change | Standard Error 0.94 |
| Imiglucerase: PAP | Percent Change From Baseline in Liver Volume (in MN) at Week 52 | 3.13 percent change | Standard Error 1.36 |
Secondary
Percent Change From Baseline in Platelet Counts at Week 208
Percent change in platelet counts = (\[platelet count at Week 208 minus platelet count at baseline\] divided by \[platelet count at baseline\]) multiplied by 100.
Time frame: Baseline, Week 208
Population: FAS population for LTTP. Number of participants analyzed = participants with both baseline and Week 208 platelet assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eliglustat: PAP | Percent Change From Baseline in Platelet Counts at Week 208 | 6.990 percent change | Standard Deviation 20.4382 |
Secondary
Percent Change From Baseline in Platelet Counts at Week 52
Percent change in platelet counts = (\[platelet count at Week 52 minus platelet count at baseline\] divided by \[platelet count at baseline\]) multiplied by 100.
Time frame: Baseline, Week 52
Population: Per protocol population for PAP. Number of participants analyzed = participants with both baseline and Week 52 platelet assessment. Eliglustat participants switching to imiglucerase were excluded.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Eliglustat: PAP | Percent Change From Baseline in Platelet Counts at Week 52 | 3.93 percent change | Standard Error 1.71 |
| Imiglucerase: PAP | Percent Change From Baseline in Platelet Counts at Week 52 | 2.63 percent change | Standard Error 2.47 |
Secondary
Percent Change From Baseline in Spleen Volume (in MN) at Week 208
Percent change in spleen volume = (\[spleen volume at Week 208 minus spleen volume at baseline\] divided by \[spleen volume at baseline\]) multiplied by 100, where all volumes are in MN.
Time frame: Baseline, Week 208
Population: FAS population for LTTP. Number of participants analyzed = participants with both baseline and Week 208 spleen volume assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eliglustat: PAP | Percent Change From Baseline in Spleen Volume (in MN) at Week 208 | -14.768 percent change | Standard Deviation 17.9435 |
Secondary
Percent Change From Baseline in Spleen Volume (MN) at Week 52
Percent change in spleen volume = (\[spleen volume at Week 52 minus spleen volume at baseline\] divided by \[spleen volume at baseline\]) multiplied by 100, where all volumes are in MN.
Time frame: Baseline, Week 52
Population: Per protocol population for PAP. Number of participants analyzed = participants with both baseline and Week 52 spleen volume assessment. Eliglustat participants switching to imiglucerase were excluded.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Eliglustat: PAP | Percent Change From Baseline in Spleen Volume (MN) at Week 52 | -6.05 percent change | Standard Error 1.57 |
| Imiglucerase: PAP | Percent Change From Baseline in Spleen Volume (MN) at Week 52 | -3.22 percent change | Standard Error 2.13 |
Secondary
Total T-Scores for Bone Mineral Density
Images of the spine and bilateral femur were obtained by dual energy X-Ray absorptiometry (DXA) to determine T-score for each bone area and total bone mineral density. T-score compares participant's bone density with that of healthy young participant. The T-score bone density categories are: normal (score greater than \[\>\]-1), osteopenia (score -2.5 to less than or equal to \[\<=\] -1), and osteoporosis (score \<= -2.5).
Time frame: Baseline
Population: Per protocol population for PAP. Number of participants analyzed = participants with baseline T-score assessment. Here, 'n' signifies participants with baseline T-score assessment for specified bone area.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eliglustat: PAP | Total T-Scores for Bone Mineral Density | Lumbar Spine T-Score (n=81, 38) | -0.56 T-score | Standard Deviation 1.309 |
| Eliglustat: PAP | Total T-Scores for Bone Mineral Density | Femur T-Score (n=80, 37) | -0.11 T-score | Standard Deviation 1.08 |
| Imiglucerase: PAP | Total T-Scores for Bone Mineral Density | Lumbar Spine T-Score (n=81, 38) | -0.33 T-score | Standard Deviation 1.169 |
| Imiglucerase: PAP | Total T-Scores for Bone Mineral Density | Femur T-Score (n=80, 37) | -0.47 T-score | Standard Deviation 1.293 |
Secondary
Total Z-Scores for Bone Mineral Density
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
Population: Per protocol population for PAP. Number of participants analyzed = participants with baseline Z-score assessment. Here, 'n' signifies participants with baseline Z-score assessment for specified bone area.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eliglustat: PAP | Total Z-Scores for Bone Mineral Density | Lumbar Spine Z-Score (n=94, 45) | -0.35 Z-score | Standard Deviation 1.26 |
| Eliglustat: PAP | Total Z-Scores for Bone Mineral Density | Femur Z-Score (n=93, 44) | 0.09 Z-score | Standard Deviation 1.02 |
| Imiglucerase: PAP | Total Z-Scores for Bone Mineral Density | Lumbar Spine Z-Score (n=94, 45) | -0.14 Z-score | Standard Deviation 1.108 |
| Imiglucerase: PAP | Total Z-Scores for Bone Mineral Density | Femur Z-Score (n=93, 44) | -0.18 Z-score | Standard Deviation 1.122 |