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A Study of Eliglustat Tartrate (Genz-112638) in Patients With Gaucher Disease Who Have Reached Therapeutic Goals With Enzyme Replacement Therapy (ENCORE) (ENCORE)

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ClinicalTrials.gov Identifier: NCT00943111
Recruitment Status : Completed
First Posted : July 22, 2009
Results First Posted : September 4, 2014
Last Update Posted : November 25, 2016
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Gaucher Disease, Type 1
Interventions Drug: Eliglustat tartrate
Drug: Imiglucerase
Enrollment 160

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.
Arm/Group Title Eliglustat: PAP Imiglucerase: PAP Eliglustat: LTTP
Hide Arm/Group Description Eliglustat tartrate (Genz-112638) 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. The 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] the next higher dose was administered whereas if the Genz-99067 trough plasma concentration was greater than or equal to [>=] 5 ng/mL the same dose was continued. The pharmacokinetic (PK) assessment at Week 2 and Week 6 were used for dose adjustment after Week 4 and Week 8, respectively. Imiglucerase (Cerezyme®) intravenous infusion every other week (q2w) up to Week 52 in doses equivalent to participant’s past enzyme replacement therapy (ERT) dose prior to any unanticipated treatment interruption, dose reduction, or regimen change.

Participants from both the arms of PAP who completed PAP were included in this arm of LTTP.

Participants originally randomized to eliglustat in PAP continued to receive eliglustat dose, based on their Genz 99067 plasma trough concentration at Week 6.

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 next higher dose was administered whereas if the Genz-99067 trough plasma concentration was >=5 ng/mL the same dose was continued. PK assessment at Week 54 and Week 58 were used for dose adjustment after Week 56 and Week 60, respectively.

Period Title: 52-Weeks Primary Analysis Period
Started 106 54 0
Treated 106 53 0
Completed 104 52 0
Not Completed 2 2 0
Reason Not Completed
Adverse Event             2             1             0
Non-Compliance with Study Drug             0             1             0
Period Title: 5 Years Long-term Treatment Period
Started 0 0 152 [1]
Completed 0 0 77
Not Completed 0 0 75
Reason Not Completed
Transition to commercial eliglustat             0             0             51
Adverse Event             0             0             9
Withdrawal by Subject             0             0             8
Pregnancy             0             0             4
Lost to Follow-up             0             0             1
Other than specified above             0             0             2
[1]
Participants from both the arms of PAP who completed PAP and remained on-study
Arm/Group Title Eliglustat: PAP Imiglucerase: PAP Total
Hide Arm/Group Description 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. 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. Total of all reporting groups
Overall Number of Baseline Participants 106 53 159
Hide Baseline Analysis Population Description
Full analysis set (FAS) for PAP: included all participants who signed informed consent and received at least 1 dose of study drug (Imiglucerase or eliglustat).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 106 participants 53 participants 159 participants
37.6  (14.17) 37.5  (14.92) 37.5  (14.37)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 106 participants 53 participants 159 participants
Female
59
  55.7%
28
  52.8%
87
  54.7%
Male
47
  44.3%
25
  47.2%
72
  45.3%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 106 participants 53 participants 159 participants
Race: White 98 48 146
Race: Black or African American 6 4 10
Race: Asian 1 1 2
Race: White/American Indian 1 0 1
Ethnicity: Hispanic or Latino 42 19 61
Ethnicity: Not Hispanic or Latino 64 34 98
Body Mass Index (BMI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Kilogram per square meter (kg/m^2)
Number Analyzed 106 participants 53 participants 159 participants
25.2  (5.24) 24.5  (4.51) 24.9  (5.01)
[1]
Measure Description: BMI was calculated as ([weight in kg] divided by [height in cm multiplied by 0.01]^2).
Weight  
Mean (Standard Deviation)
Unit of measure:  Kilogram (kg)
Number Analyzed 106 participants 53 participants 159 participants
70.8  (16.82) 67.8  (14.44) 69.8  (16.08)
Height  
Mean (Standard Deviation)
Unit of measure:  Centimeter (cm)
Number Analyzed 106 participants 53 participants 159 participants
167.6  (9.92) 166.2  (9.56) 167.1  (9.79)
1.Primary Outcome
Title Percentage of Participants Who Remained Stable for 52 Weeks During the Primary Analysis Period
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Eliglustat: PAP Imiglucerase: PAP
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 99 47
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
84.8
(76.2 to 91.3)
93.6
(82.5 to 98.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Eliglustat: PAP, Imiglucerase: PAP
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The sample size for study was based on expected stability rates of 95% for the Imiglucerase group and 85% for the Eliglustat group, power of 85%, a one-sided significance level of 0.025, a non-inferiority margin of 25%, and a 20% non-evaluable/drop-out rate. Eliglustat was declared non-inferior to Imiglucerase if the lower-bound of the 95% confidence interval for the difference was within the non-inferiority margin of 25%.
Method of Estimation Estimation Parameter Difference in Percentage Stable
Estimated Value -8.8
Confidence Interval (2-Sided) 95%
-17.6 to 4.2
Estimation Comments [Not Specified]
2.Primary Outcome
Title Percentage of Participants Who Remained Stable Annually for 4 Years During the LTTP
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Eliglustat: LTTP
Hide Arm/Group Description:

Participants from both the arms of PAP who completed PAP were included in this arm of LTTP.

Participants originally randomized to eliglustat in PAP continued to receive eliglustat dose, based on their Genz 99067 plasma trough concentration at Week 6.

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.

Overall Number of Participants Analyzed 152
Measure Type: Number
Unit of Measure: percentage of participants
Year 1 (n=127) 83.6
Year 2 (n= 115) 75.65
Year 3 (n= 92) 60.53
Year 4 (n= 41) 26.97
3.Secondary Outcome
Title Total T-Scores for Bone Mineral Density
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Eliglustat: PAP Imiglucerase: PAP
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 81 38
Mean (Standard Deviation)
Unit of Measure: T-score
Lumbar Spine T-Score (n=81, 38) -0.56  (1.309) -0.33  (1.169)
Femur T-Score (n=80, 37) -0.11  (1.080) -0.47  (1.293)
4.Secondary Outcome
Title Absolute Change From Baseline in Total T-Scores for Bone Mineral Density at Week 52
Hide Description Images of the spine and bilateral femur were obtained by DXA to determine T-score for each bone area and total bone mineral density. 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Eliglustat: PAP Imiglucerase: PAP
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 81 38
Least Squares Mean (Standard Error)
Unit of Measure: T-score
Change in Lumbar Spine T-Score (n=81, 38) 0.04  (0.03) 0.03  (0.05)
Change in Femur T-Score (n=80, 37) 0.00  (0.02) -0.03  (0.03)
5.Secondary Outcome
Title Total Z-Scores for Bone Mineral Density
Hide Description Images of the spine and bilateral femur were obtained by DXA to determine Z-score for each bone area and total bone mineral density. The Z-score bone density categories are: normal (score >-2) and below normal (score <=-2).
Time Frame Baseline
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Eliglustat: PAP Imiglucerase: PAP
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 94 45
Mean (Standard Deviation)
Unit of Measure: Z-score
Lumbar Spine Z-Score (n=94, 45) -0.35  (1.260) -0.14  (1.108)
Femur Z-Score (n=93, 44) 0.09  (1.020) -0.18  (1.122)
6.Secondary Outcome
Title Absolute Change From Baseline in Total Z-Scores for Bone Mineral Density at Week 52
Hide Description Images of the spine and bilateral femur were obtained by DXA to determine Z-score for each bone area and total bone mineral density. The Z-score bone density categories are: normal (score >-2) and below normal (score <=-2). Absolute change = Z-score at Week 52 minus Z-score at baseline.
Time Frame Baseline, Week 52
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Eliglustat: PAP Imiglucerase: PAP
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 94 45
Least Squares Mean (Standard Error)
Unit of Measure: Z-score
Change in Lumbar Spine Z-Score (n=94, 45) 0.06  (0.03) 0.06  (0.04)
Change in Femur Z-Score (n=93, 44) 0.03  (0.02) 0.02  (0.02)
7.Secondary Outcome
Title Hemoglobin Level
Hide Description [Not Specified]
Time Frame Baseline
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Per protocol population for PAP. Number of participants analyzed = participants with baseline hemoglobin assessment.
Arm/Group Title Eliglustat: PAP Imiglucerase: PAP
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 98 47
Mean (Standard Deviation)
Unit of Measure: gram per deciliter (g/dL)
13.592  (1.2467) 13.797  (1.2234)
8.Secondary Outcome
Title Absolute Change From Baseline in Hemoglobin Levels at Week 52
Hide Description Absolute change = hemoglobin level at Week 52 minus hemoglobin level at baseline.
Time Frame Baseline, Week 52
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Eliglustat: PAP Imiglucerase: PAP
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 98 47
Least Squares Mean (Standard Error)
Unit of Measure: g/dL
-0.22  (0.07) 0.05  (0.10)
9.Secondary Outcome
Title Percent Change From Baseline in Platelet Counts at Week 52
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Eliglustat: PAP Imiglucerase: PAP
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 98 47
Least Squares Mean (Standard Error)
Unit of Measure: percent change
3.93  (1.71) 2.63  (2.47)
10.Secondary Outcome
Title Percent Change From Baseline in Spleen Volume (MN) at Week 52
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Eliglustat: PAP Imiglucerase: PAP
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 70 39
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-6.05  (1.57) -3.22  (2.13)
11.Secondary Outcome
Title Percent Change From Baseline in Liver Volume (in MN) at Week 52
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Eliglustat: PAP Imiglucerase: PAP
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 98 47
Least Squares Mean (Standard Error)
Unit of Measure: percent change
1.99  (0.94) 3.13  (1.36)
12.Secondary Outcome
Title Absolute Change From Baseline in Total T-Scores for Bone Mineral Density at Week 208
Hide Description Images of the spine and bilateral femur were obtained by DXA to determine T-score for each bone area and total bone mineral density. 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Number of participants analyzed = participants with both baseline and Week 208 T-score assessment.
Arm/Group Title Eliglustat: LTTP
Hide Arm/Group Description:

Participants from both the arms of PAP who completed PAP were included in this arm of LTTP.

Participants originally randomized to eliglustat in PAP continued to receive eliglustat dose, based on their Genz 99067 plasma trough concentration at Week 6.

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.

Overall Number of Participants Analyzed 36
Mean (Standard Deviation)
Unit of Measure: T-Score
Total Spine 0.22  (0.405)
Total Femur -0.03  (0.345)
13.Secondary Outcome
Title Absolute Change From Baseline in Total Z-Scores for Bone Mineral Density at Week 208
Hide Description Images of the spine and bilateral femur were obtained by DXA to determine Z-score for each bone area and total bone mineral density. The Z-score bone density categories are: normal (score >-2) and below normal (score <=-2). Absolute change = Z-score at Week 208 minus Z-score at baseline.
Time Frame Baseline, Week 208
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Eliglustat: LTTP
Hide Arm/Group Description:

Participants from both the arms of PAP who completed PAP were included in this arm of LTTP.

Participants originally randomized to eliglustat in PAP continued to receive eliglustat dose, based on their Genz 99067 plasma trough concentration at Week 6.

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.

Overall Number of Participants Analyzed 42
Mean (Standard Deviation)
Unit of Measure: Z-score
Total Spine 0.29  (0.358)
Total Femur 0.03  (0.381)
14.Secondary Outcome
Title Absolute Change From Baseline in Hemoglobin Levels at Week 208
Hide Description Absolute change = hemoglobin level at Week 208 minus hemoglobin level at baseline.
Time Frame Baseline, Week 208
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS population for LTTP. Number of participants analyzed = participants with both baseline and Week 208 hemoglobin assessment.
Arm/Group Title Eliglustat: LTTP
Hide Arm/Group Description:

Participants from both the arms of PAP who completed PAP were included in this arm of LTTP.

Participants originally randomized to eliglustat in PAP continued to receive eliglustat dose, based on their Genz 99067 plasma trough concentration at Week 6.

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.

Overall Number of Participants Analyzed 45
Mean (Standard Deviation)
Unit of Measure: g/dL
0.297  (0.7472)
15.Secondary Outcome
Title Percent Change From Baseline in Platelet Counts at Week 208
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS population for LTTP. Number of participants analyzed = participants with both baseline and Week 208 platelet assessment.
Arm/Group Title Eliglustat: LTTP
Hide Arm/Group Description:

Participants from both the arms of PAP who completed PAP were included in this arm of LTTP.

Participants originally randomized to eliglustat in PAP continued to receive eliglustat dose, based on their Genz 99067 plasma trough concentration at Week 6.

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.

Overall Number of Participants Analyzed 45
Mean (Standard Deviation)
Unit of Measure: percent change
6.990  (20.4382)
16.Secondary Outcome
Title Percent Change From Baseline in Spleen Volume (in MN) at Week 208
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS population for LTTP. Number of participants analyzed = participants with both baseline and Week 208 spleen volume assessment.
Arm/Group Title Eliglustat: LTTP
Hide Arm/Group Description:

Participants from both the arms of PAP who completed PAP were included in this arm of LTTP.

Participants originally randomized to eliglustat in PAP continued to receive eliglustat dose, based on their Genz 99067 plasma trough concentration at Week 6.

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.

Overall Number of Participants Analyzed 33
Mean (Standard Deviation)
Unit of Measure: percent change
-14.768  (17.9435)
17.Secondary Outcome
Title Percent Change From Baseline in Liver Volume (in MN) at Week 208
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS population for LTTP. Number of participants analyzed = participants with both baseline and Week 208 liver volume assessment.
Arm/Group Title Eliglustat: LTTP
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Participants from both the arms of PAP who completed PAP were included in this arm of LTTP.

Participants originally randomized to eliglustat in PAP continued to receive eliglustat dose, based on their Genz 99067 plasma trough concentration at Week 6.

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.

Overall Number of Participants Analyzed 46
Mean (Standard Deviation)
Unit of Measure: percent change
-2.345  (12.8795)
Time Frame From signature of informed consent up to 30-37 days after the last dose of treatment (last dose = up to Week 104)
Adverse Event Reporting Description Safety set included all participants who received at least 1 dose of study drug (Eliglustat or Imiglucerase). In the event a single participant experienced both serious and non­serious forms of same adverse events (AE), individual was included in numerator (number of participants affected) of each AE table.
 
Arm/Group Title Eliglustat Imiglucerase
Hide Arm/Group Description 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. Dose adjustments after Week 4 and Week 8 were based on Genz­99067 (active moiety of eliglustat tartrate in plasma) trough plasma concentrations. LTTP: Participants originally randomized to eliglustat in PAP continued to receive eliglustat dose, based on their Genz 99067 plasma trough concentration at Week 6. PAP: Imiglucerase (Cerezyme®) 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. 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 Genz­99067 (active moiety of eliglustat tartrate in plasma) trough plasma concentrations.
All-Cause Mortality
Eliglustat Imiglucerase
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Eliglustat Imiglucerase
Affected / at Risk (%) Affected / at Risk (%)
Total   18/106 (16.98%)   7/53 (13.21%) 
Blood and lymphatic system disorders     
Polycythaemia  1  0/106 (0.00%)  1/53 (1.89%) 
Cardiac disorders     
Acute myocardial infarction  1  0/106 (0.00%)  1/53 (1.89%) 
Myocardial infarction  1  0/106 (0.00%)  1/53 (1.89%) 
Gastrointestinal disorders     
Colitis ischaemic  1  1/106 (0.94%)  0/53 (0.00%) 
Diarrhoea  1  1/106 (0.94%)  0/53 (0.00%) 
Intestinal obstruction  1  1/106 (0.94%)  0/53 (0.00%) 
General disorders     
Device malfunction  1  1/106 (0.94%)  0/53 (0.00%) 
Pain  1  1/106 (0.94%)  0/53 (0.00%) 
Pyrexia  1  1/106 (0.94%)  0/53 (0.00%) 
Hepatobiliary disorders     
Biliary colic  1  1/106 (0.94%)  0/53 (0.00%) 
Cholecystitis  1  1/106 (0.94%)  0/53 (0.00%) 
Infections and infestations     
Appendicitis  1  1/106 (0.94%)  0/53 (0.00%) 
Diverticulitis  1  1/106 (0.94%)  0/53 (0.00%) 
Injury, poisoning and procedural complications     
Injury  1  0/106 (0.00%)  1/53 (1.89%) 
Joint dislocation  1  1/106 (0.94%)  0/53 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Benign ovarian tumour  1  0/106 (0.00%)  1/53 (1.89%) 
Metastatic renal cell carcinoma  1  0/106 (0.00%)  1/53 (1.89%) 
Pancreatic carcinoma metastatic  1  0/106 (0.00%)  1/53 (1.89%) 
Uterine leiomyoma  1  1/106 (0.94%)  0/53 (0.00%) 
Nervous system disorders     
Neuropathy peripheral  1  1/106 (0.94%)  0/53 (0.00%) 
Syncope  1  3/106 (2.83%)  0/53 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Epistaxis  1  1/106 (0.94%)  0/53 (0.00%) 
Nasal septum deviation  1  1/106 (0.94%)  0/53 (0.00%) 
Surgical and medical procedures     
Mammoplasty  1  1/106 (0.94%)  0/53 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDra 18.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Eliglustat Imiglucerase
Affected / at Risk (%) Affected / at Risk (%)
Total   91/106 (85.85%)   38/53 (71.70%) 
Cardiac disorders     
Palpitations  1  8/106 (7.55%)  3/53 (5.66%) 
Gastrointestinal disorders     
Abdominal pain  1  14/106 (13.21%)  6/53 (11.32%) 
Abdominal pain lower  1  6/106 (5.66%)  0/53 (0.00%) 
Abdominal pain upper  1  26/106 (24.53%)  3/53 (5.66%) 
Constipation  1  10/106 (9.43%)  6/53 (11.32%) 
Diarrhoea  1  20/106 (18.87%)  2/53 (3.77%) 
Dyspepsia  1  15/106 (14.15%)  4/53 (7.55%) 
Gastritis  1  6/106 (5.66%)  5/53 (9.43%) 
Gastrooesophageal reflux disease  1  13/106 (12.26%)  2/53 (3.77%) 
Nausea  1  18/106 (16.98%)  7/53 (13.21%) 
Toothache  1  7/106 (6.60%)  3/53 (5.66%) 
Vomiting  1  10/106 (9.43%)  0/53 (0.00%) 
General disorders     
Asthenia  1  10/106 (9.43%)  1/53 (1.89%) 
Chest pain  1  9/106 (8.49%)  1/53 (1.89%) 
Fatigue  1  20/106 (18.87%)  7/53 (13.21%) 
Pain  1  6/106 (5.66%)  3/53 (5.66%) 
Peripheral swelling  1  6/106 (5.66%)  1/53 (1.89%) 
Pyrexia  1  2/106 (1.89%)  3/53 (5.66%) 
Hepatobiliary disorders     
Hepatomegaly  1  5/106 (4.72%)  3/53 (5.66%) 
Infections and infestations     
Bronchitis  1  8/106 (7.55%)  2/53 (3.77%) 
Gastroenteritis  1  11/106 (10.38%)  2/53 (3.77%) 
Influenza  1  20/106 (18.87%)  6/53 (11.32%) 
Nasopharyngitis  1  28/106 (26.42%)  10/53 (18.87%) 
Sinusitis  1  20/106 (18.87%)  3/53 (5.66%) 
Upper respiratory tract infection  1  21/106 (19.81%)  7/53 (13.21%) 
Urinary tract infection  1  16/106 (15.09%)  3/53 (5.66%) 
Injury, poisoning and procedural complications     
Contusion  1  7/106 (6.60%)  2/53 (3.77%) 
Laceration  1  7/106 (6.60%)  1/53 (1.89%) 
Ligament sprain  1  8/106 (7.55%)  0/53 (0.00%) 
Limb injury  1  6/106 (5.66%)  0/53 (0.00%) 
Investigations     
Blood creatine phosphokinase increased  1  16/106 (15.09%)  3/53 (5.66%) 
Mean cell volume abnormal  1  0/106 (0.00%)  3/53 (5.66%) 
Nerve conduction studies abnormal  1  7/106 (6.60%)  3/53 (5.66%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  38/106 (35.85%)  13/53 (24.53%) 
Back pain  1  23/106 (21.70%)  6/53 (11.32%) 
Bone pain  1  9/106 (8.49%)  3/53 (5.66%) 
Muscle spasms  1  6/106 (5.66%)  1/53 (1.89%) 
Musculoskeletal pain  1  8/106 (7.55%)  3/53 (5.66%) 
Myalgia  1  6/106 (5.66%)  2/53 (3.77%) 
Pain in extremity  1  21/106 (19.81%)  5/53 (9.43%) 
Nervous system disorders     
Dizziness  1  18/106 (16.98%)  4/53 (7.55%) 
Headache  1  26/106 (24.53%)  9/53 (16.98%) 
Hypoaesthesia  1  6/106 (5.66%)  1/53 (1.89%) 
Paraesthesia  1  7/106 (6.60%)  1/53 (1.89%) 
Psychiatric disorders     
Anxiety  1  10/106 (9.43%)  1/53 (1.89%) 
Depression  1  3/106 (2.83%)  3/53 (5.66%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  11/106 (10.38%)  2/53 (3.77%) 
Epistaxis  1  7/106 (6.60%)  1/53 (1.89%) 
Oropharyngeal pain  1  7/106 (6.60%)  3/53 (5.66%) 
Skin and subcutaneous tissue disorders     
Dry skin  1  5/106 (4.72%)  4/53 (7.55%) 
Vascular disorders     
Hypertension  1  6/106 (5.66%)  1/53 (1.89%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDra 18.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Results Point of Contact
Name/Title: Trial Transparency Team
Organization: Sanofi
Publications:
Responsible Party: Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT00943111     History of Changes
Other Study ID Numbers: GZGD02607
2008-005223-28 ( EudraCT Number )
EFC12812 ( Other Identifier: Sanofi )
First Submitted: July 20, 2009
First Posted: July 22, 2009
Results First Submitted: August 22, 2014
Results First Posted: September 4, 2014
Last Update Posted: November 25, 2016