Trial Outcomes & Findings for A Study of Eliglustat Tartrate (Genz-112638) in Patients With Gaucher Disease to Evaluate Once Daily Versus Twice Daily Dosing (EDGE) (NCT NCT01074944)
NCT ID: NCT01074944
Last Updated: 2017-02-06
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
170 participants
Primary outcome timeframe
PAP Baseline up to the end of PAP (Week 52)
Results posted on
2017-02-06
Participant Flow
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.
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.
Participant milestones
| Measure |
LIP, Eliglustat
All participants (except in Japan) received eliglustat 50 mg, twice daily (BID) on Day 1 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual pharmacokinetics (PK) data for up to 78 weeks. All participants in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks.
|
PAP, Eliglustat: Once Daily
All participants who were randomized after meeting all randomization criteria (defined as: no more than 1 bone crisis and was free of other clinically symptomatic bone disease \[such as bone pain attributable to osteonecrosis and/or pathological fractures) during the first 6 months of the LIP; mean hemoglobin level of ≥11 g/dL \[if female\] and ≥12 g/dL \[if male\]; mean platelet count ≥100,000/mm\^3; spleen volume ≤10 times of normal; liver volume ≤1.5 times of normal; had a dose of 50 mg BID or 100 mg BID of eliglustat for at least 4 months and a peak (2-hour) Genz-99067 plasma concentration of \<50 ng/mL) after either 26, 52 or 78 weeks of LIP received eliglustat capsules at the total daily dose (TDD) of 100 mg or 200 mg (the TDD they were on before randomization) once daily (QD) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
PAP, Eliglustat: Twice Daily
All participants who were randomized after meeting all randomization criteria (defined as: no more than 1 bone crisis and was free of other clinically symptomatic bone disease \[such as bone pain attributable to osteonecrosis and/or pathological fractures) during the first 6 months of the LIP; mean hemoglobin level of ≥11 g/dL \[if female\] and ≥12 g/dL \[if male\]; mean platelet count ≥100,000/mm\^3; spleen volume ≤10 times of normal; liver volume ≤1.5 times of normal; had a dose of 50 mg BID or 100 mg BID of eliglustat for at least 4 months and a peak (2-hour) Genz-99067 plasma concentration of \<50 ng/mL) after either 26, 52 or 78 weeks of LIP, received eliglustat at the TDD 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
LTTP, Eliglustat
All participants who entered PAP continued their blinded randomized treatment for first 4 weeks. Participants who at Week 52 of PAP maintained their therapeutic goals (defined as: no more than 2 bone crisis during PAP \[with no more than 1 bone crisis during either first 6 months or later 6 months of PAP\] and is free of other clinically symptomatic bone disease during PAP; hemoglobin level not decreased by \>1.5 g/dL from Baseline for PAP \[defined as last available assessment prior to randomization\]; platelet count not decreased by \>25% from Baseline for PAP; spleen volume not increased by 25% from Baseline for PAP; liver volume not increased by \>20% from Baseline for PAP), continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) QD till the end of the study. The participants who did not maintain all their therapeutic goals continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) BID till the end of the study.
|
ETP, Eliglustat
All participants who did not meet all the randomization criteria at Week 78 of the LIP continued in the ETP and received eliglustat capsules at the same dose as they were receiving at the end of LIP till the end of the study.
|
|---|---|---|---|---|---|
|
Lead-in Period (up to 78 Weeks)
STARTED
|
170
|
0
|
0
|
0
|
0
|
|
Lead-in Period (up to 78 Weeks)
COMPLETED
|
157
|
0
|
0
|
0
|
0
|
|
Lead-in Period (up to 78 Weeks)
NOT COMPLETED
|
13
|
0
|
0
|
0
|
0
|
|
Primary Analysis Period (up to 52 Weeks)
STARTED
|
0
|
65
|
66
|
0
|
0
|
|
Primary Analysis Period (up to 52 Weeks)
COMPLETED
|
0
|
54
|
60
|
0
|
0
|
|
Primary Analysis Period (up to 52 Weeks)
NOT COMPLETED
|
0
|
11
|
6
|
0
|
0
|
|
Long Term Treatment
STARTED
|
0
|
0
|
0
|
121
|
0
|
|
Long Term Treatment
COMPLETED
|
0
|
0
|
0
|
95
|
0
|
|
Long Term Treatment
NOT COMPLETED
|
0
|
0
|
0
|
26
|
0
|
|
Extended Treatment (up to 42 Months)
STARTED
|
0
|
0
|
0
|
0
|
25
|
|
Extended Treatment (up to 42 Months)
COMPLETED
|
0
|
0
|
0
|
0
|
20
|
|
Extended Treatment (up to 42 Months)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
5
|
Reasons for withdrawal
| Measure |
LIP, Eliglustat
All participants (except in Japan) received eliglustat 50 mg, twice daily (BID) on Day 1 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual pharmacokinetics (PK) data for up to 78 weeks. All participants in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks.
|
PAP, Eliglustat: Once Daily
All participants who were randomized after meeting all randomization criteria (defined as: no more than 1 bone crisis and was free of other clinically symptomatic bone disease \[such as bone pain attributable to osteonecrosis and/or pathological fractures) during the first 6 months of the LIP; mean hemoglobin level of ≥11 g/dL \[if female\] and ≥12 g/dL \[if male\]; mean platelet count ≥100,000/mm\^3; spleen volume ≤10 times of normal; liver volume ≤1.5 times of normal; had a dose of 50 mg BID or 100 mg BID of eliglustat for at least 4 months and a peak (2-hour) Genz-99067 plasma concentration of \<50 ng/mL) after either 26, 52 or 78 weeks of LIP received eliglustat capsules at the total daily dose (TDD) of 100 mg or 200 mg (the TDD they were on before randomization) once daily (QD) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
PAP, Eliglustat: Twice Daily
All participants who were randomized after meeting all randomization criteria (defined as: no more than 1 bone crisis and was free of other clinically symptomatic bone disease \[such as bone pain attributable to osteonecrosis and/or pathological fractures) during the first 6 months of the LIP; mean hemoglobin level of ≥11 g/dL \[if female\] and ≥12 g/dL \[if male\]; mean platelet count ≥100,000/mm\^3; spleen volume ≤10 times of normal; liver volume ≤1.5 times of normal; had a dose of 50 mg BID or 100 mg BID of eliglustat for at least 4 months and a peak (2-hour) Genz-99067 plasma concentration of \<50 ng/mL) after either 26, 52 or 78 weeks of LIP, received eliglustat at the TDD 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
LTTP, Eliglustat
All participants who entered PAP continued their blinded randomized treatment for first 4 weeks. Participants who at Week 52 of PAP maintained their therapeutic goals (defined as: no more than 2 bone crisis during PAP \[with no more than 1 bone crisis during either first 6 months or later 6 months of PAP\] and is free of other clinically symptomatic bone disease during PAP; hemoglobin level not decreased by \>1.5 g/dL from Baseline for PAP \[defined as last available assessment prior to randomization\]; platelet count not decreased by \>25% from Baseline for PAP; spleen volume not increased by 25% from Baseline for PAP; liver volume not increased by \>20% from Baseline for PAP), continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) QD till the end of the study. The participants who did not maintain all their therapeutic goals continued into the LTTP and received their TDD of eliglustat (100 mg or 200 mg) BID till the end of the study.
|
ETP, Eliglustat
All participants who did not meet all the randomization criteria at Week 78 of the LIP continued in the ETP and received eliglustat capsules at the same dose as they were receiving at the end of LIP till the end of the study.
|
|---|---|---|---|---|---|
|
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
|
|
Primary Analysis Period (up to 52 Weeks)
Adverse Event
|
0
|
2
|
3
|
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
|
|
Primary Analysis Period (up to 52 Weeks)
Pregnancy
|
0
|
1
|
0
|
0
|
0
|
|
Primary Analysis Period (up to 52 Weeks)
Non-Compliant to Protocol
|
0
|
1
|
1
|
0
|
0
|
|
Long Term Treatment
Adverse Event
|
0
|
0
|
0
|
3
|
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
Entered in Period, But Not Treated
|
0
|
0
|
0
|
1
|
0
|
|
Long Term Treatment
Withdrawal by Subject
|
0
|
0
|
0
|
2
|
0
|
|
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
|
Baseline Characteristics
A Study of Eliglustat Tartrate (Genz-112638) in Patients With Gaucher Disease to Evaluate Once Daily Versus Twice Daily Dosing (EDGE)
Baseline characteristics by cohort
| Measure |
All Participants
n=170 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.
|
|---|---|
|
Age, Continuous
|
37.7 years
STANDARD_DEVIATION 15.1 • n=5 Participants
|
|
Gender
Female
|
81 Participants
n=5 Participants
|
|
Gender
Male
|
89 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
PAP, Eliglustat: Once Daily
n=56 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
PAP, Eliglustat: Twice Daily
n=59 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
|---|---|---|
|
PAP: Percentage of Participants Who Remained Stable for 52 Weeks During the PAP
|
80.4 percentage of participants
Interval 67.6 to 89.8
|
83.1 percentage of participants
Interval 71.0 to 91.6
|
SECONDARY outcome
Timeframe: Baseline, Week 26, Week 52Population: 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.
Outcome measures
| Measure |
PAP, Eliglustat: Once Daily
n=56 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
PAP, Eliglustat: Twice Daily
n=59 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
|---|---|---|
|
PAP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26 and 52
Baseline (n=56, 59)
|
13.641 g/dL
Standard Deviation 1.214
|
13.691 g/dL
Standard Deviation 1.273
|
|
PAP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26 and 52
Week 26 (n=56, 57)
|
13.677 g/dL
Standard Deviation 1.377
|
13.946 g/dL
Standard Deviation 1.509
|
|
PAP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26 and 52
Week 52 (n=56, 59)
|
13.605 g/dL
Standard Deviation 1.432
|
13.824 g/dL
Standard Deviation 1.442
|
SECONDARY outcome
Timeframe: Baseline, Week 26, Week 52Population: 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.
Outcome measures
| Measure |
PAP, Eliglustat: Once Daily
n=56 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
PAP, Eliglustat: Twice Daily
n=59 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
|---|---|---|
|
PAP: Mean Platelet Count at Baseline, Weeks 26, 52
Week 52 (n=56, 59)
|
207.20 platelets*10^9 /L
Standard Deviation 80.62
|
176.10 platelets*10^9 /L
Standard Deviation 62.01
|
|
PAP: Mean Platelet Count at Baseline, Weeks 26, 52
Baseline (n=56, 59)
|
204.01 platelets*10^9 /L
Standard Deviation 81.49
|
171.09 platelets*10^9 /L
Standard Deviation 63.50
|
|
PAP: Mean Platelet Count at Baseline, Weeks 26, 52
Week 26 (n=56, 57)
|
195.75 platelets*10^9 /L
Standard Deviation 66.65
|
173.94 platelets*10^9 /L
Standard Deviation 65.61
|
SECONDARY outcome
Timeframe: Baseline, Week 26, Week 52Population: 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.
Outcome measures
| Measure |
PAP, Eliglustat: Once Daily
n=56 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
PAP, Eliglustat: Twice Daily
n=59 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
|---|---|---|
|
PAP: Mean Spleen Volume at Baseline, Weeks 26, 52
Baseline (n= 39, 45)
|
3.309 MN
Standard Deviation 1.465
|
3.787 MN
Standard Deviation 1.623
|
|
PAP: Mean Spleen Volume at Baseline, Weeks 26, 52
Week 26 (n= 39, 45)
|
3.066 MN
Standard Deviation 1.299
|
3.504 MN
Standard Deviation 1.365
|
|
PAP: Mean Spleen Volume at Baseline, Weeks 26, 52
Week 52 (n= 39, 45)
|
3.017 MN
Standard Deviation 1.381
|
3.394 MN
Standard Deviation 1.305
|
SECONDARY outcome
Timeframe: Baseline, Week 26 and Week 52Population: 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.
Outcome measures
| Measure |
PAP, Eliglustat: Once Daily
n=56 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
PAP, Eliglustat: Twice Daily
n=59 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
|---|---|---|
|
PAP: Mean Liver Volume at Baseline, Weeks 26, 52
Baseline (n=56, 59)
|
0.981 MN
Standard Deviation 0.187
|
1.040 MN
Standard Deviation 0.198
|
|
PAP: Mean Liver Volume at Baseline, Weeks 26, 52
Week 26 (n=56, 59)
|
0.987 MN
Standard Deviation 0.190
|
1.024 MN
Standard Deviation 0.179
|
|
PAP: Mean Liver Volume at Baseline, Weeks 26, 52
Week 52 (n=56, 59)
|
0.970 MN
Standard Deviation 0.170
|
1.009 MN
Standard Deviation 0.196
|
SECONDARY outcome
Timeframe: Baseline, Week 26, Week 52Population: 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.
Chitotriosidase biomarker was assayed from plasma.
Outcome measures
| Measure |
PAP, Eliglustat: Once Daily
n=56 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
PAP, Eliglustat: Twice Daily
n=59 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
|---|---|---|
|
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
|
1554.9 nmol/hr/mL
Standard Deviation 1895.0
|
|
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
|
1242.0 nmol/hr/mL
Standard Deviation 2012.6
|
|
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
|
1170.1 nmol/hr/mL
Standard Deviation 1683.3
|
SECONDARY outcome
Timeframe: Baseline, Week 26 and week 52Population: 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.
GL-1 on DBS biomarker was assayed from dried blood spot (DBS).
Outcome measures
| Measure |
PAP, Eliglustat: Once Daily
n=56 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
PAP, Eliglustat: Twice Daily
n=59 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
|---|---|---|
|
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
|
2.425 mcg/mL
Standard Deviation 1.378
|
|
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
|
2.563 mcg/mL
Standard Deviation 1.100
|
|
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
|
2.707 mcg/mL
Standard Deviation 1.443
|
SECONDARY outcome
Timeframe: Baseline, Week 26, Week 52Population: 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.
MIP1-beta biomarker was assayed from plasma.
Outcome measures
| Measure |
PAP, Eliglustat: Once Daily
n=56 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
PAP, Eliglustat: Twice Daily
n=59 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
|---|---|---|
|
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 68.0
|
121.0 pg/mL
Standard Deviation 204.4
|
|
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
|
118.8 pg/mL
Standard Deviation 156.3
|
|
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
|
117.9 pg/mL
Standard Deviation 165.3
|
SECONDARY outcome
Timeframe: Baseline, Week 52Population: 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.
BMD measurements of the spine and bilateral femur were acquired by dual-energy x-ray absorptiometry (DXA) scan.
Outcome measures
| Measure |
PAP, Eliglustat: Once Daily
n=56 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
PAP, Eliglustat: Twice Daily
n=59 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
|---|---|---|
|
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
|
1.081 g/cm^2
Standard Deviation 0.172
|
|
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
|
1.086 g/cm^2
Standard Deviation 0.177
|
|
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
|
1.000 g/cm^2
Standard Deviation 0.199
|
|
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
|
0.990 g/cm^2
Standard Deviation 0.196
|
|
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
|
0.996 g/cm^2
Standard Deviation 0.184
|
|
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
|
0.981 g/cm^2
Standard Deviation 0.177
|
SECONDARY outcome
Timeframe: Baseline, Week 52Population: 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.
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).
Outcome measures
| Measure |
PAP, Eliglustat: Once Daily
n=56 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
PAP, Eliglustat: Twice Daily
n=59 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
|---|---|---|
|
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
|
-0.771 T-score
Standard Deviation 1.217
|
|
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
|
-0.717 T-score
Standard Deviation 1.271
|
|
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
|
-0.368 T-score
Standard Deviation 1.347
|
|
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
|
-0.441 T-score
Standard Deviation 1.326
|
|
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
|
-0.382 T-score
Standard Deviation 1.282
|
|
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
|
-0.530 T-score
Standard Deviation 1.236
|
SECONDARY outcome
Timeframe: Baseline, Week 52Population: 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
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).
Outcome measures
| Measure |
PAP, Eliglustat: Once Daily
n=56 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
PAP, Eliglustat: Twice Daily
n=59 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
|---|---|---|
|
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
|
-0.609 Z-score
Standard Deviation 1.166
|
|
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
|
-0.555 Z-score
Standard Deviation 1.202
|
|
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
|
-0.115 Z-score
Standard Deviation 1.294
|
|
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 1.250
|
-0.183 Z-score
Standard Deviation 1.274
|
|
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
|
-0.140 Z-score
Standard Deviation 1.194
|
|
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
|
-0.260 Z-score
Standard Deviation 1.141
|
SECONDARY outcome
Timeframe: Baseline, Week 26 and Week 52Population: 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.
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.
Outcome measures
| Measure |
PAP, Eliglustat: Once Daily
n=56 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
PAP, Eliglustat: Twice Daily
n=59 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
|---|---|---|
|
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
|
0 participants
|
|
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
|
0 participants
|
|
PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52.
MS, Required Wheelchair: Baseline (n=56, 59)
|
0 participants
|
0 participants
|
|
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
|
0 participants
|
|
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
|
0 participants
|
|
PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52.
MS, Bedridden: Baseline (n=56, 59)
|
0 participants
|
0 participants
|
|
PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52.
MS, Bedridden: Week 26 (n=55, 57)
|
0 participants
|
0 participants
|
|
PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52.
MS, Bedridden: Week 52 (n=51, 58)
|
0 participants
|
0 participants
|
|
PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52.
MS, Unrestricted: Baseline (n=56, 59)
|
49 participants
|
59 participants
|
|
PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52.
MS, Unrestricted: Week 26 (n=55, 57)
|
46 participants
|
56 participants
|
|
PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52.
MS, Unrestricted: Week 52 (n=51, 58)
|
50 participants
|
57 participants
|
|
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
|
0 participants
|
|
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
|
1 participants
|
|
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
|
1 participants
|
|
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
|
0 participants
|
SECONDARY outcome
Timeframe: Baseline, Week 26, and Week 52Population: 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.
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.
Outcome measures
| Measure |
PAP, Eliglustat: Once Daily
n=56 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
PAP, Eliglustat: Twice Daily
n=59 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
|---|---|---|
|
PAP: Number of Participants With Bone Crises at Baseline, Weeks 26 and 52
Bone Crisis (0): Baseline (n=56, 59)
|
55 participants
|
57 participants
|
|
PAP: Number of Participants With Bone Crises at Baseline, Weeks 26 and 52
Bone Crisis (0): Week 26 (n=55,57)
|
54 participants
|
56 participants
|
|
PAP: Number of Participants With Bone Crises at Baseline, Weeks 26 and 52
Bone Crisis (0): Week 52 (n=56, 58)
|
56 participants
|
57 participants
|
|
PAP: Number of Participants With Bone Crises at Baseline, Weeks 26 and 52
Bone Crisis (1): Baseline (n=56, 59)
|
1 participants
|
2 participants
|
|
PAP: Number of Participants With Bone Crises at Baseline, Weeks 26 and 52
Bone Crisis (1): Week 26 (n=55, 57)
|
0 participants
|
1 participants
|
|
PAP: Number of Participants With Bone Crises at Baseline, Weeks 26 and 52
Bone Crisis (1): Week 52 (n=56, 58)
|
0 participants
|
1 participants
|
|
PAP: Number of Participants With Bone Crises at Baseline, Weeks 26 and 52
Bone Crisis (2): Baseline (n=56, 59)
|
0 participants
|
0 participants
|
|
PAP: Number of Participants With Bone Crises at Baseline, Weeks 26 and 52
Bone Crisis (2): week 26 (n=55, 57)
|
1 participants
|
0 participants
|
|
PAP: Number of Participants With Bone Crises at Baseline, Weeks 26 and 52
Bone Crisis (2): week 52 (n=56, 58)
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Baseline, Week 26, and Week 52Population: 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.
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.
Outcome measures
| Measure |
PAP, Eliglustat: Once Daily
n=56 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
PAP, Eliglustat: Twice Daily
n=59 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
|---|---|---|
|
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
|
1 participants
|
|
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
|
2 participants
|
|
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
|
1 participants
|
|
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
|
0 participants
|
|
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
|
2 participants
|
|
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
|
0 participants
|
|
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
|
0 participants
|
|
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
|
0 participants
|
|
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
|
49 participants
|
|
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
|
49 participants
|
|
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
|
45 participants
|
|
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
|
1 participants
|
|
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
|
4 participants
|
|
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
|
7 participants
|
|
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
|
3 participants
|
|
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
|
3 participants
|
|
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
|
2 participants
|
|
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
|
5 participants
|
SECONDARY outcome
Timeframe: Baseline, Week 52Population: 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.
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.
Outcome measures
| Measure |
PAP, Eliglustat: Once Daily
n=56 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
PAP, Eliglustat: Twice Daily
n=59 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
|---|---|---|
|
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
|
9.136 BMB Score
Standard Deviation 2.784
|
|
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
|
8.705 BMB Score
Standard Deviation 2.633
|
SECONDARY outcome
Timeframe: Baseline, Week 26, Week, 52, and Week 78Population: 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.
Outcome measures
| Measure |
PAP, Eliglustat: Once Daily
n=170 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
PAP, Eliglustat: Twice Daily
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
|---|---|---|
|
LIP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26, 52 and 78
Baseline (n=170)
|
13.435 g/dL
Standard Deviation 1.560
|
—
|
|
LIP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26, 52 and 78
Week 26 (n=163)
|
13.443 g/dL
Standard Deviation 1.382
|
—
|
|
LIP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26, 52 and 78
Week 52 (n=74)
|
13.434 g/dL
Standard Deviation 1.497
|
—
|
|
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 outcome
Timeframe: Baseline, Week 26, Week 52, Week 78Population: 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.
Outcome measures
| Measure |
PAP, Eliglustat: Once Daily
n=170 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
PAP, Eliglustat: Twice Daily
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
|---|---|---|
|
LIP: Mean Platelet Count at Baseline, Weeks 26, 52 and 78
Baseline (n=170)
|
178.653 platelets*10^9 /L
Standard Deviation 92.732
|
—
|
|
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
|
—
|
|
LIP: Mean Platelet Count at Baseline, Weeks 26, 52 and 78
Week 52 (n=74)
|
176.378 platelets*10^9 /L
Standard Deviation 79.880
|
—
|
|
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 outcome
Timeframe: Baseline, Week 26, Week 52, Week 78Population: 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.
Outcome measures
| Measure |
PAP, Eliglustat: Once Daily
n=170 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
PAP, Eliglustat: Twice Daily
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
|---|---|---|
|
LIP: Mean Liver Volume at Baseline, Weeks 26, 52 and 78
Baseline (n=170)
|
1.044 MN
Standard Deviation 0.243
|
—
|
|
LIP: Mean Liver Volume at Baseline, Weeks 26, 52 and 78
Week 26 (n=149)
|
1.040 MN
Standard Deviation 0.229
|
—
|
|
LIP: Mean Liver Volume at Baseline, Weeks 26, 52 and 78
Week 52 (n=68)
|
1.059 MN
Standard Deviation 0.242
|
—
|
|
LIP: Mean Liver Volume at Baseline, Weeks 26, 52 and 78
Week 78 (n=39)
|
1.062 MN
Standard Deviation 0.236
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 26, Week 52, Week 78Population: 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.
Outcome measures
| Measure |
PAP, Eliglustat: Once Daily
n=170 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
PAP, Eliglustat: Twice Daily
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
|---|---|---|
|
LIP: Mean Spleen Volume at Baseline, Weeks 26, 52 and 78
Baseline (n=119)
|
4.448 MN
Standard Deviation 2.314
|
—
|
|
LIP: Mean Spleen Volume at Baseline, Weeks 26, 52 and 78
Week 26 (n=106)
|
3.840 MN
Standard Deviation 1.801
|
—
|
|
LIP: Mean Spleen Volume at Baseline, Weeks 26, 52 and 78
Week 52 (n=52)
|
4.094 MN
Standard Deviation 1.767
|
—
|
|
LIP: Mean Spleen Volume at Baseline, Weeks 26, 52 and 78
Week 78 (n=30)
|
4.088 MN
Standard Deviation 2.089
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 26, Week 52 and Week 78Population: 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.
Chitotriosidase biomarker was assayed from plasma.
Outcome measures
| Measure |
PAP, Eliglustat: Once Daily
n=170 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
PAP, Eliglustat: Twice Daily
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
|---|---|---|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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 outcome
Timeframe: Baseline, Week 26, Week 52 and Week 78Population: 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.
GL-1 on DBS biomarker was assayed from dried blood spot.
Outcome measures
| Measure |
PAP, Eliglustat: Once Daily
n=170 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
PAP, Eliglustat: Twice Daily
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
|---|---|---|
|
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
|
—
|
|
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
|
—
|
|
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 0.730
|
—
|
|
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 1.500
|
—
|
SECONDARY outcome
Timeframe: Baseline and Week 78Population: 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.
MIP1-beta biomarker was assayed from plasma.
Outcome measures
| Measure |
PAP, Eliglustat: Once Daily
n=170 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
PAP, Eliglustat: Twice Daily
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
|---|---|---|
|
LIP: Mean Biomarker (MIP1-beta) Value at Baseline, Week 78
MIP-1beta: Baseline (n=170)
|
142.433 pg/mL
Standard Deviation 125.961
|
—
|
|
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 outcome
Timeframe: Baseline, Week 26, Week 52, Week 78Population: Analysis was performed on AT analysis set which included all participants who received at least 1 dose of eliglustat during LIP.
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.
Outcome measures
| Measure |
PAP, Eliglustat: Once Daily
n=170 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
PAP, Eliglustat: Twice Daily
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
|---|---|---|
|
LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78
MS,Unrestricted: Baseline (n=163)
|
146 participants
|
—
|
|
LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78
MS,Unrestricted: Week 26 (n=161)
|
153 participants
|
—
|
|
LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78
MS,Unrestricted: Week 52 (n=72)
|
70 participants
|
—
|
|
LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78
MS,Unrestricted: Week 78 (n= 41)
|
39 participants
|
—
|
|
LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78
MS, Walks With Difficulty: Baseline (n=163)
|
12 participants
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78
MS, Required wheelchair: Baseline (n=163)
|
2 participants
|
—
|
|
LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78
MS, Required wheelchair: Week 26 (n=161)
|
1 participants
|
—
|
|
LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78
MS, Required wheelchair: Week 52 (n=72)
|
1 participants
|
—
|
|
LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78
MS, Required wheelchair: Week 78 (n=41)
|
0 participants
|
—
|
|
LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78
MS, Bedridden: Baseline (n=163)
|
0 participants
|
—
|
|
LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78
MS, Bedridden: Week 26 (n=161)
|
0 participants
|
—
|
|
LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78
MS, Bedridden: Week 52 (n=72)
|
0 participants
|
—
|
|
LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78
MS, Bedridden: Week 78 (n=41)
|
0 participants
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 26, Week 52, Week 78Population: Analysis was performed on AT analysis set which included all participants who received at least 1 dose of eliglustat during LIP.
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.
Outcome measures
| Measure |
PAP, Eliglustat: Once Daily
n=170 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
PAP, Eliglustat: Twice Daily
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
|---|---|---|
|
LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78
Bone Crisis (0): Baseline (n=162)
|
151 participants
|
—
|
|
LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78
Bone Crisis (0): Week 26 (n=162)
|
159 participants
|
—
|
|
LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78
Bone Crisis (0): Week 52 (n=72)
|
72 participants
|
—
|
|
LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78
Bone Crisis (0): Week 78 (n=41)
|
41 participants
|
—
|
|
LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78
Bone Crisis (1): Baseline (n=162)
|
8 participants
|
—
|
|
LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78
Bone Crisis (1): Week 26 (n=162)
|
3 participants
|
—
|
|
LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78
Bone Crisis (1): Week 52 (n=72)
|
0 participants
|
—
|
|
LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78
Bone Crisis (1): Week 78 (n=41)
|
0 participants
|
—
|
|
LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78
Bone Crisis (2): Baseline (n=162)
|
1 participants
|
—
|
|
LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78
Bone Crisis (2): Week 26 (n=162)
|
0 participants
|
—
|
|
LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78
Bone Crisis (2): Week 52 (n=72)
|
0 participants
|
—
|
|
LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78
Bone Crisis (2): Week 78 (n=41)
|
0 participants
|
—
|
|
LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78
Bone Crisis (6): Baseline (n=162)
|
1 participants
|
—
|
|
LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78
Bone Crisis (6): Week 26 (n=162)
|
0 participants
|
—
|
|
LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78
Bone Crisis (6): Week 52 (n=72)
|
0 participants
|
—
|
|
LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78
Bone Crisis (6): Week 78 (n=41)
|
0 participants
|
—
|
|
LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78
Bone Crisis (24): Baseline (n=162)
|
1 participants
|
—
|
|
LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78
Bone Crisis (24): Week 26 (n=162)
|
0 participants
|
—
|
|
LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78
Bone Crisis (24): Week 52 (n=72)
|
0 participants
|
—
|
|
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 outcome
Timeframe: Baseline, Week 26, Week 52, Week 78Population: Analysis was performed on AT analysis set which included all participants who received at least 1 dose of eliglustat during LIP.
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.
Outcome measures
| Measure |
PAP, Eliglustat: Once Daily
n=170 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
PAP, Eliglustat: Twice Daily
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
|---|---|---|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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 outcome
Timeframe: 1 Year, 2 YearsPopulation: 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.
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.
Outcome measures
| Measure |
PAP, Eliglustat: Once Daily
n=121 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
PAP, Eliglustat: Twice Daily
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
|---|---|---|
|
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
Interval 85.4 to 96.6
|
—
|
|
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
Interval 67.2 to 94.7
|
—
|
|
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
Interval 85.4 to 96.6
|
—
|
|
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
Interval 63.6 to 92.8
|
—
|
|
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
Interval 86.6 to 97.3
|
—
|
|
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
Interval 67.2 to 94.7
|
—
|
|
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
Interval 86.5 to 97.2
|
—
|
|
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
Interval 66.3 to 94.5
|
—
|
|
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
Interval 88.3 to 99.1
|
—
|
|
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
Interval 75.1 to 99.9
|
—
|
SECONDARY outcome
Timeframe: Baseline, 1 year, and 2 yearsPopulation: All participants who received at least one dose of eliglustat during the LTTP.
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.
Outcome measures
| Measure |
PAP, Eliglustat: Once Daily
n=121 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
PAP, Eliglustat: Twice Daily
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
|---|---|---|
|
LTTP: Number of Participants With Mobility Status (MS) at Baseline, 1 Year and 2 Years
MS, Unrestricted: Baseline (n=120)
|
111 participants
|
—
|
|
LTTP: Number of Participants With Mobility Status (MS) at Baseline, 1 Year and 2 Years
MS, Unrestricted: 1 year (n=104)
|
97 participants
|
—
|
|
LTTP: Number of Participants With Mobility Status (MS) at Baseline, 1 Year and 2 Years
MS, Unrestricted: 2 years (n=32)
|
28 participants
|
—
|
|
LTTP: Number of Participants With Mobility Status (MS) at Baseline, 1 Year and 2 Years
MS, Walks with Difficulty: Baseline (n=120)
|
7 participants
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
LTTP: Number of Participants With Mobility Status (MS) at Baseline, 1 Year and 2 Years
MS, Required Wheelchair: Baseline (n=120)
|
2 participants
|
—
|
|
LTTP: Number of Participants With Mobility Status (MS) at Baseline, 1 Year and 2 Years
MS, Required Wheelchair: 1 year (n=104)
|
2 participants
|
—
|
|
LTTP: Number of Participants With Mobility Status (MS) at Baseline, 1 Year and 2 Years
MS, Required Wheelchair: 2 years (n=32)
|
2 participants
|
—
|
|
LTTP: Number of Participants With Mobility Status (MS) at Baseline, 1 Year and 2 Years
MS, Bedridden: Baseline (n=120)
|
0 participants
|
—
|
|
LTTP: Number of Participants With Mobility Status (MS) at Baseline, 1 Year and 2 Years
MS, Bedridden: 1 year (n=104)
|
0 participants
|
—
|
|
LTTP: Number of Participants With Mobility Status (MS) at Baseline, 1 Year and 2 Years
MS, Bedridden: 2 years (n=32)
|
0 participants
|
—
|
SECONDARY outcome
Timeframe: Baseline, 1 year and 2 yearsPopulation: All participants who received at least one dose of eliglustat during the LTTP.
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.
Outcome measures
| Measure |
PAP, Eliglustat: Once Daily
n=121 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
PAP, Eliglustat: Twice Daily
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
|---|---|---|
|
LTTP: Number of Participants With Bone Crises Assessment at Baseline, 1 Year and 2 Years
Bone Crisis (0): Baseline (n=120)
|
119 participants
|
—
|
|
LTTP: Number of Participants With Bone Crises Assessment at Baseline, 1 Year and 2 Years
Bone Crisis (0): 1 year (n=104)
|
104 participants
|
—
|
|
LTTP: Number of Participants With Bone Crises Assessment at Baseline, 1 Year and 2 Years
Bone Crisis (0): 2 years (n=32)
|
32 participants
|
—
|
|
LTTP: Number of Participants With Bone Crises Assessment at Baseline, 1 Year and 2 Years
Bone Crisis (1): Baseline (n=120)
|
1 participants
|
—
|
|
LTTP: Number of Participants With Bone Crises Assessment at Baseline, 1 Year and 2 Years
Bone Crisis (1): 1 year (n=104)
|
0 participants
|
—
|
|
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 outcome
Timeframe: Baseline, 1 year and 2 yearsPopulation: All participants who received at least one dose of eliglustat during the LTTP.
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.
Outcome measures
| Measure |
PAP, Eliglustat: Once Daily
n=121 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
PAP, Eliglustat: Twice Daily
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
|---|---|---|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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 outcome
Timeframe: Baseline, 1 year, and 2 yearsPopulation: All participants who received at least one dose of eliglustat during the LTTP.
BMD measurements of the spine and bilateral femur were acquired by DXA scan.
Outcome measures
| Measure |
PAP, Eliglustat: Once Daily
n=121 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
PAP, Eliglustat: Twice Daily
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
|---|---|---|
|
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
|
—
|
|
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
|
—
|
|
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 0.190
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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 0.220
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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 outcome
Timeframe: Baseline, 1 year, and 2 yearsPopulation: All participants who received at least one dose of eliglustat during the LTTP.
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).
Outcome measures
| Measure |
PAP, Eliglustat: Once Daily
n=121 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
PAP, Eliglustat: Twice Daily
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
|---|---|---|
|
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
|
—
|
|
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
|
—
|
|
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 1.370
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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 1.360
|
—
|
|
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
|
—
|
|
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 outcome
Timeframe: Baseline, 1 year, and 2 yearsPopulation: All participants who received at least one dose of eliglustat during the LTTP.
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).
Outcome measures
| Measure |
PAP, Eliglustat: Once Daily
n=121 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
PAP, Eliglustat: Twice Daily
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
|---|---|---|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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 1.270
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
SECONDARY outcome
Timeframe: Baseline, 1 year, and 2 yearsPopulation: All participants who received at least one dose of eliglustat during the LTTP.
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.
Outcome measures
| Measure |
PAP, Eliglustat: Once Daily
n=121 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
PAP, Eliglustat: Twice Daily
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
|---|---|---|
|
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
|
—
|
|
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
|
—
|
|
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 outcome
Timeframe: Baseline, 1 year, and 2 yearsPopulation: All participants who received at least one dose of eliglustat during the LTTP.
Chitotriosidase biomarker was assayed from plasma.
Outcome measures
| Measure |
PAP, Eliglustat: Once Daily
n=121 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
PAP, Eliglustat: Twice Daily
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
|---|---|---|
|
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
|
—
|
|
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
|
—
|
|
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 outcome
Timeframe: Baseline, 1 year, and 2 yearsPopulation: All participants who received at least one dose of eliglustat during the LTTP.
GL-1 on DBS biomarker was assayed from dried blood spot.
Outcome measures
| Measure |
PAP, Eliglustat: Once Daily
n=121 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
PAP, Eliglustat: Twice Daily
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
|---|---|---|
|
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 1.350
|
—
|
|
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
|
—
|
|
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 outcome
Timeframe: Baseline, 1 year, and 2 yearsPopulation: All participants who received at least one dose of eliglustat during the LTTP.
MIP1-beta biomarker was assayed from plasma.
Outcome measures
| Measure |
PAP, Eliglustat: Once Daily
n=121 Participants
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat at the TDD of 100 mg or 200 mg (the TDD they were on before randomization) QD from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
PAP, Eliglustat: Twice Daily
All participants who were randomized after either 26, 52 or 78 weeks of LIP received eliglustat 50 mg BID or 100 mg BID (the TDD they were on before randomization) from Day 1 up to Week 52 in PAP (50 or 100 mg capsules).
|
|---|---|---|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
Adverse Events
Eliglustat
Serious events: 40 serious events
Other events: 144 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Eliglustat
n=170 participants at risk
All participants who received eliglustat at the TDD of 100 mg or 200 mg in the LIP, PAP, LTTP or ETP.
|
|---|---|
|
Cardiac disorders
Angina pectoris
|
1.2%
2/170
Adverse events data was planned to be reported for overall population.
|
|
Cardiac disorders
Arrhythmia
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
Cardiac disorders
Cardiac arrest
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
Gastrointestinal disorders
Abdominal wall haematoma
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
Gastrointestinal disorders
Mallory-Weiss syndrome
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
General disorders
Device dislocation
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
General disorders
Disuse syndrome
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
General disorders
Hernia
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
General disorders
Impaired healing
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
General disorders
Medical device pain
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
Hepatobiliary disorders
Cholecystitis
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
Hepatobiliary disorders
Cholecystitis chronic
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
Infections and infestations
Acute hepatitis B
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
Infections and infestations
Appendicitis
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
Infections and infestations
Hepatitis A
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
Infections and infestations
Staphylococcal sepsis
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
Injury, poisoning and procedural complications
Fall
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
1.2%
2/170
Adverse events data was planned to be reported for overall population.
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
Injury, poisoning and procedural complications
Forearm fracture
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
Injury, poisoning and procedural complications
Incisional hernia
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
Injury, poisoning and procedural complications
Injury
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
Injury, poisoning and procedural complications
Radius fracture
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
Injury, poisoning and procedural complications
Spinal fracture
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
Investigations
Hepatic enzyme increased
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
1.2%
2/170
Adverse events data was planned to be reported for overall population.
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
Musculoskeletal and connective tissue disorders
Joint range of motion decreased
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
1.8%
3/170
Adverse events data was planned to be reported for overall population.
|
|
Musculoskeletal and connective tissue disorders
Osteonecrosis
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lipoma
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Papillary thyroid cancer
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
Nervous system disorders
Dizziness
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
Nervous system disorders
Epilepsy
|
1.2%
2/170
Adverse events data was planned to be reported for overall population.
|
|
Nervous system disorders
Ischaemic stroke
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
Nervous system disorders
Presyncope
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
Nervous system disorders
Seizure
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
Nervous system disorders
Syncope
|
1.8%
3/170
Adverse events data was planned to be reported for overall population.
|
|
Pregnancy, puerperium and perinatal conditions
Ectopic pregnancy
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
Psychiatric disorders
Conversion disorder
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
Psychiatric disorders
Major depression
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
Renal and urinary disorders
Calculus urinary
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
Reproductive system and breast disorders
Uterine polyp
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
Vascular disorders
Aortic aneurysm
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
Vascular disorders
Haemorrhage
|
0.59%
1/170
Adverse events data was planned to be reported for overall population.
|
|
Vascular disorders
Hypertension
|
1.2%
2/170
Adverse events data was planned to be reported for overall population.
|
Other adverse events
| Measure |
Eliglustat
n=170 participants at risk
All participants who received eliglustat at the TDD of 100 mg or 200 mg in the LIP, PAP, LTTP or ETP.
|
|---|---|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
5.3%
9/170
Adverse events data was planned to be reported for overall population.
|
|
Cardiac disorders
Palpitations
|
6.5%
11/170
Adverse events data was planned to be reported for overall population.
|
|
Gastrointestinal disorders
Abdominal distension
|
5.3%
9/170
Adverse events data was planned to be reported for overall population.
|
|
Gastrointestinal disorders
Abdominal pain
|
8.8%
15/170
Adverse events data was planned to be reported for overall population.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
15.3%
26/170
Adverse events data was planned to be reported for overall population.
|
|
Gastrointestinal disorders
Constipation
|
9.4%
16/170
Adverse events data was planned to be reported for overall population.
|
|
Gastrointestinal disorders
Diarrhoea
|
14.1%
24/170
Adverse events data was planned to be reported for overall population.
|
|
Gastrointestinal disorders
Dyspepsia
|
11.2%
19/170
Adverse events data was planned to be reported for overall population.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
5.3%
9/170
Adverse events data was planned to be reported for overall population.
|
|
Gastrointestinal disorders
Nausea
|
10.6%
18/170
Adverse events data was planned to be reported for overall population.
|
|
Gastrointestinal disorders
Vomiting
|
8.2%
14/170
Adverse events data was planned to be reported for overall population.
|
|
General disorders
Fatigue
|
10.0%
17/170
Adverse events data was planned to be reported for overall population.
|
|
General disorders
Pyrexia
|
9.4%
16/170
Adverse events data was planned to be reported for overall population.
|
|
Hepatobiliary disorders
Hepatomegaly
|
5.3%
9/170
Adverse events data was planned to be reported for overall population.
|
|
Infections and infestations
Gastroenteritis
|
8.8%
15/170
Adverse events data was planned to be reported for overall population.
|
|
Infections and infestations
Influenza
|
13.5%
23/170
Adverse events data was planned to be reported for overall population.
|
|
Infections and infestations
Nasopharyngitis
|
30.6%
52/170
Adverse events data was planned to be reported for overall population.
|
|
Infections and infestations
Upper respiratory tract infection
|
12.9%
22/170
Adverse events data was planned to be reported for overall population.
|
|
Infections and infestations
Urinary tract infection
|
8.2%
14/170
Adverse events data was planned to be reported for overall population.
|
|
Infections and infestations
Viral infection
|
5.9%
10/170
Adverse events data was planned to be reported for overall population.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
17.6%
30/170
Adverse events data was planned to be reported for overall population.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
17.1%
29/170
Adverse events data was planned to be reported for overall population.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
5.9%
10/170
Adverse events data was planned to be reported for overall population.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
6.5%
11/170
Adverse events data was planned to be reported for overall population.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
14.1%
24/170
Adverse events data was planned to be reported for overall population.
|
|
Nervous system disorders
Dizziness
|
16.5%
28/170
Adverse events data was planned to be reported for overall population.
|
|
Nervous system disorders
Headache
|
21.8%
37/170
Adverse events data was planned to be reported for overall population.
|
|
Psychiatric disorders
Depression
|
5.9%
10/170
Adverse events data was planned to be reported for overall population.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
12.4%
21/170
Adverse events data was planned to be reported for overall population.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
7.6%
13/170
Adverse events data was planned to be reported for overall population.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
10.6%
18/170
Adverse events data was planned to be reported for overall population.
|
|
Vascular disorders
Hypertension
|
5.3%
9/170
Adverse events data was planned to be reported for overall population.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER