A Study of Eliglustat Tartrate (Genz-112638) in Patients With Gaucher Disease to Evaluate Once Daily Versus Twice Daily Dosing (EDGE)
Sponsor
Genzyme, a Sanofi Company (Industry)
Overall Status
Completed
CT.gov ID
NCT01074944
Collaborator
(none)
170
46
2
64
3.7
0.1
Study Details
Study Description
Brief Summary
The primary objective of this study was to evaluate the efficacy and safety of once daily (QD) versus twice daily (BID) dosing of eliglustat tartrate (Genz-112638) in participants with Gaucher disease type 1 who had demonstrated clinical stability on BID dosing of eliglustat tartrate (Genz-112638). The secondary objective was to evaluate the pharmacokinetics (PK) of Genz-99067 when eliglustat tartrate (Genz-112638) was administered QD and BID in participants with Gaucher disease type 1 who had demonstrated clinical stability on BID dosing of eliglustat tartrate (Genz-112638).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
NOTE: Other Phase 3 studies being conducted with eliglustat tartrate (Genz-112638) are GZGD02507 (ENGAGE): NCT00891202 and GZGD02607 (ENCORE): NCT00943111
Study Design
Study Type:
Interventional
Actual Enrollment
:
170 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Randomized, Multi-Center, Multi-National, Double-Blind Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Once Daily Versus Twice Daily Dosing of Genz-112638 in Patients With Gaucher Disease Type 1 Who Have Demonstrated Clinical Stability on a Twice Daily Dose of Genz-112638
Study Start Date
:
Jun 1, 2010
Actual Primary Completion Date
:
Oct 1, 2015
Actual Study Completion Date
:
Oct 1, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Twice Daily (BID) Dose Regimen Patients will receive either 50 mg BID or 100 mg BID |
Drug: Eliglustat tartrate
Oral Capsule in 50 mg or 100 mg dosages
Other Names:
|
| Experimental: Once Daily (QD) Dose Regimen Patients will receive either 100 mg QD or 200 mg QD |
Drug: Eliglustat tartrate
Oral Capsule in 50 mg or 100 mg dosages
Other Names:
|
Outcome Measures
Primary Outcome Measures
- PAP: Percentage of Participants Who Remained Stable for 52 Weeks During the PAP [PAP Baseline up to the end of PAP (Week 52)]
Participants were considered as stable if they met all of the following criteria: 1) no more than 2 bone crisis during PAP (with no more than 1 bone crisis during either the first 6 months or the later 6 months of the period), and were free of other clinically symptomatic bone disease during the entire 52-week PAP; 2) hemoglobin level not decreased >1.5 g/dL from Baseline for PAP; 3) platelet count not decreased >25% from Baseline for PAP; 4) spleen volume (in multiples of normal [MN]) did not increase >25% from Baseline for PAP; 5) liver volume (in MN) did not increase >20% from Baseline for PAP. Baseline for PAP was defined as the last assessment prior to randomization.
Secondary Outcome Measures
- PAP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26 and 52 [Baseline, Week 26, Week 52]
- PAP: Mean Platelet Count at Baseline, Weeks 26, 52 [Baseline, Week 26, Week 52]
- PAP: Mean Spleen Volume at Baseline, Weeks 26, 52 [Baseline, Week 26, Week 52]
- PAP: Mean Liver Volume at Baseline, Weeks 26, 52 [Baseline, Week 26 and Week 52]
- PAP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26 and Week 52 [Baseline, Week 26, Week 52]
Chitotriosidase biomarker was assayed from plasma.
- PAP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26 and Week 52 [Baseline, Week 26 and week 52]
GL-1 on DBS biomarker was assayed from dried blood spot (DBS).
- PAP: Mean Biomarker Macrophage Inflammatory Protein-1 Beta (MIP1-beta) Value at Baseline, Weeks 26, 52 [Baseline, Week 26, Week 52]
MIP1-beta biomarker was assayed from plasma.
- PAP: Bone Mineral Density (BMD) at Baseline and Week 52 [Baseline, Week 52]
BMD measurements of the spine and bilateral femur were acquired by dual-energy x-ray absorptiometry (DXA) scan.
- PAP: Total T-Scores for BMD at Baseline and Week 52 [Baseline, Week 52]
Images of the spine and bilateral femur were obtained by DXA to determine T-score for each bone area and total bone mineral density. The T-score bone density categories were: normal (score >-1), osteopenia (score -2.5 to <=-1), and osteoporosis (score <= -2.5).
- PAP: Total Z-scores for BMD at Baseline and Week 52 [Baseline, Week 52]
Images of the spine and bilateral femur were obtained by DXA to determine Z-score for each bone area and total bone mineral density. The Z-score bone density categories are: normal (score >-2) and below normal (score <=-2).
- PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52. [Baseline, Week 26 and Week 52]
Mobility, i.e., ability to walk was assessed as a part of Gaucher disease assessment in participants. In this outcome, number of participants with their different mobility status along with the use of mobility aids (unrestricted mobility, walks with difficulty, walks with orthopaedic aid, requires wheelchair, bedridden) at specified time points were reported.
- PAP: Number of Participants With Bone Crises at Baseline, Weeks 26 and 52 [Baseline, Week 26, and Week 52]
Bone crisis was assessed as a part of Gaucher disease assessment in participants. Acute, excruciating episodic bone pain is characteristic of Gaucher bone crisis, which typically causes debilitation lasting several days or longer and requires treatment with immobilization, hydration, and opioid analgesics. Participants were categorized as 0= no bone crisis, 1= 1 bone crisis, and 2= 2 bone crises during the assessment period. In this outcome, number of participants with different bone crises levels at specified time points were reported.
- PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 [Baseline, Week 26, and Week 52]
Bone pain was assessed as a part of Gaucher disease assessment in participants. Participants were categorized as none (no bone pain), very mild bone pain, mild bone pain, moderate bone pain, severe bone pain and extreme bone pain during the past 4 weeks. In this outcome, number of participants with different level of bone pain during the past 4 weeks at specified time points were reported.
- PAP: Total Bone Marrow Burden Score (BMB) at Baseline and Week 52 [Baseline, Week 52]
BMB Score was measured using magnetic resonance imaging (MRI), range from 0 (no abnormalities) to 8 points (severe disease) for the lumbar spine and from 0 (no abnormalities) to 8 points (severe disease) for the femurs. The total score was calculated as the sum of scores for femur and lumbar spine regions which ranged from 0 (no abnormalities) -16 (severe disease) points. A higher BMB score signified more severe bone marrow involvement.
- LIP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26, 52 and 78 [Baseline, Week 26, Week, 52, and Week 78]
- LIP: Mean Platelet Count at Baseline, Weeks 26, 52 and 78 [Baseline, Week 26, Week 52, Week 78]
- LIP: Mean Liver Volume at Baseline, Weeks 26, 52 and 78 [Baseline, Week 26, Week 52, Week 78]
- LIP: Mean Spleen Volume at Baseline, Weeks 26, 52 and 78 [Baseline, Week 26, Week 52, Week 78]
- LIP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26, 52, and 78 [Baseline, Week 26, Week 52 and Week 78]
Chitotriosidase biomarker was assayed from plasma.
- LIP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26, Week 52, and Week 78 [Baseline, Week 26, Week 52 and Week 78]
GL-1 on DBS biomarker was assayed from dried blood spot.
- LIP: Mean Biomarker (MIP1-beta) Value at Baseline, Week 78 [Baseline and Week 78]
MIP1-beta biomarker was assayed from plasma.
- LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78 [Baseline, Week 26, Week 52, Week 78]
Mobility, i.e., ability to walk was assessed as a part of Gaucher disease assessment in participants. In this outcome, number of participants with their different mobility status along with the use of mobility aids (unrestricted mobility, walks with difficulty, walks with orthopaedic aid, requires wheelchair, bedridden) at specified time points were reported.
- LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78 [Baseline, Week 26, Week 52, Week 78]
Bone crises was assessed as a part of Gaucher disease assessment in participants. Acute, excruciating episodic bone pain is characteristic of Gaucher bone crises, which typically causes debilitation lasting several days or longer and requires treatment with immobilization, hydration, and opioid analgesics. Participants were categorized as 0= no bone crisis, 1= 1 bone crisis, 2= 2 bone crises, 6= 6 bone crises, and 24= 24 bone crises during the assessment period. In this outcome, number of participants with different bone crises levels at specified time points were reported.
- LIP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78 [Baseline, Week 26, Week 52, Week 78]
Bone pain was assessed as a part of Gaucher disease assessment in participants. Participants were categorized as none (no bone pain), very mild bone pain, mild bone pain, moderate bone pain, severe bone pain and extreme bone pain. In this outcome, number of participants with different type of bone pain during the past 4 weeks at specified time points were reported.
- LTTP: Percentage of Participants Who Maintained a Stable Bone Criterion ,Hemoglobin Level, Platelet Count, Liver Volume and Spleen Volume at 1 Year and 2 Years [1 Year, 2 Years]
Participant were considered as stable if they met the following criteria: hemoglobin level did not decrease >1.5 g/dL from baseline for PAP, platelet count does not decrease >25% below Baseline for PAP, liver volume does not increase >20% above Baseline for PAP, spleen volume does not increase >25% above Baseline for PAP. Baseline for PAP was defined as last available assessment prior to randomization.
- LTTP: Number of Participants With Mobility Status (MS) at Baseline, 1 Year and 2 Years [Baseline, 1 year, and 2 years]
Mobility, i.e., ability to walk was assessed as a part of Gaucher disease assessment in participants. In this outcome, number of participants with their different mobility status along with the use of mobility aids (unrestricted mobility, walks with difficulty, walks with orthopaedic aid, requires wheelchair, bedridden) at specified time points were reported.
- LTTP: Number of Participants With Bone Crises Assessment at Baseline, 1 Year and 2 Years [Baseline, 1 year and 2 years]
Bone crises was assessed as a part of Gaucher disease assessment in participants. Acute, excruciating episodic bone pain is characteristic of Gaucher bone crises, which typically causes debilitation lasting several days or longer and requires treatment with immobilization, hydration, and opioid analgesics. Participants were categorized as 0= no bone crises, 1= 1 bone crisis during the assessment period. In this outcome, number of participants with different bone crises levels at specified time points were reported.
- LTTP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, 1 Year, and 2 Years [Baseline, 1 year and 2 years]
Bone pain was assessed as a part of Gaucher disease assessment in participants. Participants were categorized as none (no bone pain), very mild bone pain, mild bone pain, moderate bone pain, severe bone pain and extreme bone pain. In this outcome, number of participants with different level of bone pain during the past 4 weeks at specified time points were reported.
- LTTP: Bone Mineral Density (BMD) at Baseline, 1 Year, and 2 Years [Baseline, 1 year, and 2 years]
BMD measurements of the spine and bilateral femur were acquired by DXA scan.
- LTTP: Total T-Scores for BMD at Baseline, 1 Year, and 2 Years [Baseline, 1 year, and 2 years]
Images of the spine and bilateral femur were obtained by DXA to determine T-score for each bone area and total bone mineral density. The T-score bone density categories were: normal (score >-1), osteopenia (score -2.5 to <=-1), and osteoporosis (score <= -2.5).
- LTTP: Total Z-scores for BMD at Baseline, 1 Year, and 2 Years [Baseline, 1 year, and 2 years]
Images of the spine and bilateral femur were obtained by DXA to determine Z-score for each bone area and total bone mineral density. The Z-score bone density categories are: normal (score >-2) and below normal (score <=-2).
- LTTP: Total Bone Marrow Burden Score (BMB) at Baseline, 1 Year, and 2 Years [Baseline, 1 year, and 2 years]
BMB Score was measured using MRI, range from 0 (no abnormalities) to 8 points (severe disease) for the lumbar spine and from 0 (no abnormalities) to 8 points (severe disease) for the femurs. The total score was calculated as the sum of scores for femur and lumbar spine regions which ranged from 0 (no abnormalities) -16 (severe disease) points. A higher BMB score signified more severe bone marrow involvement.
- LTTP: Mean Biomarker (Chitotriosidase) Value at Baseline, 1 Year, and 2 Years [Baseline, 1 year, and 2 years]
Chitotriosidase biomarker was assayed from plasma.
- LTTP: Mean Biomarker (GL-1 on DBS) Value at Baseline, 1 Year, and 2 Years [Baseline, 1 year, and 2 years]
GL-1 on DBS biomarker was assayed from dried blood spot.
- LTTP: Mean Biomarker (MIP1-beta) Value at Baseline, 1 Year, and 2 Years [Baseline, 1 year, and 2 years]
MIP1-beta biomarker was assayed from plasma.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
The participant who was willing and provided signed informed consent prior to any study-related procedures.
-
The participant was ≥18 years of age.
-
The participant diagnosed with GD 1 confirmed by a documented deficiency of acid β-glucosidase activity by enzyme assay.
-
Female participants of childbearing potential had a documented negative pregnancy test prior to administration of the first dose of eliglustat tartrate (Genz-112638) in this study. In addition, all female participants of childbearing potential used a medically accepted form of contraception throughout the study, i.e., either a barrier method or hormonal contraceptive with norethindrone and ethinyl estradiol or similar active components
-
The participant met all of the following criteria at the time of screening: hemoglobin level ≥9 g/dL (mean of 2 measurements); platelet count ≥70,000/mm^3 (mean of 2 measurements); spleen volume ≤25 multiples of normal (MN); liver volume ≤2.0 MN.
-
The participant consented to provide a blood sample for genotyping for Gaucher disease and for CYP2D6 to categorize the participant's predicted rate of metabolism, if these genotyping results were not already available for the participant.
-
The participant was willing to abstain from consumption of grapefruit, grapefruit juice, or grapefruit products for 72 hours prior to administration of the first dose of Genz-112638 and throughout the duration of the study.
Exclusion Criteria:
-
The participant was participating in GZGD02607 study, "A Phase 3, Randomized, Multi-Center, Multi-National, Open-Label, Active Comparator Study to Evaluate the Efficacy and Safety of Genz-112638 in Participants with GD1 who have been Stabilized with Cerezyme ® ," or was eligible for inclusion in GZGD02607 (while enrollment was ongoing) and had access to a physician participating in GZGD02607, or the participant was participating in GZGD02507 study, "A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study Confirming the Efficacy and Safety of Genz-112638 in Participants with GD1," or was eligible for inclusion in GZGD02507 (while enrollment was ongoing) and had access to a physician participating in GZGD02507.
-
The participant received miglustat within 6 months prior to administration of the first dose of Genz-112638 in this study.
-
The participant had a partial or total splenectomy within 3 years prior to randomization.
-
The participant received pharmacological chaperones or miglustat within 6 months prior to administration of the first dose of eliglustat tartrate (Genz-112638) in this study.
-
The participant had any evidence of neurologic disorder (e.g., peripheral neuropathy, tremor, seizures, Parkinsonism or cognitive impairment) or pulmonary involvement (e.g., pulmonary hypertension) as related to Gaucher disease.
-
The participant was transfusion-dependent.
-
The participant had a documented deficiency of iron, vitamin B-12, or folate that requires treatment not yet initiated or, if initiated, the participant had not been stable under treatment for at least 3 months prior to administration of the first dose of Genz-112638 in this study.
-
The participant had documented prior esophageal varices or clinically significant liver infarction or current liver enzymes (alanine transaminase [ALT]/aspartate aminotransferase [AST]) or total bilirubin >2 times the upper limit of normal (ULN), unless the participant had a diagnosis of Gilbert Syndrome.
-
The participant had any clinically significant disease, other than Gaucher disease, including cardiovascular, renal, hepatic, gastrointestinal, pulmonary, neurologic, endocrine, metabolic (including hypokalaemia or hypomagnesemia), or psychiatric disease, other medical conditions, or serious intercurrent illnesses that, in the opinion of the Investigator, precluded participation in the study.
-
The participant was known to have any of the following: Clinically significant coronary artery disease including history of myocardial infarction [MI] or ongoing signs or symptoms consistent with cardiac ischemia or heart failure; or clinically significant arrhythmias or conduction defect such as 2nd or 3rd degree AV block, complete bundle branch block, prolonged QTc interval, or sustained ventricular tachycardia (VT).
-
The participant who tested positive for the human immunodeficiency virus (HIV) antibody, Hepatitis C antibody, or Hepatitis B surface antigen.
-
The participant received an investigational product (other than eliglustat tartrate (Genz-112638)) within 30 days prior to administration of the first dose of eliglustat tartrate (Genz-112638) in this study.
-
The participant was scheduled for in-participant hospitalization, including elective surgery, during the study.
-
The participant had a history of cancer, with the exception of basal cell carcinoma, within 5 years prior to administration of the first dose of Genz-112638 in this study.
-
The participant was pregnant or lactating.
-
The participant had received any medication that may cause QTc interval prolongation within 30 days prior to the first dose of Genz-112638. Exception: Diphenhydramine (Benadryl) or other medications used as premedication for ERT infusions were allowed up to 7 days prior to the first dose of Genz-112638.
-
The participant had received for the first time (i.e., the participant was not already chronically using) any of the following medications within 30 days prior to the first dose of Genz-112638:
-
Strong inhibitors of CYP2D6 or CYP3A4;
-
Inducers of CYP3A4. Exception: Premedications for ERT infusions were allowed up to 7 days prior to the first dose of Genz-112638.
-
The participant was a CYP2D6 non-poor metabolizer or an indeterminate metabolizer with one allele identified as active who was chronically receiving both a strong competitive inhibitor of CYP2D6 and a strong competitive inhibitor of CYP3A4 and for whom no reasonable alternative medication exists. or
-
The participant was a CYP2D6 poor metabolizer or an indeterminate metabolizer with neither allele known to be active who was chronically receiving a strong competitive inhibitor of CYP3A4 and for whom no reasonable alternative medication exists.
Exception for both cases: Premedications for ERT infusions were allowed up to 7 days prior to the first dose of Genz-112638.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of California, San Diego Medical Center | San Diego | California | United States | |
| 2 | Yale University School of Medicine | New Haven | Connecticut | United States | |
| 3 | Emory University Medical Center | Decatur | Georgia | United States | |
| 4 | Children's Memorial Hospital | Chicago | Illinois | United States | |
| 5 | Mount Sinai Medical Center | New York | New York | United States | |
| 6 | New York University School of Medicine | New York | New York | United States | |
| 7 | Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | United States | |
| 8 | Children's Hospital of Pittsburgh | Pittsburgh | Pennsylvania | United States | |
| 9 | University of Utah | Salt Lake City | Utah | United States | |
| 10 | O and O Alpan LLC | Springfield | Virginia | United States | |
| 11 | Royal Prince Alfred Hospital | Camperdown | Australia | ||
| 12 | Monash Medical Centre | Clayton, VIC | Australia | ||
| 13 | Royal Perth Hospital | Perth, WA | Australia | ||
| 14 | Medical University Vienna | Vienna | Austria | ||
| 15 | Hospital das Clinicas da UFMG | Belo Horizonte | Brazil | ||
| 16 | Cettro - Centro de Tratamento de Oncologia e Hematologia | Brasília | Brazil | ||
| 17 | Hemocentro - UNICAMP | Campinas | Brazil | ||
| 18 | Instituto Tropical de Medicina Reprodutiva e Menopausa - INTRO | Cuiaba | Brazil | ||
| 19 | Hospital Universitario Walter Cantidio - HUWC | Fortaleza | Brazil | ||
| 20 | Hemocentro de Ribeirão Preto Núcleo de Hemoterapia de Franca | Franca | Brazil | ||
| 21 | Hemorio | Rio de Janeiro | Brazil | ||
| 22 | Hospital de Clínicas da Universidade Federal do Parana | Sao Paulo | Brazil | ||
| 23 | IGEIM - Institute of Genetic and Inborn Erros of Metabolism | Sao Paulo | Brazil | ||
| 24 | Mount Sinai Hospital | Toronto | Canada | ||
| 25 | Peking Union Medical College Hospital | Beijing | China | ||
| 26 | Peking University People's Hospital | Beijing | China | ||
| 27 | Shanghai Xinhua Hospital Shanghai Xinhua Hospital | Shanghai | China | ||
| 28 | Tianjin Hematonosis Hospital | Tianjin | China | ||
| 29 | University Hospital Centre Zagreb | Zagreb | Croatia | ||
| 30 | Hôpital Haut Lévêque | Bordeaux | France | ||
| 31 | Hôpital Femme Mère Enfant Centre de référence des maladies Héréditaires du métabolisme | Bron | France | ||
| 32 | General Hospital of Athens "G. Gennimatas" | Athens | Greece | ||
| 33 | King Edward Memorial (KEM) Hospital | Mumbai | India | ||
| 34 | Hiroshima University Hospital | Hiroshima | Japan | ||
| 35 | Jikei University Hospital | Tokyo | Japan | ||
| 36 | Juntendo University Hospital | Tokyo | Japan | ||
| 37 | Mie Chuou Medical Center | Tsu, Mie | Japan | ||
| 38 | Academic Medical Center | Amsterdam | Netherlands | ||
| 39 | Hospital de Santa Maria | Lisboa | Portugal | ||
| 40 | Hospital do Divíno Espírito Santo | Ponta Delgada - São Miguel - Açores | Portugal | ||
| 41 | Spitaulu Clinic de Urgenta | Cluj-Napoca | Romania | ||
| 42 | State Medical and Prophylactic Healthcare Institution; Chelyabinsk Regional Clinical Hospital | Chelyabinsk | Russian Federation | ||
| 43 | Hematology Research Center of Russian Academy of Medical Sciences | Moscow | Russian Federation | ||
| 44 | St. Petersburg State Medical Pavlov University | St. Petersburg | Russian Federation | ||
| 45 | Clinical Centre of Serbia | Belgrade | Serbia | ||
| 46 | University Hospital Lund | Lund | Sweden |
Sponsors and Collaborators
- Genzyme, a Sanofi Company
Investigators
- Study Director: Medical Monitor, Genzyme, a Sanofi Company
Study Documents (Full-Text)
None provided.More Information
Additional Information:
- GZGD02507 (NCT00891202) eliglustat tartrate (Genz-112638) Phase 3 Clinical Study in untreated patients with Gaucher disease type 1
- GZGD02607 (NCT00943111) eliglustat tartrate (Genz-112638) Phase 3 Clinical Study in patients with Gaucher disease type 1 who have been stabilized on Cerezyme
Publications
- Lukina E, Watman N, Arreguin EA, Banikazemi M, Dragosky M, Iastrebner M, Rosenbaum H, Phillips M, Pastores GM, Rosenthal DI, Kaper M, Singh T, Puga AC, Bonate PL, Peterschmitt MJ. A phase 2 study of eliglustat tartrate (Genz-112638), an oral substrate reduction therapy for Gaucher disease type 1. Blood. 2010 Aug 12;116(6):893-9. doi: 10.1182/blood-2010-03-273151. Epub 2010 May 3.
- Lukina E, Watman N, Arreguin EA, Dragosky M, Iastrebner M, Rosenbaum H, Phillips M, Pastores GM, Kamath RS, Rosenthal DI, Kaper M, Singh T, Puga AC, Peterschmitt MJ. Improvement in hematological, visceral, and skeletal manifestations of Gaucher disease type 1 with oral eliglustat tartrate (Genz-112638) treatment: 2-year results of a phase 2 study. Blood. 2010 Nov 18;116(20):4095-8. doi: 10.1182/blood-2010-06-293902. Epub 2010 Aug 16. Erratum in: Blood. 2011 May 19;117(20):5551.
- McEachern KA, Fung J, Komarnitsky S, Siegel CS, Chuang WL, Hutto E, Shayman JA, Grabowski GA, Aerts JM, Cheng SH, Copeland DP, Marshall J. A specific and potent inhibitor of glucosylceramide synthase for substrate inhibition therapy of Gaucher disease. Mol Genet Metab. 2007 Jul;91(3):259-67. Epub 2007 May 16.
Responsible Party:
Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier:
NCT01074944
Other Study ID Numbers:
- GZGD03109
- 2009-015811-42
- EFC12818
First Posted:
Feb 24, 2010
Last Update Posted:
Feb 6, 2017
Last Verified:
Dec 1, 2016
Keywords provided by Genzyme, a Sanofi Company
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | The study was conducted at 45 centers in 17 countries between 1 June 2010 and 6 October 2015. A total of 219 participants were screened, out of which 170 entered into the lead in period (LIP). Remaining 48 participants were screen failures and 1 participant withdrew before entering into the LIP. |
|---|---|
| Pre-assignment Detail | 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. |
| Arm/Group Title | LIP, Eliglustat | PAP, Eliglustat: Once Daily | PAP, Eliglustat: Twice Daily | LTTP, Eliglustat | ETP, Eliglustat |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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). | 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). | 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. | 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. |
| Period Title: Lead-in Period (up to 78 Weeks) | |||||
| STARTED | 170 | 0 | 0 | 0 | 0 |
| COMPLETED | 157 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 13 | 0 | 0 | 0 | 0 |
| Period Title: Lead-in Period (up to 78 Weeks) | |||||
| STARTED | 0 | 65 | 66 | 0 | 0 |
| COMPLETED | 0 | 54 | 60 | 0 | 0 |
| NOT COMPLETED | 0 | 11 | 6 | 0 | 0 |
| Period Title: Lead-in Period (up to 78 Weeks) | |||||
| STARTED | 0 | 0 | 0 | 121 | 0 |
| COMPLETED | 0 | 0 | 0 | 95 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 26 | 0 |
| Period Title: Lead-in Period (up to 78 Weeks) | |||||
| STARTED | 0 | 0 | 0 | 0 | 25 |
| COMPLETED | 0 | 0 | 0 | 0 | 20 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 5 |
Baseline Characteristics
| Arm/Group Title | All Participants |
|---|---|
| Arm/Group Description | 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. |
| Overall Participants | 170 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
37.7
(15.1)
|
| Gender (Count of Participants) | |
| Female |
81
47.6%
|
| Male |
89
52.4%
|
Outcome Measures
| Title | PAP: Percentage of Participants Who Remained Stable for 52 Weeks During the PAP |
|---|---|
| Description | Participants were considered as stable if they met all of the following criteria: 1) no more than 2 bone crisis during PAP (with no more than 1 bone crisis during either the first 6 months or the later 6 months of the period), and were free of other clinically symptomatic bone disease during the entire 52-week PAP; 2) hemoglobin level not decreased >1.5 g/dL from Baseline for PAP; 3) platelet count not decreased >25% from Baseline for PAP; 4) spleen volume (in multiples of normal [MN]) did not increase >25% from Baseline for PAP; 5) liver volume (in MN) did not increase >20% from Baseline for PAP. Baseline for PAP was defined as the last assessment prior to randomization. |
| Time Frame | PAP Baseline up to the end of PAP (Week 52) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on per protocol (PP) population which included all participants who were at least 80% compliant with investigational medicinal product (IMP) dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. |
| Arm/Group Title | PAP, Eliglustat: Once Daily | PAP, Eliglustat: Twice Daily |
|---|---|---|
| Arm/Group Description | 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). | 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). |
| Measure Participants | 56 | 59 |
| Number (95% Confidence Interval) [percentage of participants] |
80.4
47.3%
|
83.1
NaN
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | PAP, Eliglustat: Once Daily, PAP, Eliglustat: Twice Daily |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Eliglustat QD treatment was declared non-inferior to BID treatment if the lower bound of the 95% confidence interval (CI) for the difference was within the non-inferiority margin of -0.15 (or -15%). | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in Percentage Stable |
| Estimated Value | -2.7 | |
| Confidence Interval |
(2-Sided) 95% -17.7 to 11.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | PAP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26 and 52 |
|---|---|
| Description | |
| Time Frame | Baseline, Week 26, Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PP population included all participants who were at least 80% compliant with IMP dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. Here 'n' signifies number of participants with available data at specified time points for each arm respectively. |
| Arm/Group Title | PAP, Eliglustat: Once Daily | PAP, Eliglustat: Twice Daily |
|---|---|---|
| Arm/Group Description | 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). | 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). |
| Measure Participants | 56 | 59 |
| Baseline (n=56, 59) |
13.641
(1.214)
|
13.691
(1.273)
|
| Week 26 (n=56, 57) |
13.677
(1.377)
|
13.946
(1.509)
|
| Week 52 (n=56, 59) |
13.605
(1.432)
|
13.824
(1.442)
|
| Title | PAP: Mean Platelet Count at Baseline, Weeks 26, 52 |
|---|---|
| Description | |
| Time Frame | Baseline, Week 26, Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PP population included all participants who were at least 80% compliant with IMP dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. Here 'n' signifies number of participants with available data at specified time points for each arm respectively. |
| Arm/Group Title | PAP, Eliglustat: Once Daily | PAP, Eliglustat: Twice Daily |
|---|---|---|
| Arm/Group Description | 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). | 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). |
| Measure Participants | 56 | 59 |
| Baseline (n=56, 59) |
204.01
(81.49)
|
171.09
(63.50)
|
| Week 26 (n=56, 57) |
195.75
(66.65)
|
173.94
(65.61)
|
| Week 52 (n=56, 59) |
207.20
(80.62)
|
176.10
(62.01)
|
| Title | PAP: Mean Spleen Volume at Baseline, Weeks 26, 52 |
|---|---|
| Description | |
| Time Frame | Baseline, Week 26, Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PP population included all participants who were at least 80% compliant with IMP dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. Here 'n' signifies number of participants with available data for specified category for each arm respectively. |
| Arm/Group Title | PAP, Eliglustat: Once Daily | PAP, Eliglustat: Twice Daily |
|---|---|---|
| Arm/Group Description | 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). | 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). |
| Measure Participants | 56 | 59 |
| Baseline (n= 39, 45) |
3.309
(1.465)
|
3.787
(1.623)
|
| Week 26 (n= 39, 45) |
3.066
(1.299)
|
3.504
(1.365)
|
| Week 52 (n= 39, 45) |
3.017
(1.381)
|
3.394
(1.305)
|
| Title | PAP: Mean Liver Volume at Baseline, Weeks 26, 52 |
|---|---|
| Description | |
| Time Frame | Baseline, Week 26 and Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PP population included all participants who were at least 80% compliant with IMP dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. |
| Arm/Group Title | PAP, Eliglustat: Once Daily | PAP, Eliglustat: Twice Daily |
|---|---|---|
| Arm/Group Description | 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). | 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). |
| Measure Participants | 56 | 59 |
| Baseline (n=56, 59) |
0.981
(0.187)
|
1.040
(0.198)
|
| Week 26 (n=56, 59) |
0.987
(0.190)
|
1.024
(0.179)
|
| Week 52 (n=56, 59) |
0.970
(0.170)
|
1.009
(0.196)
|
| Title | PAP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26 and Week 52 |
|---|---|
| Description | Chitotriosidase biomarker was assayed from plasma. |
| Time Frame | Baseline, Week 26, Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PP population which all participants who were at least 80% compliant with IMP dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. Here, 'n' signifies number of participants with available data for specified category for each arm respectively. |
| Arm/Group Title | PAP, Eliglustat: Once Daily | PAP, Eliglustat: Twice Daily |
|---|---|---|
| Arm/Group Description | 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). | 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). |
| Measure Participants | 56 | 59 |
| Baseline (n=55, 59) |
1523.7
(2556.6)
|
1554.9
(1895.0)
|
| Week 26 (n=52, 54) |
1279.6
(2328.1)
|
1242.0
(2012.6)
|
| Week 52 (n=54, 55) |
1076.6
(1855.8)
|
1170.1
(1683.3)
|
| Title | PAP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26 and Week 52 |
|---|---|
| Description | GL-1 on DBS biomarker was assayed from dried blood spot (DBS). |
| Time Frame | Baseline, Week 26 and week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PP population included all participants who were at least 80% compliant with IMP dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. Here 'n' signifies number of participants with available data at specified time points for each arm respectively. |
| Arm/Group Title | PAP, Eliglustat: Once Daily | PAP, Eliglustat: Twice Daily |
|---|---|---|
| Arm/Group Description | 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). | 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). |
| Measure Participants | 56 | 59 |
| GL-1 on DBS: Baseline (n=54, 55) |
2.257
(0.835)
|
2.425
(1.378)
|
| GL-1 on DBS: week 26 (n=54, 54) |
2.481
(1.037)
|
2.563
(1.100)
|
| GL-1 on DBS: week 52 (n=53, 55) |
2.853
(1.383)
|
2.707
(1.443)
|
| Title | PAP: Mean Biomarker Macrophage Inflammatory Protein-1 Beta (MIP1-beta) Value at Baseline, Weeks 26, 52 |
|---|---|
| Description | MIP1-beta biomarker was assayed from plasma. |
| Time Frame | Baseline, Week 26, Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PP population included all participants who were at least 80% compliant with dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. Here, 'n' signifies number of participants with available data for specified category for each arm respectively. |
| Arm/Group Title | PAP, Eliglustat: Once Daily | PAP, Eliglustat: Twice Daily |
|---|---|---|
| Arm/Group Description | 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). | 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). |
| Measure Participants | 56 | 59 |
| Baseline (n=54, 58) |
77.7
(74.4)
|
118.8
(156.3)
|
| Week 26 (n=52, 54) |
74.5
(68.0)
|
121.0
(204.4)
|
| Week 52 (n=54, 55) |
81.3
(82.8)
|
117.9
(165.3)
|
| Title | PAP: Bone Mineral Density (BMD) at Baseline and Week 52 |
|---|---|
| Description | BMD measurements of the spine and bilateral femur were acquired by dual-energy x-ray absorptiometry (DXA) scan. |
| Time Frame | Baseline, Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PP population included all participants who were at least 80% compliant with IMP dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. Here, 'n' signifies number of participants with available data at specified time points for each arm respectively. |
| Arm/Group Title | PAP, Eliglustat: Once Daily | PAP, Eliglustat: Twice Daily |
|---|---|---|
| Arm/Group Description | 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). | 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). |
| Measure Participants | 56 | 59 |
| Lumbar Spine: Baseline (n=51, 55) |
1.073
(0.177)
|
1.081
(0.172)
|
| Lumbar Spine: Week 52 (n=51, 55) |
1.089
(0.183)
|
1.086
(0.177)
|
| Left Femur: Baseline (n=48, 47) |
0.979
(0.219)
|
1.000
(0.199)
|
| Left Femur: Week 52 (n=48, 47) |
0.972
(0.211)
|
0.990
(0.196)
|
| Right Femur: Baseline (n=48, 47) |
0.971
(0.217)
|
0.996
(0.184)
|
| Right Femur: Week 52 (n=48, 47) |
0.967
(0.213)
|
0.981
(0.177)
|
| Title | PAP: Total T-Scores for BMD at Baseline and Week 52 |
|---|---|
| Description | Images of the spine and bilateral femur were obtained by DXA to determine T-score for each bone area and total bone mineral density. The T-score bone density categories were: normal (score >-1), osteopenia (score -2.5 to <=-1), and osteoporosis (score <= -2.5). |
| Time Frame | Baseline, Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PP population included all participants who were at least 80% compliant with IMP dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. Here 'n' signifies number of participants with available data at specified time points for each arm respectively. |
| Arm/Group Title | PAP, Eliglustat: Once Daily | PAP, Eliglustat: Twice Daily |
|---|---|---|
| Arm/Group Description | 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). | 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). |
| Measure Participants | 56 | 59 |
| Lumbar Spine T-Score: Baseline (n=49, 52) |
-0.722
(1.415)
|
-0.771
(1.217)
|
| Lumbar Spine T-Score: Week 52 (n=49, 52) |
-0.580
(1.476)
|
-0.717
(1.271)
|
| Left Femur T-Score: Baseline (n=46, 44) |
-0.459
(1.385)
|
-0.368
(1.347)
|
| Left Femur T-Score: Week 52 (n=46, 44) |
-0.509
(1.342)
|
-0.441
(1.326)
|
| Right Femur T-score: Baseline (n=46, 44) |
-0.574
(1.327)
|
-0.382
(1.282)
|
| Right Femur T-score: Week 52 (n=46, 44) |
-0.607
(1.308)
|
-0.530
(1.236)
|
| Title | PAP: Total Z-scores for BMD at Baseline and Week 52 |
|---|---|
| Description | Images of the spine and bilateral femur were obtained by DXA to determine Z-score for each bone area and total bone mineral density. The Z-score bone density categories are: normal (score >-2) and below normal (score <=-2). |
| Time Frame | Baseline, Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PP population included all participants who were at least 80% compliant with IMP dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. Here 'n' signifies number of participants with available data for specified category for each arm respectively |
| Arm/Group Title | PAP, Eliglustat: Once Daily | PAP, Eliglustat: Twice Daily |
|---|---|---|
| Arm/Group Description | 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). | 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). |
| Measure Participants | 56 | 59 |
| Lumbar Spine Z-scores: Baseline (n=51, 55) |
-0.492
(1.517)
|
-0.609
(1.166)
|
| Lumbar Spine Z-scores: Week 52 (n=51, 55) |
-0.324
(1.559)
|
-0.555
(1.202)
|
| Left Femur Z-scores: Baseline (n= 48, 47) |
-0.171
(1.316)
|
-0.115
(1.294)
|
| Left Femur Z-scores: Week 52 (n= 48, 47) |
-0.202
(1.250)
|
-0.183
(1.274)
|
| Right Femur Z-scores: Baseline (n= 48, 47) |
-0.235
(1.251)
|
-0.140
(1.194)
|
| Right Femur Z-scores: Week 52 (n= 48, 47) |
-0.248
(1.214)
|
-0.260
(1.141)
|
| Title | PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52. |
|---|---|
| Description | Mobility, i.e., ability to walk was assessed as a part of Gaucher disease assessment in participants. In this outcome, number of participants with their different mobility status along with the use of mobility aids (unrestricted mobility, walks with difficulty, walks with orthopaedic aid, requires wheelchair, bedridden) at specified time points were reported. |
| Time Frame | Baseline, Week 26 and Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PP population included all participants who were at least 80% compliant with IMP dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. |
| Arm/Group Title | PAP, Eliglustat: Once Daily | PAP, Eliglustat: Twice Daily |
|---|---|---|
| Arm/Group Description | 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). | 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). |
| Measure Participants | 56 | 59 |
| MS, Unrestricted: Baseline (n=56, 59) |
49
28.8%
|
59
NaN
|
| MS, Unrestricted: Week 26 (n=55, 57) |
46
27.1%
|
56
NaN
|
| MS, Unrestricted: Week 52 (n=51, 58) |
50
29.4%
|
57
NaN
|
| MS, Walks with Difficulty: Baseline (n=56, 59) |
6
3.5%
|
0
NaN
|
| MS, Walks with Difficulty: Week 26 (n=55, 57) |
8
4.7%
|
1
NaN
|
| Ms, Walks with Difficulty: Week 52 (n=51, 58) |
5
2.9%
|
1
NaN
|
| MS, Walks with Orthopedic Aid: Baseline (n=56, 59) |
1
0.6%
|
0
NaN
|
| MS, Walks with Orthopedic Aid: Week 26 (n=55, 57) |
1
0.6%
|
0
NaN
|
| MS, Walks with Orthopedic Aid: Week 52 (n=51, 58) |
0
0%
|
0
NaN
|
| MS, Required Wheelchair: Baseline (n=56, 59) |
0
0%
|
0
NaN
|
| MS, Required Wheelchair: Week 26 (n=55, 57) |
0
0%
|
0
NaN
|
| MS, Required Wheelchair: Week 52 (n=51, 58) |
1
0.6%
|
0
NaN
|
| MS, Bedridden: Baseline (n=56, 59) |
0
0%
|
0
NaN
|
| MS, Bedridden: Week 26 (n=55, 57) |
0
0%
|
0
NaN
|
| MS, Bedridden: Week 52 (n=51, 58) |
0
0%
|
0
NaN
|
| Title | PAP: Number of Participants With Bone Crises at Baseline, Weeks 26 and 52 |
|---|---|
| Description | Bone crisis was assessed as a part of Gaucher disease assessment in participants. Acute, excruciating episodic bone pain is characteristic of Gaucher bone crisis, which typically causes debilitation lasting several days or longer and requires treatment with immobilization, hydration, and opioid analgesics. Participants were categorized as 0= no bone crisis, 1= 1 bone crisis, and 2= 2 bone crises during the assessment period. In this outcome, number of participants with different bone crises levels at specified time points were reported. |
| Time Frame | Baseline, Week 26, and Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PP population included all participants who were at least 80% compliant with IMP dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. |
| Arm/Group Title | PAP, Eliglustat: Once Daily | PAP, Eliglustat: Twice Daily |
|---|---|---|
| Arm/Group Description | 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). | 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). |
| Measure Participants | 56 | 59 |
| Bone Crisis (0): Baseline (n=56, 59) |
55
32.4%
|
57
NaN
|
| Bone Crisis (0): Week 26 (n=55,57) |
54
31.8%
|
56
NaN
|
| Bone Crisis (0): Week 52 (n=56, 58) |
56
32.9%
|
57
NaN
|
| Bone Crisis (1): Baseline (n=56, 59) |
1
0.6%
|
2
NaN
|
| Bone Crisis (1): Week 26 (n=55, 57) |
0
0%
|
1
NaN
|
| Bone Crisis (1): Week 52 (n=56, 58) |
0
0%
|
1
NaN
|
| Bone Crisis (2): Baseline (n=56, 59) |
0
0%
|
0
NaN
|
| Bone Crisis (2): week 26 (n=55, 57) |
1
0.6%
|
0
NaN
|
| Bone Crisis (2): week 52 (n=56, 58) |
0
0%
|
0
NaN
|
| Title | PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52 |
|---|---|
| Description | Bone pain was assessed as a part of Gaucher disease assessment in participants. Participants were categorized as none (no bone pain), very mild bone pain, mild bone pain, moderate bone pain, severe bone pain and extreme bone pain during the past 4 weeks. In this outcome, number of participants with different level of bone pain during the past 4 weeks at specified time points were reported. |
| Time Frame | Baseline, Week 26, and Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PP population included all participants who were at least 80% compliant with IMP dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. |
| Arm/Group Title | PAP, Eliglustat: Once Daily | PAP, Eliglustat: Twice Daily |
|---|---|---|
| Arm/Group Description | 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). | 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). |
| Measure Participants | 56 | 59 |
| None: Baseline (n=56, 59) |
42
24.7%
|
49
NaN
|
| None: Week 26 (n=55, 57) |
42
24.7%
|
49
NaN
|
| None: Week 52 (n=56, 58) |
41
24.1%
|
45
NaN
|
| Very Mild: Baseline (n=56, 59) |
2
1.2%
|
1
NaN
|
| Very Mild: Week 26 (n=55, 57) |
3
1.8%
|
4
NaN
|
| Very Mild: Week 52 (n=56, 58) |
3
1.8%
|
7
NaN
|
| Mild: Baseline (n=56, 59) |
7
4.1%
|
3
NaN
|
| Mild: Week 26 (n=55, 57) |
5
2.9%
|
3
NaN
|
| Mild: Week 52 (n=56, 58) |
6
3.5%
|
2
NaN
|
| Moderate: Baseline (n=56, 59) |
4
2.4%
|
5
NaN
|
| Moderate: Week 26 (n=55, 57) |
5
2.9%
|
1
NaN
|
| Moderate: Week 52 (56, 58) |
6
3.5%
|
2
NaN
|
| Severe: Baseline (n=56, 59) |
1
0.6%
|
1
NaN
|
| Severe: Week 26 (n=55, 57) |
0
0%
|
0
NaN
|
| Severe: Week 52 (n=56, 58) |
0
0%
|
2
NaN
|
| Extreme: Baseline (n=56, 59) |
0
0%
|
0
NaN
|
| Extreme: Week 26 (n=55, 57) |
0
0%
|
0
NaN
|
| Extreme: Week 52 (n=56, 58) |
0
0%
|
0
NaN
|
| Title | PAP: Total Bone Marrow Burden Score (BMB) at Baseline and Week 52 |
|---|---|
| Description | BMB Score was measured using magnetic resonance imaging (MRI), range from 0 (no abnormalities) to 8 points (severe disease) for the lumbar spine and from 0 (no abnormalities) to 8 points (severe disease) for the femurs. The total score was calculated as the sum of scores for femur and lumbar spine regions which ranged from 0 (no abnormalities) -16 (severe disease) points. A higher BMB score signified more severe bone marrow involvement. |
| Time Frame | Baseline, Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PP population included all participants who were at least 80% compliant with IMP dosing during PAP, had all of the necessary Baseline and Week 52 assessments to evaluate the primary endpoint, and did not have major protocol deviations. Here, 'n' signifies number of participants with available data at specified time points for each arm respectively. |
| Arm/Group Title | PAP, Eliglustat: Once Daily | PAP, Eliglustat: Twice Daily |
|---|---|---|
| Arm/Group Description | 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). | 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). |
| Measure Participants | 56 | 59 |
| BMB Score: Baseline (n=52, 49) |
8.276
(2.891)
|
9.136
(2.784)
|
| BMB Score: Week 52 (n=51, 48) |
7.971
(2.689)
|
8.705
(2.633)
|
| Title | LIP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26, 52 and 78 |
|---|---|
| Description | |
| Time Frame | Baseline, Week 26, Week, 52, and Week 78 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on all treated (AT) analysis set which included all participants who received at least 1 dose of eliglustat during lead in period. Here 'n' signifies number of participants with available data at specified time points. |
| Arm/Group Title | LIP: Eliglustat |
|---|---|
| Arm/Group Description | All participants (except in Japan) received eliglustat 50 mg BID on Day 1 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. All participants in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. |
| Measure Participants | 170 |
| Baseline (n=170) |
13.435
(1.560)
|
| Week 26 (n=163) |
13.443
(1.382)
|
| Week 52 (n=74) |
13.434
(1.497)
|
| Week 78 (n=41) |
13.329
(1.528)
|
| Title | LIP: Mean Platelet Count at Baseline, Weeks 26, 52 and 78 |
|---|---|
| Description | |
| Time Frame | Baseline, Week 26, Week 52, Week 78 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on AT analysis set which included all participants who received at least 1 dose of eliglustat during LIP. Here 'n' signifies number of participants with available data at specified time points. |
| Arm/Group Title | LIP: Eliglustat |
|---|---|
| Arm/Group Description | All participants (except in Japan) received eliglustat 50 mg BID on Day 1 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. All participants in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. |
| Measure Participants | 170 |
| Baseline (n=170) |
178.653
(92.732)
|
| Week 26 (n=163) |
180.021
(85.426)
|
| Week 52 (n=74) |
176.378
(79.880)
|
| Week 78 (n=41) |
168.720
(74.117)
|
| Title | LIP: Mean Liver Volume at Baseline, Weeks 26, 52 and 78 |
|---|---|
| Description | |
| Time Frame | Baseline, Week 26, Week 52, Week 78 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on AT participants which included all participants who received at least 1 dose of eliglustat during lead in period. Here, 'n' signifies number of participants with available data at specified time points. |
| Arm/Group Title | LIP: Eliglustat |
|---|---|
| Arm/Group Description | All participants (except in Japan) received eliglustat 50 mg BID on Day 1 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. All participants in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. |
| Measure Participants | 170 |
| Baseline (n=170) |
1.044
(0.243)
|
| Week 26 (n=149) |
1.040
(0.229)
|
| Week 52 (n=68) |
1.059
(0.242)
|
| Week 78 (n=39) |
1.062
(0.236)
|
| Title | LIP: Mean Spleen Volume at Baseline, Weeks 26, 52 and 78 |
|---|---|
| Description | |
| Time Frame | Baseline, Week 26, Week 52, Week 78 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on AT participants which included all participants who received at least 1 dose of eliglustat during lead in period. Here 'n' signifies number of participants with available data at specified time points. |
| Arm/Group Title | LIP: Eliglustat |
|---|---|
| Arm/Group Description | All participants (except in Japan) received eliglustat 50 mg BID on Day 1 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. All participants in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. |
| Measure Participants | 170 |
| Baseline (n=119) |
4.448
(2.314)
|
| Week 26 (n=106) |
3.840
(1.801)
|
| Week 52 (n=52) |
4.094
(1.767)
|
| Week 78 (n=30) |
4.088
(2.089)
|
| Title | LIP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26, 52, and 78 |
|---|---|
| Description | Chitotriosidase biomarker was assayed from plasma. |
| Time Frame | Baseline, Week 26, Week 52 and Week 78 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on AT analysis set which included all participants who received at least 1 dose of eliglustat during LIP. Here 'n' signifies number of participants with available data at specified time points. |
| Arm/Group Title | LIP: Eliglustat |
|---|---|
| Arm/Group Description | All participants (except in Japan) received eliglustat 50 mg, twice daily (BID) on Day 1 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. All participants in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. |
| Measure Participants | 170 |
| Chitotriosidase: Baseline (n=170) |
2437.92
(3291.25)
|
| Chitotriosidase: week 26 (n=157) |
1802.93
(2529.29)
|
| Chitotriosidase: week 52 (n=72) |
1755.70
(2649.14)
|
| Chitotriosidase: week 78 (n=41) |
1677.02
(2718.75)
|
| Title | LIP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26, Week 52, and Week 78 |
|---|---|
| Description | GL-1 on DBS biomarker was assayed from dried blood spot. |
| Time Frame | Baseline, Week 26, Week 52 and Week 78 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on AT analysis set which included all participants who received at least 1 dose of eliglustat during LIP. Here 'n' signifies number of participants with available data at specified time points. |
| Arm/Group Title | LIP: Eliglustat |
|---|---|
| Arm/Group Description | All participants (except in Japan) received eliglustat 50 mg, twice daily (BID) on Day 1 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. All participants in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. |
| Measure Participants | 170 |
| GL-1 on DBS: Baseline (n=159) |
4.358
(2.155)
|
| GL-1 on DBS: Week 26 (n=144) |
2.340
(0.868)
|
| GL-1 on DBS: Week 52 (n=68) |
2.279
(0.730)
|
| GL-1 on DBS: Week 78 (n=39) |
2.495
(1.500)
|
| Title | LIP: Mean Biomarker (MIP1-beta) Value at Baseline, Week 78 |
|---|---|
| Description | MIP1-beta biomarker was assayed from plasma. |
| Time Frame | Baseline and Week 78 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on AT analysis set which included all participants who received at least 1 dose of eliglustat during LIP. Here 'n' signifies number of participants with available data at specified time points. |
| Arm/Group Title | LIP: Eliglustat |
|---|---|
| Arm/Group Description | All participants (except in Japan) received eliglustat 50 mg, twice daily (BID) on Day 1 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. All participants in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. |
| Measure Participants | 170 |
| MIP-1beta: Baseline (n=170) |
142.433
(125.961)
|
| MIP-1beta: Week 78 (n=41) |
132.180
(189.454)
|
| Title | LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78 |
|---|---|
| Description | Mobility, i.e., ability to walk was assessed as a part of Gaucher disease assessment in participants. In this outcome, number of participants with their different mobility status along with the use of mobility aids (unrestricted mobility, walks with difficulty, walks with orthopaedic aid, requires wheelchair, bedridden) at specified time points were reported. |
| Time Frame | Baseline, Week 26, Week 52, Week 78 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on AT analysis set which included all participants who received at least 1 dose of eliglustat during LIP. |
| Arm/Group Title | LIP: Eliglustat |
|---|---|
| Arm/Group Description | All participants (except in Japan) received eliglustat 50 mg, twice daily (BID) on Day 1 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. All participants in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. |
| Measure Participants | 170 |
| MS,Unrestricted: Baseline (n=163) |
146
85.9%
|
| MS,Unrestricted: Week 26 (n=161) |
153
90%
|
| MS,Unrestricted: Week 52 (n=72) |
70
41.2%
|
| MS,Unrestricted: Week 78 (n= 41) |
39
22.9%
|
| MS, Walks With Difficulty: Baseline (n=163) |
12
7.1%
|
| MS, Walks With Difficulty: Week 26 (n=161) |
6
3.5%
|
| MS, Walks With Difficulty: Week 52 (n=72) |
1
0.6%
|
| MS, Walks With Difficulty: Week 78 (n=41) |
2
1.2%
|
| MS, Walks With Orthopedic Aid: Baseline (n=163) |
3
1.8%
|
| MS, Walks With Orthopedic Aid: Week 26 (n=161) |
1
0.6%
|
| MS, Walks With Orthopedic Aid: Week 52 (n=72) |
0
0%
|
| MS, Walks With Orthopedic Aid: Week 78 (n=41) |
0
0%
|
| MS, Required wheelchair: Baseline (n=163) |
2
1.2%
|
| MS, Required wheelchair: Week 26 (n=161) |
1
0.6%
|
| MS, Required wheelchair: Week 52 (n=72) |
1
0.6%
|
| MS, Required wheelchair: Week 78 (n=41) |
0
0%
|
| MS, Bedridden: Baseline (n=163) |
0
0%
|
| MS, Bedridden: Week 26 (n=161) |
0
0%
|
| MS, Bedridden: Week 52 (n=72) |
0
0%
|
| MS, Bedridden: Week 78 (n=41) |
0
0%
|
| Title | LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78 |
|---|---|
| Description | Bone crises was assessed as a part of Gaucher disease assessment in participants. Acute, excruciating episodic bone pain is characteristic of Gaucher bone crises, which typically causes debilitation lasting several days or longer and requires treatment with immobilization, hydration, and opioid analgesics. Participants were categorized as 0= no bone crisis, 1= 1 bone crisis, 2= 2 bone crises, 6= 6 bone crises, and 24= 24 bone crises during the assessment period. In this outcome, number of participants with different bone crises levels at specified time points were reported. |
| Time Frame | Baseline, Week 26, Week 52, Week 78 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on AT analysis set which included all participants who received at least 1 dose of eliglustat during LIP. |
| Arm/Group Title | LIP: Eliglustat |
|---|---|
| Arm/Group Description | All participants (except in Japan) received eliglustat 50 mg, twice daily (BID) on Day 1 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. All participants in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. |
| Measure Participants | 170 |
| Bone Crisis (0): Baseline (n=162) |
151
88.8%
|
| Bone Crisis (0): Week 26 (n=162) |
159
93.5%
|
| Bone Crisis (0): Week 52 (n=72) |
72
42.4%
|
| Bone Crisis (0): Week 78 (n=41) |
41
24.1%
|
| Bone Crisis (1): Baseline (n=162) |
8
4.7%
|
| Bone Crisis (1): Week 26 (n=162) |
3
1.8%
|
| Bone Crisis (1): Week 52 (n=72) |
0
0%
|
| Bone Crisis (1): Week 78 (n=41) |
0
0%
|
| Bone Crisis (2): Baseline (n=162) |
1
0.6%
|
| Bone Crisis (2): Week 26 (n=162) |
0
0%
|
| Bone Crisis (2): Week 52 (n=72) |
0
0%
|
| Bone Crisis (2): Week 78 (n=41) |
0
0%
|
| Bone Crisis (6): Baseline (n=162) |
1
0.6%
|
| Bone Crisis (6): Week 26 (n=162) |
0
0%
|
| Bone Crisis (6): Week 52 (n=72) |
0
0%
|
| Bone Crisis (6): Week 78 (n=41) |
0
0%
|
| Bone Crisis (24): Baseline (n=162) |
1
0.6%
|
| Bone Crisis (24): Week 26 (n=162) |
0
0%
|
| Bone Crisis (24): Week 52 (n=72) |
0
0%
|
| Bone Crisis (24): Week 78 (n=41) |
0
0%
|
| Title | LIP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78 |
|---|---|
| Description | Bone pain was assessed as a part of Gaucher disease assessment in participants. Participants were categorized as none (no bone pain), very mild bone pain, mild bone pain, moderate bone pain, severe bone pain and extreme bone pain. In this outcome, number of participants with different type of bone pain during the past 4 weeks at specified time points were reported. |
| Time Frame | Baseline, Week 26, Week 52, Week 78 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on AT analysis set which included all participants who received at least 1 dose of eliglustat during LIP. |
| Arm/Group Title | LIP: Eliglustat |
|---|---|
| Arm/Group Description | All participants (except in Japan) received eliglustat 50 mg, twice daily (BID) on Day 1 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. All participants in Japan received eliglustat 50 mg once only on Day 1 and then eliglustat 50 mg BID from Day 2 titrated up to 100 mg BID (50 or 100 mg capsules) based on their individual PK data for up to 78 weeks. |
| Measure Participants | 170 |
| None: Baseline (n=163) |
112
65.9%
|
| None: Week 26 (n=161) |
125
73.5%
|
| None: Week 52 (n=72) |
62
36.5%
|
| None: Week 78 (n=41) |
39
22.9%
|
| Very Mild: Baseline (n=163) |
17
10%
|
| Very Mild: Week 26 (n=161) |
14
8.2%
|
| Very Mild: Week 52 (n=72) |
4
2.4%
|
| Very Mild: Week 78 (n=41) |
1
0.6%
|
| Mild: Baseline (n=163) |
22
12.9%
|
| Mild: Week 26 (n=161) |
10
5.9%
|
| Mild: Week 52 (n=72) |
3
1.8%
|
| Mild: Week 78 (n=41) |
0
0%
|
| Moderate: Baseline (n=163) |
8
4.7%
|
| Moderate: Week 26 (n=161) |
10
5.9%
|
| Moderate: Week 52 (n=72) |
3
1.8%
|
| Moderate: Week 78 (n=41) |
1
0.6%
|
| Severe: Baseline (n=163) |
4
2.4%
|
| Severe: Week 26 (n=161) |
2
1.2%
|
| Severe: Week 52 (n=72) |
0
0%
|
| Severe: Week 78 (n=41) |
0
0%
|
| Extreme: Baseline (n=163) |
0
0%
|
| Extreme: Week 26 (n=161) |
0
0%
|
| Extreme: Week 52 (n=72) |
0
0%
|
| Extreme: Week 78 (n=41) |
0
0%
|
| Title | 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 |
|---|---|
| Description | Participant were considered as stable if they met the following criteria: hemoglobin level did not decrease >1.5 g/dL from baseline for PAP, platelet count does not decrease >25% below Baseline for PAP, liver volume does not increase >20% above Baseline for PAP, spleen volume does not increase >25% above Baseline for PAP. Baseline for PAP was defined as last available assessment prior to randomization. |
| Time Frame | 1 Year, 2 Years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on intent to treat (ITT) population which included all participants who received at least 1 dose of eliglustat after randomization. Here 'n' signifies number of participants with available data at specified time points. |
| Arm/Group Title | LTTP: Eliglustat |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 121 |
| Bone Criterion Stable at 1 year (n=104) |
92.3
54.3%
|
| Bone Criterion Stable at 2 years (n=32) |
84.4
49.6%
|
| Hemoglobin Level Stable at 1 year (n=104) |
92.3
54.3%
|
| Hemoglobin Level Stable at 2 years (n=32) |
81.3
47.8%
|
| Platelet Count Stable at 1 year (n=104) |
93.3
54.9%
|
| Platelet Count Stable at 2 years (n=32) |
84.4
49.6%
|
| Liver Volume Stable at 1 year (n=103) |
93.2
54.8%
|
| Liver Volume Stable at 2 years (n=31) |
83.9
49.4%
|
| Spleen Volume Stable at 1 year (n=72) |
95.8
56.4%
|
| Spleen Volume Stable at 2 years (n=20) |
95.0
55.9%
|
| Title | LTTP: Number of Participants With Mobility Status (MS) at Baseline, 1 Year and 2 Years |
|---|---|
| Description | Mobility, i.e., ability to walk was assessed as a part of Gaucher disease assessment in participants. In this outcome, number of participants with their different mobility status along with the use of mobility aids (unrestricted mobility, walks with difficulty, walks with orthopaedic aid, requires wheelchair, bedridden) at specified time points were reported. |
| Time Frame | Baseline, 1 year, and 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of eliglustat during the LTTP. |
| Arm/Group Title | LTTP: Eliglustat |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 121 |
| MS, Unrestricted: Baseline (n=120) |
111
65.3%
|
| MS, Unrestricted: 1 year (n=104) |
97
57.1%
|
| MS, Unrestricted: 2 years (n=32) |
28
16.5%
|
| MS, Walks with Difficulty: Baseline (n=120) |
7
4.1%
|
| MS, Walks with Difficulty: 1 year (n=104) |
4
2.4%
|
| Ms, Walks with Difficulty: 2 years (n=32) |
2
1.2%
|
| MS, Walks with Orthopedic Aid: Baseline (n=120) |
0
0%
|
| MS, Walks with Orthopedic Aid: 1 year (n=104) |
1
0.6%
|
| MS, Walks with Orthopedic Aid: 2 years (n=32) |
0
0%
|
| MS, Required Wheelchair: Baseline (n=120) |
2
1.2%
|
| MS, Required Wheelchair: 1 year (n=104) |
2
1.2%
|
| MS, Required Wheelchair: 2 years (n=32) |
2
1.2%
|
| MS, Bedridden: Baseline (n=120) |
0
0%
|
| MS, Bedridden: 1 year (n=104) |
0
0%
|
| MS, Bedridden: 2 years (n=32) |
0
0%
|
| Title | LTTP: Number of Participants With Bone Crises Assessment at Baseline, 1 Year and 2 Years |
|---|---|
| Description | Bone crises was assessed as a part of Gaucher disease assessment in participants. Acute, excruciating episodic bone pain is characteristic of Gaucher bone crises, which typically causes debilitation lasting several days or longer and requires treatment with immobilization, hydration, and opioid analgesics. Participants were categorized as 0= no bone crises, 1= 1 bone crisis during the assessment period. In this outcome, number of participants with different bone crises levels at specified time points were reported. |
| Time Frame | Baseline, 1 year and 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of eliglustat during the LTTP. |
| Arm/Group Title | LTTP: Eliglustat |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 121 |
| Bone Crisis (0): Baseline (n=120) |
119
70%
|
| Bone Crisis (0): 1 year (n=104) |
104
61.2%
|
| Bone Crisis (0): 2 years (n=32) |
32
18.8%
|
| Bone Crisis (1): Baseline (n=120) |
1
0.6%
|
| Bone Crisis (1): 1 year (n=104) |
0
0%
|
| Bone Crisis (1): 2 years (n=32) |
0
0%
|
| Title | LTTP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, 1 Year, and 2 Years |
|---|---|
| Description | Bone pain was assessed as a part of Gaucher disease assessment in participants. Participants were categorized as none (no bone pain), very mild bone pain, mild bone pain, moderate bone pain, severe bone pain and extreme bone pain. In this outcome, number of participants with different level of bone pain during the past 4 weeks at specified time points were reported. |
| Time Frame | Baseline, 1 year and 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of eliglustat during the LTTP. |
| Arm/Group Title | LTTP: Eliglustat |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 121 |
| None: Baseline (n=120) |
91
53.5%
|
| None: 1 year (n=104) |
83
48.8%
|
| None: 2 years (n=32) |
32
18.8%
|
| Very Mild: Baseline (n=120) |
12
7.1%
|
| Very Mild: 1 year (n=104) |
9
5.3%
|
| Very Mild: 2 years (n=32) |
0
0%
|
| Mild: Baseline (n=120) |
8
4.7%
|
| Mild: 1 year (n=104) |
10
5.9%
|
| Mild: 2 years (n=32) |
0
0%
|
| Moderate: Baseline (n=120) |
7
4.1%
|
| Moderate: 1 year (n=104) |
1
0.6%
|
| Moderate: 2 years (n=32) |
0
0%
|
| Severe: Baseline (n=120) |
2
1.2%
|
| Severe: 1 year (n=104) |
0
0%
|
| Severe: 2 years (n=32) |
0
0%
|
| Extreme: Baseline (n=120) |
0
0%
|
| Extreme: 1 year (n=104) |
1
0.6%
|
| Extreme: 2 years (n=32) |
0
0%
|
| Title | LTTP: Bone Mineral Density (BMD) at Baseline, 1 Year, and 2 Years |
|---|---|
| Description | BMD measurements of the spine and bilateral femur were acquired by DXA scan. |
| Time Frame | Baseline, 1 year, and 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of eliglustat during the LTTP. |
| Arm/Group Title | LTTP: Eliglustat |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 121 |
| Lumbar Spine: Baseline (n=113) |
1.087
(0.182)
|
| Lumbar Spine: 1 year (n=101) |
1.083
(0.183)
|
| Lumbar Spine: 2 years (n=26) |
1.082
(0.190)
|
| Left Femur: Baseline (n=107) |
0.986
(0.205)
|
| Left Femur: 1 year (n=95) |
0.994
(0.226)
|
| Left Femur: 2 years (n=22) |
0.950
(0.220)
|
| Right Femur: Baseline (n=103) |
0.983
(0.201)
|
| Right Femur: 1 year (n=91) |
0.979
(0.202)
|
| Right Femur: 2 years (n=21) |
0.908
(0.131)
|
| Title | LTTP: Total T-Scores for BMD at Baseline, 1 Year, and 2 Years |
|---|---|
| Description | Images of the spine and bilateral femur were obtained by DXA to determine T-score for each bone area and total bone mineral density. The T-score bone density categories were: normal (score >-1), osteopenia (score -2.5 to <=-1), and osteoporosis (score <= -2.5). |
| Time Frame | Baseline, 1 year, and 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of eliglustat during the LTTP. |
| Arm/Group Title | LTTP: Eliglustat |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 121 |
| Lumbar Spine T-Score: Baseline (n=110) |
-0.674
(1.383)
|
| Lumbar Spine T-Score: 1 year (n=98) |
-0.718
(1.394)
|
| Lumbar Spine T-Score: 2 years (n=26) |
-0.750
(1.370)
|
| Left Femur T-Score: Baseline (n=103) |
-0.421
(1.377)
|
| Left Femur T-Score: 1 year (n=91) |
-0.382
(1.551)
|
| Left Femur T-Score: 2 years (n=22) |
-0.682
(1.532)
|
| Right Femur T-Score: Baseline (n=99) |
-0.461
(1.360)
|
| Right Femur T-Score: 1 year (n=87) |
-0.500
(1.381)
|
| Right Femur T-Score: 2 years (n=21) |
-1.005
(0.931)
|
| Title | LTTP: Total Z-scores for BMD at Baseline, 1 Year, and 2 Years |
|---|---|
| Description | Images of the spine and bilateral femur were obtained by DXA to determine Z-score for each bone area and total bone mineral density. The Z-score bone density categories are: normal (score >-2) and below normal (score <=-2). |
| Time Frame | Baseline, 1 year, and 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of eliglustat during the LTTP. |
| Arm/Group Title | LTTP: Eliglustat |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 121 |
| Lumbar Spine Z-Score: Baseline (n=113) |
-0.460
(1.376)
|
| Lumbar Spine Z-Score: 1 year (n=101) |
-0.512
(1.368)
|
| Lumbar Spine Z-Score: 2 years (n=26) |
-0.385
(1.316)
|
| Left Femur Z-Score: Baseline (n=107) |
-0.164
(1.277)
|
| Left Femur Z-Score: 1 year (n=95) |
-0.132
(1.459)
|
| Left Femur Z-Score: 2 years (n=22) |
-0.264
(1.525)
|
| Right Femur Z-Score: Baseline (n=103) |
-0.214
(1.227)
|
| Right Femur Z-Score: 1 year (n=91) |
-0.262
(1.270)
|
| Right Femur Z-Score: 2 years (n=21) |
-0.605
(0.957)
|
| Title | LTTP: Total Bone Marrow Burden Score (BMB) at Baseline, 1 Year, and 2 Years |
|---|---|
| Description | BMB Score was measured using MRI, range from 0 (no abnormalities) to 8 points (severe disease) for the lumbar spine and from 0 (no abnormalities) to 8 points (severe disease) for the femurs. The total score was calculated as the sum of scores for femur and lumbar spine regions which ranged from 0 (no abnormalities) -16 (severe disease) points. A higher BMB score signified more severe bone marrow involvement. |
| Time Frame | Baseline, 1 year, and 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of eliglustat during the LTTP. |
| Arm/Group Title | LTTP: Eliglustat |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 121 |
| BMB Score: Baseline (n=115) |
8.164
(2.646)
|
| BMB Score: 1 year (n=26) |
7.853
(2.497)
|
| BMB Score: 2 years (n=17) |
8.059
(1.918)
|
| Title | LTTP: Mean Biomarker (Chitotriosidase) Value at Baseline, 1 Year, and 2 Years |
|---|---|
| Description | Chitotriosidase biomarker was assayed from plasma. |
| Time Frame | Baseline, 1 year, and 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of eliglustat during the LTTP. |
| Arm/Group Title | LTTP: Eliglustat |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 121 |
| Chitotriosidase: Baseline (n=118) |
1188.983
(1857.521)
|
| Chitotriosidase: 1 year (n=97)) |
1221.753
(2072.446)
|
| Chitotriosidase: 2 years (n=31) |
598.161
(1463.603)
|
| Title | LTTP: Mean Biomarker (GL-1 on DBS) Value at Baseline, 1 Year, and 2 Years |
|---|---|
| Description | GL-1 on DBS biomarker was assayed from dried blood spot. |
| Time Frame | Baseline, 1 year, and 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of eliglustat during the LTTP. |
| Arm/Group Title | LTTP: Eliglustat |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 121 |
| GL-1 on DBS: Baseline (n=114) |
2.725
(1.350)
|
| GL-1 on DBS: 1 year (n=98) |
2.500
(1.031)
|
| GL-1 on DBS: 2 years (n=29) |
2.238
(0.658)
|
| Title | LTTP: Mean Biomarker (MIP1-beta) Value at Baseline, 1 Year, and 2 Years |
|---|---|
| Description | MIP1-beta biomarker was assayed from plasma. |
| Time Frame | Baseline, 1 year, and 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of eliglustat during the LTTP. |
| Arm/Group Title | LTTP: Eliglustat |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 121 |
| MIP-1beta: Baseline (n=114) |
97.857
(125.857)
|
| MIP-1beta: 1 year (n=94) |
90.398
(90.549)
|
| MIP-1beta: 2 years (n=31) |
68.445
(64.774)
|
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | Adverse events data was planned to be reported for overall population. | |
| Arm/Group Title | Eliglustat | |
| Arm/Group Description | All participants who received eliglustat at the TDD of 100 mg or 200 mg in the LIP, PAP, LTTP or ETP. | |
All Cause Mortality |
||
| Eliglustat | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Eliglustat | ||
| Affected / at Risk (%) | # Events | |
| Total | 40/170 (23.5%) | |
| Cardiac disorders | ||
| Angina pectoris | 2/170 (1.2%) | |
| Arrhythmia | 1/170 (0.6%) | |
| Cardiac arrest | 1/170 (0.6%) | |
| Gastrointestinal disorders | ||
| Abdominal wall haematoma | 1/170 (0.6%) | |
| Mallory-Weiss syndrome | 1/170 (0.6%) | |
| General disorders | ||
| Device dislocation | 1/170 (0.6%) | |
| Disuse syndrome | 1/170 (0.6%) | |
| Hernia | 1/170 (0.6%) | |
| Impaired healing | 1/170 (0.6%) | |
| Medical device pain | 1/170 (0.6%) | |
| Hepatobiliary disorders | ||
| Cholecystitis | 1/170 (0.6%) | |
| Cholecystitis chronic | 1/170 (0.6%) | |
| Infections and infestations | ||
| Acute hepatitis B | 1/170 (0.6%) | |
| Appendicitis | 1/170 (0.6%) | |
| Hepatitis A | 1/170 (0.6%) | |
| Staphylococcal sepsis | 1/170 (0.6%) | |
| Injury, poisoning and procedural complications | ||
| Fall | 1/170 (0.6%) | |
| Femoral neck fracture | 2/170 (1.2%) | |
| Femur fracture | 1/170 (0.6%) | |
| Forearm fracture | 1/170 (0.6%) | |
| Incisional hernia | 1/170 (0.6%) | |
| Injury | 1/170 (0.6%) | |
| Radius fracture | 1/170 (0.6%) | |
| Spinal fracture | 1/170 (0.6%) | |
| Investigations | ||
| Hepatic enzyme increased | 1/170 (0.6%) | |
| Musculoskeletal and connective tissue disorders | ||
| Arthralgia | 2/170 (1.2%) | |
| Arthritis | 1/170 (0.6%) | |
| Joint range of motion decreased | 1/170 (0.6%) | |
| Muscular weakness | 1/170 (0.6%) | |
| Osteoarthritis | 3/170 (1.8%) | |
| Osteonecrosis | 1/170 (0.6%) | |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
| Lipoma | 1/170 (0.6%) | |
| Papillary thyroid cancer | 1/170 (0.6%) | |
| Nervous system disorders | ||
| Dizziness | 1/170 (0.6%) | |
| Epilepsy | 2/170 (1.2%) | |
| Ischaemic stroke | 1/170 (0.6%) | |
| Presyncope | 1/170 (0.6%) | |
| Seizure | 1/170 (0.6%) | |
| Syncope | 3/170 (1.8%) | |
| Pregnancy, puerperium and perinatal conditions | ||
| Ectopic pregnancy | 1/170 (0.6%) | |
| Psychiatric disorders | ||
| Conversion disorder | 1/170 (0.6%) | |
| Major depression | 1/170 (0.6%) | |
| Renal and urinary disorders | ||
| Calculus urinary | 1/170 (0.6%) | |
| Reproductive system and breast disorders | ||
| Uterine polyp | 1/170 (0.6%) | |
| Vascular disorders | ||
| Aortic aneurysm | 1/170 (0.6%) | |
| Haemorrhage | 1/170 (0.6%) | |
| Hypertension | 2/170 (1.2%) | |
Other (Not Including Serious) Adverse Events |
||
| Eliglustat | ||
| Affected / at Risk (%) | # Events | |
| Total | 144/170 (84.7%) | |
| Blood and lymphatic system disorders | ||
| Thrombocytopenia | 9/170 (5.3%) | |
| Cardiac disorders | ||
| Palpitations | 11/170 (6.5%) | |
| Gastrointestinal disorders | ||
| Abdominal distension | 9/170 (5.3%) | |
| Abdominal pain | 15/170 (8.8%) | |
| Abdominal pain upper | 26/170 (15.3%) | |
| Constipation | 16/170 (9.4%) | |
| Diarrhoea | 24/170 (14.1%) | |
| Dyspepsia | 19/170 (11.2%) | |
| Gastrooesophageal reflux disease | 9/170 (5.3%) | |
| Nausea | 18/170 (10.6%) | |
| Vomiting | 14/170 (8.2%) | |
| General disorders | ||
| Fatigue | 17/170 (10%) | |
| Pyrexia | 16/170 (9.4%) | |
| Hepatobiliary disorders | ||
| Hepatomegaly | 9/170 (5.3%) | |
| Infections and infestations | ||
| Gastroenteritis | 15/170 (8.8%) | |
| Influenza | 23/170 (13.5%) | |
| Nasopharyngitis | 52/170 (30.6%) | |
| Upper respiratory tract infection | 22/170 (12.9%) | |
| Urinary tract infection | 14/170 (8.2%) | |
| Viral infection | 10/170 (5.9%) | |
| Musculoskeletal and connective tissue disorders | ||
| Arthralgia | 30/170 (17.6%) | |
| Back pain | 29/170 (17.1%) | |
| Musculoskeletal pain | 10/170 (5.9%) | |
| Myalgia | 11/170 (6.5%) | |
| Pain in extremity | 24/170 (14.1%) | |
| Nervous system disorders | ||
| Dizziness | 28/170 (16.5%) | |
| Headache | 37/170 (21.8%) | |
| Psychiatric disorders | ||
| Depression | 10/170 (5.9%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Cough | 21/170 (12.4%) | |
| Epistaxis | 13/170 (7.6%) | |
| Oropharyngeal pain | 18/170 (10.6%) | |
| Vascular disorders | ||
| Hypertension | 9/170 (5.3%) | |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Results Point of Contact
| Name/Title | Trial Transparency Team |
|---|---|
| Organization | Sanofi |
| Phone | |
| Contact-US@sanofi.com |
Responsible Party:
Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier:
NCT01074944
Other Study ID Numbers:
- GZGD03109
- 2009-015811-42
- EFC12818
First Posted:
Feb 24, 2010
Last Update Posted:
Feb 6, 2017
Last Verified:
Dec 1, 2016