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Trial record 20 of 87 for:    "gaucher disease"

A Study of Eliglustat Tartrate (Genz-112638) in Patients With Gaucher Disease to Evaluate Once Daily Versus Twice Daily Dosing (EDGE)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier:
NCT01074944
First received: February 23, 2010
Last updated: October 7, 2016
Last verified: October 2016
  Purpose
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 Intervention Phase
Gaucher Disease
Drug: Eliglustat tartrate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • PAP: Percentage of Participants Who Remained Stable for 52 Weeks During the PAP [ Time Frame: PAP Baseline up to the end of PAP (Week 52) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 26, Week 52 ] [ Designated as safety issue: No ]
  • PAP: Mean Platelet Count at Baseline, Weeks 26, 52 [ Time Frame: Baseline, Week 26, Week 52 ] [ Designated as safety issue: No ]
  • PAP: Mean Spleen Volume at Baseline, Weeks 26, 52 [ Time Frame: Baseline, Week 26, Week 52 ] [ Designated as safety issue: No ]
  • PAP: Mean Liver Volume at Baseline, Weeks 26, 52 [ Time Frame: Baseline, Week 26 and Week 52 ] [ Designated as safety issue: No ]
  • PAP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26 and Week 52 [ Time Frame: Baseline, Week 26, Week 52 ] [ Designated as safety issue: No ]
    Chitotriosidase biomarker was assayed from plasma.

  • PAP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26 and Week 52 [ Time Frame: Baseline, Week 26 and week 52 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 26, Week 52 ] [ Designated as safety issue: No ]
    MIP1-beta biomarker was assayed from plasma.

  • PAP: Bone Mineral Density (BMD) at Baseline and Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    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. [ Time Frame: Baseline, Week 26 and Week 52 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 26, and Week 52 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 26, and Week 52 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 26, Week, 52, and Week 78 ] [ Designated as safety issue: No ]
  • LIP: Mean Platelet Count at Baseline, Weeks 26, 52 and 78 [ Time Frame: Baseline, Week 26, Week 52, Week 78 ] [ Designated as safety issue: No ]
  • LIP: Mean Liver Volume at Baseline, Weeks 26, 52 and 78 [ Time Frame: Baseline, Week 26, Week 52, Week 78 ] [ Designated as safety issue: No ]
  • LIP: Mean Spleen Volume at Baseline, Weeks 26, 52 and 78 [ Time Frame: Baseline, Week 26, Week 52, Week 78 ] [ Designated as safety issue: No ]
  • LIP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26, 52, and 78 [ Time Frame: Baseline, Week 26, Week 52 and Week 78 ] [ Designated as safety issue: No ]
    Chitotriosidase biomarker was assayed from plasma.

  • LIP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26, Week 52, and Week 78 [ Time Frame: Baseline, Week 26, Week 52 and Week 78 ] [ Designated as safety issue: No ]
    GL-1 on DBS biomarker was assayed from dried blood spot.

  • LIP: Mean Biomarker (MIP1-beta) Value at Baseline, Week 78 [ Time Frame: Baseline and Week 78 ] [ Designated as safety issue: No ]
    MIP1-beta biomarker was assayed from plasma.

  • LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78 [ Time Frame: Baseline, Week 26, Week 52, Week 78 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 26, Week 52, Week 78 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Week 26, Week 52, Week 78 ] [ Designated as safety issue: No ]
    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 [ Time Frame: 1 Year, 2 Years ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, 1 year, and 2 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, 1 year and 2 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, 1 year and 2 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, 1 year, and 2 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, 1 year, and 2 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, 1 year, and 2 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, 1 year, and 2 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, 1 year, and 2 years ] [ Designated as safety issue: No ]
    Chitotriosidase biomarker was assayed from plasma.

  • LTTP: Mean Biomarker (GL-1 on DBS) Value at Baseline, 1 Year, and 2 Years [ Time Frame: Baseline, 1 year, and 2 years ] [ Designated as safety issue: No ]
    GL-1 on DBS biomarker was assayed from dried blood spot.

  • LTTP: Mean Biomarker (MIP1-beta) Value at Baseline, 1 Year, and 2 Years [ Time Frame: Baseline, 1 year, and 2 years ] [ Designated as safety issue: No ]
    MIP1-beta biomarker was assayed from plasma.


Enrollment: 170
Study Start Date: June 2010
Study Completion Date: October 2015
Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Genz-112638
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 Name: Genz-112638

Detailed Description:
NOTE: Other Phase 3 studies being conducted with eliglustat tartrate (Genz-112638) are GZGD02507 (ENGAGE): NCT00891202 and GZGD02607 (ENCORE): NCT00943111
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01074944

  Show 46 Study Locations
Sponsors and Collaborators
Genzyme, a Sanofi Company
Investigators
Study Director: Medical Monitor Genzyme, a Sanofi Company
  More Information

Additional Information:
Publications:
Responsible Party: Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier: NCT01074944     History of Changes
Other Study ID Numbers: GZGD03109  2009-015811-42  EFC12818 
Study First Received: February 23, 2010
Results First Received: October 7, 2016
Last Updated: October 7, 2016
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Canada: Health Canada
China: Food and Drug Administration
Croatia: Ministry of Health and Social Care
France: Ministry of Health
Greece: Ministry of Health and Welfare
India: Drugs Controller General of India
Japan: Ministry of Health, Labor and Welfare
Portugal: National Pharmacy and Medicines Institute
Russia: Pharmacological Committee, Ministry of Health
Serbia and Montenegro: Agency for Drugs and Medicinal Devices
Sweden: The National Board of Health and Welfare
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Austria: Federal Office for Safety in Health Care
Romania: National Medicines Agency

Keywords provided by Sanofi:
Gaucher disease
Genz-112638
beta-glucosidase
acid β-glucosidase
glucocerebrosidase
glucosylceramide
D-glucosyl-N-acylsphingosine glucohydrolase
substrate reduction therapy

Additional relevant MeSH terms:
Gaucher Disease
Sphingolipidoses
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lipidoses
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders
Eliglustat
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on December 02, 2016