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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01074944




Registration number
NCT01074944
Ethics application status
Date submitted
23/02/2010
Date registered
24/02/2010
Date last updated
6/02/2017

Titles & IDs
Public title
A Study of Eliglustat Tartrate (Genz-112638) in Patients With Gaucher Disease to Evaluate Once Daily Versus Twice Daily Dosing (EDGE)
Scientific 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
Secondary ID [1] 0 0
2009-015811-42
Secondary ID [2] 0 0
GZGD03109
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gaucher Disease 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Eliglustat tartrate

Experimental: Twice Daily (BID) Dose Regimen - Patients will receive either 50 mg BID or 100 mg BID

Experimental: Once Daily (QD) Dose Regimen - Patients will receive either 100 mg QD or 200 mg QD


Treatment: Drugs: Eliglustat tartrate
Oral Capsule in 50 mg or 100 mg dosages

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
PAP: Percentage of Participants Who Remained Stable for 52 Weeks During the PAP
Timepoint [1] 0 0
PAP Baseline up to the end of PAP (Week 52)
Secondary outcome [1] 0 0
PAP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26 and 52
Timepoint [1] 0 0
Baseline, Week 26, Week 52
Secondary outcome [2] 0 0
PAP: Mean Platelet Count at Baseline, Weeks 26, 52
Timepoint [2] 0 0
Baseline, Week 26, Week 52
Secondary outcome [3] 0 0
PAP: Mean Spleen Volume at Baseline, Weeks 26, 52
Timepoint [3] 0 0
Baseline, Week 26, Week 52
Secondary outcome [4] 0 0
PAP: Mean Liver Volume at Baseline, Weeks 26, 52
Timepoint [4] 0 0
Baseline, Week 26 and Week 52
Secondary outcome [5] 0 0
PAP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26 and Week 52
Timepoint [5] 0 0
Baseline, Week 26, Week 52
Secondary outcome [6] 0 0
PAP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26 and Week 52
Timepoint [6] 0 0
Baseline, Week 26 and week 52
Secondary outcome [7] 0 0
PAP: Mean Biomarker Macrophage Inflammatory Protein-1 Beta (MIP1-beta) Value at Baseline, Weeks 26, 52
Timepoint [7] 0 0
Baseline, Week 26, Week 52
Secondary outcome [8] 0 0
PAP: Bone Mineral Density (BMD) at Baseline and Week 52
Timepoint [8] 0 0
Baseline, Week 52
Secondary outcome [9] 0 0
PAP: Total T-Scores for BMD at Baseline and Week 52
Timepoint [9] 0 0
Baseline, Week 52
Secondary outcome [10] 0 0
PAP: Total Z-scores for BMD at Baseline and Week 52
Timepoint [10] 0 0
Baseline, Week 52
Secondary outcome [11] 0 0
PAP: Number of Participants With Mobility Status Asessments (MS) at Baseline, Weeks 26, and 52.
Timepoint [11] 0 0
Baseline, Week 26 and Week 52
Secondary outcome [12] 0 0
PAP: Number of Participants With Bone Crises at Baseline, Weeks 26 and 52
Timepoint [12] 0 0
Baseline, Week 26, and Week 52
Secondary outcome [13] 0 0
PAP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26 and 52
Timepoint [13] 0 0
Baseline, Week 26, and Week 52
Secondary outcome [14] 0 0
PAP: Total Bone Marrow Burden Score (BMB) at Baseline and Week 52
Timepoint [14] 0 0
Baseline, Week 52
Secondary outcome [15] 0 0
LIP: Mean Hemoglobin (Hb) Level at Baseline, Weeks 26, 52 and 78
Timepoint [15] 0 0
Baseline, Week 26, Week, 52, and Week 78
Secondary outcome [16] 0 0
LIP: Mean Platelet Count at Baseline, Weeks 26, 52 and 78
Timepoint [16] 0 0
Baseline, Week 26, Week 52, Week 78
Secondary outcome [17] 0 0
LIP: Mean Liver Volume at Baseline, Weeks 26, 52 and 78
Timepoint [17] 0 0
Baseline, Week 26, Week 52, Week 78
Secondary outcome [18] 0 0
LIP: Mean Spleen Volume at Baseline, Weeks 26, 52 and 78
Timepoint [18] 0 0
Baseline, Week 26, Week 52, Week 78
Secondary outcome [19] 0 0
LIP: Mean Biomarker (Chitotriosidase) Value at Baseline, Weeks 26, 52, and 78
Timepoint [19] 0 0
Baseline, Week 26, Week 52 and Week 78
Secondary outcome [20] 0 0
LIP: Mean Biomarker (GL-1 on DBS) Value at Baseline, Week 26, Week 52, and Week 78
Timepoint [20] 0 0
Baseline, Week 26, Week 52 and Week 78
Secondary outcome [21] 0 0
LIP: Mean Biomarker (MIP1-beta) Value at Baseline, Week 78
Timepoint [21] 0 0
Baseline and Week 78
Secondary outcome [22] 0 0
LIP: Number of Participants With Mobility Status (MS) at Baseline, Weeks 26, 52 and 78
Timepoint [22] 0 0
Baseline, Week 26, Week 52, Week 78
Secondary outcome [23] 0 0
LIP: Number of Participants With Bone Crises Assessment at Baseline, Weeks 26, 52 and 78
Timepoint [23] 0 0
Baseline, Week 26, Week 52, Week 78
Secondary outcome [24] 0 0
LIP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, Weeks 26, 52 and 78
Timepoint [24] 0 0
Baseline, Week 26, Week 52, Week 78
Secondary outcome [25] 0 0
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
Timepoint [25] 0 0
1 Year, 2 Years
Secondary outcome [26] 0 0
LTTP: Number of Participants With Mobility Status (MS) at Baseline, 1 Year and 2 Years
Timepoint [26] 0 0
Baseline, 1 year, and 2 years
Secondary outcome [27] 0 0
LTTP: Number of Participants With Bone Crises Assessment at Baseline, 1 Year and 2 Years
Timepoint [27] 0 0
Baseline, 1 year and 2 years
Secondary outcome [28] 0 0
LTTP: Number of Participants With Bone Pain Levels During the Past 4 Weeks at Baseline, 1 Year, and 2 Years
Timepoint [28] 0 0
Baseline, 1 year and 2 years
Secondary outcome [29] 0 0
LTTP: Bone Mineral Density (BMD) at Baseline, 1 Year, and 2 Years
Timepoint [29] 0 0
Baseline, 1 year, and 2 years
Secondary outcome [30] 0 0
LTTP: Total T-Scores for BMD at Baseline, 1 Year, and 2 Years
Timepoint [30] 0 0
Baseline, 1 year, and 2 years
Secondary outcome [31] 0 0
LTTP: Total Z-scores for BMD at Baseline, 1 Year, and 2 Years
Timepoint [31] 0 0
Baseline, 1 year, and 2 years
Secondary outcome [32] 0 0
LTTP: Total Bone Marrow Burden Score (BMB) at Baseline, 1 Year, and 2 Years
Timepoint [32] 0 0
Baseline, 1 year, and 2 years
Secondary outcome [33] 0 0
LTTP: Mean Biomarker (Chitotriosidase) Value at Baseline, 1 Year, and 2 Years
Timepoint [33] 0 0
Baseline, 1 year, and 2 years
Secondary outcome [34] 0 0
LTTP: Mean Biomarker (GL-1 on DBS) Value at Baseline, 1 Year, and 2 Years
Timepoint [34] 0 0
Baseline, 1 year, and 2 years
Secondary outcome [35] 0 0
LTTP: Mean Biomarker (MIP1-beta) Value at Baseline, 1 Year, and 2 Years
Timepoint [35] 0 0
Baseline, 1 year, and 2 years

Eligibility
Key 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 ß-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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
Monash Medical Centre - Clayton, VIC
Recruitment hospital [3] 0 0
Royal Perth Hospital - Perth, WA
Recruitment postcode(s) [1] 0 0
- Camperdown
Recruitment postcode(s) [2] 0 0
- Clayton, VIC
Recruitment postcode(s) [3] 0 0
- Perth, WA
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Pennsylvania
Country [7] 0 0
United States of America
State/province [7] 0 0
Utah
Country [8] 0 0
United States of America
State/province [8] 0 0
Virginia
Country [9] 0 0
Austria
State/province [9] 0 0
Vienna
Country [10] 0 0
Brazil
State/province [10] 0 0
Belo Horizonte
Country [11] 0 0
Brazil
State/province [11] 0 0
Brasília
Country [12] 0 0
Brazil
State/province [12] 0 0
Campinas
Country [13] 0 0
Brazil
State/province [13] 0 0
Cuiaba
Country [14] 0 0
Brazil
State/province [14] 0 0
Fortaleza
Country [15] 0 0
Brazil
State/province [15] 0 0
Franca
Country [16] 0 0
Brazil
State/province [16] 0 0
Rio de Janeiro
Country [17] 0 0
Brazil
State/province [17] 0 0
Sao Paulo
Country [18] 0 0
Canada
State/province [18] 0 0
Toronto
Country [19] 0 0
China
State/province [19] 0 0
Beijing
Country [20] 0 0
China
State/province [20] 0 0
Shanghai
Country [21] 0 0
China
State/province [21] 0 0
Tianjin
Country [22] 0 0
Croatia
State/province [22] 0 0
Zagreb
Country [23] 0 0
France
State/province [23] 0 0
Bordeaux
Country [24] 0 0
France
State/province [24] 0 0
Bron
Country [25] 0 0
Greece
State/province [25] 0 0
Athens
Country [26] 0 0
India
State/province [26] 0 0
Mumbai
Country [27] 0 0
Japan
State/province [27] 0 0
Hiroshima
Country [28] 0 0
Japan
State/province [28] 0 0
Tokyo
Country [29] 0 0
Japan
State/province [29] 0 0
Tsu, Mie
Country [30] 0 0
Netherlands
State/province [30] 0 0
Amsterdam
Country [31] 0 0
Portugal
State/province [31] 0 0
Lisboa
Country [32] 0 0
Portugal
State/province [32] 0 0
Ponta Delgada - São Miguel - Açores
Country [33] 0 0
Romania
State/province [33] 0 0
Cluj-Napoca
Country [34] 0 0
Russian Federation
State/province [34] 0 0
Chelyabinsk
Country [35] 0 0
Russian Federation
State/province [35] 0 0
Moscow
Country [36] 0 0
Russian Federation
State/province [36] 0 0
St. Petersburg
Country [37] 0 0
Serbia
State/province [37] 0 0
Belgrade
Country [38] 0 0
Sweden
State/province [38] 0 0
Lund

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Genzyme, a Sanofi Company
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Monitor
Address 0 0
Genzyme, a Sanofi Company
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.