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

NCT ID: NCT01074944

Last Updated: 2017-02-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 170 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-06-30
• Study Completion Date: 2015-10-31

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).

Detailed Description

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

Conditions

Gaucher Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Twice Daily (BID) Dose Regimen

Patients will receive either 50 mg BID or 100 mg BID

Group Type: EXPERIMENTAL

Eliglustat tartrate

Intervention Type: DRUG

Oral Capsule in 50 mg or 100 mg dosages

Once Daily (QD) Dose Regimen

Patients will receive either 100 mg QD or 200 mg QD

Group Type: EXPERIMENTAL

Eliglustat tartrate

Intervention Type: DRUG

Oral Capsule in 50 mg or 100 mg dosages

Interventions

Eliglustat tartrate

Oral Capsule in 50 mg or 100 mg dosages

Intervention Type: DRUG

Other Intervention Names

Genz-112638

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Genzyme, a Sanofi Company

Locations

University of California, San Diego Medical Center

San Diego, California, United States

Yale University School of Medicine

New Haven, Connecticut, United States

Emory University Medical Center

Decatur, Georgia, United States

Children's Memorial Hospital

Chicago, Illinois, United States

Mount Sinai Medical Center

New York, New York, United States

New York University School of Medicine

New York, New York, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

University of Utah

Salt Lake City, Utah, United States

O and O Alpan LLC

Springfield, Virginia, United States

Royal Prince Alfred Hospital

Camperdown, , Australia

Monash Medical Centre

Clayton, VIC, , Australia

Royal Perth Hospital

Perth, WA, , Australia

Medical University Vienna

Vienna, , Austria

Hospital das Clinicas da UFMG

Belo Horizonte, , Brazil

Cettro - Centro de Tratamento de Oncologia e Hematologia

Brasília, , Brazil

Hemocentro - UNICAMP

Campinas, , Brazil

Instituto Tropical de Medicina Reprodutiva e Menopausa - INTRO

Cuiabá, , Brazil

Hospital Universitario Walter Cantidio - HUWC

Fortaleza, , Brazil

Hemocentro de Ribeirão Preto Núcleo de Hemoterapia de Franca

Franca, , Brazil

Hemorio

Rio de Janeiro, , Brazil

Hospital de Clínicas da Universidade Federal do Parana

São Paulo, , Brazil

IGEIM - Institute of Genetic and Inborn Erros of Metabolism

São Paulo, , Brazil

Mount Sinai Hospital

Toronto, , Canada

Peking Union Medical College Hospital

Beijing, , China

Peking University People's Hospital

Beijing, , China

Shanghai Xinhua Hospital Shanghai Xinhua Hospital

Shanghai, , China

Tianjin Hematonosis Hospital

Tianjin, , China

University Hospital Centre Zagreb

Zagreb, , Croatia

Hôpital Haut Lévêque

Bordeaux, , France

Hôpital Femme Mère Enfant Centre de référence des maladies Héréditaires du métabolisme

Bron, , France

General Hospital of Athens "G. Gennimatas"

Athens, , Greece

King Edward Memorial (KEM) Hospital

Mumbai, , India

Hiroshima University Hospital

Hiroshima, , Japan

Jikei University Hospital

Tokyo, , Japan

Juntendo University Hospital

Tokyo, , Japan

Mie Chuou Medical Center

Tsu, Mie, , Japan

Academic Medical Center

Amsterdam, , Netherlands

Hospital de Santa Maria

Lisbon, , Portugal

Hospital do Divíno Espírito Santo

Ponta Delgada - São Miguel - Açores, , Portugal

Spitaulu Clinic de Urgenta

Cluj-Napoca, , Romania

State Medical and Prophylactic Healthcare Institution; Chelyabinsk Regional Clinical Hospital

Chelyabinsk, , Russia

Hematology Research Center of Russian Academy of Medical Sciences

Moscow, , Russia

St. Petersburg State Medical Pavlov University

Saint Petersburg, , Russia

Clinical Centre of Serbia

Belgrade, , Serbia

University Hospital Lund

Lund, , Sweden

Countries

United States; Australia; Austria; Brazil; Canada; China; Croatia; France; Greece; India; Japan; Netherlands; Portugal; Romania; Russia; Serbia; Sweden

References

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. doi: 10.1016/j.ymgme.2007.04.001. Epub 2007 May 16.

Reference Type: BACKGROUND

PMID: 17509920 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20439622 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20713962 (View on PubMed)

Charrow J, Fraga C, Gu X, Ida H, Longo N, Lukina E, Nonino A, Gaemers SJM, Jouvin MH, Li J, Wu Y, Xue Y, Peterschmitt MJ. Once- versus twice-daily dosing of eliglustat in adults with Gaucher disease type 1: The Phase 3, randomized, double-blind EDGE trial. Mol Genet Metab. 2018 Mar;123(3):347-356. doi: 10.1016/j.ymgme.2017.12.001. Epub 2018 Jan 4.

Reference Type: DERIVED

PMID: 29358012 (View on PubMed)

Related Links

http://clinicaltrials.gov/ct2/show/NCT00891202?term=genz+ENGAGE&rank=1

GZGD02507 (NCT00891202) eliglustat tartrate (Genz-112638) Phase 3 Clinical Study in untreated patients with Gaucher disease type 1

http://clinicaltrials.gov/ct2/show/NCT00943111?term=genz+encore&rank=1

GZGD02607 (NCT00943111) eliglustat tartrate (Genz-112638) Phase 3 Clinical Study in patients with Gaucher disease type 1 who have been stabilized on Cerezyme

Other Identifiers

2009-015811-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EFC12818

Identifier Type: OTHER

Identifier Source: secondary_id

GZGD03109

Identifier Type: -

Identifier Source: org_study_id