A Study of Eliglustat Tartrate (Genz-112638) in Patients With Gaucher Disease to Evaluate Once Daily Versus Twice Daily Dosing (EDGE)
Condition: Gaucher Disease
MeSH terms: Gaucher Disease
Intervention: Eliglustat tartrate
Intervention description: Oral Capsule in 50 mg or 100 mg dosages
Intervention MeSH terms: Eliglustat
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 170.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Gaucher disease; Genz-112638; beta-glucosidase; acid β-glucosidase; glucocerebrosidase; glucosylceramide; D-glucosyl-N-acylsphingosine glucohydrolase; substrate reduction therapy

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).
    

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.