A Study of the Efficacy and Safety of Eliglustat Tartrate (Genz-112638) in Type 1 Gaucher Patients
Condition: Gaucher Disease, Type 1; Cerebroside Lipidosis Syndrome; Glucocerebrosidase Deficiency Disease; Glucosylceramide Beta-Glucosidase Deficiency Disease; Gaucher Disease, Non-Neuronopathic Form
MeSH terms: Gaucher Disease; Lipidoses; Deficiency Diseases
Intervention: Eliglustat tartrate
Intervention description: Eliglustat (Genz-112638) capsule as single 50 mg dose on Day 1 then eliglustat 50 mg twice daily (BID) from Day 2 to Day 19, then either eliglustat 50 mg BID (if Genz-99067[active moiety of eliglustat in plasma] trough plasma concentration was greater than or equal to [>=]5 nanogram per milliliter [ng/mL] on Day 10) or eliglustat 100 mg BID(if Genz-99067 trough plasma concentration was less than [<] 5 ng/mL), from day 20 to Year 4. After primary completion date (Week 52) participants underwent treatment interruption period of approximately 2 weeks before continuing same treatment through study completion (Year 9). Participant receiving 100 mg BID could be considered for further dose increase to 150 mg BID at Week 24 if they met certain criteria (for example, had been on treatment for at least 24 months, had not reached therapeutic goals established for participants receiving Cerezyme, and if all other causes for lack of treatment effect had been evaluated and ruled out).
Intervention MeSH terms: Eliglustat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 26.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Type 1 Gaucher Disease; Glucocerebrosidase Deficiency Disease

Summary:

      Gaucher disease is a genetic disease that results in a deficiency of an enzyme acid
      beta-glucosidase, also known as glucocerebrosidase. This enzyme is needed to digest a
      substrate (lipid) called glucosylceramide and, to a lesser degree, glucosylsphingosine. In
      participants with Gaucher disease, the liver, spleen, bone marrow and brain show increases in
      lipid concentration, specifically in cells derived from the monocyte/macrophage system.

      Eliglustat tartrate (Genz-112638) is an oral drug that may regulate the Gaucher disease
      process by decreasing the synthesis of glucosylceramide. The primary objective of this study
      is to evaluate the efficacy, safety and pharmacokinetics (PK) of eliglustat tartrate,
      administered as an oral dose of either 50 milligram (mg) twice daily (BID) or 100 mg BID, to
      men and women with Gaucher disease Type 1 for 52 weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          -  The participant had a diagnosis of Gaucher Type I disease and a documented deficiency
             of glucocerebrosidase activity by enzyme assay and was willing and able to provide
             written informed consent prior to initiating any study-related procedures;

          -  The participant was 18 to 65 years old and weighed between 50 and 120 kilogram (kg) at
             enrollment;

          -  The participant had the following symptoms of Gaucher disease identified within 28
             days of enrollment (at screening);

               -  Anemia - indicated by hemoglobin measurements taken during the screening phase (8
                  to 10 gram per deciliter (g/dL) if female, 8 to 11 g/dL if male);

               -  Thrombocytopenia - indicated by platelet count measurements taken during the
                  screening phase (60000 to 100000 per cubic millimeter);

               -  Splenomegaly, as indicated by magnetic resonance imaging (MRI) or spiral computed
                  tomography (CT) (>= 10 multiples of normal);

          -  Female participants of child-bearing potential must had a documented negative serum
             pregnancy test prior to dosing. Female participants agreed to use a reliable method of
             birth control throughout duration of trial.

        Exclusion Criteria:

          -  Participant had a partial or total splenectomy or infarcted areas of the spleen;

          -  Participant had documented prior bleeding varices or liver infarction;

          -  Participant received miglustat within 12 months prior to study enrollment;

          -  The participant had received an investigational product within 30 days prior to study
             enrollment;

          -  Participant had neurologic or pulmonary involvement;

          -  Participant had new pathological bone involvement or bone crisis in the 12 months
             prior to enrollment;

          -  Participant was transfusion-dependent;

          -  Participant had a documented etiology of anemia due to causes other than Gaucher
             disease;

          -  The participant had cardiac functional and/or anatomical abnormalities, a history of
             cancer or tested positive for human immunodeficiency virus (HIV) antibody or
             Hepatitis;

          -  Participant had a clinically significant disease, other than Gaucher disease,
             including cardiovascular, renal, hepatic, gastrointestinal, pulmonary, neurologic,
             endocrine, metabolic, or psychiatric disease, other medical conditions, or serious
             intercurrent illnesses that, in the opinion of the Investigator, might preclude
             participation in the study.