A Study of Eliglustat Tartrate (Genz-112638) in Patients With Gaucher Disease (ENGAGE)
Condition: Gaucher Disease, Type 1
MeSH terms: Gaucher Disease
Intervention: Eliglustat tartrate; Placebo
Intervention description: PAP: Eliglustat tartrate (ET) capsule 50 mg orally on Day 1 followed by ET 50 mg capsule twice daily (BID) from Day 2 to Week 4, then either ET 50 mg capsule BID (participants with Genz-99067 [active moiety of ET in plasma] trough plasma concentration >=5 ng/mL) or ET 100 mg capsule BID (participants with Genz-99067 trough plasma concentration <5 ng/mL), up to Week 39. PK assessment at Week 2 used for dose adjustment after Week 4. LTTP: Participants of the eliglustat arm in PAP who completed PAP were included in LTTP and received ET capsule 50 mg BID orally from Day 1 (post Week 39) until Week 43 followed by ET 50 mg or 100 mg capsule BID up to Week 47, then ET 50 mg or 100 mg or 150 mg capsule BID up to Week 312. Dose adjustments at Week 43 and Week 47 were based on Genz-99067 trough plasma concentrations (if trough plasma concentration <5 ng/mL: next higher dose administered; if >=5 ng/mL: same dose continued) at Week 41 & Week 45, respectively.; PAP: Matching placebo capsule once daily on Day 1 followed by matching placebo capsule BID from Day 2 through Week 39. LTTP: Participants of the placebo arm in PAP who completed PAP were included in LTTP and received eliglustat tartrate from Day 1 (post Week 39) up to Week 312. Day 1 (post Week 39) was considered as baseline for LTTP. On Day 1, participants received eliglustat tartrate capsule 50 mg BID orally until Week 43 followed by eliglustat tartrate 50 mg or 100 mg capsule BID up to Week 47, then eliglustat tartrate 50 mg or 100 mg or 150 mg capsule BID up to Week 312. Dose adjustments at Week 43 and Week 47 were based on Genz-99067 trough plasma concentrations (if trough plasma concentration <5 ng/mL: next higher dose administered; if >=5 ng/mL: same dose continued) at Week 41 & Week 45, respectively.
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: 40.0
Sex: All
Minimum age: 16 Years
Healthy volunteers: No
Keywords: Gaucher,; beta-glucosidase,; acid ß-glucosidase,; glucocerebrosidase,; glucosylceramide,; D-glucosyl-N-acylsphingosine glucohydrolase,; substrate reduction therapy

Summary:

      This Phase 3 study was designed to confirm the efficacy and safety of eliglustat tartrate
      (Genz-112638) in participants with Gaucher disease Type 1.
    

Eligibility criteria:

        Inclusion Criteria:

          -  The participant (and/or their parent/legal guardian) was willing and able to provide
             signed informed consent prior to any study-related procedures to be performed;

          -  The participant was at least 16 years old at the time of randomization;

          -  The participant had a confirmed diagnosis of Gaucher disease Type 1;

          -  Female participants of childbearing potential must had a documented negative pregnancy
             test prior to dosing. In addition all female participants of childbearing potential
             must use a medically accepted form of contraception throughout the study.

        Exclusion Criteria:

          -  The participant has had a partial or total splenectomy;

          -  The participant had received pharmacological chaperones or miglustat within 6 months
             prior to randomization;

          -  The participant had received enzyme replacement therapy within 9 months prior to
             randomization;

          -  The participant had Type 2 or 3 Gaucher disease or was suspected of having Type 3
             Gaucher disease;

          -  The participant had any clinically significant disease, other than Gaucher disease,
             including cardiovascular, renal, hepatic, gastrointestinal (GI), pulmonary,
             neurologic, endocrine, metabolic, (for example, hypokalemia, hypomagnesemia), or
             psychiatric disease, other medical conditions, or serious intercurrent illness that
             might confound the study results, or, on the opinion of the investigator, might
             preclude participation in the study;

          -  The participant had tested positive for the human immunodeficiency virus (HIV)
             antibody, Hepatitis C antibody, or Hepatitis B surface antigen;

          -  The participant had received an investigational product within 30 days prior to
             randomization;

          -  The participant was pregnant or lactating.