Conditions: Gaucher Disease, Type 1
Keywords: Gaucher disease, Genz-112638, beta-glucosidase, acid ß-glucosidase, glucocerebrosidase, glucosylceramide, D-glucosyl-N-acylsphingosine glucohydrolase, substrate reduction therapy
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 160
Healthy volunteers: no

Brief 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 who had reached therapeutic goals with enzyme replacement therapy (ERT).

Detailed description:
Gaucher disease is characterized by lysosomal accumulation of glucosylceramide due to impaired glucosylceramide hydrolysis. Gaucher disease type 1, which is the most common form, accounts for greater than (\>) 90% of cases and does not involve the central nervous system (CNS). Typical manifestations of Gaucher disease type 1 include splenomegaly, hepatomegaly, thrombocytopenia, anemia, bone disease, and decreased quality of life. The disease manifestations are caused by the accumulation of glucosylceramide (storage material) in macrophages (called Gaucher cells) which have infiltrated the spleen and liver as well as other tissues.

Eliglustat tartrate is a small molecule drug developed as an oral therapy which acts to specifically inhibit production of this storage material in Gaucher cells.

This study was designed to determine the efficacy, safety, and PK of eliglustat tartrate in adult participants with Gaucher disease type 1 who had been stabilized on ERT.

Arms:
arm 1: Eliglustat tartrate arm 2: None

Interventions: intervention 1: Eliglustat tartrate intervention 2: Imiglucerase
Intervention descriptions: intervention 1: Primary analysis period (PAP): Eliglustat tartrate capsule 50 milligram (mg) twice daily (BID) orally from Day 1 to Week 4 followed by eliglustat tartrate 50 mg or 100 mg capsule BID up to Week 8, and then eliglustat tartrate 50 mg or 100 mg or 150 mg capsule BID up to Week 52. Dose adjustments after Week 4 and Week 8 were based on Genz-99067 (active moiety of eliglustat tartrate in plasma) trough plasma concentrations. If Genz-99067 trough plasma concentration was less than (\<) 5 nanogram per milliliter \[ng/mL\] next higher dose was administered whereas if Genz-99067 trough plasma concentration was greater than or equal to (\>=) 5 ng/mL same dose was continued. Pharmacokinetic (PK) assessment at Week 2 and 6 were used for dose adjustment after Week 4 and Week 8, respectively.

Long-term treatment period (LTTP): Participants originally randomized to eliglustat in PAP continued to receive eliglustat dose, based on their Genz 99067 plasma trough concentration at Week 6. intervention 2: PAP: Imiglucerase intravenous infusion every other week (q2w) up to Week 52 in doses equivalent to participant's past ERT dose prior to any unanticipated treatment interruption, dose reduction, or regimen change.

LTTP: Participants originally randomized to imiglucerase received eliglustat tartrate capsule 50 mg BID orally from Week 52+1 Day to Week 56 followed by eliglustat tartrate 50 mg or 100 mg capsule BID up to Week 60, and then eliglustat tartrate 50 mg or 100 mg or 150 mg capsule BID up to 5 years. The dose adjustments after Week 56 and Week 60 were based on Genz-99067 (active moiety of eliglustat tartrate in plasma) trough plasma concentrations. If Genz-99067 trough plasma concentration was \<5 ng/mL the next higher dose was administered whereas if the Genz-99067 trough plasma concentration was \>=5 ng/mL the same dose was continued. The PK assessment at Week 54 and Week 58 were used for dose adjustment after Week 56 and Week 60, respectively.

Protocol document: