a study of the efficacy and safety of eliglustat tartrate (genz-112638) in type 1 gaucher patients

Conditions: Gaucher Disease, Type 1; Cerebroside Lipidosis Syndrome; Glucocerebrosidase Deficiency Disease; Glucosylceramide Beta-Glucosidase Deficiency Disease; Gaucher Disease, Non-Neuronopathic Form

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.

this study consists of several phases: screening (-28 to -1 days), dose adjustment/treatment (day 1 \[treatment baseline\] to day 30), initial steady-state treatment (post-day 30 through week 52 post-baseline), a treatment interruption period (week 52 through approximately week 54), long-term steady-state treatment (approximately week 54 through study completion), and safety follow-up (30 to 37 days after a participant withdraws from or completes the study). the primary analysis period is from baseline through week 52. the extension period is from week 52 through study completion (that is, participant withdrawal, the study is terminated, eliglustat tartrate becomes commercially available, or where applicable, specific regulatory requirements have been met).

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.

Keywords: type 1 gaucher disease glucocerebrosidase deficiency disease