Health Condition 1: null- Gaucher Disease Type 1 Health Condition 2: E752- Other sphingolipidosis
Conditions
Interventions
Intervention1: Genz-112638: Capsule: 50, 100 or 150 mg BID
Control Intervention1: Placebo: Capsule
Sponsors
Genzyme Europe BV
Eligibility
Inclusion criteria
Inclusion criteria: The patient (and/or their parent/legal guardian) is willing and able to provide signed informed consent prior to any study-related procedures to be performed. The patient is at least 16 years old at the time of randomization. The patient¡¯s Tanner Stage should be ¡Ý 4 prior to randomization. The patient has a diagnosis of Gaucher disease type 1 confirmed by a documented deficiency of acid ¦Â-glucosidase activity by enzyme assay. The patient has the following symptoms of Gaucher disease during the Screening period: A. At least one of the following laboratory abnormalities: 1. Hemoglobin level of 8.0 to 11.0 g/dL if female or 8.0 to 12.0 g/dL if male (the mean of 2 measurements from separate blood samples collected at least 24 hours apart during Screening). 2. Platelet count of 50,000 to 130,000/mm3 (the mean of 2 measurements from separate blood samples collected at least 24 hours apart during Screening). B. Splenomegaly (spleen volume of 6 to 30 MN). C. If hepatomegaly is present, the liver volume must be 2.5MN. The patient consents to provide a blood sample to Genzyme for genotyping for Gaucher disease, chitotriosidase, and CYP2D6 (to categorize the patient¡¯s predicted rate of metabolism), unless the patient¡¯s genotypes for Gaucher disease, chitotriosidase, and CYP2D6 are already available. Female patients of childbearing potential must have a documented negative pregnancy test prior to randomization. In addition, all female patients of childbearing potential must use a medically accepted form of contraception throughout the study (either a barrier method or hormonal contraceptive with ethinyl estradiol and norethindrone or similar active components). The patient is willing to abstain from consumption of grapefruit or grapefruit juice for 72 hours prior to administration of the first dose of study medication and throughout the duration of the Double-Blind Primary Analysis Period.
Exclusion criteria
Exclusion criteria: The patient has had a partial or total splenectomy. The patient has received pharmacological chaperone or substrate reduction therapies for Gaucher disease within 6 months prior to randomization. The patient has received enzyme replacement therapy for Gaucher disease within 9 months prior to randomization. The patient has any evidence of neurologic (e.g., peripheral neuropathy, tremor, seizures, Parkinsonism, or cognitive impairment) or pulmonary involvement (e.g., pulmonary hypertension) as related to Gaucher disease. The patient has current symptomatic bone disease such as bone pain attributable to osteonecrosis and/or pathologic fracture, or has had a bone crisis in the 12 months prior to randomization. The patient is transfusion-dependent. The patient has the following laboratory abnormalities during the Screening period: A. Hemoglobin level 8 g/dL (the mean of 2 measurements from separate blood samples collected at least 24 hours apart during Screening). B. Platelet count of 50,000/mm3 (the mean of 2 measurements from separate blood samples collected at least 24 hours apart during Screening). The patient has documented anemia due to causes other than Gaucher disease that requires treatment not yet initiated or not yet stable under treatment for at least 3 months (e.g., iron, vitamin B-12, and/or folate deficiency) prior to randomization. The patient has documented thalassemia minor or sickle cell trait with a platelet count of 50,000 or 130,000/mm3. The patient has ever had any radiation treatment in the abdominal region. The patient has documented prior esophageal varices or liver infarction or current liver enzymes (alanine aminotransferase [ALT]/ aspartate aminotransferase [AST]) or total bilirubin 2 times the upper limit of normal (ULN), unless the patient has a diagnosis of Gilbert Syndrome. The patient has any clinically significant disease, other than Gaucher disease, including cardiovascular, renal, hepatic, GI, pulmonary, neurologic, endocrine, metabolic (e.g. hypokalemia, hypomagnesemia), or psychiatric disease, other medical conditions, or serious intercurrent illnesses that, in the opinion of the Investigator, may preclude participation in the study. The patient is 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 patient has tested positive for the human immunodeficiency virus (HIV) antibody, Hepatitis C antibody, or Hepatitis B surface antigen. The patient has received an investigational product within 30 days prior to randomization. The patient is scheduled for in-patient hospitalization, including elective surgery, during the study. The patient has a history of cancer within 5 years of randomization, with the exception of basal cell carcinoma. The patient is pregnant or lactating. The patient has received any medication that may cause QTc interval prolongation within 30 days prior to randomization. The patient has received (acute or chronic) treatment with a CYP3A4 or CYP2D6 inducer within 30 days prior to randomization. The patient is not a CYP2D6 poor metabolizer, and has received any medication that is
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| The secondary objectives for this study include an evaluation of safety and the effects on disease manifestations and disease specific bio-markersTimepoint: Time Frame: 39 weeks | — |
Primary
| Measure | Time frame |
|---|---|
| The Primary objective is to compare the effects of Genz-112638 as compared to placebo in patients with Type 1 Gaucher Disease Timepoint: Time Frame: 39 weeks | — |
Countries
Bulgaria, Canada, Chile, Colombia, India, Israel, Jordan, Lebanon, Mexico, Netherlands, Russian Federation, Saudi Arabia, Tunisia, United Kingdom, United States of America
Contacts
Public ContactDr Senthilnathan Mohanasundaram
Genzyme
Outcome results
None listed