Trientine Tetrahydrochloride (TETA 4HCL) for the Treatment of Wilson's Disease

Inclusion Criteria

• Patient is able to provide, and has provided, written informed consent
• Written documentation has been obtained in accordance with the relevant country and local privacy requirements, where applicable, including: For US sites: Authorization for Use and Release of Health Research Study Information and for EU sites: Data Protection Consent
• Male or female, aged ≥ 18 and ≤ 75 years of age at time of consent
• Patient has a diagnosis of Wilson's disease, as defined by a prior or current Leipzig score of ≥ 4
• Patient's Wilson's disease is clinically stable, in the opinion of the investigator, and being treated with penicillamine for at least 1 year (52 weeks) prior to the screening/enrolment visit
• Patient is on a stable dose and regimen of penicillamine for at least 4 months (16 weeks) prior to the screening/enrolment visit (other prescribed treatments for Wilson's disease not permitted during this study)
• No anticipated need that patient will require additional pharmacological therapies other than study medication, including prescribed zinc therapy, for the management of copper levels during the study
• Patient must be willing to maintain stable diet throughout the study, and avoid foods with high copper content, including the Penicillamine Baseline Period
• Patient considered suitable to receive therapy with both TETA 4HCl and penicillamine administered twice a day
• Negative central laboratory tests for HIV and viral hepatitis (results will be available after start of run-in period)
• For female patients of childbearing potential, negative urine pregnancy test (at screening/enrolment visit and prior to randomization)
• For females of childbearing potential, use of a reliable form of contraceptive
• Patient is considered as able to complete study requirements and attend the study visits, in the opinion of the investigator

Additional inclusion criteria following receipt of Screening laboratory results

• Patient is adequately controlled and tolerating penicillamine therapy as defined by fulfilment of all of the following: a. Serum non-ceruloplasmin bound copper (NCC) level between ≥ 25 and ≤ 150 μg/L* b. 24-hour urinary copper excretion of between ≥ 100 and ≤ 900 μg/24 hours* c. Alanine transaminase (ALT) 4 (result may not be available until after start of run in period since based on lab results*)
• decompensated cirrhosis
• acute hemolytic anemia
• acute hepatitis
• hepatic malignancy
• evidence of acute liver failure
• Cause of patient's liver disease is due to another condition, in the investigator's opinion
• Patient has severe anemia defined as hemoglobin of ≤ 9 g/dL (result will be available after start of run-in period*)
• Patient has experienced a gastrointestinal bleed within 6 months (24 weeks) prior to screening/enrolment visit
• Patient has renal impairment defined as creatinine clearance of ≤ 30 mL/min (result may not be available until after start of run-in period*), or patient has nephritis or nephrotic syndrome, in the opinion of the investigator
• Patient has neurological disease that prevents swallowing of study medication (e.g., requires a nasogastric feeding tube) or requires intensive in-patient medical care
• Patient is currently taking medication containing trientine for management of Wilson's disease or has taken it within 4 months (16 weeks) of screening/enrolment visit
• Patient is currently receiving prescribed zinc therapy for management of Wilson's disease or has taken it within 4 months (16 weeks) of screening/enrolment visit
• Patient is taking any of the following concomitant therapies: gold therapy, antimalarial therapy, cytotoxic drugs, oxyphenbutazone, phenyl butazone
• Patient has a known intolerance, allergy or sensitivity to penicillamine (that is uncontrolled) or to TETA 4HCl, including any component of the study medication
• For female patients of childbearing potential, planning a pregnancy during study period or currently n