What Is Trientine?
Trientine is an FDA-approved medication for Wilson Disease. It functions as a chelating agent, meaning it binds to and helps remove excess copper from the body. In conditions such as Wilson Disease, an inherited disorder, copper can accumulate to toxic levels in various organs, leading to serious health issues. By facilitating the elimination of this excess copper, trientine helps to mitigate its damaging effects.
Beyond its approved use, trientine is also under investigation for its potential in treating certain cancers. Research suggests that removing copper from the body may contribute to stopping the growth of cancer cells. For example, it has been studied in combination with other therapies for advanced cancers. Trientine dihydrochloride, the form typically studied, is a white to pale yellow crystalline powder. Overall, trientine has been investigated in 11 clinical trials involving 487 participants, with studies ranging from 1999 to 2021.
Uses and Conditions Under Study
Trientine is primarily studied for conditions involving excess copper in the body, but its potential applications extend to various other diseases, particularly cancers. Clinical trials have explored trientine across a range of conditions:
- Wilson Disease: Trientine is a well-established treatment for Wilson Disease, a genetic disorder where the body accumulates excessive copper. As a chelating agent, trientine helps remove this harmful buildup. This condition has been the focus of 3 trials.
- Cancers: Trientine is being investigated for its potential to inhibit cancer cell growth by reducing copper levels. Copper is essential for many cellular processes, and its removal may disrupt cancer progression. Conditions studied include Fallopian Tube Cancer, Ovarian Neoplasms Malignant (Excl Germ Cell), Peritoneal Carcinoma, and Advanced Cancers. One study specifically evaluated trientine in combination with vemurafenib for BRAF mutated metastatic melanoma.
- Eye Conditions: Trientine has been studied for its effects on certain eye disorders. These include Diabetic Retinopathy, a complication of diabetes affecting the eyes, and Macular Edema Following Cataract Surgery, a swelling in the retina after cataract removal. Each of these conditions has been the subject of 1 trial.
- Hypertrophic Cardiomyopathy: This is a condition where the heart muscle becomes abnormally thick. Trientine has been investigated in 1 trial for its potential role in managing this cardiac disorder.
In total, 7 completed trials have investigated trientine, with no trials currently recruiting new participants. These studies have involved a total of 487 participants across various institutions, including the University of British Columbia, Univar BV, and Yale University.
Dosing
Trientine is primarily studied as trientine dihydrochloride, typically administered orally in capsule form. Clinical trials have investigated various dosing regimens and strengths for different conditions.
Commonly, patients have taken their prescribed dose of trientine dihydrochloride 300mg. This dosage has been administered orally once daily, though studies have explored different dose levels. For instance, some trials have specified "trientine dihydrochloride 300MG/CAPSULE PO daily" with varying dose levels to assess safety and efficacy.
Trientine has also been studied in combination with other medications. In some cancer trials, it was investigated alongside vemurafenib for BRAF mutated metastatic melanoma. Other studies have explored trientine in combination with chemotherapy agents like carboplatin, with specific groups for determining the maximum tolerated dose (MTD) and evaluating pharmacokinetic (PK) properties of the combination.
The dosage forms studied include trientine dihydrochloride capsules, and it has been evaluated both as a standalone treatment and as part of combination therapies.
Side Effects
No specific side effect data for Trientine was provided in the clinical trial results reviewed for this section.
Clinical Trial Results
Wilson Disease
In a study (NCT01472874) evaluating a single daily dosage of Trientine for maintenance treatment of Wilson disease, several markers related to liver function and copper metabolism were observed. Patients treated with Trientine showed a mean reduction in ALT (alanine aminotransferase) levels from 50.89 U/L to 41.38 U/L, indicating an improvement in liver enzyme levels. Urinary copper excretion, a key indicator of the body's ability to remove excess copper, increased from a mean of 287.9 mcg/24hr to 313.4 mcg/24hr. Serum copper levels also saw a slight decrease from a mean of 0.54 mcg/24h to 0.52 mcg/24h. Other measures, such as albumin and INR (international normalized ratio), remained stable, with mean albumin levels at 0.54 g/dL and 0.52 g/dL, and INR values around 0.99 and 1.05, suggesting stable liver synthetic function and blood clotting. Urinary zinc levels decreased from a mean of 2214 mcg/24hr to 1959 mcg/24hr.
Epithelial Ovarian Cancer
A trial (NCT03480750) investigated Trientine in combination with chemotherapy (pegylated liposomal doxorubicin and carboplatin) for epithelial ovarian cancer. The study found that Trientine's maximum plasma concentration (Cmax) generally increased with higher doses, ranging from a median of 1.87 mg/L at a 300mg daily dose to 29.35 mg/L at an 1800mg daily dose. Importantly, across all tested dose levels of Trientine (from 300mg/d to 1800mg/d), there were no dose-limiting toxicities observed in any participants, suggesting the combination was well-tolerated within these dose ranges. The median overall survival for participants receiving Trientine with chemotherapy was 14.4 months. The median progression-free survival was 4.6 months. Measurable tumor treatment response, assessed by RECIST Criteria 1.1, was observed in 25.0% and 43.8% of participants, indicating that a notable proportion of patients experienced a reduction in tumor size or disappearance of tumors.