Clinical Trial of Deferasirox Combination Treatment With Deferiprone In Thalassaemia Patients

China Medical University

Status: Completed

Conditions: Beta-thalassemia Major

Treatments: Drug: DFP(Deferiprone); Drug: DFX(Deferasirox)

Study type: Interventional

Funder types: Other

Identifiers

NCT02198508

DMR-096-IRB-037

Details and patient eligibility

About

Background: Three iron chelators now available on the market differ in toxicity and organ specificity; evidence on standardized chelation protocol remains inconclusive, but patients with transfusion-dependent beta-thalassemia treated with DFO infusion show significant differences in the limitations of daily activities, physical activity, and quality of life when treated with oral chelator. With licensing of DFP in America, it is reasonable to combine DFP with DFX. Patients find two oral chelators more acceptable than one oral and one injectable. This pilot study rates use of DFP for improving iron excretion profile of deferasirox.

Methods: The investigators enrolled 13 beta-thalassemia patients in China Medical University Children's Hospital in May 2009-October 2011. Five refused to take part in pharmacokinetics; they only participated in iron excretion study. Seven with irregular bowel function were unable to collect feces in the screening period as baseline data. Subjects were randomly assigned and rotated to undergo all treatments (with informed consent): (A) single oral dose of DFX 30 mg/kg once daily, (B) single oral dose of DFP 40 mg/kg twice a day, (C) oral doses of DFX and DFP administered sequentially (DFX 30 mg/kg/d, deferiprone 40 mg/kg/d and deferiprone 40 mg/kg/d at 7-hour intervals). Three-day drug dosage was followed by four-day washout. Collections of urine and stool proceeded 24 hours per day, each analyzed separately. Through a venous catheter, serial blood samples (1 mL/each sampling) were collected in glass tubes containing heparin as anticoagulant at Time 0 (pre-dosing) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 6, 7, 8, 10, 12 and 24 hours after dose; plasma concentrations of DFP and DFX were measured.

Enrollment: 13 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 18 years of age or older
• serum ferritin greater than 2000 ng/mL,
• serum creatinine within normal range for a measuring laboratory
• platelet count exceeding 140000/mm3
• body weight at least 40 Kg
• None had a history of clinical significant of gastrointestinal, hepatic, renal, endocrine, oncologic, infectious, pulmonary or cardiovascular disease

Exclusion criteria

• HIV positive, history of immunologic hypersensitivity to any medication
• women pregnant or breast feeding
• drug or alcohol abuse
• patients showed abnormal or irregular bowel function (defined as more than three bowel movements a day or less than one bowel movement every other day)
• receiving warfarin, digoxin, or anti-arrhythmic or antiseizure medication.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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13 participants in 3 patient groups

DFX single treatment

Active Comparator group

Description:

a single oral dose of DFX 30 mg/kg once daily, (Exjade®, Novartis Pharmaceuticals Corporation, USA )

Treatment:

Drug: DFX(Deferasirox)

DFP single treatment

Active Comparator group

Description:

single oral dose of DFP 40 mg/kg/day twice a day, (Kelfer®, Cipla Ltd., India)

Treatment:

Drug: DFP(Deferiprone)

combination treatment

Experimental group

Description:

sequential oral doses of DFX 30 mg/kg/d, DFP 40 mg/kg/d and DFP 40 mg/kg/d (dosing interval: seven hours).

Treatment:

Drug: DFP(Deferiprone)

Drug: DFX(Deferasirox)