Clinical Trial of Deferasirox Combination Treatment With Deferiprone In Thalassaemia Patients

• ClinicalTrials.gov Identifier: NCT02198508
• Recruitment Status: Completed
• First Posted: July 23, 2014
• Last Update Posted: July 23, 2014
• Sponsor: China Medical University Hospital
• Information provided by (Responsible Party): Ching-Tien Peng, China Medical University, Taiwan

Tracking Information

• First Submitted Date: July 19, 2014
• First Posted Date: July 23, 2014
• Last Update Posted Date: July 23, 2014
• Study Start Date: July 2007
• Actual Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 22, 2014)

iron excretion from urine and feces by flame atomic absorption spectroscopy [ Time Frame: 25-days ]

Collections of urine and stool (made 24 hours a day) were analyzed separately.

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: July 22, 2014)

drug concentration in plasma by pharmacokinetics analysis [ Time Frame: 25-day ]

Through a venous catheter, serial blood samples (1 mL/each sampling) were collected into glass tubes containing heparin as an 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 dosing. Blood samples were centrifuged, with plasma collected and frozen at -20°C until analysis.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Clinical Trial of Deferasirox Combination Treatment With Deferiprone In Thalassaemia Patients
• Official Title: The Shuttle Effect : Combination Therapy With Deferiprone and Deferasirox in Transfusion-dependent Thalassemia Patients.

Brief Summary

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Beta-thalassemia Major

Intervention

• Drug: DFX(Deferasirox)
  Other Name: Exjade®, Novartis Pharmaceuticals Corporation, USA
• Drug: DFP(Deferiprone)
  Other Name: Kelfer®, Cipla Ltd., India

Study Arms

• Active Comparator: DFX single treatment
  a single oral dose of DFX 30 mg/kg once daily, (Exjade®, Novartis Pharmaceuticals Corporation, USA )
  Intervention: Drug: DFX(Deferasirox)
• Active Comparator: DFP single treatment
  single oral dose of DFP 40 mg/kg/day twice a day, (Kelfer®, Cipla Ltd., India)
  Intervention: Drug: DFP(Deferiprone)
• Experimental: combination treatment
  sequential oral doses of DFX 30 mg/kg/d, DFP 40 mg/kg/d and DFP 40 mg/kg/d (dosing interval: seven hours).
  Interventions:

  • Drug: DFX(Deferasirox)
  • Drug: DFP(Deferiprone)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 22, 2014): 13
• Original Actual Enrollment: Same as current
• Study Completion Date: Not Provided
• Actual Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT02198508
• Other Study ID Numbers: DMR-096-IRB-037
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Ching-Tien Peng, China Medical University, Taiwan
• Original Responsible Party: Same as current
• Current Study Sponsor: China Medical University Hospital
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: China Medical University Hospital
• Verification Date: July 2014