NCT00749515

Pilot Pharmacokinetic Study In Patients With Inadequate Response To Deferasirox (Exjade)

Completed Phase 4 Results posted Last updated 8 February 2024

What this trial tests

Phase 4 trial testing Deferoxamine in Transfusion-dependent Hemachromatosis in 15 participants. Completed in 1 November 2008.

Timeline

1 March 2008

Primary endpoint
1 October 2008

1 November 2008

Quick facts

Lead sponsor	Boston Children's Hospital
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	15
Start date	1 March 2008
Primary completion	1 October 2008
Estimated completion	1 November 2008
Sites	1 location across United States

Drugs / interventions tested

• Deferoxamine (DEFEROXAMINE) — full drug profile →
• Deferasirox (DEFERASIROX) — full drug profile →
• HIDA

Conditions studied

• Transfusion-dependent Hemachromatosis — all drugs for Transfusion-dependent Hemachromatosis →
• Thalassemia Major — all drugs for Thalassemia Major →
• Sickle Cell Disease — all drugs for Sickle Cell Disease →

Sponsor

Boston Children's Hospital

Who can join

6 and older, any sex, with Transfusion-dependent Hemachromatosis or Thalassemia Major. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Area Under the Curve of Deferasirox After a Dose of 35 mg/kg
  Time frame: 0, 1, 2, 4, 6, 8, 12, and 24 hours post dose
  Area Under the Curve (AUC) 0 to 24 hours post dose
• Half-Life of Deferasirox
  Time frame: 0, 1, 2, 4, 6, 8, 12, and 24 hours post dose.
  All patients received the same interventions of deferoxamine challenge, deferasirox dose with pharmacokinetic monitoring. Then we compared responses between patients who were known to be slow responders to deferasirox and those who were known to be rapid responders (chelated well). Deferoxamine: After a 3-day washout period from all chelation, all patients have a 12 hour infusion of 50mg/kg of de
• Volume of Distribution/Bioavailability of Deferasirox After a Dose of 35 mg/kg
  Time frame: 0, 1, 2, 4, 6, 8, 12, and 24 hours post dose
  Volume of distribution/bioavailability (Vd/F)
• Volume of Distribution/Bioavailability of Deferasirox After a Dose of 35 mg/kg
  Time frame: 0, 1, 2, 4, 6, 8, 12, and 24 hours post dose
  Volume of distribution/bioavailability (Vd/F), adjusted per kilogram body weight
• Clearance/Bioavailability of Deferasirox in Patients With Poor Response to Deferasirox Compared to Patients With Good Response After a Dose of 35 mg/kg
  Time frame: 0, 1, 2, 4, 6, 8, 12, and 24 hours post dose.
  Clearance/bioavailability (CL/F)

Sponsor's own description

This purpose of this study is to understand the differences between people who have a good response to deferasirox (exjade) compared to people who have a poor response to this medication when used for transfusion-dependent iron overload.

The hypothesis is that patients with poor responses have physiologic barriers to deferasirox that may include absorption, pharmacokinetics of drug metabolism, hepatic clearance and/or genetic factors.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Iron homeostasis and ferroptosis in human diseases: mechanisms and therapeutic prospects.
   Ru Q, Li Y, Chen L, Wu Y, et al · · 2024 · cited 365× · PMID 39396974 · DOI 10.1038/s41392-024-01969-z
2. Deferasirox pharmacokinetics in patients with adequate versus inadequate response.
   Chirnomas D, Smith AL, Braunstein J, Finkelstein Y, et al · · 2009 · cited 69× · PMID 19724055 · DOI 10.1182/blood-2009-05-222729