An Open Label Study to Evaluate the Pharmacokinetics, Safety, Tolerability and Efficacy of Deferasirox Administered to Chinese Patients With β-thalassemia Major Aged From 2 to Less Than 6 Years Old (MACS2163)

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01724138
First received: October 24, 2012
Last updated: August 21, 2014
Last verified: August 2014
  Purpose

To characterize the PK of deferasirox in pediatric β-thalassemia major patients aged from 2 to less than 6 years old, when administrated with a fixed starting dose of 20 mg/kg/day.


Condition Intervention Phase
β-thalassemia Major
Drug: Deferasirox
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label Study to Evaluate the Pharmacokinetics, Safety, Tolerability and Efficacy of Deferasirox Administered to Chinese Patients With β-thalassemia Major Aged From 2 to Less Than 6 Years Old

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • the PK profile of deferasirox in pediatric β-thalassemia major patients aged from 2 to less than 6 years old. [ Time Frame: PK sampling times are 0.5, 2.5, 6, 10h in Day 1 postdose; Day 2, 3, 4 and 5 predose and 0.5, 2.5, 6, 10h post dose on Day 4, then pre-dose at each subsequent visit until Week 49. Day -1 PK sample will be treated as Day 1 predose sample. ] [ Designated as safety issue: No ]
    Area under the plasma concentration-time curve from time zero to the end of the dosing interval.

  • the PK profile of deferasirox in pediatric β-thalassemia major patients aged from 2 to less than 6 years old: Cmax [ Time Frame: PK sampling times are 0.5, 2.5, 6, 10h in Day 1 postdose; Day 2, 3, 4 and 5 predose and 0.5, 2.5, 6, 10h post dose on Day 4, then pre-dose at each subsequent visit until Week 49. Day -1 PK sample will be treated as Day 1 predose sample. ] [ Designated as safety issue: No ]
    The maximum plasma concentration of study medication.

  • the PK profile of deferasirox in pediatric β-thalassemia major patients aged from 2 to less than 6 years old: Tmax [ Time Frame: PK sampling times are 0.5, 2.5, 6, 10h in Day 1 postdose; Day 2, 3, 4 and 5 predose and 0.5, 2.5, 6, 10h post dose on Day 4, then pre-dose at each subsequent visit until Week 49. Day -1 PK sample will be treated as Day 1 predose sample. ] [ Designated as safety issue: No ]
    Tmax was directly determined from the raw plasma concentration-time data.


Secondary Outcome Measures:
  • The safety and tolerability of deferasirox following multiple dosing in pediatric β-thalassemia major patients. [ Time Frame: Baseline, every 4 weeks until 48 weeks after taking the drug ] [ Designated as safety issue: Yes ]
    The adverse events and abnormal measurements of hematology, blood chemistry, urinalysis, urinary protein/creatinine ratio, physical examination, auditory and ocular examinations, ECG, ECHO, and growth development are collected for the measurement of safety and tolerability.

  • The efficacy of deferasirox in pediatric β-thalassemia patients as measured by change of serum ferritin. [ Time Frame: Baseline, every 4 weeks until 48 weeks after taking the drug ] [ Designated as safety issue: No ]
    Changes in serum ferritin from baseline to every 4 weeks are collected for the measurement of efficacy.


Enrollment: 0
Study Start Date: June 2013
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Deferasirox
The study will provide PK, safety, tolerability and efficacy data collected during 48 weeks of treatment with deferasirox in Chinese pediatric patients with transfusion dependent -thalassemia major, aged 2 to <6 years at enrollment. The target patient pool consists of 20 patients with evidence of iron overload measured by serum ferritin level at the start of study. Patients will start their deferasirox treatment with a dose of 20 mg/kg/day. Serum ferritin will be monitored every month and the dose of deferasirox will be adjusted if necessary every 3 months based on the trends in serum ferritin. Other possible dose adjustments will be based on the patient's safety assessments.
Drug: Deferasirox
Patients will start their deferasirox treatment with a dose of 20 mg/kg/day.

  Eligibility

Ages Eligible for Study:   2 Years to 71 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Pediatric patients aged from 2 to less than 6 years old.
  • Patients with transfusion dependent β-thalassemia major.
  • Serum ferritin values ≥ 1000 ng/ml at screening.
  • Written informed consent must be obtained from the patient's legal guardian in accordance with local law and regulation prior to any screening procedures.

Exclusion Criteria:

  • Non-transfusion-dependent thalassemia.
  • Systemic diseases which would prevent study treatment (e.g. uncontrolled hypertension, cardiovascular, renal, hepatic, metabolic, etc.)
  • Serum creatinine > age adjusted ULN.
  • Significant proteinuria as indicated by a urinary protein/creatinine ratio (UPCR) ≥ 0.5mg/mg in a non-first void urine sample at screening. If UPCR is found to be ≥ 0.5 mg/mg the test can be repeated after 1 month.
  • ALT/AST > 2.5xULN and total bilirubin > 1×ULN.
  • Left ventricular ejection fraction < 56% by echocardiography.
  • Patient has a known history of HIV seropositivity or history of active/treated hepatitis B or C (a test for screening is not required).
  • A history of clinically relevant ocular and/or auditory toxicity related to iron chelation therapy
  • Any surgical or medical conditions which will significantly alter the absorption, distribution, metabolism or excretion of the drug(e.g. ulcerative disease, uncontrolled nausea, vomiting, malabsorption syndrome, obstruction, or stomach and/or small bowel resection).
  • Other conditions which investigator deems potential harm to patients if participate the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01724138

Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01724138     History of Changes
Other Study ID Numbers: CICL670ACN02
Study First Received: October 24, 2012
Last Updated: August 21, 2014
Health Authority: China: Food and Drug Administration

Keywords provided by Novartis:
deferasirox

Additional relevant MeSH terms:
Thalassemia
Beta-Thalassemia
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Deferasirox
Iron Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 02, 2014