transfusional haemosiderosis MedDRA version: 14.1 Level: PT Classification code 10019024 Term: Haemosiderosis System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Trade Name: Deferasirox (Exjade®) dispersible tablets 125 mg
Product Name: Exjade 125 mg
Pharmaceutical Form: Dispersible tablet
INN or Proposed INN: Deferasirox
CAS Number: 201530-41-8
Current Sponso
Sponsors
University College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Adults 18 years and over Ability to provide informed consent Ability to meet all study requirements Adequate renal function (e.g. creatinine clearance= 60ml/min), Wllingness to stop other iron chelation therapy, No known allergies to the drug Not pregnant or breast feeding and willing to use effective contraception For non-naive cohort: male or female participants with transfusional iron overload as defined by a minimum of 20 lifetime transfusion episodes and transfusional iron loading with ferritin levels >500 mcg/L and/or liver iron concentration >3 mg of iron/g dry weight (as previously demonstrated by liver biopsy or MRI prior to the study); established on deferasirox therapy for at least 1 year and suffering GI side effects believed to be related to their therapy as suggested by at least one of the following: - The temporal relationship of gastrointestinal side effects occurrence with the administration of deferasirox …. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 64 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: Patients with gastrointestinal symptoms assumed or known NOT to be caused by deferasirox. Patients who are treated for any condition with aspirin daily, patients under chronic steroid therapy and patients on anticoagulant therapy that could all lead to potential gastrointestinal symptoms/bleeding. Presence of gastrointestinal disease that may significantly alter the absorption of deferasirox (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhoea, malabsorption syndrome, gastrointestinal or rectal bleeding). History of gastrointestinal surgery (except appendicitis and cholecystectomy) e.g. stomach/bowel surgery or awaiting elective surgery in the next 2 months. Undergoing acute medical intervention or hospitalization. Psychiatric illness (schizophrenia, major depression) which may interfere with study requirements Any other medical condition that, in the opinion of the site investigator would interfere with completing the study (visual problems or cognitive impairment. Platelet count less than 100 000 Currently on treatment for Hepatitis C Patients with severe iron loading in the heart (T2* less than 10 ms) and/or patients with severe total body iron load (liver iron concentration over 30 mg/g dry weight) Patients who have historical evidence of severe iron loading in the heart Women of child-bearing potential who are planning a pregnancy, pregnant, lactating and unwilling to use effective means of contraception. Inadequate renal function (e.g. Creatinine clearance < 60ml/min) Patients unwilling to stop using other iron chelation therapy for the trial duration Known allergy to the drug Patients on aluminium containing antacid preparations Patients who are on Vitamin C at doses higher than 200mg/day Patients receiving or having received any investigational drug within 30 days prior to study enrolment Patients unable to understand oral or written English
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the gastrointestinal (GI) tolerability of deferasirox administered before and after meals in patients with iron overload due to multiple blood transfusions, on established deferasirox therapy. The primary endpoint is the difference in mean individual Gastrointestinal Quality of Life Index (GIQLI)score change from baseline to end of study in the before-meals arm versus after-meals arm.;Secondary Objective: 1) To describe the gastrointestinal tolerability of deferasirox administered before and after meals in patients with transfusional iron overload naive to deferasirox therapy. The secondary endpoint is the difference in mean individual GIQLI score change from baseline to 1 month and 2 months of before meal versus after meal deferasirox administration. 2) To compare steady state pharmacokinetics profile characteristics (AUCss, Cmax ss, Cmin ss) following 1 month of deferasirox administered either before or after meals in a crossover design in patients with established deferasirox therapy. where AUCss is Area Under the Curve at steady state (a measure of bioavailability of drug and drug clearance) Cmax ss is the maximum concentration of drug at steady state Cmin ss is the minimum concentration of drug at steady state Exploratory: 1) To investigate the relationship between plasma level of the iron-drug complex and plasma iron parameters.;Primary end point(s): Primary endpoint is the between-treatment arm-difference of the mean individual change of Gastrointestinal Quality of Life Index(GIQLI) (follow-up minus baseline) in the non-naive cohort (patients on established deferasirox therapy).;Timepoint(s) of evaluation of this end point: Four weeks after treatment 1 in the non-naive cohort Four weeks after crossover day 1 in the non-naive cohort | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Difference between mean follow-up ( 1 month and 2 months) vs baseline changes of GIQLI per arm in naive cohort 2) Difference of the mean GSRS score changes in both arms of the established cohort and the naive cohort 3) Difference of the mean SF-36 score changes in both arms of the established cohort and the naive cohort 4) Arm difference of geometric mean steady state Cmin at visit 3 and visit 4 in the cross-over group 5) Arm difference of geometric mean AUC and Cmax at Visit 3 and visit 4 in cross-over group 6) Arm difference of geometric mean steady-state Cmin at Visit 3 for all patients (after 1 month of treatment) 7)Effect of food on systemic exposure of deferasirox as assessed by Pharmacokinetics approach. Pooled PK data from all arms will be analysed with a population PK model and appropriate covariates will be examined for clinical and statistical relevance.;Timepoint(s) of evaluation of this end point: 4 weeks and 8 weeks after treatment day 1 | — |
Countries
United Kingdom
Outcome results
None listed