NCT01363908 - Safety, Efficacy and Pharmacokinetics of an Oral Iron Chelator Given for a Year to Pediatric Patients With Iron Overload | Crick

Eligibility

Sex: ALLMin age: 6 YearsMax age: 17 Years

Medical Language ↔ Plain English

Inclusion Criteria * Parents willing and able to sign the approved informed consent for their children and subjects between the ages of 6 and \<18 years willing and able to provide their assent (based on institutional guidelines). * Able to swallow whole capsules. * Age \>6 and \<18 years. * Transfusion-dependent subjects who have transfusional iron overload requiring chronic treatment with deferoxamine, deferasirox, or deferiprone. A transfusion dependent subject is defined in this study as one with a minimum transfusion history totaling more than 20 units of packed red blood cells OR a calculated iron load based on transfusion history of 200mg/kg AND a transfusion requirement of 7 or more transfusions per year; or, in subjects with sickle cell anemia, be iron overloaded but can be receiving transfusion exchange therapy in lieu of transfusions. * In the opinion of the Investigator (and in consultation with the subject's parents), the subject is able to discontinue all existing iron chelation therapies for a minimum period of 1-5 days prior first dose of SSP-004184AQ, for the initial pharmacokinetic period of 8 days (if applicable), and for up to 49 weeks if continuing into the chronic dosing phase. * Subjects able to have an MRI must have: 1. liver iron concentration \>2 and \<30mg/g (dry weight, liver) by FerriScan® R2 2. cardiac MRI T2\* \>10ms (Note: Subjects not able to have an MRI will be considered iron overloaded on the basis of serum ferritin only.) * Serum ferritin \>500ng/mL at Screening. * Mean of the previous 3 pre-transfusion hemoglobin concentrations greater than or equal to 7.5g/dL. * If appropriate, depending on age, female subjects of child-bearing potential need to use a medically acceptable method for birth control from screening until 30 days after the last dose of the study drug. Females of child-bearing potential must have a negative serum beta-HCG pregnancy test at the Screening Visit and a negative urine pregnancy test at the Baseline Visit. Females of child-bearing potential must agree to abstain from sexual activity that could result in pregnancy or agree to use acceptable methods of contraception. Exclusion Criteria * As a result of medical review, physical examination (including height and weight) or Screening investigations, the Principal Investigator considers the subject unfit for the study. * Iron overload from causes other than transfusional hemosiderosis. * Severe cardiac dysfunction. * Non-elective hospitalization within the 30 days prior to Baseline testing. * Evidence of clinically significant oral, cardiovascular, gastrointestinal, hepatic, biliary, renal, endocrine, pulmonary, neurologic, psychiatric, or skin disorder that contra-indicates dosing with SSP-004184AQ. * Evidence of significant renal insufficiency, eg, serum creatinine above the upper limit of normal or proteinuria greater than 1 gm per day. * Known sensitivity to any ingredient in the SSP-004184AQ formulation. * Platelet count below 100,000/µL or absolute neutrophil count less than 1500/mm3 at Screening. * ALT \>180 IU/L at Screening. * Use of any investigational agent within the 30 days prior to Baseline testing. * Pregnant or lactating females. * Cardiac left ventricular ejection fraction a) Below the locally determined normal range in the 12 months prior to screening by echocardiography or MRI or \<50% at Baseline testing by MRI (echocardiograph is acceptable for LVEF if MRI information is not available).

Outcomes

Primary Outcomes

Maximum Observed Plasma Concentration (Cmax) of SPD602 After a Single Oral Dose

The pharmacokinetic (PK) parameters of SPD602 were measured in plasma of all patients following a single capsule dose of SPD602 at 16 mg/kg at start of treatment on Day 1 and at the clinic visit on Day 2. PK blood samples were collected as follows: Pre-dose on Day 1 (within 60 minutes prior to investigational product administration) and at 0.5, 1, 2, 3, 4, 8 hours (±3 minutes) and 24 hours (±30 minutes) post-dose. Plasma concentrations of SPD602 were determined using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The PK parameters were determined from plasma concentration-time data for SPD602 (total) by non-compartmental analysis.