Safety, Efficacy and Pharmacokinetics of an Oral Iron Chelator Given for a Year to Pediatric Patients With Iron Overload
- Registration Number
- NCT01363908
- Lead Sponsor
- Shire
- Brief Summary
This is an open-label study to assess the pharmacokinetics, safety, efficacy and tolerability of SSP-004184AQ. The study consists of two phases: the pharmacokinetic phase, using a single 16 mg/kg dose of SSP-004184AQ; and the chronic dosing phase, during which patients will receive an additional 48 weeks of SSP-004184AQ dosing. Two age groups will be studied: 6-\<12, and 12-\<18 years old. The study is designed to initially assess the pharmacokinetics and safety of SSP-004184AQ in older children (adolescents, 12-\<18 years old) and then if deemed safe, in younger children (6-\<12 years old).
- Detailed Description
Pharmacokinetic Phase: Patients will receive a single 16 mg/kg dose of SSP-004184AQ in capsule form.
Chronic Dosing Phase: Patients will receive SSP-004184AQ capsules daily for 48 weeks. Doses may range from 8-60 mg/kg/d.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 30
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description SPD602 (36 mg/kg) SPD602 Oral SSP-004184AQ taken once daily for 48 weeks. Starting dose based on transfusion burden and iron overload status. Doses may range from 8-60mg/kg/day depending on clinical response. SPD602 (16 mg/kg) SPD602 A single dose given in the initial pharmacokinetic phase. SPD602 (26 mg/kg) SPD602 Oral SSP-004184AQ taken once daily for 48 weeks
- Primary Outcome Measures
Name Time Method Maximum Observed Plasma Concentration (Cmax) of SPD602 After a Single Oral Dose Day 1 and up to 24 hours post-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.
Area Under The Plasma Concentration-Time Curve (AUC) From The Time of Dosing to The Last Measurable Concentration (AUClast) of SPD602 After a Single Oral Dose Day 1 and up to 24 hours post-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.
Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by FerriScan R2 MRI Baseline, 24 weeks, and 48 weeks The efficacy of SPD602 was assessed by determining LIC and adjusting for transfusional iron intake. Abdominal MRI data were collected by using FerriScan R2 standard procedures and used to determine LIC. A negative change from baseline indicates that LIC decreased.
Fraction Of Orally Administered Drug Excreted Unchanged In Urine (fe) of SPD602 After a Single Oral Dose Day 1 and up to 24 hours post-dose The pharmacokinetic (PK) parameters of SPD602 were measured in urine of 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. Children who could cooperate provided urine samples for PK assessment on Day 1 over 3 time intervals: 0-4, 4-8, and 8-24 hours after the last dose (continued into Day 2). Urine concentrations of SPD602 were determined using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The PK parameters were determined from urine concentration-time data for SPD602 (total) by non-compartmental analysis.
Time of Maximum Observed Plasma Concentration Sampled During a Dosing Interval (Tmax) of SPD602 After a Single Oral Dose Day 1 and up to 24 hours post-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.
Terminal Half-life (t1/2) of SPD602 After a Single Oral Dose Day 1 and up to 24 hours post-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.
Renal Clearance (CLr) of SPD602 After a Single Oral Dose Day 1 and up to 24 hours post-dose The pharmacokinetic (PK) parameters of SPD602 were measured in urine of 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. Children who could cooperate provided urine samples for PK assessment on Day 1 over 3 time intervals: 0-4, 4-8, and 8-24 hours after the last dose (continued into Day 2). Urine concentrations of SPD602 were determined using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The PK parameters were determined from urine concentration-time data for SPD602 (total) by non-compartmental analysis.
Amount Excreted Into Urine (Ue) of SPD602 After a Single Oral Dose Day 1 and up to 24 hours post-dose The pharmacokinetic (PK) parameters of SPD602 were measured in urine of 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. Children who could cooperate provided urine samples for PK assessment on Day 1 over 3 time intervals: 0-4, 4-8, and 8-24 hours after the last dose (continued into Day 2). Urine concentrations of SPD602 were determined using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The PK parameters were determined from urine concentration-time data for SPD602 (total) by non-compartmental analysis.
Change From Baseline in Liver Iron Concentration (LIC) Assessed by FerriScan R2 Magnetic Resonance Imaging (MRI) Baseline, 24 weeks, and 48 weeks The efficacy of SPD602 was assessed by determining LIC. Abdominal MRI data were collected by using FerriScan R2 standard procedures and used to determine LIC. A negative change from baseline indicates that LIC decreased.
- Secondary Outcome Measures
Name Time Method Change From Baseline in LIC Assessed by R2* MRI Baseline, 24 weeks, and 48 weeks The efficacy of SPD602 was assessed by determining LIC. Abdominal MRI data were collected by using R2\* standard procedures and used to determine LIC. A negative change from baseline indicates that LIC decreased.
Change From Baseline in Cardiac Iron Load Assessed by T2* MRI Baseline, 24 weeks, and 48 weeks The efficacy of SPD602 was assessed by determining cardiac iron load. Cardiac MRI data were collected by using T2\* standard procedures and used to determine iron load. A negative change from baseline indicates that iron load increased.
Change From Baseline in Serum Ferritin Baseline, 24 weeks, and 48 weeks Serum ferritin levels were assessed to determine if a participant was a successful responder and were determined from serum biochemistry analyses conducted at the central laboratories. A negative change from baseline indicates that serum ferritin decreased.
Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by R2* MRI Baseline, 24 weeks, and 48 weeks The efficacy of SPD602 was assessed by determining LIC and adjusting for transfusional iron intake. Abdominal MRI data were collected by using R2\* standard procedures and used to determine LIC. A negative change from baseline indicates that LIC decreased.
Trial Locations
- Locations (9)
Children's Hospital Boston
🇺🇸Boston, Massachusetts, United States
Ege University Hospital
🇹🇷Izmir, Turkey
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Ospedale Regionale Mecrocitemie
🇮🇹Cagliari, Italy
Toronto Sick Kids Hospital
🇨🇦Toronto, Ontario, Canada
Thalassemia Center San Luigi Hospital
🇮🇹Orbassano, Italy
Centro della Microcitemia e delle Anemie Congenite
🇮🇹Genoa, Italy
Chronic Care Center
🇱🇧Beirut, Lebanon
American University of Beirut Medical Center
🇱🇧Beirut, Lebanon