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

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ClinicalTrials.gov Identifier: NCT01363908
Recruitment Status : Terminated (This study was terminated due to treatment stop resulting in an inability to draw conclusions from the data. Evaluation of nonclinical rat findings is ongoing.)
First Posted : June 2, 2011
Results First Posted : May 27, 2015
Last Update Posted : June 14, 2021
Sponsor:
Information provided by (Responsible Party):
Takeda ( Shire )

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Transfusional Iron Overload
Beta-Thalassemia
Intervention Drug: SPD602
Enrollment 30
Recruitment Details  
Pre-assignment Details The study consisted a pharmacokinetic (PK) phase and a chronic dosing (CD) phase. A sufficient number of participants were screened to enroll 16 participants into the PK phase (8 participants per age cohort). These participants could consent to participate in the CD phase. Additional participants also participated in the CD phase.
Arm/Group Title 6 to <12 Year Old 12 to <18 Year Old
Hide Arm/Group Description During the pharmacokinetic phase, participants aged 6 to less than 12 years received a single oral dose of SPD602 16mg/kg. During the chronic dosing phase, participants commenced 48 weeks of treatment with an initial dose of SPD602 26mg/kg/day or 36mg/kg/day. Over the course of treatment, the dose could range from 8-60mg/kg/day depending on clinical response. During the pharmacokinetic phase, participants aged 12 to less than 18 years received a single oral dose of SPD602 16mg/kg. During the chronic dosing phase, participants commenced 48 weeks of treatment with an initial dose of SPD602 26mg/kg/day or 36mg/kg/day. Over the course of treatment, the dose could range from 8-60mg/kg/day depending on clinical response.
Period Title: Screening/Enrollment
Started 14 16
Completed 13 [1] 16
Not Completed 1 0
[1]
One participant did not receive investigational product.
Period Title: Pharmacokinetic (PK) Phase
Started 8 [1] 8 [1]
Completed 8 8
Not Completed 0 0
[1]
Per study design, at least 8 participants in each age cohort participated in the PK phase.
Period Title: Chronic Dosing (CD) Phase
Started 13 [1] 16 [1]
Completed 3 10
Not Completed 10 6
Reason Not Completed
Adverse Event             1             1
Patient decision             0             1
Physician Decision             0             1
Early study termination             9             3
[1]
The CD phase enrolled willing participants who completed the PK phase plus additional participants.
Arm/Group Title 6 to <12 Year Old 12 to <18 Year Old Total
Hide Arm/Group Description During the pharmacokinetic phase, participants aged 6 to less than 12 years received a single oral dose of SPD602 16mg/kg. During the chronic dosing phase, participants commenced 48 weeks of treatment with an initial dose of SPD602 26mg/kg/day or 36mg/kg/day. Over the course of treatment, the dose could range from 8-60mg/kg/day depending on clinical response. During the pharmacokinetic phase, participants aged 12 to less than 18 years received a single oral dose of SPD602 16mg/kg. During the chronic dosing phase, participants commenced 48 weeks of treatment with an initial dose of SPD602 26mg/kg/day or 36mg/kg/day. Over the course of treatment, the dose could range from 8-60mg/kg/day depending on clinical response. Total of all reporting groups
Overall Number of Baseline Participants 13 16 29
Hide Baseline Analysis Population Description
The Safety Analysis Set, defined as all participants who had taken at least 1 dose of investigational product.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 13 participants 16 participants 29 participants
8.6  (1.85) 14.4  (1.78) 11.8  (3.42)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 16 participants 29 participants
Female
7
  53.8%
8
  50.0%
15
  51.7%
Male
6
  46.2%
8
  50.0%
14
  48.3%
1.Primary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of SPD602 After a Single Oral Dose
Hide Description 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.
Time Frame Day 1 and up to 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
The Pharmacokinetic (PK) set, defined as all participants in the Safety Analysis Set for whom the primary PK data were considered sufficient and interpretable. The Safety Analysis Set was defined as all participants who had taken at least 1 dose of investigational product. Treatment assignment was based on the treatment actually received.
Arm/Group Title 6 to <12 Year Old 12 to <18 Year Old
Hide Arm/Group Description:
During the pharmacokinetic phase, participants aged 6 to less than 12 years received a single oral dose of SPD602 16mg/kg. During the chronic dosing phase, participants commenced 48 weeks of treatment with an initial dose of SPD602 26mg/kg/day or 36mg/kg/day. Over the course of treatment, the dose could range from 8-60mg/kg/day depending on clinical response.
During the pharmacokinetic phase, participants aged 12 to less than 18 years received a single oral dose of SPD602 16mg/kg. During the chronic dosing phase, participants commenced 48 weeks of treatment with an initial dose of SPD602 26mg/kg/day or 36mg/kg/day. Over the course of treatment, the dose could range from 8-60mg/kg/day depending on clinical response.
Overall Number of Participants Analyzed 8 8
Mean (Standard Deviation)
Unit of Measure: ng/mL
31737.5  (10116.74) 28300.0  (7309.88)
2.Primary Outcome
Title Time of Maximum Observed Plasma Concentration Sampled During a Dosing Interval (Tmax) of SPD602 After a Single Oral Dose
Hide Description 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.
Time Frame Day 1 and up to 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
The PK set, defined as all participants in the Safety Analysis Set for whom the primary PK data were considered sufficient and interpretable.
Arm/Group Title 6 to <12 Year Old 12 to <18 Year Old
Hide Arm/Group Description:
During the pharmacokinetic phase, participants aged 6 to less than 12 years received a single oral dose of SPD602 16mg/kg. During the chronic dosing phase, participants commenced 48 weeks of treatment with an initial dose of SPD602 26mg/kg/day or 36mg/kg/day. Over the course of treatment, the dose could range from 8-60mg/kg/day depending on clinical response.
During the pharmacokinetic phase, participants aged 12 to less than 18 years received a single oral dose of SPD602 16mg/kg. During the chronic dosing phase, participants commenced 48 weeks of treatment with an initial dose of SPD602 26mg/kg/day or 36mg/kg/day. Over the course of treatment, the dose could range from 8-60mg/kg/day depending on clinical response.
Overall Number of Participants Analyzed 8 8
Median (Full Range)
Unit of Measure: hours
1.0
(0.5 to 1.0)
1.0
(0.6 to 2.0)
3.Primary Outcome
Title 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
Hide Description 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.
Time Frame Day 1 and up to 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
The PK set, defined as all participants in the Safety Analysis Set for whom the primary PK data were considered sufficient and interpretable.
Arm/Group Title 6 to <12 Year Old 12 to <18 Year Old
Hide Arm/Group Description:
During the pharmacokinetic phase, participants aged 6 to less than 12 years received a single oral dose of SPD602 16mg/kg. During the chronic dosing phase, participants commenced 48 weeks of treatment with an initial dose of SPD602 26mg/kg/day or 36mg/kg/day. Over the course of treatment, the dose could range from 8-60mg/kg/day depending on clinical response.
During the pharmacokinetic phase, participants aged 12 to less than 18 years received a single oral dose of SPD602 16mg/kg. During the chronic dosing phase, participants commenced 48 weeks of treatment with an initial dose of SPD602 26mg/kg/day or 36mg/kg/day. Over the course of treatment, the dose could range from 8-60mg/kg/day depending on clinical response.
Overall Number of Participants Analyzed 8 8
Mean (Standard Deviation)
Unit of Measure: h*mg/L
69.4  (27.39) 71.6  (22.70)
4.Primary Outcome
Title Terminal Half-life (t1/2) of SPD602 After a Single Oral Dose
Hide Description 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.
Time Frame Day 1 and up to 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
The PK set, defined as all participants in the Safety Analysis Set for whom the primary PK data were considered sufficient and interpretable.
Arm/Group Title 6 to <12 Year Old 12 to <18 Year Old
Hide Arm/Group Description:
During the pharmacokinetic phase, participants aged 6 to less than 12 years received a single oral dose of SPD602 16mg/kg. During the chronic dosing phase, participants commenced 48 weeks of treatment with an initial dose of SPD602 26mg/kg/day or 36mg/kg/day. Over the course of treatment, the dose could range from 8-60mg/kg/day depending on clinical response.
During the pharmacokinetic phase, participants aged 12 to less than 18 years received a single oral dose of SPD602 16mg/kg. During the chronic dosing phase, participants commenced 48 weeks of treatment with an initial dose of SPD602 26mg/kg/day or 36mg/kg/day. Over the course of treatment, the dose could range from 8-60mg/kg/day depending on clinical response.
Overall Number of Participants Analyzed 8 8
Mean (Standard Deviation)
Unit of Measure: hours
3.7  (0.93) 3.6  (0.97)
5.Primary Outcome
Title Renal Clearance (CLr) of SPD602 After a Single Oral Dose
Hide Description 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 Frame Day 1 and up to 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
The PK set, defined as all participants in the Safety Analysis Set for whom the primary PK data were considered sufficient and interpretable.
Arm/Group Title 6 to <12 Year Old 12 to <18 Year Old
Hide Arm/Group Description:
During the pharmacokinetic phase, participants aged 6 to less than 12 years received a single oral dose of SPD602 16mg/kg. During the chronic dosing phase, participants commenced 48 weeks of treatment with an initial dose of SPD602 26mg/kg/day or 36mg/kg/day. Over the course of treatment, the dose could range from 8-60mg/kg/day depending on clinical response.
During the pharmacokinetic phase, participants aged 12 to less than 18 years received a single oral dose of SPD602 16mg/kg. During the chronic dosing phase, participants commenced 48 weeks of treatment with an initial dose of SPD602 26mg/kg/day or 36mg/kg/day. Over the course of treatment, the dose could range from 8-60mg/kg/day depending on clinical response.
Overall Number of Participants Analyzed 8 8
Mean (Standard Deviation)
Unit of Measure: L/h
3.6  (2.06) 5.4  (2.38)
6.Primary Outcome
Title Amount Excreted Into Urine (Ue) of SPD602 After a Single Oral Dose
Hide Description 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 Frame Day 1 and up to 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
The PK set, defined as all participants in the Safety Analysis Set for whom the primary PK data were considered sufficient and interpretable.
Arm/Group Title 6 to <12 Year Old 12 to <18 Year Old
Hide Arm/Group Description:
During the pharmacokinetic phase, participants aged 6 to less than 12 years received a single oral dose of SPD602 16mg/kg. During the chronic dosing phase, participants commenced 48 weeks of treatment with an initial dose of SPD602 26mg/kg/day or 36mg/kg/day. Over the course of treatment, the dose could range from 8-60mg/kg/day depending on clinical response.
During the pharmacokinetic phase, participants aged 12 to less than 18 years received a single oral dose of SPD602 16mg/kg. During the chronic dosing phase, participants commenced 48 weeks of treatment with an initial dose of SPD602 26mg/kg/day or 36mg/kg/day. Over the course of treatment, the dose could range from 8-60mg/kg/day depending on clinical response.
Overall Number of Participants Analyzed 8 8
Mean (Standard Deviation)
Unit of Measure: mg
227.9  (107.44) 369.7  (140.17)
7.Primary Outcome
Title Fraction Of Orally Administered Drug Excreted Unchanged In Urine (fe) of SPD602 After a Single Oral Dose
Hide Description 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 Frame Day 1 and up to 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
The PK set, defined as all participants in the Safety Analysis Set for whom the primary PK data were considered sufficient and interpretable.
Arm/Group Title 6 to <12 Year Old 12 to <18 Year Old
Hide Arm/Group Description:
During the pharmacokinetic phase, participants aged 6 to less than 12 years received a single oral dose of SPD602 16mg/kg. During the chronic dosing phase, participants commenced 48 weeks of treatment with an initial dose of SPD602 26mg/kg/day or 36mg/kg/day. Over the course of treatment, the dose could range from 8-60mg/kg/day depending on clinical response.
During the pharmacokinetic phase, participants aged 12 to less than 18 years received a single oral dose of SPD602 16mg/kg. During the chronic dosing phase, participants commenced 48 weeks of treatment with an initial dose of SPD602 26mg/kg/day or 36mg/kg/day. Over the course of treatment, the dose could range from 8-60mg/kg/day depending on clinical response.
Overall Number of Participants Analyzed 8 8
Mean (Standard Deviation)
Unit of Measure: percentage of total dose
42.1  (14.34) 52.5  (20.52)
8.Primary Outcome
Title Change From Baseline in Liver Iron Concentration (LIC) Assessed by FerriScan R2 Magnetic Resonance Imaging (MRI)
Hide Description 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.
Time Frame Baseline, 24 weeks, and 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS), defined as all participants in the Safety Analysis Set who had at least 1 post-baseline primary efficacy assessment, which was considered as the LICs assessed from FerriScan R2 MRI.
Arm/Group Title 6 to <12 Year Old 12 to <18 Year Old
Hide Arm/Group Description:
During the pharmacokinetic phase, participants aged 6 to less than 12 years received a single oral dose of SPD602 16mg/kg. During the chronic dosing phase, participants commenced 48 weeks of treatment with an initial dose of SPD602 26mg/kg/day or 36mg/kg/day. Over the course of treatment, the dose could range from 8-60mg/kg/day depending on clinical response.
During the pharmacokinetic phase, participants aged 12 to less than 18 years received a single oral dose of SPD602 16mg/kg. During the chronic dosing phase, participants commenced 48 weeks of treatment with an initial dose of SPD602 26mg/kg/day or 36mg/kg/day. Over the course of treatment, the dose could range from 8-60mg/kg/day depending on clinical response.
Overall Number of Participants Analyzed 10 15
Mean (Standard Deviation)
Unit of Measure: mg Fe/g*dw
Week 24, n=7,15 -1.8  (2.8) 0.8  (2.7)
Week 48, n=2,10 0.8  (0.4) -0.2  (1.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 6 to <12 Year Old
Comments Analysis of 6 to <12 year olds at 24 weeks
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0781
Comments The P-value was from the analysis of Wilcoxon signed rank test at post-treatment time point vs baseline.
Method Wilcoxon signed rank test
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 6 to <12 Year Old
Comments Analysis of 6 to <12 year olds at 48 weeks
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5000
Comments The P-value was from the analysis of Wilcoxon signed rank test at post-treatment time point vs baseline.
Method Wilcoxon signed rank test
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 12 to <18 Year Old
Comments Analysis of 12 to <18 year olds at 24 weeks
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2609
Comments The P-value was from the analysis of Wilcoxon signed rank test at post-treatment time point vs baseline.
Method Wilcoxon signed rank test
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 12 to <18 Year Old
Comments Analysis of 12 to <18 year olds at 48 weeks
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9219
Comments The P-value was from the analysis of Wilcoxon signed rank test at post-treatment time point vs baseline.
Method Wilcoxon signed rank test
Comments [Not Specified]
9.Primary Outcome
Title Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by FerriScan R2 MRI
Hide Description 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.
Time Frame Baseline, 24 weeks, and 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS, defined as all participants in the Safety Analysis Set who had at least 1 post-baseline primary efficacy assessment, which was considered as the LICs assessed from FerriScan R2 MRI.
Arm/Group Title 6 to <12 Year Old 12 to <18 Year Old
Hide Arm/Group Description:
During the pharmacokinetic phase, participants aged 6 to less than 12 years received a single oral dose of SPD602 16mg/kg. During the chronic dosing phase, participants commenced 48 weeks of treatment with an initial dose of SPD602 26mg/kg/day or 36mg/kg/day. Over the course of treatment, the dose could range from 8-60mg/kg/day depending on clinical response.
During the pharmacokinetic phase, participants aged 12 to less than 18 years received a single oral dose of SPD602 16mg/kg. During the chronic dosing phase, participants commenced 48 weeks of treatment with an initial dose of SPD602 26mg/kg/day or 36mg/kg/day. Over the course of treatment, the dose could range from 8-60mg/kg/day depending on clinical response.
Overall Number of Participants Analyzed 10 15
Mean (Standard Deviation)
Unit of Measure: mg Fe/g*dw
Week 24, n=7,15 -8.3  (3.7) -4.0  (3.1)
Week 48, n=2,10 -13.7  (5.3) -11.9  (5.4)
10.Secondary Outcome
Title Change From Baseline in LIC Assessed by R2* MRI
Hide Description 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.
Time Frame Baseline, 24 weeks, and 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS, defined as all participants in the Safety Analysis Set who had at least 1 post-baseline primary efficacy assessment, which was considered as the LICs assessed from FerriScan R2 MRI.
Arm/Group Title 6 to <12 Year Old 12 to <18 Year Old
Hide Arm/Group Description:
During the pharmacokinetic phase, participants aged 6 to less than 12 years received a single oral dose of SPD602 16mg/kg. During the chronic dosing phase, participants commenced 48 weeks of treatment with an initial dose of SPD602 26mg/kg/day or 36mg/kg/day. Over the course of treatment, the dose could range from 8-60mg/kg/day depending on clinical response.
During the pharmacokinetic phase, participants aged 12 to less than 18 years received a single oral dose of SPD602 16mg/kg. During the chronic dosing phase, participants commenced 48 weeks of treatment with an initial dose of SPD602 26mg/kg/day or 36mg/kg/day. Over the course of treatment, the dose could range from 8-60mg/kg/day depending on clinical response.
Overall Number of Participants Analyzed 10 15
Mean (Standard Deviation)
Unit of Measure: mg Fe/g*dw
Week 24, n=7,15 0.3  (1.7) 0.2  (1.4)
Week 48, n=3,10 0.6  (4.1) 0.3  (1.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 6 to <12 Year Old
Comments Analysis of 6 to <12 year olds at 24 weeks
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6875
Comments The P-value was from analysis of Wilcoxon signed-rank test at post-treatment time point vs. baseline.
Method Wilcoxon signed-rank test
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 6 to <12 Year Old
Comments Analysis of 6 to <12 year olds at 48 weeks
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0000
Comments The P-value was from analysis of Wilcoxon signed-rank test at post-treatment time point vs. baseline.
Method Wilcoxon signed-rank test
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 12 to <18 Year Old
Comments Analysis of 12 to <18 year olds at 24 weeks
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8181
Comments The P-value was from analysis of Wilcoxon signed-rank test at post-treatment time point vs. baseline.
Method Wilcoxon signed-rank test
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 12 to <18 Year Old
Comments Analysis of 12 to <18 year olds at 48 weeks
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5566
Comments P-value was from analysis of Wilcoxon signed-rank test at post-treatment time point vs. baseline.
Method Wilcoxon signed-rank
Comments [Not Specified]
11.Secondary Outcome
Title Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by R2* MRI
Hide Description 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.
Time Frame Baseline, 24 weeks, and 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS, defined as all participants in the Safety Analysis Set who had at least 1 post-baseline primary efficacy assessment, which was considered as the LICs assessed from FerriScan R2 MRI.
Arm/Group Title 6 to <12 Year Old 12 to <18 Year Old
Hide Arm/Group Description:
During the pharmacokinetic phase, participants aged 6 to less than 12 years received a single oral dose of SPD602 16mg/kg. During the chronic dosing phase, participants commenced 48 weeks of treatment with an initial dose of SPD602 26mg/kg/day or 36mg/kg/day. Over the course of treatment, the dose could range from 8-60mg/kg/day depending on clinical response.
During the pharmacokinetic phase, participants aged 12 to less than 18 years received a single oral dose of SPD602 16mg/kg. During the chronic dosing phase, participants commenced 48 weeks of treatment with an initial dose of SPD602 26mg/kg/day or 36mg/kg/day. Over the course of treatment, the dose could range from 8-60mg/kg/day depending on clinical response.
Overall Number of Participants Analyzed 10 15
Mean (Standard Deviation)
Unit of Measure: mg Fe/g*dw
Week 24, n=7,15 -6.2  (2.2) -4.6  (3.4)
Week 48, n=3,10 -9.1  (5.6) -11.4  (5.2)
12.Secondary Outcome
Title Change From Baseline in Cardiac Iron Load Assessed by T2* MRI
Hide Description 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.
Time Frame Baseline, 24 weeks, and 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS, defined as all participants in the Safety Analysis Set who had at least 1 post-baseline primary efficacy assessment, which was considered as the LICs assessed from FerriScan R2 MRI.
Arm/Group Title 6 to <12 Year Old 12 to <18 Year Old
Hide Arm/Group Description:
During the pharmacokinetic phase, participants aged 6 to less than 12 years received a single oral dose of SPD602 16mg/kg. During the chronic dosing phase, participants commenced 48 weeks of treatment with an initial dose of SPD602 26mg/kg/day or 36mg/kg/day. Over the course of treatment, the dose could range from 8-60mg/kg/day depending on clinical response.
During the pharmacokinetic phase, participants aged 12 to less than 18 years received a single oral dose of SPD602 16mg/kg. During the chronic dosing phase, participants commenced 48 weeks of treatment with an initial dose of SPD602 26mg/kg/day or 36mg/kg/day. Over the course of treatment, the dose could range from 8-60mg/kg/day depending on clinical response.
Overall Number of Participants Analyzed 10 15
Mean (Standard Deviation)
Unit of Measure: milliseconds
Week 24, n=7,15 -9.63  (10.766) -6.27  (13.731)
Week 48, n=3,10 -10.60  (20.893) -9.40  (14.693)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 6 to <12 Year Old
Comments Analysis of 6 to <12 year olds at 24 weeks
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0475
Comments The P-value was from paired t test for log-transformed data at post-treatment time point vs. baseline.
Method paired t test
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 6 to <12 Year Old
Comments Analysis of 6 to <12 year olds at 48 weeks
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4410
Comments The P-value was from paired t test for log-transformed data at post-treatment time point vs. baseline.
Method paired t test
Comments The P-value was from paired t test for log-transformed data at post-treatment time point vs. baseline.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 12 to <18 Year Old
Comments Analysis of 12 to <18 year olds at 24 weeks
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0417
Comments The P-value was from paired t test for log-transformed data at post-treatment time point vs. baseline.
Method paired t test
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 12 to <18 Year Old
Comments Analysis of 12 to <18 year olds at 48 weeks
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0409
Comments The P-value was from paired t test for log-transformed data at post-treatment time point vs. baseline.
Method paired t test
Comments [Not Specified]
13.Secondary Outcome
Title Change From Baseline in Serum Ferritin
Hide Description 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.
Time Frame Baseline, 24 weeks, and 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS, defined as all participants in the Safety Analysis Set who had at least 1 post-baseline primary efficacy assessment, which was considered as the LICs assessed from FerriScan R2 MRI.
Arm/Group Title 6 to <12 Year Old 12 to <18 Year Old
Hide Arm/Group Description:
During the pharmacokinetic phase, participants aged 6 to less than 12 years received a single oral dose of SPD602 16mg/kg. During the chronic dosing phase, participants commenced 48 weeks of treatment with an initial dose of SPD602 26mg/kg/day or 36mg/kg/day. Over the course of treatment, the dose could range from 8-60mg/kg/day depending on clinical response.
During the pharmacokinetic phase, participants aged 12 to less than 18 years received a single oral dose of SPD602 16mg/kg. During the chronic dosing phase, participants commenced 48 weeks of treatment with an initial dose of SPD602 26mg/kg/day or 36mg/kg/day. Over the course of treatment, the dose could range from 8-60mg/kg/day depending on clinical response.
Overall Number of Participants Analyzed 10 15
Mean (Standard Deviation)
Unit of Measure: ng/mL
Week 24, n=7,15 73.19  (706.423) -981.49  (1694.314)
Week 48, n=3,10 -590.21  (843.249) -1119.90  (1503.732)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 6 to <12 Year Old
Comments Analysis of 6 to <12 year olds at 24 weeks
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9901
Comments The P-value was from paired t test for log-transformed data at post-treatment time point vs. baseline.
Method paired t test
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 6 to <12 Year Old
Comments Analysis of 6 to <12 year olds at 48 weeks
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3039
Comments The P-value was from paired t test for log-transformed data at post-treatment time point vs. baseline.
Method paired t test
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 12 to <18 Year Old
Comments Analysis of 12 to <18 year olds at 24 weeks
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0044
Comments The P-value was from paired t test for log-transformed data at post-treatment time point vs. baseline.
Method paired t test
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 12 to <18 Year Old
Comments Analysis of 12 to <18 year olds at 48 weeks
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0395
Comments The P-value was from paired t test for log-transformed data at post-treatment time point vs. baseline.
Method paired t test
Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title 6 to <12 Year Old 12 to <18 Year Old
Hide Arm/Group Description During the pharmacokinetic phase, participants aged 6 to less than 12 years received a single oral dose of SPD602 16mg/kg. During the chronic dosing phase, participants commenced 48 weeks of treatment with an initial dose of SPD602 26mg/kg/day or 36mg/kg/day. Over the course of treatment, the dose could range from 8-60mg/kg/day depending on clinical response. During the pharmacokinetic phase, participants aged 12 to less than 18 years received a single oral dose of SPD602 16mg/kg. During the chronic dosing phase, participants commenced 48 weeks of treatment with an initial dose of SPD602 26mg/kg/day or 36mg/kg/day. Over the course of treatment, the dose could range from 8-60mg/kg/day depending on clinical response.
All-Cause Mortality
6 to <12 Year Old 12 to <18 Year Old
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
6 to <12 Year Old 12 to <18 Year Old
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/13 (0.00%)      0/16 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
6 to <12 Year Old 12 to <18 Year Old
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   13/13 (100.00%)      15/16 (93.75%)    
Blood and lymphatic system disorders     
Anaemia  1  1/13 (7.69%)  2 1/16 (6.25%)  4
Lymphadenopathy  1  0/13 (0.00%)  0 1/16 (6.25%)  1
Neutropenia  1  0/13 (0.00%)  0 3/16 (18.75%)  3
Ear and labyrinth disorders     
Ear pain  1  0/13 (0.00%)  0 1/16 (6.25%)  1
Hearing impaired  1  1/13 (7.69%)  1 0/16 (0.00%)  0
Tinnitus  1  0/13 (0.00%)  0 2/16 (12.50%)  5
Gastrointestinal disorders     
Abdominal discomfort  1  1/13 (7.69%)  1 0/16 (0.00%)  0
Abdominal pain  1  4/13 (30.77%)  6 3/16 (18.75%)  7
Abdominal pain upper  1  1/13 (7.69%)  1 0/16 (0.00%)  0
Constipation  1  0/13 (0.00%)  0 2/16 (12.50%)  5
Diarrhoea  1  2/13 (15.38%)  2 3/16 (18.75%)  3
Flatulence  1  0/13 (0.00%)  0 1/16 (6.25%)  1
Nausea  1  5/13 (38.46%)  6 2/16 (12.50%)  7
Vomiting  1  4/13 (30.77%)  6 5/16 (31.25%)  5
General disorders     
Asthenia  1  1/13 (7.69%)  1 2/16 (12.50%)  2
Chest discomfort  1  0/13 (0.00%)  0 1/16 (6.25%)  1
Chest pain  1  1/13 (7.69%)  1 0/16 (0.00%)  0
Influenza like illness  1  1/13 (7.69%)  2 2/16 (12.50%)  3
Pyrexia  1  2/13 (15.38%)  2 5/16 (31.25%)  8
Infections and infestations     
Bronchitis  1  1/13 (7.69%)  1 0/16 (0.00%)  0
Gastroenteritis  1  0/13 (0.00%)  0 2/16 (12.50%)  2
Hordeolum  1  1/13 (7.69%)  1 0/16 (0.00%)  0
Influenza  1  2/13 (15.38%)  2 1/16 (6.25%)  2
Molluscum contagiosum  1  0/13 (0.00%)  0 1/16 (6.25%)  1
Nasopharyngitis  1  1/13 (7.69%)  1 2/16 (12.50%)  2
Otitis externa  1  0/13 (0.00%)  0 1/16 (6.25%)  1
Pharyngitis  1  1/13 (7.69%)  1 2/16 (12.50%)  5
Pharyngitis streptococcal  1  0/13 (0.00%)  0 1/16 (6.25%)  1
Rhinitis  1  2/13 (15.38%)  3 1/16 (6.25%)  1
Sinusitis  1  0/13 (0.00%)  0 1/16 (6.25%)  2
Tonsillitis  1  1/13 (7.69%)  1 1/16 (6.25%)  1
Upper respiratory tract infection  1  2/13 (15.38%)  2 1/16 (6.25%)  1
Urinary tract infection  1  0/13 (0.00%)  0 1/16 (6.25%)  1
Injury, poisoning and procedural complications     
Fall  1  2/13 (15.38%)  2 0/16 (0.00%)  0
Foot fracture  1  0/13 (0.00%)  0 1/16 (6.25%)  1
Head injury  1  1/13 (7.69%)  1 0/16 (0.00%)  0
Joint injury  1  1/13 (7.69%)  1 0/16 (0.00%)  0
Joint sprain  1  1/13 (7.69%)  1 0/16 (0.00%)  0
Limb injury  1  0/13 (0.00%)  0 1/16 (6.25%)  1
Skin laceration  1  1/13 (7.69%)  1 0/16 (0.00%)  0
Investigations     
Alanine aminotransferase increased  1  1/13 (7.69%)  1 0/16 (0.00%)  0
Aspartate aminotransferase increased  1  1/13 (7.69%)  1 0/16 (0.00%)  0
Glucose tolerance test abnormal  1  0/13 (0.00%)  0 1/16 (6.25%)  1
Neutrophil count decreased  1  0/13 (0.00%)  0 1/16 (6.25%)  3
Spleen palpable  1  0/13 (0.00%)  0 1/16 (6.25%)  1
Transaminases increased  1  0/13 (0.00%)  0 1/16 (6.25%)  1
White blood cell count decreased  1  0/13 (0.00%)  0 1/16 (6.25%)  1
Metabolism and nutrition disorders     
Folate deficiency  1  0/13 (0.00%)  0 1/16 (6.25%)  1
Musculoskeletal and connective tissue disorders     
Arthralgia  1  3/13 (23.08%)  4 1/16 (6.25%)  1
Back pain  1  1/13 (7.69%)  1 0/16 (0.00%)  0
Myalgia  1  1/13 (7.69%)  1 0/16 (0.00%)  0
Osteochondrosis  1  1/13 (7.69%)  1 0/16 (0.00%)  0
Pain in extremity  1  0/13 (0.00%)  0 1/16 (6.25%)  1
Sensation of heaviness  1  1/13 (7.69%)  1 0/16 (0.00%)  0
Nervous system disorders     
Dizziness  1  0/13 (0.00%)  0 1/16 (6.25%)  1
Head discomfort  1  0/13 (0.00%)  0 1/16 (6.25%)  1
Headache  1  4/13 (30.77%)  10 8/16 (50.00%)  13
Hypoaesthesia  1  0/13 (0.00%)  0 1/16 (6.25%)  2
Hyporeflexia  1  0/13 (0.00%)  0 1/16 (6.25%)  1
Muscle contractions involuntary  1  0/13 (0.00%)  0 2/16 (12.50%)  3
Neuropathy peripheral  1  0/13 (0.00%)  0 1/16 (6.25%)  1
Paraesthesia  1  2/13 (15.38%)  3 1/16 (6.25%)  2
Peripheral sensory neuropathy  1  1/13 (7.69%)  1 0/16 (0.00%)  0
Presyncope  1  0/13 (0.00%)  0 1/16 (6.25%)  1
Sinus headache  1  0/13 (0.00%)  0 1/16 (6.25%)  1
Psychiatric disorders     
Insomnia  1  0/13 (0.00%)  0 1/16 (6.25%)  1
Renal and urinary disorders     
Chromaturia  1  0/13 (0.00%)  0 1/16 (6.25%)  1
Reproductive system and breast disorders     
Amenorrhoea  1  0/13 (0.00%)  0 1/16 (6.25%)  1
Respiratory, thoracic and mediastinal disorders     
Cough  1  4/13 (30.77%)  7 0/16 (0.00%)  0
Nasal congestion  1  1/13 (7.69%)  1 0/16 (0.00%)  0
Oropharyngeal pain  1  5/13 (38.46%)  5 2/16 (12.50%)  3
Pharyngeal erythema  1  1/13 (7.69%)  1 0/16 (0.00%)  0
Pharyngeal haemorrhage  1  0/13 (0.00%)  0 1/16 (6.25%)  1
Productive cough  1  0/13 (0.00%)  0 1/16 (6.25%)  1
Upper airway obstruction  1  0/13 (0.00%)  0 1/16 (6.25%)  1
Wheezing  1  1/13 (7.69%)  1 0/16 (0.00%)  0
Skin and subcutaneous tissue disorders     
Blister  1  0/13 (0.00%)  0 1/16 (6.25%)  1
Dry skin  1  1/13 (7.69%)  1 0/16 (0.00%)  0
Rash  1  1/13 (7.69%)  1 0/16 (0.00%)  0
Rash macular  1  1/13 (7.69%)  2 0/16 (0.00%)  0
Skin haemorrhage  1  0/13 (0.00%)  0 1/16 (6.25%)  1
Urticaria  1  0/13 (0.00%)  0 1/16 (6.25%)  1
Vascular disorders     
Haematoma  1  0/13 (0.00%)  0 1/16 (6.25%)  1
Hyperaemia  1  1/13 (7.69%)  1 1/16 (6.25%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (12.1)
This study was terminated early because of non-clinical safety results. As such, not all subjects completed the study. The available efficacy data were summarized and analyzed as specified in the SAP; however, no efficacy conclusions could be drawn.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Shire
Phone: +1 866 842 5335
EMail: ClinicalTransparency@shire.com
Layout table for additonal information
Responsible Party: Takeda ( Shire )
ClinicalTrials.gov Identifier: NCT01363908    
Other Study ID Numbers: SPD602-202
SSP-004184AQ ( Other Identifier: Shire )
First Submitted: May 30, 2011
First Posted: June 2, 2011
Results First Submitted: May 6, 2015
Results First Posted: May 27, 2015
Last Update Posted: June 14, 2021