Trial Outcomes & Findings for Safety, Efficacy and Pharmacokinetics of an Oral Iron Chelator Given for a Year to Pediatric Patients With Iron Overload (NCT NCT01363908)
NCT ID: NCT01363908
Last Updated: 2021-06-14
Results Overview
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.
TERMINATED
PHASE2
30 participants
Day 1 and up to 24 hours post-dose
2021-06-14
Participant Flow
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.
Participant milestones
| Measure |
6 to <12 Year Old
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.
|
12 to <18 Year Old
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.
|
|---|---|---|
|
Screening/Enrollment
STARTED
|
14
|
16
|
|
Screening/Enrollment
COMPLETED
|
13
|
16
|
|
Screening/Enrollment
NOT COMPLETED
|
1
|
0
|
|
Pharmacokinetic (PK) Phase
STARTED
|
8
|
8
|
|
Pharmacokinetic (PK) Phase
COMPLETED
|
8
|
8
|
|
Pharmacokinetic (PK) Phase
NOT COMPLETED
|
0
|
0
|
|
Chronic Dosing (CD) Phase
STARTED
|
13
|
16
|
|
Chronic Dosing (CD) Phase
COMPLETED
|
3
|
10
|
|
Chronic Dosing (CD) Phase
NOT COMPLETED
|
10
|
6
|
Reasons for withdrawal
| Measure |
6 to <12 Year Old
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.
|
12 to <18 Year Old
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.
|
|---|---|---|
|
Chronic Dosing (CD) Phase
Adverse Event
|
1
|
1
|
|
Chronic Dosing (CD) Phase
Patient decision
|
0
|
1
|
|
Chronic Dosing (CD) Phase
Physician Decision
|
0
|
1
|
|
Chronic Dosing (CD) Phase
Early study termination
|
9
|
3
|
Baseline Characteristics
Safety, Efficacy and Pharmacokinetics of an Oral Iron Chelator Given for a Year to Pediatric Patients With Iron Overload
Baseline characteristics by cohort
| Measure |
6 to <12 Year Old
n=13 Participants
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.
|
12 to <18 Year Old
n=16 Participants
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
n=29 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
8.6 years
STANDARD_DEVIATION 1.85 • n=5 Participants
|
14.4 years
STANDARD_DEVIATION 1.78 • n=7 Participants
|
11.8 years
STANDARD_DEVIATION 3.42 • n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 1 and up to 24 hours post-dosePopulation: 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.
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.
Outcome measures
| Measure |
6 to <12 Year Old
n=8 Participants
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.
|
12 to <18 Year Old
n=8 Participants
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.
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of SPD602 After a Single Oral Dose
|
31737.5 ng/mL
Standard Deviation 10116.74
|
28300.0 ng/mL
Standard Deviation 7309.88
|
PRIMARY outcome
Timeframe: Day 1 and up to 24 hours post-dosePopulation: The PK set, defined as all participants in the Safety Analysis Set for whom the primary PK data were considered sufficient and interpretable.
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.
Outcome measures
| Measure |
6 to <12 Year Old
n=8 Participants
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.
|
12 to <18 Year Old
n=8 Participants
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.
|
|---|---|---|
|
Time of Maximum Observed Plasma Concentration Sampled During a Dosing Interval (Tmax) of SPD602 After a Single Oral Dose
|
1.0 hours
Interval 0.5 to 1.0
|
1.0 hours
Interval 0.6 to 2.0
|
PRIMARY outcome
Timeframe: Day 1 and up to 24 hours post-dosePopulation: The PK set, defined as all participants in the Safety Analysis Set for whom the primary PK data were considered sufficient and interpretable.
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.
Outcome measures
| Measure |
6 to <12 Year Old
n=8 Participants
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.
|
12 to <18 Year Old
n=8 Participants
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.
|
|---|---|---|
|
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
|
69.4 h*mg/L
Standard Deviation 27.39
|
71.6 h*mg/L
Standard Deviation 22.70
|
PRIMARY outcome
Timeframe: Day 1 and up to 24 hours post-dosePopulation: The PK set, defined as all participants in the Safety Analysis Set for whom the primary PK data were considered sufficient and interpretable.
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.
Outcome measures
| Measure |
6 to <12 Year Old
n=8 Participants
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.
|
12 to <18 Year Old
n=8 Participants
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.
|
|---|---|---|
|
Terminal Half-life (t1/2) of SPD602 After a Single Oral Dose
|
3.7 hours
Standard Deviation 0.93
|
3.6 hours
Standard Deviation 0.97
|
PRIMARY outcome
Timeframe: Day 1 and up to 24 hours post-dosePopulation: The PK set, defined as all participants in the Safety Analysis Set for whom the primary PK data were considered sufficient and interpretable.
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.
Outcome measures
| Measure |
6 to <12 Year Old
n=8 Participants
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.
|
12 to <18 Year Old
n=8 Participants
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.
|
|---|---|---|
|
Renal Clearance (CLr) of SPD602 After a Single Oral Dose
|
3.6 L/h
Standard Deviation 2.06
|
5.4 L/h
Standard Deviation 2.38
|
PRIMARY outcome
Timeframe: Day 1 and up to 24 hours post-dosePopulation: The PK set, defined as all participants in the Safety Analysis Set for whom the primary PK data were considered sufficient and interpretable.
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.
Outcome measures
| Measure |
6 to <12 Year Old
n=8 Participants
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.
|
12 to <18 Year Old
n=8 Participants
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.
|
|---|---|---|
|
Amount Excreted Into Urine (Ue) of SPD602 After a Single Oral Dose
|
227.9 mg
Standard Deviation 107.44
|
369.7 mg
Standard Deviation 140.17
|
PRIMARY outcome
Timeframe: Day 1 and up to 24 hours post-dosePopulation: The PK set, defined as all participants in the Safety Analysis Set for whom the primary PK data were considered sufficient and interpretable.
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.
Outcome measures
| Measure |
6 to <12 Year Old
n=8 Participants
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.
|
12 to <18 Year Old
n=8 Participants
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.
|
|---|---|---|
|
Fraction Of Orally Administered Drug Excreted Unchanged In Urine (fe) of SPD602 After a Single Oral Dose
|
42.1 percentage of total dose
Standard Deviation 14.34
|
52.5 percentage of total dose
Standard Deviation 20.52
|
PRIMARY outcome
Timeframe: Baseline, 24 weeks, and 48 weeksPopulation: 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.
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.
Outcome measures
| Measure |
6 to <12 Year Old
n=10 Participants
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.
|
12 to <18 Year Old
n=15 Participants
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.
|
|---|---|---|
|
Change From Baseline in Liver Iron Concentration (LIC) Assessed by FerriScan R2 Magnetic Resonance Imaging (MRI)
Week 24, n=7,15
|
-1.8 mg Fe/g*dw
Standard Deviation 2.8
|
0.8 mg Fe/g*dw
Standard Deviation 2.7
|
|
Change From Baseline in Liver Iron Concentration (LIC) Assessed by FerriScan R2 Magnetic Resonance Imaging (MRI)
Week 48, n=2,10
|
0.8 mg Fe/g*dw
Standard Deviation 0.4
|
-0.2 mg Fe/g*dw
Standard Deviation 1.8
|
PRIMARY outcome
Timeframe: Baseline, 24 weeks, and 48 weeksPopulation: 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.
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.
Outcome measures
| Measure |
6 to <12 Year Old
n=10 Participants
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.
|
12 to <18 Year Old
n=15 Participants
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.
|
|---|---|---|
|
Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by FerriScan R2 MRI
Week 24, n=7,15
|
-8.3 mg Fe/g*dw
Standard Deviation 3.7
|
-4.0 mg Fe/g*dw
Standard Deviation 3.1
|
|
Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by FerriScan R2 MRI
Week 48, n=2,10
|
-13.7 mg Fe/g*dw
Standard Deviation 5.3
|
-11.9 mg Fe/g*dw
Standard Deviation 5.4
|
SECONDARY outcome
Timeframe: Baseline, 24 weeks, and 48 weeksPopulation: 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.
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.
Outcome measures
| Measure |
6 to <12 Year Old
n=10 Participants
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.
|
12 to <18 Year Old
n=15 Participants
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.
|
|---|---|---|
|
Change From Baseline in LIC Assessed by R2* MRI
Week 24, n=7,15
|
0.3 mg Fe/g*dw
Standard Deviation 1.7
|
0.2 mg Fe/g*dw
Standard Deviation 1.4
|
|
Change From Baseline in LIC Assessed by R2* MRI
Week 48, n=3,10
|
0.6 mg Fe/g*dw
Standard Deviation 4.1
|
0.3 mg Fe/g*dw
Standard Deviation 1.9
|
SECONDARY outcome
Timeframe: Baseline, 24 weeks, and 48 weeksPopulation: 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.
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.
Outcome measures
| Measure |
6 to <12 Year Old
n=10 Participants
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.
|
12 to <18 Year Old
n=15 Participants
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.
|
|---|---|---|
|
Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by R2* MRI
Week 24, n=7,15
|
-6.2 mg Fe/g*dw
Standard Deviation 2.2
|
-4.6 mg Fe/g*dw
Standard Deviation 3.4
|
|
Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by R2* MRI
Week 48, n=3,10
|
-9.1 mg Fe/g*dw
Standard Deviation 5.6
|
-11.4 mg Fe/g*dw
Standard Deviation 5.2
|
SECONDARY outcome
Timeframe: Baseline, 24 weeks, and 48 weeksPopulation: 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.
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.
Outcome measures
| Measure |
6 to <12 Year Old
n=10 Participants
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.
|
12 to <18 Year Old
n=15 Participants
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.
|
|---|---|---|
|
Change From Baseline in Cardiac Iron Load Assessed by T2* MRI
Week 24, n=7,15
|
-9.63 milliseconds
Standard Deviation 10.766
|
-6.27 milliseconds
Standard Deviation 13.731
|
|
Change From Baseline in Cardiac Iron Load Assessed by T2* MRI
Week 48, n=3,10
|
-10.60 milliseconds
Standard Deviation 20.893
|
-9.40 milliseconds
Standard Deviation 14.693
|
SECONDARY outcome
Timeframe: Baseline, 24 weeks, and 48 weeksPopulation: 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.
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.
Outcome measures
| Measure |
6 to <12 Year Old
n=10 Participants
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.
|
12 to <18 Year Old
n=15 Participants
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.
|
|---|---|---|
|
Change From Baseline in Serum Ferritin
Week 24, n=7,15
|
73.19 ng/mL
Standard Deviation 706.423
|
-981.49 ng/mL
Standard Deviation 1694.314
|
|
Change From Baseline in Serum Ferritin
Week 48, n=3,10
|
-590.21 ng/mL
Standard Deviation 843.249
|
-1119.90 ng/mL
Standard Deviation 1503.732
|
Adverse Events
6 to <12 Year Old
12 to <18 Year Old
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
6 to <12 Year Old
n=13 participants at risk
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.
|
12 to <18 Year Old
n=16 participants at risk
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.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
7.7%
1/13 • Number of events 2
|
6.2%
1/16 • Number of events 4
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
0.00%
0/13
|
6.2%
1/16 • Number of events 1
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/13
|
18.8%
3/16 • Number of events 3
|
|
Ear and labyrinth disorders
Ear pain
|
0.00%
0/13
|
6.2%
1/16 • Number of events 1
|
|
Ear and labyrinth disorders
Hearing impaired
|
7.7%
1/13 • Number of events 1
|
0.00%
0/16
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/13
|
12.5%
2/16 • Number of events 5
|
|
Gastrointestinal disorders
Abdominal discomfort
|
7.7%
1/13 • Number of events 1
|
0.00%
0/16
|
|
Gastrointestinal disorders
Abdominal pain
|
30.8%
4/13 • Number of events 6
|
18.8%
3/16 • Number of events 7
|
|
Gastrointestinal disorders
Abdominal pain upper
|
7.7%
1/13 • Number of events 1
|
0.00%
0/16
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/13
|
12.5%
2/16 • Number of events 5
|
|
Gastrointestinal disorders
Diarrhoea
|
15.4%
2/13 • Number of events 2
|
18.8%
3/16 • Number of events 3
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/13
|
6.2%
1/16 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
38.5%
5/13 • Number of events 6
|
12.5%
2/16 • Number of events 7
|
|
Gastrointestinal disorders
Vomiting
|
30.8%
4/13 • Number of events 6
|
31.2%
5/16 • Number of events 5
|
|
General disorders
Asthenia
|
7.7%
1/13 • Number of events 1
|
12.5%
2/16 • Number of events 2
|
|
General disorders
Chest discomfort
|
0.00%
0/13
|
6.2%
1/16 • Number of events 1
|
|
General disorders
Chest pain
|
7.7%
1/13 • Number of events 1
|
0.00%
0/16
|
|
General disorders
Influenza like illness
|
7.7%
1/13 • Number of events 2
|
12.5%
2/16 • Number of events 3
|
|
General disorders
Pyrexia
|
15.4%
2/13 • Number of events 2
|
31.2%
5/16 • Number of events 8
|
|
Infections and infestations
Bronchitis
|
7.7%
1/13 • Number of events 1
|
0.00%
0/16
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/13
|
12.5%
2/16 • Number of events 2
|
|
Infections and infestations
Hordeolum
|
7.7%
1/13 • Number of events 1
|
0.00%
0/16
|
|
Infections and infestations
Influenza
|
15.4%
2/13 • Number of events 2
|
6.2%
1/16 • Number of events 2
|
|
Infections and infestations
Molluscum contagiosum
|
0.00%
0/13
|
6.2%
1/16 • Number of events 1
|
|
Infections and infestations
Nasopharyngitis
|
7.7%
1/13 • Number of events 1
|
12.5%
2/16 • Number of events 2
|
|
Infections and infestations
Otitis externa
|
0.00%
0/13
|
6.2%
1/16 • Number of events 1
|
|
Infections and infestations
Pharyngitis
|
7.7%
1/13 • Number of events 1
|
12.5%
2/16 • Number of events 5
|
|
Infections and infestations
Pharyngitis streptococcal
|
0.00%
0/13
|
6.2%
1/16 • Number of events 1
|
|
Infections and infestations
Rhinitis
|
15.4%
2/13 • Number of events 3
|
6.2%
1/16 • Number of events 1
|
|
Infections and infestations
Sinusitis
|
0.00%
0/13
|
6.2%
1/16 • Number of events 2
|
|
Infections and infestations
Tonsillitis
|
7.7%
1/13 • Number of events 1
|
6.2%
1/16 • Number of events 1
|
|
Infections and infestations
Upper respiratory tract infection
|
15.4%
2/13 • Number of events 2
|
6.2%
1/16 • Number of events 1
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/13
|
6.2%
1/16 • Number of events 1
|
|
Injury, poisoning and procedural complications
Fall
|
15.4%
2/13 • Number of events 2
|
0.00%
0/16
|
|
Injury, poisoning and procedural complications
Foot fracture
|
0.00%
0/13
|
6.2%
1/16 • Number of events 1
|
|
Injury, poisoning and procedural complications
Head injury
|
7.7%
1/13 • Number of events 1
|
0.00%
0/16
|
|
Injury, poisoning and procedural complications
Joint injury
|
7.7%
1/13 • Number of events 1
|
0.00%
0/16
|
|
Injury, poisoning and procedural complications
Joint sprain
|
7.7%
1/13 • Number of events 1
|
0.00%
0/16
|
|
Injury, poisoning and procedural complications
Limb injury
|
0.00%
0/13
|
6.2%
1/16 • Number of events 1
|
|
Injury, poisoning and procedural complications
Skin laceration
|
7.7%
1/13 • Number of events 1
|
0.00%
0/16
|
|
Investigations
Alanine aminotransferase increased
|
7.7%
1/13 • Number of events 1
|
0.00%
0/16
|
|
Investigations
Aspartate aminotransferase increased
|
7.7%
1/13 • Number of events 1
|
0.00%
0/16
|
|
Investigations
Glucose tolerance test abnormal
|
0.00%
0/13
|
6.2%
1/16 • Number of events 1
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/13
|
6.2%
1/16 • Number of events 3
|
|
Investigations
Spleen palpable
|
0.00%
0/13
|
6.2%
1/16 • Number of events 1
|
|
Investigations
Transaminases increased
|
0.00%
0/13
|
6.2%
1/16 • Number of events 1
|
|
Investigations
White blood cell count decreased
|
0.00%
0/13
|
6.2%
1/16 • Number of events 1
|
|
Metabolism and nutrition disorders
Folate deficiency
|
0.00%
0/13
|
6.2%
1/16 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
23.1%
3/13 • Number of events 4
|
6.2%
1/16 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
7.7%
1/13 • Number of events 1
|
0.00%
0/16
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
7.7%
1/13 • Number of events 1
|
0.00%
0/16
|
|
Musculoskeletal and connective tissue disorders
Osteochondrosis
|
7.7%
1/13 • Number of events 1
|
0.00%
0/16
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/13
|
6.2%
1/16 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Sensation of heaviness
|
7.7%
1/13 • Number of events 1
|
0.00%
0/16
|
|
Nervous system disorders
Dizziness
|
0.00%
0/13
|
6.2%
1/16 • Number of events 1
|
|
Nervous system disorders
Head discomfort
|
0.00%
0/13
|
6.2%
1/16 • Number of events 1
|
|
Nervous system disorders
Headache
|
30.8%
4/13 • Number of events 10
|
50.0%
8/16 • Number of events 13
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/13
|
6.2%
1/16 • Number of events 2
|
|
Nervous system disorders
Hyporeflexia
|
0.00%
0/13
|
6.2%
1/16 • Number of events 1
|
|
Nervous system disorders
Muscle contractions involuntary
|
0.00%
0/13
|
12.5%
2/16 • Number of events 3
|
|
Nervous system disorders
Neuropathy peripheral
|
0.00%
0/13
|
6.2%
1/16 • Number of events 1
|
|
Nervous system disorders
Paraesthesia
|
15.4%
2/13 • Number of events 3
|
6.2%
1/16 • Number of events 2
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
7.7%
1/13 • Number of events 1
|
0.00%
0/16
|
|
Nervous system disorders
Presyncope
|
0.00%
0/13
|
6.2%
1/16 • Number of events 1
|
|
Nervous system disorders
Sinus headache
|
0.00%
0/13
|
6.2%
1/16 • Number of events 1
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/13
|
6.2%
1/16 • Number of events 1
|
|
Renal and urinary disorders
Chromaturia
|
0.00%
0/13
|
6.2%
1/16 • Number of events 1
|
|
Reproductive system and breast disorders
Amenorrhoea
|
0.00%
0/13
|
6.2%
1/16 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
30.8%
4/13 • Number of events 7
|
0.00%
0/16
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
7.7%
1/13 • Number of events 1
|
0.00%
0/16
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
38.5%
5/13 • Number of events 5
|
12.5%
2/16 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal erythema
|
7.7%
1/13 • Number of events 1
|
0.00%
0/16
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal haemorrhage
|
0.00%
0/13
|
6.2%
1/16 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.00%
0/13
|
6.2%
1/16 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Upper airway obstruction
|
0.00%
0/13
|
6.2%
1/16 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
7.7%
1/13 • Number of events 1
|
0.00%
0/16
|
|
Skin and subcutaneous tissue disorders
Blister
|
0.00%
0/13
|
6.2%
1/16 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
7.7%
1/13 • Number of events 1
|
0.00%
0/16
|
|
Skin and subcutaneous tissue disorders
Rash
|
7.7%
1/13 • Number of events 1
|
0.00%
0/16
|
|
Skin and subcutaneous tissue disorders
Rash macular
|
7.7%
1/13 • Number of events 2
|
0.00%
0/16
|
|
Skin and subcutaneous tissue disorders
Skin haemorrhage
|
0.00%
0/13
|
6.2%
1/16 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/13
|
6.2%
1/16 • Number of events 1
|
|
Vascular disorders
Haematoma
|
0.00%
0/13
|
6.2%
1/16 • Number of events 1
|
|
Vascular disorders
Hyperaemia
|
7.7%
1/13 • Number of events 1
|
6.2%
1/16 • Number of events 1
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER