Transfusional Iron OverloadPhase 2NCT01363908

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

A Phase 2 study testing SPD602 in people with Transfusional Iron Overload and Beta-Thalassemia, run by Shire at 9 sites in 5 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 6 to 17 years
Conditions the study is for: Transfusional Iron Overload, Beta-Thalassemia
What is being tested?: SPD602
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 30 participants
Where: 9 sitesin 5 countries
Study dates: 10 Aug 2011to 13 May 2014
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 6 to 17 years
All sexes
No healthy volunteers
Child

Who may be able to join

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:

Show all 11Show fewer

liver iron concentration >2 and <30mg/g (dry weight, liver) by FerriScan® R2
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.

Who cannot join

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.

Show all 12Show fewer

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).

Trial locations and contacts

9 sites in 5 countries.

Country

City, postcode or hospital

9 sites in 5 countries

Italy3 sites

Ospedale Regionale Mecrocitemie
Cagliari, 09121
Centro della Microcitemia e delle Anemie Congenite
Genoa
Thalassemia Center San Luigi Hospital
Orbassano

Other trials in Italy

United States2 sites

Children's Hospital Boston
Boston, Massachusetts, 02115
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104

Other trials in United States

Lebanon2 sites

American University of Beirut Medical Center
Beirut
Chronic Care Center
Beirut

Other trials in Lebanon

Canada1 site

Toronto Sick Kids Hospital
Toronto, Ontario

Other trials in Canada

Turkey (Türkiye)1 site

Ege University Hospital
Izmir, 35100

Other trials in Turkey (Türkiye)

About this study

Official title: A Phase 2, Open Label, Multi-Center, Single-Dose Pharmacokinetics, and Multiple Dose Study of the Safety, Efficacy and Tolerability of SSP-004184 (SPD602) in a Pediatric Population With Transfusional Iron Overload

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).

Read the 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.

Conditions: Transfusional Iron Overload, Beta-Thalassemia
Being tested: SPD602
Keywords: Beta-Thalassemia, Sickle Cell Anemia, Transfusional iron overload, Iron Overload, Iron Chelation
Medical subject headings: beta-Thalassemia, Anemia, Sickle Cell, Iron Overload

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

SPD602Drug
Also called SSP-004184, deferitazole

Study groups in NCT01363908
Study group	Role	What they receive
SPD602 (26 mg/kg)	Experimental	Oral SSP-004184AQ taken once daily for 48 weeks Receives: Drug: SPD602
SPD602 (36 mg/kg)	Experimental	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. Receives: Drug: SPD602
SPD602 (16 mg/kg)	Experimental	A single dose given in the initial pharmacokinetic phase. Receives: Drug: SPD602

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Day 1 and up to 24 hours post-dose
Time of Maximum Observed Plasma Concentration Sampled During a Dosing Interval (Tmax) 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.
Measured: Day 1 and up to 24 hours post-dose
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
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.
Measured: Day 1 and up to 24 hours post-dose
Terminal Half-life (t1/2) 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.
Measured: Day 1 and up to 24 hours post-dose
Renal Clearance (CLr) of SPD602 After a Single Oral 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.
Measured: Day 1 and up to 24 hours post-dose
Amount Excreted Into Urine (Ue) of SPD602 After a Single Oral 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.
Measured: Day 1 and up to 24 hours post-dose
Fraction Of Orally Administered Drug Excreted Unchanged In Urine (fe) of SPD602 After a Single Oral 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.
Measured: Day 1 and up to 24 hours post-dose
Change From Baseline in Liver Iron Concentration (LIC) Assessed by FerriScan R2 Magnetic Resonance Imaging (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.
Measured: Baseline, 24 weeks, and 48 weeks
Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by 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.
Measured: Baseline, 24 weeks, and 48 weeks

Secondary outcomes (4)

Change From Baseline in LIC Assessed by 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.
Measured: Baseline, 24 weeks, and 48 weeks
Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by 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.
Measured: Baseline, 24 weeks, and 48 weeks
Change From Baseline in Cardiac Iron Load Assessed by T2* 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.
Measured: Baseline, 24 weeks, and 48 weeks
Change From Baseline in Serum Ferritin
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.
Measured: Baseline, 24 weeks, and 48 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

10 Aug 201113 May 2014

First posted2 Jun 2011 (estimated)
Study start10 Aug 2011
Primary completion13 May 2014
Study completion13 May 2014

Why it stopped: 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.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Transfusional Iron OverloadStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 30 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01363908
Sponsor's protocol ID: SPD602-202
Other IDs: SSP-004184AQ
Status last verified: Jun 2021
First submitted: 30 May 2011
Last updated: 14 Jun 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Study at a glance

From the registry record, last updated by the sponsor on 14 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 2, Open Label, Multi-Center, Single-Dose Pharmacokinetics, and Multiple Dose Study of the Safety, Efficacy and Tolerability of SSP-004184 (SPD602) in a Pediatric Population With Transfusional Iron Overload
ClinicalTrials.gov ID: NCT01363908
Acronym / sponsor ID: SPD602-202
Conditions: Transfusional Iron Overload, Beta-Thalassemia
Keywords: Beta-Thalassemia, Sickle Cell Anemia, Transfusional iron overload, Iron Overload, Iron Chelation
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: 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.
Enrolment: 30 participants (actual)
Lead sponsor: ShireIndustry (pharma, biotech, devices)
Study start: 10 Aug 2011 (actual)
Primary completion: 13 May 2014 (actual)
Study completion: 13 May 2014 (actual)
First posted: 2 Jun 2011 (estimated)
Results: Posted 27 May 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
SPD602 (26 mg/kg)	Experimental	Drug: SPD602Oral SSP-004184AQ taken once daily for 48 weeks
SPD602 (36 mg/kg)	Experimental	Drug: SPD602Oral 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)	Experimental	Drug: SPD602A single dose given in the initial pharmacokinetic phase.

Who may qualify

Ages: 6 to 17 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (11 listed)

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.

Key exclusion criteria (12 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
SPD602Also: SSP-004184, deferitazole	Drug	SPD602 (16 mg/kg), SPD602 (26 mg/kg), SPD602 (36 mg/kg)

Primary outcome

Maximum Observed Plasma Concentration (Cmax) of SPD602 After a Single Oral Dose
Time frame: 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.
Time of Maximum Observed Plasma Concentration Sampled During a Dosing Interval (Tmax) of SPD602 After a Single Oral Dose
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
Fraction Of Orally Administered Drug Excreted Unchanged In Urine (fe) of SPD602 After a Single Oral Dose
Time frame: 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)
Time frame: 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.
Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by FerriScan R2 MRI
Time frame: 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.

4 secondary outcomes

Change From Baseline in LIC Assessed by R2* MRI
Time frame: Baseline, 24 weeks, and 48 weeks
Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by R2* MRI
Time frame: Baseline, 24 weeks, and 48 weeks
Change From Baseline in Cardiac Iron Load Assessed by T2* MRI
Time frame: Baseline, 24 weeks, and 48 weeks
Change From Baseline in Serum Ferritin
Time frame: Baseline, 24 weeks, and 48 weeks

Results and safety

Results posted to the registry on 27 May 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
6 to <12 Year Old	14	13
12 to <18 Year Old	16	16

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

Time frame: Day 1 and up to 24 hours post-dose. Mean (Standard Deviation). Unit: ng/mL

Measure	6 to <12 Year Old n = 8	12 to <18 Year Old n = 8
Value	31737.5 (10116.74)	28300.0 (7309.88)

Population analysed: 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.

Primary outcome: Time of Maximum Observed Plasma Concentration Sampled During a Dosing Interval (Tmax) of SPD602 After a Single Oral Dose

Time frame: Day 1 and up to 24 hours post-dose. Median (Full Range). Unit: hours

Measure	6 to <12 Year Old n = 8	12 to <18 Year Old n = 8
Value	1.0 (0.5 to 1.0)	1.0 (0.6 to 2.0)

Population analysed: The PK set, defined as all participants in the Safety Analysis Set for whom the primary PK data were considered sufficient and interpretable.

Primary outcome: 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

Time frame: Day 1 and up to 24 hours post-dose. Mean (Standard Deviation). Unit: h*mg/L

Measure	6 to <12 Year Old n = 8	12 to <18 Year Old n = 8
Value	69.4 (27.39)	71.6 (22.70)

Population analysed: The PK set, defined as all participants in the Safety Analysis Set for whom the primary PK data were considered sufficient and interpretable.

Primary outcome: Terminal Half-life (t1/2) of SPD602 After a Single Oral Dose

Time frame: Day 1 and up to 24 hours post-dose. Mean (Standard Deviation). Unit: hours

Measure	6 to <12 Year Old n = 8	12 to <18 Year Old n = 8
Value	3.7 (0.93)	3.6 (0.97)

Population analysed: The PK set, defined as all participants in the Safety Analysis Set for whom the primary PK data were considered sufficient and interpretable.

4 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
6 to <12 Year Old	0 of 13 (0%)	13 of 13 (100%)	Not reported
12 to <18 Year Old	0 of 16 (0%)	15 of 16 (93.8%)	Not reported

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Study Director study director

Takeda

9 sites in 5 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing SPD602 in people with Transfusional Iron Overload and Beta-Thalassemia, run by Shire at 9 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 14 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Italy, United States, Lebanon, Canada, Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 May 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Observed Plasma Concentration (Cmax) of SPD602 After a Single Oral Dose (time frame: Day 1 and up to 24 hours post-dose). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01363908.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jun 2021.