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

This study has been 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.)
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT01363908
First received: May 30, 2011
Last updated: May 27, 2015
Last verified: August 2014
Results First Received: May 6, 2015  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Transfusional Iron Overload
Beta-Thalassemia
Intervention: Drug: SPD602

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups
  Description
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.

Participant Flow for 3 periods

Period 1:   Screening/Enrollment
    6 to <12 Year Old     12 to <18 Year Old  
STARTED     14     16  
COMPLETED     13 [1]   16  
NOT COMPLETED     1     0  
[1] One participant did not receive investigational product.

Period 2:   Pharmacokinetic (PK) Phase
    6 to <12 Year Old     12 to <18 Year Old  
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 3:   Chronic Dosing (CD) Phase
    6 to <12 Year Old     12 to <18 Year Old  
STARTED     13 [1]   16 [1]
COMPLETED     3     10  
NOT COMPLETED     10     6  
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.



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Safety Analysis Set, defined as all participants who had taken at least 1 dose of investigational product.

Reporting Groups
  Description
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.
Total Total of all reporting groups

Baseline Measures
    6 to <12 Year Old     12 to <18 Year Old     Total  
Number of Participants  
[units: participants]
  13     16     29  
Age  
[units: years]
Mean (Standard Deviation)
  8.6  (1.85)     14.4  (1.78)     11.8  (3.42)  
Gender  
[units: participants]
     
Female     7     8     15  
Male     6     8     14  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Maximum Observed Plasma Concentration (Cmax) of SPD602 After a Single Oral Dose   [ Time Frame: Day 1 and up to 24 hours post-dose ]

2.  Primary:   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 ]

3.  Primary:   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 ]

4.  Primary:   Terminal Half-life (t1/2) of SPD602 After a Single Oral Dose   [ Time Frame: Day 1 and up to 24 hours post-dose ]

5.  Primary:   Renal Clearance (CLr) of SPD602 After a Single Oral Dose   [ Time Frame: Day 1 and up to 24 hours post-dose ]

6.  Primary:   Amount Excreted Into Urine (Ue) of SPD602 After a Single Oral Dose   [ Time Frame: Day 1 and up to 24 hours post-dose ]

7.  Primary:   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 ]

8.  Primary:   Change From Baseline in Liver Iron Concentration (LIC) Assessed by FerriScan R2 Magnetic Resonance Imaging (MRI)   [ Time Frame: Baseline, 24 weeks, and 48 weeks ]

9.  Primary:   Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by FerriScan R2 MRI   [ Time Frame: Baseline, 24 weeks, and 48 weeks ]

10.  Secondary:   Change From Baseline in LIC Assessed by R2* MRI   [ Time Frame: Baseline, 24 weeks, and 48 weeks ]

11.  Secondary:   Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by R2* MRI   [ Time Frame: Baseline, 24 weeks, and 48 weeks ]

12.  Secondary:   Change From Baseline in Cardiac Iron Load Assessed by T2* MRI   [ Time Frame: Baseline, 24 weeks, and 48 weeks ]

13.  Secondary:   Change From Baseline in Serum Ferritin   [ Time Frame: Baseline, 24 weeks, and 48 weeks ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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.


  More Information
  Hide More Information

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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Study Physician
Organization: Shire Development LLC
phone: +1 866 842 5335



Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT01363908     History of Changes
Other Study ID Numbers: SPD602-202
SSP-004184AQ ( Other Identifier: Shire )
Study First Received: May 30, 2011
Results First Received: May 6, 2015
Last Updated: May 27, 2015
Health Authority: United States: Food and Drug Administration