Efficacy and Safety of Oral UT-15C Tablets to Treat Pulmonary Arterial Hypertension (FREEDOM-C2)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
United Therapeutics
ClinicalTrials.gov Identifier:
NCT00887978
First received: April 23, 2009
Last updated: December 7, 2012
Last verified: December 2012
Results First Received: November 2, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Pulmonary Hypertension
Interventions: Drug: UT-15C SR
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The recruitment period for this study was June 2009 to July 2011. Sites were located in North America, Europe and Asia.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The 310 subjects who received a dose of study drug are presented here.

Reporting Groups
  Description
UT-15C SR Doses were initiated at 0.25 mg BID and increased by 0.25 mg BID every three days (as clinically indicated based on tolerability and symptoms of PAH), to a max dose of 16 mg BID.
Placebo Identical placebo tablets to UT-15C, doses were titrated in the same manner

Participant Flow:   Overall Study
    UT-15C SR   Placebo
STARTED   157   153 
COMPLETED   132   138 
NOT COMPLETED   25   15 
Adverse Event                18                5 
Clinical Worsening                4                4 
Death                2                3 
Withdrawal by Subject                1                2 
Lost to Follow-up                0                1 



  Baseline Characteristics
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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.
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Reporting Groups
  Description
UT-15C SR Doses were initiated at 0.25 mg BID and increased by 0.25 mg BID every three days (as clinically indicated based on tolerability and symptoms of PAH), to a max dose of 16 mg BID.
Placebo Identical placebo tablets to UT-15C, doses were titrated in the same manner
Total Total of all reporting groups

Baseline Measures
   UT-15C SR   Placebo   Total 
Overall Participants Analyzed 
[Units: Participants]
 157   153   310 
Age 
[Units: Participants]
     
<=18 years   0   0   0 
Between 18 and 65 years   119   122   241 
>=65 years   38   31   69 
Age 
[Units: Years]
Mean (Full Range)
 51.5 
 (18 to 76) 
 50.4 
 (20 to 75) 
 51.0 
 (18 to 76) 
Gender 
[Units: Participants]
     
Female   119   122   241 
Male   38   31   69 
PAH Etiology 
[Units: Participants]
     
Idiopathic or familial   104   99   203 
Collagen vascular disease   48   49   97 
HIV infection   2   4   6 
Repaired congenital heart disease   3   1   4 
World Health Organization (WHO) Functional Class [1] 
[Units: Participants]
     
Class II   43   37   80 
Class III   110   115   225 
Class IV   3   0   3 
Unknown   1   1   2 
[1] Class I: No limitation of physical activity. Class II: Slight limitation of physical activity. Class III: Marked limitation of physical activity. Class IV: Inability to carry out any physical activity without symptoms.
Baseline Six-minute walk distance 
[Units: Meters]
Mean (Standard Deviation)
 329.4  (69.2)   336.8  (63.5)   333  (66.4) 
Background PAH therapy [1] 
[Units: Participants]
     
PDE-5i   67   65   132 
ERA   25   28   53 
PDE-5i + ERA   65   60   125 
[1] Eligible subjects were receiving background PAH therapy of either a phosphodiesterase-5 inhibitor (PDE-5i) and/or endothelin receptor antagonist (ERA)
Time since PAH diagnosis 
[Units: Years]
Mean (Standard Deviation)
 2.5  (2.6)   3.3  (4.1)   2.9  (3.4) 


  Outcome Measures
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1.  Primary:   6-minute Walk Distance (6MWD)   [ Time Frame: Baseline and 16 weeks ]

2.  Secondary:   Clinical Worsening Assessment   [ Time Frame: Baseline and 16 Weeks ]

3.  Secondary:   Borg Dyspnea Score   [ Time Frame: Baseline and 16 Weeks ]

4.  Secondary:   World Health Organization (WHO) Functional Class   [ Time Frame: Baseline and 16 Weeks ]

5.  Secondary:   Symptoms of PAH   [ Time Frame: Baseline and 16 Weeks ]

6.  Secondary:   Dyspnea Fatigue Index   [ Time Frame: Baseline and 16 Weeks ]

7.  Secondary:   N-terminal proBNP (NT-proBNP)   [ Time Frame: Baseline and 16 Weeks ]

8.  Secondary:   Quality of Life (QoL) Assessment: Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR)   [ Time Frame: Baseline and 16 Weeks ]

9.  Post-Hoc:   6-minute Walk Distance by PAH Etiology: Idiopathic PAH (IPAH) / Heritable PAH(HPAH)   [ Time Frame: Baseline and 16 Weeks ]

10.  Post-Hoc:   6-minute Walk Distance by Background PAH Therapy: PDE-5i Only   [ Time Frame: 16 weeks ]

11.  Post-Hoc:   6-minute Walk Test by Background PAH Therapy: ERA Only   [ Time Frame: Baseline and 16 weeks ]

12.  Post-Hoc:   6-minute Walk Test by Background PAH Therapy: ERA + PDE-5i   [ Time Frame: 16 weeks ]

13.  Post-Hoc:   6-minute Walk Distance by Time to PAH Diagnosis: 0 - 0.9 Years   [ Time Frame: Baseline and 16 weeks ]

14.  Post-Hoc:   6-minute Walk Distance by Time Since PAH Diagnosis: 0.9 - 1.74 Years   [ Time Frame: 16 Weeks ]

15.  Post-Hoc:   6-minute Walk Distance by Years Since PAH Diagnosis: 1.8 - 3.5 Years   [ Time Frame: Baseline and 16 weeks ]

16.  Post-Hoc:   6-minute Walk Distance by Time Since PAH Diagnosis: 3.6 - 26.4 Years   [ Time Frame: Baseline and 16 weeks ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
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  More Information
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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: Kevin Laliberte, PharmD
Organization: United Therapeutics Corporation
phone: 919-425-8350
e-mail: klaliberte@unither.com


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: United Therapeutics
ClinicalTrials.gov Identifier: NCT00887978     History of Changes
Other Study ID Numbers: TDE-PH-308
Study First Received: April 23, 2009
Results First Received: November 2, 2012
Last Updated: December 7, 2012