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;   Endpoint Classification: Safety/Efficacy Study;   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.
No text entered.

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  
Number of Participants  
[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  
Baseline Six-minute walk distance  
[units: meters]
Mean ± Standard Deviation
  329.4  ± 69.2     336.8  ± 63.5     333  ± 66.4  
Background PAH therapy [2]
[units: participants]
     
PDE-5i     67     65     132  
ERA     25     28     53  
PDE-5i + ERA     65     60     125  
Time since PAH diagnosis  
[units: years]
Mean ± Standard Deviation
  2.5  ± 2.6     3.3  ± 4.1     2.9  ± 3.4  
[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.
[2] Eligible subjects were receiving background PAH therapy of either a phosphodiesterase-5 inhibitor (PDE-5i) and/or endothelin receptor antagonist (ERA)



  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


No publications provided by United Therapeutics

Publications automatically indexed to this study:

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
Health Authority: United States: Food and Drug Administration