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Addition of UT-15C SR to Pulmonary Arterial Hypertension Patients Currently Receiving Tyvaso®

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01477333
Recruitment Status : Completed
First Posted : November 22, 2011
Results First Posted : March 6, 2017
Last Update Posted : March 6, 2017
Sponsor:
Information provided by (Responsible Party):
United Therapeutics

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Pulmonary Arterial Hypertension
Interventions Drug: UT-15C SR
Drug: Tyvaso Inhalation Solution
Enrollment 18

Recruitment Details The recruitment period for this study was October 2011 to November 2013.
Pre-assignment Details  
Arm/Group Title UT-15C SR BID
Hide Arm/Group Description UT-15C SR: Initiated at 0.125 mg BID, titrated as clinically indicated.
Period Title: Overall Study
Started 18
Completed 15
Not Completed 3
Reason Not Completed
Adverse Event             1
Withdrawal by Subject             1
Clinical Deterioration             1
Arm/Group Title UT-15C SR BID
Hide Arm/Group Description UT-15C SR: Initiated at 0.125 mg BID, titrated as clinically indicated.
Overall Number of Baseline Participants 18
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants
<=18 years
0
   0.0%
Between 18 and 65 years
14
  77.8%
>=65 years
4
  22.2%
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 18 participants
51.3
(20 to 70)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants
Female
13
  72.2%
Male
5
  27.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants
Hispanic or Latino
2
  11.1%
Not Hispanic or Latino
16
  88.9%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
18
 100.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 18 participants
18
1.Primary Outcome
Title Change in Hemodynamic Parameters From Baseline to Week 24.
Hide Description

Hemodynamics (via right heart catheterization [RHC]) were assessed at Baseline and Week 24 or at the time of premature termination of study drug if prior to the Week 24 visit.

Cardiopulmonary hemodynamic measurements included the following: mean pulmonary arterial pressure (PAPm), mean systemic arterial pressure (SAPm), mean right atrial pressure (RAPm), and mean pulmonary capillary wedge pressure (PCWPm).

Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population with data available at Baseline and Week 24.
Arm/Group Title UT-15C SR BID
Hide Arm/Group Description:
UT-15C SR: Initiated at 0.125 mg BID, titrated as clinically indicated.
Overall Number of Participants Analyzed 15
Median (Full Range)
Unit of Measure: mmHg
Systolic systemic arterial pressure (mmHg)
-2.0
(-22 to 21)
Diastolic systemic arterial pressure (mmHg)
0
(-20 to 18)
Mean systemic arterial pressure (mmHg)
-1.0
(-29 to 18)
Systolic pulmonary arterial pressure (mmHg)
3.0
(-51 to 12)
Diastolic pulmonary arterial pressure (mmHg)
0
(-16 to 10)
Mean pulmonary arterial pressure (mmHg)
0
(-26 to 10)
Mean right atrial pressure (mmHg)
0
(-9 to 6)
Mean pulmonary capillary wedge pressure (mmHg)
-1.0
(-15 to 8)
2.Primary Outcome
Title Change in Hemodynamic Parameter (Heart Rate) From Baseline to Week 24.
Hide Description Heart rate was assessed at Baseline and Week 24 or at the time of premature termination of study drug if prior to the Week 24 visit.
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population with data available at Baseline and Week 24.
Arm/Group Title UT-15C SR BID
Hide Arm/Group Description:
UT-15C SR: Initiated at 0.125 mg BID, titrated as clinically indicated.
Overall Number of Participants Analyzed 15
Median (Full Range)
Unit of Measure: beats/min
4.00
(-29.0 to 25.0)
3.Primary Outcome
Title Change in Hemodynamic Parameters (Arterial and Venous Oxygen Saturation) From Baseline to Week 24.
Hide Description

Hemodynamics (via right heart catheterization [RHC]) were assessed at Baseline and Week 24 or at the time of premature termination of study drug if prior to the Week 24 visit.

Cardiopulmonary hemodynamic measurements included arterial oxygen saturation (SaO2) and mixed venous oxygen saturation (SvO2).

Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population with data available at Baseline and Week 24.
Arm/Group Title UT-15C SR BID
Hide Arm/Group Description:
UT-15C SR: Initiated at 0.125 mg BID, titrated as clinically indicated.
Overall Number of Participants Analyzed 15
Median (Full Range)
Unit of Measure: percentage bound to hemoglobin
Arterial oxygen saturation (%)
1.0
(-5 to 5)
Mixed venous oxygen saturation (%)
0
(-9 to 4)
4.Primary Outcome
Title Change in Hemodynamic Parameter (Cardiac Output) From Baseline to Week 24.
Hide Description Hemodynamics (via right heart catheterization [RHC]) were assessed at Baseline and Week 24 or at the time of premature termination of study drug if prior to the Week 24 visit.
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population with data available at Baseline and Week 24.
Arm/Group Title UT-15C SR BID
Hide Arm/Group Description:
UT-15C SR: Initiated at 0.125 mg BID, titrated as clinically indicated.
Overall Number of Participants Analyzed 15
Median (Full Range)
Unit of Measure: L/min
0
(-1 to 4)
5.Primary Outcome
Title Change in Hemodynamic Parameter (Cardiac Index) From Baseline to Week 24.
Hide Description

Hemodynamics (via right heart catheterization [RHC]) were assessed at Baseline and Week 24 or at the time of premature termination of study drug if prior to the Week 24 visit.

Cardiopulmonary hemodynamic measurements included cardiac index (CI).

Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population with data available at Baseline and Week 24.
Arm/Group Title UT-15C SR BID
Hide Arm/Group Description:
UT-15C SR: Initiated at 0.125 mg BID, titrated as clinically indicated.
Overall Number of Participants Analyzed 15
Median (Full Range)
Unit of Measure: L/min/m^2
0
(0 to 1)
6.Primary Outcome
Title Change in Hemodynamic Parameter (Pulmonary Vascular Resistance Index) From Baseline to Week 24.
Hide Description

Hemodynamics (via right heart catheterization [RHC]) were assessed at Baseline and Week 24 or at the time of premature termination of study drug if prior to the Week 24 visit.

Cardiopulmonary hemodynamic measurements included the following: pulmonary vascular resistance index (PVRI).

Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population with data available at Baseline and Week 24.
Arm/Group Title UT-15C SR BID
Hide Arm/Group Description:
UT-15C SR: Initiated at 0.125 mg BID, titrated as clinically indicated.
Overall Number of Participants Analyzed 15
Median (Full Range)
Unit of Measure: dyn*s/cm^5*m^2
0.2
(-10 to 7)
7.Secondary Outcome
Title Change in Exercise Capacity as Measured by the 6-minute Walk Test (6MWT) Over the 24-week Treatment Period.
Hide Description The 6MWT was conducted at Baseline, 2 to 4 hours after the last Tyvaso dose, and prior to first dose of UT-15C SR. The 6MWT was also performed at Weeks 4, 12, and 24, or at the time of premature termination of study drug if prior to the Week 24 visit.
Time Frame Baseline and Weeks 4, 12, and 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population with data available at Baseline and Week 24.
Arm/Group Title UT-15C SR BID
Hide Arm/Group Description:
UT-15C SR: Initiated at 0.125 mg BID, titrated as clinically indicated.
Overall Number of Participants Analyzed 18
Median (Full Range)
Unit of Measure: Meters
Week 4 (n=18)
20.5
(-111 to 119)
Week 12 (n=18)
12.4
(-70 to 101)
Week 24 (n=15)
14.9
(-178 to 101)
8.Secondary Outcome
Title Time to Clinical Worsening Over the Treatment Period.
Hide Description Clinical worsening was assessed continuously from Baseline through each subject’s last study visit. Clinical worsening was defined as the occurrence of any one or more of the following: death (all causes), hospitalization as a result of worsening pulmonary arterial hypertension (PAH), and initiation of a parenteral prostacyclin.
Time Frame Clinical worsening was assessed continuously from Baseline through each subject’s last study visit
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population with data available at Baseline and Week 24.
Arm/Group Title UT-15C SR BID
Hide Arm/Group Description:
UT-15C SR: Initiated at 0.125 mg BID, titrated as clinically indicated.
Overall Number of Participants Analyzed 18
Mean (Standard Deviation)
Unit of Measure: Days
234  (200.3)
9.Secondary Outcome
Title Shift From Baseline in World Health Organization (WHO) Functional Class Over the 24-week Treatment Period.
Hide Description The WHO functional classification for pulmonary hypertension was assessed at Baseline prior to starting UT-15C SR, Weeks 4, 8, 12, and 24, or at the time of premature termination if prior to Week 24. The WHO functional classification ranges from I (patient's disease does not affect daily activities) to IV (patient's disease causes severe impairment).
Time Frame Baseline and Weeks 4, 8, 12, and 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population with data available at Baseline and Week 24.
Arm/Group Title Class II to Class II Class II to Class III Class III to Class II Class III to Class III
Hide Arm/Group Description:
UT-15C SR BID
UT-15C SR BID
UT-15C SR BID
UT-15C SR BID
Overall Number of Participants Analyzed 18 18 18 18
Measure Type: Number
Unit of Measure: participants
Week 4 (n=18) 8 1 0 9
Week 8 (n=18) 6 3 2 7
Week 12 (n=18) 9 0 1 8
Week 24 (n=15) 7 1 2 5
10.Secondary Outcome
Title N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) Over the 24-week Treatment Period.
Hide Description NT-proBNP was assessed at Baseline prior to starting UT-15C SR, Weeks 12 and 24, or at the time of premature termination if prior to Week 24. Blood for NT-proBNP assessment was collected before the 6MWT was conducted.
Time Frame Weeks 12 and 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population with data available at Baseline and Week 24.
Arm/Group Title UT-15C SR BID
Hide Arm/Group Description:
UT-15C SR: Initiated at 0.125 mg BID, titrated as clinically indicated.
Overall Number of Participants Analyzed 16
Mean (Standard Deviation)
Unit of Measure: pg/mL
Week 12 (n=16) -99  (295)
Week 24 (n=13) 144  (464)
Time Frame Adverse events were recorded throughout the 24-week study, including the screening phase, as well as during the long-term follow-up period.
Adverse Event Reporting Description Adverse events were recorded throughout the course of the study, including a 24-week treatment period and a long-term follow up period through each subject’s last study visit (up to 553 days).
 
Arm/Group Title UT-15C SR BID
Hide Arm/Group Description UT-15C SR: Initiated at 0.125 mg BID, titrated as clinically indicated.
All-Cause Mortality
UT-15C SR BID
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
UT-15C SR BID
Affected / at Risk (%) # Events
Total   2/18 (11.11%)    
Gastrointestinal disorders   
Ascites * 1  1/18 (5.56%)  1
Diarrhea * 1  1/18 (5.56%)  1
Metabolism and nutrition disorders   
Fluid overload * 1  1/18 (5.56%)  1
Hyponatremia * 1  1/18 (5.56%)  1
Malnutrition * 1  1/18 (5.56%)  1
Renal and urinary disorders   
Renal failure acute * 1  1/18 (5.56%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (11.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
UT-15C SR BID
Affected / at Risk (%) # Events
Total   18/18 (100.00%)    
Blood and lymphatic system disorders   
Anemia * 1  2/18 (11.11%)  2
Cardiac disorders   
Palpitations * 1  2/18 (11.11%)  2
Atrial fibrillatioin * 1  1/18 (5.56%)  1
Pericarditis * 1  1/18 (5.56%)  1
Sinus bradycardia * 1  1/18 (5.56%)  1
Gastrointestinal disorders   
Diarrhea * 1  11/18 (61.11%)  11
Nausea * 1  12/18 (66.67%)  12
Abdominal pain * 1  3/18 (16.67%)  3
Abdominal distension * 1  2/18 (11.11%)  2
Abdominal pain upper * 1  2/18 (11.11%)  2
Constipation * 1  2/18 (11.11%)  2
Dyspepsia * 1  2/18 (11.11%)  2
Flatulence * 1  2/18 (11.11%)  2
Duodenal polyp * 1  1/18 (5.56%)  1
Gastroesophageal reflux disease * 1  1/18 (5.56%)  1
Gingival bleeding * 1  1/18 (5.56%)  1
Hiatus hernia * 1  1/18 (5.56%)  1
Vomiting * 1  1/18 (5.56%)  1
General disorders   
Fatigue * 1  6/18 (33.33%)  6
Edema peripheral * 1  4/18 (22.22%)  5
Chest discomfort * 1  3/18 (16.67%)  3
Chest pain * 1  3/18 (16.67%)  3
Chills * 1  1/18 (5.56%)  1
Face edema * 1  1/18 (5.56%)  1
Local swelling * 1  1/18 (5.56%)  1
Edema * 1  1/18 (5.56%)  1
Pain * 1  1/18 (5.56%)  1
Infections and infestations   
Nasopharyngitis * 1  3/18 (16.67%)  3
Bronchitis * 1  2/18 (11.11%)  3
Sinusitis * 1  2/18 (11.11%)  3
Upper respiratory tract infection * 1  2/18 (11.11%)  3
Atypical pneumonia * 1  1/18 (5.56%)  2
Influenza * 1  1/18 (5.56%)  1
Lower respiratory tract infection * 1  1/18 (5.56%)  1
Respiratory tract infection * 1  1/18 (5.56%)  1
Injury, poisoning and procedural complications   
Eye burns * 1  1/18 (5.56%)  1
Muscle strain * 1  1/18 (5.56%)  1
Contusion * 1  1/18 (5.56%)  1
Investigations   
Blood urea increased * 1  2/18 (11.11%)  2
Blood creatinine increased * 1  1/18 (5.56%)  1
Blood pressure increased * 1  1/18 (5.56%)  1
Hematocrit decreased * 1  1/18 (5.56%)  1
Hemoglobin decreased * 1  1/18 (5.56%)  1
Red blood cell count decreased * 1  1/18 (5.56%)  1
Weight decreased * 1  1/18 (5.56%)  1
Weight increased * 1  1/18 (5.56%)  1
Metabolism and nutrition disorders   
Hypokalemia * 1  2/18 (11.11%)  3
Musculoskeletal and connective tissue disorders   
Pain in extremity * 1  4/18 (22.22%)  4
Arthralgia * 1  2/18 (11.11%)  3
Muscular weakness * 1  2/18 (11.11%)  2
Arthritis * 1  1/18 (5.56%)  1
Back pain * 1  1/18 (5.56%)  1
Groin pain * 1  1/18 (5.56%)  1
Pain in jaw * 1  1/18 (5.56%)  1
Synovial cyst * 1  1/18 (5.56%)  1
Muscle tightness * 1  1/18 (5.56%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Skin papilloma * 1  1/18 (5.56%)  1
Nervous system disorders   
Headache * 1  14/18 (77.78%)  14
Presyncope * 1  2/18 (11.11%)  2
Syncope * 1  2/18 (11.11%)  2
Dizziness * 1  1/18 (5.56%)  1
Dysguesia * 1  1/18 (5.56%)  1
Psychiatric disorders   
Anxiety * 1  1/18 (5.56%)  1
Depression * 1  1/18 (5.56%)  1
Restlessness * 1  1/18 (5.56%)  1
Affect lability * 1  1/18 (5.56%)  1
Renal and urinary disorders   
Hematuria * 1  1/18 (5.56%)  1
Renal cyst * 1  1/18 (5.56%)  1
Respiratory, thoracic and mediastinal disorders   
Dyspnea * 1  5/18 (27.78%)  5
Cough * 1  4/18 (22.22%)  4
Nasal congestion * 1  3/18 (16.67%)  3
Epistaxis * 1  2/18 (11.11%)  2
Dysphonia * 1  1/18 (5.56%)  1
Dyspnea paroxysmal nocturnal * 1  1/18 (5.56%)  1
Hiccups * 1  1/18 (5.56%)  1
Productive cough * 1  1/18 (5.56%)  1
Sinus congestion * 1  1/18 (5.56%)  1
Skin and subcutaneous tissue disorders   
Rash * 1  2/18 (11.11%)  2
Dermatitis contact * 1  1/18 (5.56%)  1
Hyperhidrosis * 1  1/18 (5.56%)  1
Pruritus * 1  1/18 (5.56%)  1
Vascular disorders   
Flushing * 1  8/18 (44.44%)  8
Hypotension * 1  3/18 (16.67%)  3
Hot flush * 1  1/18 (5.56%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (11.1)
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.
Institution and/or Principal Investigator agree not to publish or publicly present any interim results of the study without the prior written consent of Sponsor, not to be unreasonably withheld or delayed, except as provided below. Institution and/or Principal Investigator further agree to provide Sponsor with drafts of any such publication or presentation for review and approval no less than 30 days prior to submission for publication or the date of public presentation.
Results Point of Contact
Name/Title: Kevin LaLiberte, PharmD
Organization: United Therapeutics Corp.
Phone: 919-425-8176
Responsible Party: United Therapeutics
ClinicalTrials.gov Identifier: NCT01477333     History of Changes
Other Study ID Numbers: TDE-PH-203
First Submitted: November 14, 2011
First Posted: November 22, 2011
Results First Submitted: August 1, 2016
Results First Posted: March 6, 2017
Last Update Posted: March 6, 2017