Back to resultsRemodulin® to Oral Treprostinil Transition
Primary Purpose
Pulmonary Arterial Hypertension
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
UT-15C SR
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Arterial Hypertension focused on measuring Pulmonary Arterial Hypertension, UT-15C SR, PAH
Eligibility Criteria
Inclusion Criteria:
- Between 15 and 80 years of age, inclusive, weigh at least 40 kg and have a diagnosis of PAH
- Have stable disease as confirmed by recent right heart catheterization and a Baseline 6MWD of at least 250 meters
- Have been receiving Remodulin for at least 90 days and at a stable dose for at least 30 days prior to the Baseline visit; the dose of Remodulin must be between 25-75 ng/kg/min, inclusive
- Must be also receiving an endothelin receptor antagonist (ERA) and/or a phosphodiesterase-5 inhibitor (PDE-5i) for at least 90 days and have been at a stable dose for at least 30 days prior to Baseline
Exclusion Criteria:
- WHO functional class III and IV subjects will be excluded
Sites / Locations
- Arizona Pulmonary Specialists
- University of Arizona Clinical and Translational Science (CATS) Research Center
- Washington University School of Medicine
- University of Rochester
- The Ohio State University
- University of Pittsburgh Medical Center (UPMC)
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
UT-15C SR
Arm Description
Outcomes
Primary Outcome Measures
Number of Participants That Were Succesfully Transitioned From Parenteral Remodulin to UT-15C.
Successful transition was based on the number of participants that completely transitioned to oral treprostinil by the week 4 study visit and clinically maintained on oral treprostinil treatment through Week 24.
Secondary Outcome Measures
Change From Baseline in Six-minute Walk Distance at Week 24
The purpose of the 6MWT is to evaluate exercise capacity associated with carrying out activities of daily living. Patients were instructed to walk down a corridor at a comfortable speed as far as they could manage for six minutes, resting whenever they needed. Distance <500 meters suggests considerable exercise limitation; Distance 500-800 meters suggests moderate limitation; Distance >800 meters (with no rests) suggests mild or no limitation.
Change in Borg Dyspnea Score (Following 6MWT) From Baseline to Week 24
The Borg dyspnea score is a 10-point scale rating the maximum level of dyspnea (difficulty in breathing) experienced during the six-minute walk test (6MWT). The Borg dyspnea score was assessed immediately following the 6MWT. Scores ranged from 0 (for no shortness of breath) to 10 (for the greatest shortness of breath ever experienced).
Change in Quality of Life (QoL) Assessment: Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) From Baseline to Week 24
The CAMPHOR is a health related quality of life instrument validated for pulmonary hypertension that assesses impairment (symptoms), disability (activities) and quality of life. The questionnaire is divided into three sections; Symptoms (Scores 0-25; high scores indicate more symptoms), Activity (Score 0-30; low score indicates good functioning) and Quality of Life (0-25; high scores indicate poor QoL). The sum of these scores equates to the Total score (0-80). In the CAMPHOR scores, lower scores indicate improvements.
Change in World Health Organization (WHO) Functional Classification From Baseline to Week 24
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.
Change in Dyspnea-fatigue Index From Baseline to Week 24
The dyspnea-fatigue index has three components, each rated on a scale of 0 to 4, for the magnitude of the task that evokes dyspnea or fatigue, the magnitude of the pace (or effort) with which the task is performed and the associated functional impairment in general activities. The ratings for each component were added to form an aggregate score, which could range from 0, for the worst condition, to 12, for the best.
Change From Baseline to Week 24 in Pharmacokinetic Parameters: Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), and Trough Plasma Concentration (Cmin)
Treprostinil pharmacokinetics (PK) were evaluated on two occasions during this study, once while the subject was still receiving Remodulin and again at Week 24 when the subject was receiving a stable dose of oral treprostinil. Blood samples were scheduled to be drawn from each subject initially at time 0 and the following subsequent times: 2, 4, 5, 6, 8, 10 and 12 hours after time of study drug administration (time 0) for a total of eight samples.
Change From Baseline to Week 24 in Pharmacokinetics Parameter: Peak Time to Reach Peak Plasma Concentration [Tmax (h)]
Treprostinil pharmacokinetics (PK) were evaluated on two occasions during this study, once while the subject was still receiving Remodulin and again at Week 24 when the subject was receiving a stable dose of oral treprostinil. Blood samples were scheduled to be drawn from each subject initially at time 0 and the following subsequent times: 2, 4, 5, 6, 8, 10 and 12 hours after time of study drug administration (time 0) for a total of eight samples.
Change From Baseline to Week 24 in Pharmacokinetics Parameters: Area Under the Plasma Concentration Curve (AUC) [h(ng/mL)]
Treprostinil pharmacokinetics (PK) were evaluated on two occasions during this study, once while the subject was still receiving Remodulin and again at Week 24 when the subject was receiving a stable dose of oral treprostinil. Blood samples were scheduled to be drawn from each subject initially at time 0 and the following subsequent times: 2, 4, 5, 6, 8, 10 and 12 hours after time of study drug administration (time 0) for a total of eight samples.
Change From Baseline to Week 24 in Hemodynamics Parameters: Mean Pulmonary Artery Pressure (PAPm), Mean Right Atrial Pressure (RAPm) and Mean Pulmonary Capillary Wedge Pressure (PCWPm)
Pulmonary hypertension (PH) is an increase in pressure in the pulmonary vasculature defined as a mean pulmonary artery pressure (PAPm) greater than 25 mmHg at rest or greater than 30 mmHg with exercise, as measured by right heart catheterization. Right Atrial Pressure (RAP) is the pressure of blood in the right atrium of the heart. Pulmonary Capillary Wedge Pressure (PCWP) is used to calculated pulmonary vascular resistance and can help guide therapeutic efficacy. The PAPm, RAPm and PCWPm values and their respective changes from Baseline to Week 24 at peak exercise were measured by Swan-Ganz right heart catheterization.
Change From Baseline to Week 24 in Hemodynamics Parameters: Arterial Oxygen Saturation (SaO2) (%) and Mixed Venous Oxygen Saturation (SvO2) (%)
SaO2 measured by Arterial Blood Draw and Blood Gas Analyzer and SvO2 measured via Pulmonary Artery Catheter, are both Hemodynamics Parameters collected during right heart catheterization. Mixed venous oxygen saturation (SvO2) can help to determine whether the cardiac output and oxygen delivery is high enough to meet a patient's needs
Change From Baseline to Week 24 in Hemodynamics Parameters: Cardiac Output (CO) (L/Min)
Cardiac Output (CO) is the volume of blood ejected by the heart per minute, as measured by right heart catheterization. The value and change from Baseline to Week 24 at peak exercise was measured by Swan-Ganz right heart catheterization.
Change From Baseline to Week 24 in Hemodynamics Parameters: Cardiac Index (CI) (L/Min/m^2)
Cardiac Index (CI) relates the cardiac output (CO) from left ventricle to body surface area (BSA), thus relating heart performance to the size of the individual. The CI values and their respective changes from Baseline to Week 24 at peak exercise was measured by Swan-Ganz right heart catheterization.
Change From Baseline to Week 24 in Hemodynamics Parameters: Pulmonary Vascular Resistance Index (PVRI) (mmHg*Min*m^2/L)
Pulmonary Vascular Resistance Index (PVRI) is calculated using Mean Pulmonary Arterial Pressure(PAPm), Pulmonary Capillary Wedge Pressure (PCWP) and Cardiac Index (CI ), to provide information about right ventricular overload. The PVRI values and their respective changes from Baseline to Week 24 at peak exercise was measured by Swan-Ganz right heart catheterization.
Change From Baseline to Week 24 in Hemodynamics Parameters: Pulmonary Vascular Resistance (PVR) (mmHg*Min/L)
pulmonary vascular resistance (PVR) is the resistance the right ventricle must overcome to pump blood into the pulmonary arteries. The change in PVR values from Baseline to Week 24 at peak exercise were measured by Swan-Ganz right heart catheterization.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01588405
Brief Title
Remodulin® to Oral Treprostinil Transition
Official Title
A Multicenter, Open-Label Study of the Safety and Tolerability of Transitioning From Remodulin® to Oral Treprostinil in Subjects With Pulmonary Arterial Hypertension
Study Type
Interventional
2. Study Status
Record Verification Date
April 2016
Overall Recruitment Status
Completed
Study Start Date
April 2012 (undefined)
Primary Completion Date
July 2014 (Actual)
Study Completion Date
December 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
United Therapeutics
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This multi-center, open-label study will assess the tolerability and safety of transitioning subjects with stable Pulmonary Arterial Hypertension (PAH) from continuous intravenous (IV) or subcutaneous (SC) Remodulin infusion to oral treprostinil (UT-15C sustained release (SR) tablets).
This study will consist of an in-hospital transition phase, dose optimization/evaluation phase, and follow up phase.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Arterial Hypertension
Keywords
Pulmonary Arterial Hypertension, UT-15C SR, PAH
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
33 (Actual)
8. Arms, Groups, and Interventions
Arm Title
UT-15C SR
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
UT-15C SR
Intervention Description
Subjects will transition in the hospital from Remodulin to UT-15C SR within 5 days of the start of the transition. The dose of Remodulin will be decreased as the dose of UT-15C SR is increased over the 5 days. Once subjects have been transitioned from Remodulin, the dose of UT-15C SR will continue to be modified / titrated to the appropriate optimal dose for that subject throughout the rest of the study.
Primary Outcome Measure Information:
Title
Number of Participants That Were Succesfully Transitioned From Parenteral Remodulin to UT-15C.
Description
Successful transition was based on the number of participants that completely transitioned to oral treprostinil by the week 4 study visit and clinically maintained on oral treprostinil treatment through Week 24.
Time Frame
Up to 24 weeks
Secondary Outcome Measure Information:
Title
Change From Baseline in Six-minute Walk Distance at Week 24
Description
The purpose of the 6MWT is to evaluate exercise capacity associated with carrying out activities of daily living. Patients were instructed to walk down a corridor at a comfortable speed as far as they could manage for six minutes, resting whenever they needed. Distance <500 meters suggests considerable exercise limitation; Distance 500-800 meters suggests moderate limitation; Distance >800 meters (with no rests) suggests mild or no limitation.
Time Frame
Baseline and week 24
Title
Change in Borg Dyspnea Score (Following 6MWT) From Baseline to Week 24
Description
The Borg dyspnea score is a 10-point scale rating the maximum level of dyspnea (difficulty in breathing) experienced during the six-minute walk test (6MWT). The Borg dyspnea score was assessed immediately following the 6MWT. Scores ranged from 0 (for no shortness of breath) to 10 (for the greatest shortness of breath ever experienced).
Time Frame
Baseline and week 24
Title
Change in Quality of Life (QoL) Assessment: Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) From Baseline to Week 24
Description
The CAMPHOR is a health related quality of life instrument validated for pulmonary hypertension that assesses impairment (symptoms), disability (activities) and quality of life. The questionnaire is divided into three sections; Symptoms (Scores 0-25; high scores indicate more symptoms), Activity (Score 0-30; low score indicates good functioning) and Quality of Life (0-25; high scores indicate poor QoL). The sum of these scores equates to the Total score (0-80). In the CAMPHOR scores, lower scores indicate improvements.
Time Frame
Baseline and week 24
Title
Change in World Health Organization (WHO) Functional Classification From Baseline to Week 24
Description
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.
Time Frame
Baseline and Week 24
Title
Change in Dyspnea-fatigue Index From Baseline to Week 24
Description
The dyspnea-fatigue index has three components, each rated on a scale of 0 to 4, for the magnitude of the task that evokes dyspnea or fatigue, the magnitude of the pace (or effort) with which the task is performed and the associated functional impairment in general activities. The ratings for each component were added to form an aggregate score, which could range from 0, for the worst condition, to 12, for the best.
Time Frame
Baseline and Week 24
Title
Change From Baseline to Week 24 in Pharmacokinetic Parameters: Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), and Trough Plasma Concentration (Cmin)
Description
Treprostinil pharmacokinetics (PK) were evaluated on two occasions during this study, once while the subject was still receiving Remodulin and again at Week 24 when the subject was receiving a stable dose of oral treprostinil. Blood samples were scheduled to be drawn from each subject initially at time 0 and the following subsequent times: 2, 4, 5, 6, 8, 10 and 12 hours after time of study drug administration (time 0) for a total of eight samples.
Time Frame
Baseline and Week 24
Title
Change From Baseline to Week 24 in Pharmacokinetics Parameter: Peak Time to Reach Peak Plasma Concentration [Tmax (h)]
Description
Treprostinil pharmacokinetics (PK) were evaluated on two occasions during this study, once while the subject was still receiving Remodulin and again at Week 24 when the subject was receiving a stable dose of oral treprostinil. Blood samples were scheduled to be drawn from each subject initially at time 0 and the following subsequent times: 2, 4, 5, 6, 8, 10 and 12 hours after time of study drug administration (time 0) for a total of eight samples.
Time Frame
Baseline and Week 24
Title
Change From Baseline to Week 24 in Pharmacokinetics Parameters: Area Under the Plasma Concentration Curve (AUC) [h(ng/mL)]
Description
Treprostinil pharmacokinetics (PK) were evaluated on two occasions during this study, once while the subject was still receiving Remodulin and again at Week 24 when the subject was receiving a stable dose of oral treprostinil. Blood samples were scheduled to be drawn from each subject initially at time 0 and the following subsequent times: 2, 4, 5, 6, 8, 10 and 12 hours after time of study drug administration (time 0) for a total of eight samples.
Time Frame
Baseline and Week 24
Title
Change From Baseline to Week 24 in Hemodynamics Parameters: Mean Pulmonary Artery Pressure (PAPm), Mean Right Atrial Pressure (RAPm) and Mean Pulmonary Capillary Wedge Pressure (PCWPm)
Description
Pulmonary hypertension (PH) is an increase in pressure in the pulmonary vasculature defined as a mean pulmonary artery pressure (PAPm) greater than 25 mmHg at rest or greater than 30 mmHg with exercise, as measured by right heart catheterization. Right Atrial Pressure (RAP) is the pressure of blood in the right atrium of the heart. Pulmonary Capillary Wedge Pressure (PCWP) is used to calculated pulmonary vascular resistance and can help guide therapeutic efficacy. The PAPm, RAPm and PCWPm values and their respective changes from Baseline to Week 24 at peak exercise were measured by Swan-Ganz right heart catheterization.
Time Frame
Baseline and week 24
Title
Change From Baseline to Week 24 in Hemodynamics Parameters: Arterial Oxygen Saturation (SaO2) (%) and Mixed Venous Oxygen Saturation (SvO2) (%)
Description
SaO2 measured by Arterial Blood Draw and Blood Gas Analyzer and SvO2 measured via Pulmonary Artery Catheter, are both Hemodynamics Parameters collected during right heart catheterization. Mixed venous oxygen saturation (SvO2) can help to determine whether the cardiac output and oxygen delivery is high enough to meet a patient's needs
Time Frame
Baseline and Week 24
Title
Change From Baseline to Week 24 in Hemodynamics Parameters: Cardiac Output (CO) (L/Min)
Description
Cardiac Output (CO) is the volume of blood ejected by the heart per minute, as measured by right heart catheterization. The value and change from Baseline to Week 24 at peak exercise was measured by Swan-Ganz right heart catheterization.
Time Frame
Baseline and week 24
Title
Change From Baseline to Week 24 in Hemodynamics Parameters: Cardiac Index (CI) (L/Min/m^2)
Description
Cardiac Index (CI) relates the cardiac output (CO) from left ventricle to body surface area (BSA), thus relating heart performance to the size of the individual. The CI values and their respective changes from Baseline to Week 24 at peak exercise was measured by Swan-Ganz right heart catheterization.
Time Frame
Baseline and week 24
Title
Change From Baseline to Week 24 in Hemodynamics Parameters: Pulmonary Vascular Resistance Index (PVRI) (mmHg*Min*m^2/L)
Description
Pulmonary Vascular Resistance Index (PVRI) is calculated using Mean Pulmonary Arterial Pressure(PAPm), Pulmonary Capillary Wedge Pressure (PCWP) and Cardiac Index (CI ), to provide information about right ventricular overload. The PVRI values and their respective changes from Baseline to Week 24 at peak exercise was measured by Swan-Ganz right heart catheterization.
Time Frame
Baseline and week 24
Title
Change From Baseline to Week 24 in Hemodynamics Parameters: Pulmonary Vascular Resistance (PVR) (mmHg*Min/L)
Description
pulmonary vascular resistance (PVR) is the resistance the right ventricle must overcome to pump blood into the pulmonary arteries. The change in PVR values from Baseline to Week 24 at peak exercise were measured by Swan-Ganz right heart catheterization.
Time Frame
Baseline and week 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
15 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Between 15 and 80 years of age, inclusive, weigh at least 40 kg and have a diagnosis of PAH
Have stable disease as confirmed by recent right heart catheterization and a Baseline 6MWD of at least 250 meters
Have been receiving Remodulin for at least 90 days and at a stable dose for at least 30 days prior to the Baseline visit; the dose of Remodulin must be between 25-75 ng/kg/min, inclusive
Must be also receiving an endothelin receptor antagonist (ERA) and/or a phosphodiesterase-5 inhibitor (PDE-5i) for at least 90 days and have been at a stable dose for at least 30 days prior to Baseline
Exclusion Criteria:
WHO functional class III and IV subjects will be excluded
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cynthia Madden, MD, MPH
Organizational Affiliation
Senior Clinical Research Physician
Official's Role
Study Chair
Facility Information:
Facility Name
Arizona Pulmonary Specialists
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85013
Country
United States
Facility Name
University of Arizona Clinical and Translational Science (CATS) Research Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
Washington University School of Medicine
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
University of Rochester
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
The Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43221
Country
United States
Facility Name
University of Pittsburgh Medical Center (UPMC)
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Remodulin® to Oral Treprostinil Transition
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