Pulmonary Arterial Hypertension
Conditions
Keywords
Pulmonary Arterial Hypertension, UT-15C SR, PAH
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.
Interventions
DRUGUT-15C SR
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.
Sponsors
United Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
15 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants That Were Succesfully Transitioned From Parenteral Remodulin to UT-15C. | Up to 24 weeks | 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
| Measure | Time frame | Description |
|---|---|---|
| Change in Borg Dyspnea Score (Following 6MWT) From Baseline to Week 24 | Baseline and 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 | Baseline and 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 | Baseline and 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 | Baseline and 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) | Baseline and Week 24 | 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)] | Baseline and Week 24 | 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 in Six-minute Walk Distance at Week 24 | Baseline and 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 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) | Baseline and week 24 | 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) (%) | Baseline and Week 24 | 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) | Baseline and week 24 | 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) | Baseline and week 24 | 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) | Baseline and week 24 | 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) | Baseline and week 24 | 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. |
| Change From Baseline to Week 24 in Pharmacokinetics Parameters: Area Under the Plasma Concentration Curve (AUC) [h(ng/mL)] | Baseline and Week 24 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| UT-15C SR UT-15C SR: 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. | 33 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Clinical Worsening | 1 |
Baseline characteristics
| Characteristic | UT-15C SR |
|---|---|
| Age, Continuous | 50.0 years |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 28 Participants |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 32 / 33 |
| serious Total, serious adverse events | 9 / 33 |
Outcome results
Primary
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.
Time frame: Up to 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| UT-15C SR | Number of Participants That Were Succesfully Transitioned From Parenteral Remodulin to UT-15C. | 31 participants |
Secondary
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.
Time frame: Baseline and week 24
Population: One subject completed the Week 24 visit but was unable to undergo all assessments. As such, the evaluable data at Week 24 was summarized mainly using an N of 30 subjects.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| UT-15C SR | Change From Baseline in Six-minute Walk Distance at Week 24 | 6MWD at Week 24 | 467 meters |
| UT-15C SR | Change From Baseline in Six-minute Walk Distance at Week 24 | 6MWD Change from Baseline | 16.7 meters |
Secondary
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
Time frame: Baseline and Week 24
Population: One subject completed the Week 24 visit but was unable to undergo all assessments. As such, the evaluable data at Week 24 was summarized mainly using an N of 30 subjects.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| UT-15C SR | Change From Baseline to Week 24 in Hemodynamics Parameters: Arterial Oxygen Saturation (SaO2) (%) and Mixed Venous Oxygen Saturation (SvO2) (%) | SaO2 (%) | -0.1 Percent of Oxygen saturation | Standard Deviation 3.4 |
| UT-15C SR | Change From Baseline to Week 24 in Hemodynamics Parameters: Arterial Oxygen Saturation (SaO2) (%) and Mixed Venous Oxygen Saturation (SvO2) (%) | SvO2 (%) | -3.2 Percent of Oxygen saturation | Standard Deviation 5.2 |
Secondary
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.
Time frame: Baseline and week 24
Population: Both the Thermodilution (n=6) and Fick (n=29) methods were used to determine CO and in some cases both methods were utilized; however, only the Fick method was used for (CI) for the purpose of this analysis and included only 29 subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| UT-15C SR | Change From Baseline to Week 24 in Hemodynamics Parameters: Cardiac Index (CI) (L/Min/m^2) | -0.1 L/min/m^2 | Standard Deviation 0.7 |
Secondary
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.
Time frame: Baseline and week 24
Population: One subject completed the Week 24 visit but was unable to undergo all assessments. As such, the evaluable data at Week 24 was summarized mainly using an N of 30 subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| UT-15C SR | Change From Baseline to Week 24 in Hemodynamics Parameters: Cardiac Output (CO) (L/Min) | -0.3 L/min | Standard Deviation 1.3 |
Secondary
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.
Time frame: Baseline and week 24
Population: One subject completed the Week 24 visit but was unable to undergo these assessments. As such, the evaluable data at Week 24 was summarized using an N of 30 subjects, which is why the number of participants analyzed is inconsistent with the participant flow module.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| UT-15C SR | 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) | PAPm (mmHg) | 2.2 mmHg | Standard Deviation 8.6 |
| UT-15C SR | 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) | RAPm (mmHg) | 0.5 mmHg | Standard Deviation 3.7 |
| UT-15C SR | 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) | PCWPm (mmHg) | 0.6 mmHg | Standard Deviation 4.6 |
Secondary
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.
Time frame: Baseline and week 24
Population: One subject completed the Week 24 visit but was unable to undergo all assessments. As such, the evaluable data at Week 24 was summarized mainly using an N of 30 subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| UT-15C SR | Change From Baseline to Week 24 in Hemodynamics Parameters: Pulmonary Vascular Resistance Index (PVRI) (mmHg*Min*m^2/L) | 1.6 mmHg*min*m^2/L | Standard Deviation 4.8 |
Secondary
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.
Time frame: Baseline and week 24
Population: One subject completed the Week 24 visit but was unable to undergo all assessments. As such, the evaluable data at Week 24 was summarized mainly using an N of 30 subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| UT-15C SR | Change From Baseline to Week 24 in Hemodynamics Parameters: Pulmonary Vascular Resistance (PVR) (mmHg*Min/L) | 0.8 mmHg*min/L | Standard Deviation 2.4 |
Secondary
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.
Time frame: Baseline and Week 24
Population: Dosing frequency was modified for BID to TID during the study, reported separately for patients on BID vs TID dosing at week 24. The number of participants analyzed is inconsistent with participant flow because it includes data from an early termination patient. A pharmacokinetics sample collected at early termination was included in the analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| UT-15C SR | Change From Baseline to Week 24 in Pharmacokinetic Parameters: Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), and Trough Plasma Concentration (Cmin) | Cavg (ng/mL) | 7.22 (ng/mL) |
| UT-15C SR | Change From Baseline to Week 24 in Pharmacokinetic Parameters: Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), and Trough Plasma Concentration (Cmin) | Cmax (ng/mL) | 8.76 (ng/mL) |
| UT-15C SR | Change From Baseline to Week 24 in Pharmacokinetic Parameters: Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), and Trough Plasma Concentration (Cmin) | Cmin (ng/mL) | 5.63 (ng/mL) |
| UT-15C SR (BID) | Change From Baseline to Week 24 in Pharmacokinetic Parameters: Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), and Trough Plasma Concentration (Cmin) | Cavg (ng/mL) | 6.89 (ng/mL) |
| UT-15C SR (BID) | Change From Baseline to Week 24 in Pharmacokinetic Parameters: Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), and Trough Plasma Concentration (Cmin) | Cmax (ng/mL) | 13 (ng/mL) |
| UT-15C SR (BID) | Change From Baseline to Week 24 in Pharmacokinetic Parameters: Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), and Trough Plasma Concentration (Cmin) | Cmin (ng/mL) | 1.94 (ng/mL) |
| UT-15C SR (TID) | Change From Baseline to Week 24 in Pharmacokinetic Parameters: Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), and Trough Plasma Concentration (Cmin) | Cmax (ng/mL) | 12.1 (ng/mL) |
| UT-15C SR (TID) | Change From Baseline to Week 24 in Pharmacokinetic Parameters: Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), and Trough Plasma Concentration (Cmin) | Cmin (ng/mL) | 2.45 (ng/mL) |
| UT-15C SR (TID) | Change From Baseline to Week 24 in Pharmacokinetic Parameters: Peak Plasma Concentration (Cmax), Average Plasma Concentration (Cavg), and Trough Plasma Concentration (Cmin) | Cavg (ng/mL) | 6.64 (ng/mL) |
Secondary
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.
Time frame: Baseline and Week 24
Population: Dosing frequency was modified for BID to TID during the study, reported separately for patients on BID vs TID dosing at week 24. The number of participants analyzed is inconsistent with participant flow because it includes data from an early termination patient. A pharmacokinetics sample collected at early termination was included in the analysis.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| UT-15C SR | Change From Baseline to Week 24 in Pharmacokinetics Parameter: Peak Time to Reach Peak Plasma Concentration [Tmax (h)] | 4.01 [Tmax (h)] |
| UT-15C SR (BID) | Change From Baseline to Week 24 in Pharmacokinetics Parameter: Peak Time to Reach Peak Plasma Concentration [Tmax (h)] | 5.60 [Tmax (h)] |
| UT-15C SR (TID) | Change From Baseline to Week 24 in Pharmacokinetics Parameter: Peak Time to Reach Peak Plasma Concentration [Tmax (h)] | 3.92 [Tmax (h)] |
Secondary
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.
Time frame: Baseline and Week 24
Population: The number of participants analyzed is inconsistent with participant flow because it includes data from an early termination patient. A pharmacokinetics sample collected at early termination was included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| UT-15C SR | Change From Baseline to Week 24 in Pharmacokinetics Parameters: Area Under the Plasma Concentration Curve (AUC) [h(ng/mL)] | 86.3 [h(ng/mL)] |
| UT-15C SR (BID) | Change From Baseline to Week 24 in Pharmacokinetics Parameters: Area Under the Plasma Concentration Curve (AUC) [h(ng/mL)] | 82.5 [h(ng/mL)] |
| UT-15C SR (TID) | Change From Baseline to Week 24 in Pharmacokinetics Parameters: Area Under the Plasma Concentration Curve (AUC) [h(ng/mL)] | 81.8 [h(ng/mL)] |
Secondary
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).
Time frame: Baseline and week 24
Population: One subject completed the Week 24 visit but was unable to undergo all assessments. As such, the evaluable data at Week 24 was summarized mainly using an N of 30 subjects.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| UT-15C SR | Change in Borg Dyspnea Score (Following 6MWT) From Baseline to Week 24 | 0.0 units on a scale |
Secondary
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.
Time frame: Baseline and Week 24
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| UT-15C SR | Change in Dyspnea-fatigue Index From Baseline to Week 24 | 1.0 units on a scale |
Secondary
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.
Time frame: Baseline and week 24
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| UT-15C SR | Change in Quality of Life (QoL) Assessment: Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) From Baseline to Week 24 | Symptom | -1.0 units on a scale |
| UT-15C SR | Change in Quality of Life (QoL) Assessment: Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) From Baseline to Week 24 | Activity | 0.0 units on a scale |
| UT-15C SR | Change in Quality of Life (QoL) Assessment: Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) From Baseline to Week 24 | Quality of Life | 0.0 units on a scale |
| UT-15C SR | Change in Quality of Life (QoL) Assessment: Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) From Baseline to Week 24 | Total Camphor Score | -2.0 units on a scale |
Secondary
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.
Time frame: Baseline and Week 24
Population: The World Health Organization (WHO) Functional Classification was only conducted at baseline for one subject, because the subject discontinued the study prior to the collection of this assessment at the next visit. One subject had this assessment prior to study discontinuation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| UT-15C SR | Change in World Health Organization (WHO) Functional Classification From Baseline to Week 24 | I to I | 3 participants |
| UT-15C SR | Change in World Health Organization (WHO) Functional Classification From Baseline to Week 24 | I to II | 2 participants |
| UT-15C SR | Change in World Health Organization (WHO) Functional Classification From Baseline to Week 24 | I to III | 1 participants |
| UT-15C SR | Change in World Health Organization (WHO) Functional Classification From Baseline to Week 24 | II to I | 3 participants |
| UT-15C SR | Change in World Health Organization (WHO) Functional Classification From Baseline to Week 24 | II to II | 21 participants |
| UT-15C SR | Change in World Health Organization (WHO) Functional Classification From Baseline to Week 24 | II to III | 1 participants |
| UT-15C SR | Change in World Health Organization (WHO) Functional Classification From Baseline to Week 24 | Missing | 1 participants |