Trial Outcomes & Findings for Remodulin® to Oral Treprostinil Transition (NCT NCT01588405)
NCT ID: NCT01588405
Last Updated: 2016-05-16
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
33 participants
Primary outcome timeframe
Up to 24 weeks
Results posted on
2016-05-16
Participant Flow
Participant milestones
| Measure |
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.
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|---|---|
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Overall Study
STARTED
|
33
|
|
Overall Study
COMPLETED
|
31
|
|
Overall Study
NOT COMPLETED
|
2
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Reasons for withdrawal
| Measure |
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.
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|---|---|
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Overall Study
Adverse Event
|
1
|
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Overall Study
Clinical Worsening
|
1
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Baseline Characteristics
Remodulin® to Oral Treprostinil Transition
Baseline characteristics by cohort
| Measure |
UT-15C SR
n=33 Participants
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.
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|---|---|
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Age, Continuous
|
50.0 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
25 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
28 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 24 weeksSuccessful 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.
Outcome measures
| Measure |
UT-15C SR
n=33 Participants
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.
|
UT-15C SR (BID)
Subjects who were on BID dosing of UT-15C SR at week 24
|
UT-15C SR (TID)
Subjects who were on TID dosing of UT-15C SR at week 24
|
|---|---|---|---|
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Number of Participants That Were Succesfully Transitioned From Parenteral Remodulin to UT-15C.
|
31 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and week 24Population: 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.
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.
Outcome measures
| Measure |
UT-15C SR
n=30 Participants
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.
|
UT-15C SR (BID)
Subjects who were on BID dosing of UT-15C SR at week 24
|
UT-15C SR (TID)
Subjects who were on TID dosing of UT-15C SR at week 24
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|---|---|---|---|
|
Change From Baseline in Six-minute Walk Distance at Week 24
6MWD at Week 24
|
467 meters
Interval 305.0 to 715.0
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—
|
—
|
|
Change From Baseline in Six-minute Walk Distance at Week 24
6MWD Change from Baseline
|
16.7 meters
Interval -98.0 to 95.0
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—
|
—
|
SECONDARY outcome
Timeframe: Baseline and week 24Population: 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.
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).
Outcome measures
| Measure |
UT-15C SR
n=30 Participants
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.
|
UT-15C SR (BID)
Subjects who were on BID dosing of UT-15C SR at week 24
|
UT-15C SR (TID)
Subjects who were on TID dosing of UT-15C SR at week 24
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|---|---|---|---|
|
Change in Borg Dyspnea Score (Following 6MWT) From Baseline to Week 24
|
0.0 units on a scale
Interval -3.5 to 3.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and week 24The 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.
Outcome measures
| Measure |
UT-15C SR
n=31 Participants
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.
|
UT-15C SR (BID)
Subjects who were on BID dosing of UT-15C SR at week 24
|
UT-15C SR (TID)
Subjects who were on TID dosing of UT-15C SR at week 24
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|---|---|---|---|
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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
Interval -11.0 to 7.0
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—
|
—
|
|
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
Interval -8.0 to 8.0
|
—
|
—
|
|
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
Interval -14.0 to 3.0
|
—
|
—
|
|
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
Interval -25.0 to 17.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: 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.
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.
Outcome measures
| Measure |
UT-15C SR
n=32 Participants
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.
|
UT-15C SR (BID)
Subjects who were on BID dosing of UT-15C SR at week 24
|
UT-15C SR (TID)
Subjects who were on TID dosing of UT-15C SR at week 24
|
|---|---|---|---|
|
Change in World Health Organization (WHO) Functional Classification From Baseline to Week 24
I to I
|
3 participants
|
—
|
—
|
|
Change in World Health Organization (WHO) Functional Classification From Baseline to Week 24
I to II
|
2 participants
|
—
|
—
|
|
Change in World Health Organization (WHO) Functional Classification From Baseline to Week 24
I to III
|
1 participants
|
—
|
—
|
|
Change in World Health Organization (WHO) Functional Classification From Baseline to Week 24
II to I
|
3 participants
|
—
|
—
|
|
Change in World Health Organization (WHO) Functional Classification From Baseline to Week 24
II to II
|
21 participants
|
—
|
—
|
|
Change in World Health Organization (WHO) Functional Classification From Baseline to Week 24
II to III
|
1 participants
|
—
|
—
|
|
Change in World Health Organization (WHO) Functional Classification From Baseline to Week 24
Missing
|
1 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and Week 24The 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.
Outcome measures
| Measure |
UT-15C SR
n=31 Participants
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.
|
UT-15C SR (BID)
Subjects who were on BID dosing of UT-15C SR at week 24
|
UT-15C SR (TID)
Subjects who were on TID dosing of UT-15C SR at week 24
|
|---|---|---|---|
|
Change in Dyspnea-fatigue Index From Baseline to Week 24
|
1.0 units on a scale
Interval -3.0 to 4.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: 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.
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.
Outcome measures
| Measure |
UT-15C SR
n=32 Participants
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.
|
UT-15C SR (BID)
n=6 Participants
Subjects who were on BID dosing of UT-15C SR at week 24
|
UT-15C SR (TID)
n=26 Participants
Subjects who were on TID dosing of UT-15C SR at week 24
|
|---|---|---|---|
|
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)
Interval 3.91 to 20.9
|
13 (ng/mL)
Interval 9.41 to 20.8
|
12.1 (ng/mL)
Interval 0.899 to 38.9
|
|
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)
Interval 2.85 to 15.4
|
6.89 (ng/mL)
Interval 4.26 to 11.2
|
6.64 (ng/mL)
Interval 0.345 to 22.6
|
|
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)
Interval 2.09 to 11.9
|
1.94 (ng/mL)
Interval 1.3 to 2.97
|
2.45 (ng/mL)
Interval 0.0489 to 18.6
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: 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.
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.
Outcome measures
| Measure |
UT-15C SR
n=32 Participants
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.
|
UT-15C SR (BID)
n=6 Participants
Subjects who were on BID dosing of UT-15C SR at week 24
|
UT-15C SR (TID)
n=26 Participants
Subjects who were on TID dosing of UT-15C SR at week 24
|
|---|---|---|---|
|
Change From Baseline to Week 24 in Pharmacokinetics Parameter: Peak Time to Reach Peak Plasma Concentration [Tmax (h)]
|
4.01 [Tmax (h)]
Interval 0.0 to 12.0
|
5.60 [Tmax (h)]
Interval 3.98 to 6.0
|
3.92 [Tmax (h)]
Interval 0.0 to 8.17
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: 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.
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.
Outcome measures
| Measure |
UT-15C SR
n=32 Participants
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.
|
UT-15C SR (BID)
n=6 Participants
Subjects who were on BID dosing of UT-15C SR at week 24
|
UT-15C SR (TID)
n=26 Participants
Subjects who were on TID dosing of UT-15C SR at week 24
|
|---|---|---|---|
|
Change From Baseline to Week 24 in Pharmacokinetics Parameters: Area Under the Plasma Concentration Curve (AUC) [h(ng/mL)]
|
86.3 [h(ng/mL)]
Interval 34.2 to 185.0
|
82.5 [h(ng/mL)]
Interval 49.7 to 134.0
|
81.8 [h(ng/mL)]
Interval 7.18 to 277.0
|
SECONDARY outcome
Timeframe: Baseline and week 24Population: 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.
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.
Outcome measures
| Measure |
UT-15C SR
n=30 Participants
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.
|
UT-15C SR (BID)
Subjects who were on BID dosing of UT-15C SR at week 24
|
UT-15C SR (TID)
Subjects who were on TID dosing of UT-15C SR at week 24
|
|---|---|---|---|
|
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
|
—
|
—
|
|
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
|
—
|
—
|
|
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 outcome
Timeframe: Baseline and Week 24Population: 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.
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
Outcome measures
| Measure |
UT-15C SR
n=30 Participants
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.
|
UT-15C SR (BID)
Subjects who were on BID dosing of UT-15C SR at week 24
|
UT-15C SR (TID)
Subjects who were on TID dosing of UT-15C SR at week 24
|
|---|---|---|---|
|
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
|
—
|
—
|
|
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 outcome
Timeframe: Baseline and week 24Population: 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.
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.
Outcome measures
| Measure |
UT-15C SR
n=30 Participants
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.
|
UT-15C SR (BID)
Subjects who were on BID dosing of UT-15C SR at week 24
|
UT-15C SR (TID)
Subjects who were on TID dosing of UT-15C SR at week 24
|
|---|---|---|---|
|
Change From Baseline to Week 24 in Hemodynamics Parameters: Cardiac Output (CO) (L/Min)
|
-0.3 L/min
Standard Deviation 1.3
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and week 24Population: 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.
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.
Outcome measures
| Measure |
UT-15C SR
n=29 Participants
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.
|
UT-15C SR (BID)
Subjects who were on BID dosing of UT-15C SR at week 24
|
UT-15C SR (TID)
Subjects who were on TID dosing of UT-15C SR at week 24
|
|---|---|---|---|
|
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 outcome
Timeframe: Baseline and week 24Population: 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.
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.
Outcome measures
| Measure |
UT-15C SR
n=30 Participants
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.
|
UT-15C SR (BID)
Subjects who were on BID dosing of UT-15C SR at week 24
|
UT-15C SR (TID)
Subjects who were on TID dosing of UT-15C SR at week 24
|
|---|---|---|---|
|
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 outcome
Timeframe: Baseline and week 24Population: 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.
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.
Outcome measures
| Measure |
UT-15C SR
n=30 Participants
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.
|
UT-15C SR (BID)
Subjects who were on BID dosing of UT-15C SR at week 24
|
UT-15C SR (TID)
Subjects who were on TID dosing of UT-15C SR at week 24
|
|---|---|---|---|
|
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
|
—
|
—
|
Adverse Events
UT-15C SR
Serious events: 9 serious events
Other events: 32 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
UT-15C SR
n=33 participants at risk
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.
|
|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
6.1%
2/33 • Number of events 2 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Gastrointestinal disorders
Nausea
|
6.1%
2/33 • Number of events 2 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Nervous system disorders
Vertigo
|
6.1%
2/33 • Number of events 2 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Gastrointestinal disorders
Abdominal Distension
|
3.0%
1/33 • Number of events 1 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Blood and lymphatic system disorders
Anemia
|
3.0%
1/33 • Number of events 1 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Hepatobiliary disorders
Ascites
|
3.0%
1/33 • Number of events 1 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Cardiac disorders
Atrial Flutter
|
3.0%
1/33 • Number of events 1 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
3.0%
1/33 • Number of events 1 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Gastrointestinal disorders
Gastric Ulcer
|
3.0%
1/33 • Number of events 1 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Infections and infestations
Gastroenteritis Viral
|
3.0%
1/33 • Number of events 1 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung carcinoma cell type unspecified stage IV
|
3.0%
1/33 • Number of events 1 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to bone
|
3.0%
1/33 • Number of events 1 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Cardiac disorders
Palpitations
|
3.0%
1/33 • Number of events 1 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Cardiac disorders
Pleurisy
|
3.0%
1/33 • Number of events 1 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Renal and urinary disorders
Renal Failure Acute
|
3.0%
1/33 • Number of events 1 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Immune system disorders
Systemic Lupus Erythematosus
|
3.0%
1/33 • Number of events 1 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Cardiac disorders
Ventricular Extrasystoles
|
3.0%
1/33 • Number of events 1 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Gastrointestinal disorders
Vomiting
|
3.0%
1/33 • Number of events 1 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Hepatobiliary disorders
Chronic Hepatic Failure
|
3.0%
1/33 • Number of events 1 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
Other adverse events
| Measure |
UT-15C SR
n=33 participants at risk
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.
|
|---|---|
|
Nervous system disorders
Headache
|
84.8%
28/33 • Number of events 29 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Gastrointestinal disorders
Nausea
|
66.7%
22/33 • Number of events 26 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Vascular disorders
Flushing
|
69.7%
23/33 • Number of events 28 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Gastrointestinal disorders
Diarrhoea
|
60.6%
20/33 • Number of events 23 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
General disorders
Fatigue
|
48.5%
16/33 • Number of events 16 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Gastrointestinal disorders
Vomiting
|
42.4%
14/33 • Number of events 19 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Gastrointestinal disorders
Dyspepsia
|
39.4%
13/33 • Number of events 13 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
27.3%
9/33 • Number of events 12 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Respiratory, thoracic and mediastinal disorders
Upper Resipiratory Tract Infection
|
30.3%
10/33 • Number of events 12 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Nervous system disorders
Dizziness
|
24.2%
8/33 • Number of events 10 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
24.2%
8/33 • Number of events 8 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Musculoskeletal and connective tissue disorders
Pain in jaw
|
24.2%
8/33 • Number of events 8 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Metabolism and nutrition disorders
Fluid Retention
|
18.2%
6/33 • Number of events 7 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal Congestion
|
18.2%
6/33 • Number of events 6 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Gastrointestinal disorders
Abdominal distension
|
12.1%
4/33 • Number of events 6 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Gastrointestinal disorders
Abdominal Pain
|
15.2%
5/33 • Number of events 5 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
15.2%
5/33 • Number of events 5 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Cardiac disorders
Palpitations
|
12.1%
4/33 • Number of events 4 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Cardiac disorders
Tachycardia
|
15.2%
5/33 • Number of events 5 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Gastrointestinal disorders
Constipation
|
12.1%
4/33 • Number of events 4 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Psychiatric disorders
Insomnia
|
12.1%
4/33 • Number of events 4 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Eye disorders
Edema Peripheral
|
12.1%
4/33 • Number of events 5 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Skin and subcutaneous tissue disorders
Rash
|
12.1%
4/33 • Number of events 5 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Psychiatric disorders
Anxiety
|
9.1%
3/33 • Number of events 3 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Respiratory, thoracic and mediastinal disorders
Bronchitis
|
9.1%
3/33 • Number of events 4 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
9.1%
3/33 • Number of events 3 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Respiratory, thoracic and mediastinal disorders
Nasopharyngitis
|
9.1%
3/33 • Number of events 4 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
General disorders
Pain
|
9.1%
3/33 • Number of events 3 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Renal and urinary disorders
Renal Failure Acute
|
9.1%
3/33 • Number of events 4 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Investigations
Weight Decreased
|
9.1%
3/33 • Number of events 3 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Investigations
Weight Increased
|
9.1%
3/33 • Number of events 3 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
9.1%
3/33 • Number of events 3 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.1%
2/33 • Number of events 3 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Respiratory, thoracic and mediastinal disorders
Chest Discomfort
|
6.1%
2/33 • Number of events 2 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
General disorders
Chills
|
6.1%
2/33 • Number of events 2 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
6.1%
2/33 • Number of events 2 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
General disorders
Dry Mouth
|
6.1%
2/33 • Number of events 2 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea Exertional
|
6.1%
2/33 • Number of events 2 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Vascular disorders
Epistaxis
|
6.1%
2/33 • Number of events 2 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Gastrointestinal disorders
Gastroenteritis
|
6.1%
2/33 • Number of events 2 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Vascular disorders
Hypotension
|
6.1%
2/33 • Number of events 3 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Blood and lymphatic system disorders
Iron Deficiency Anemia
|
6.1%
2/33 • Number of events 2 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Musculoskeletal and connective tissue disorders
Muscle Spasms
|
6.1%
2/33 • Number of events 2 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain
|
6.1%
2/33 • Number of events 2 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
6.1%
2/33 • Number of events 2 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Eye disorders
Ocular hyperemia
|
6.1%
2/33 • Number of events 2 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
General disorders
Pyrexia
|
6.1%
2/33 • Number of events 2 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Gastrointestinal disorders
Rectal Hemorrhage
|
6.1%
2/33 • Number of events 2 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis
|
6.1%
2/33 • Number of events 2 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhea
|
6.1%
2/33 • Number of events 2 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Immune system disorders
Sinusitis
|
6.1%
2/33 • Number of events 3 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
6.1%
2/33 • Number of events 2 • Adverse events were recorded throughout the 24-week study, including the screening and follow-up phase, as well as 30 days post end of study visit.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER