Trial Outcomes & Findings for A Dose Response Study of UT-15C SR in Patients With Exercise-Induced Pulmonary Hypertension (NCT NCT01104870)

Last Updated: 2016-05-27

Results Overview

The effects of 12-week treatment with different doses of UT-15C on peak TPRI during exercise will be evaluated by comparing the change from Baseline to Week 12 at peak wattage on a pairwise basis between treatment groups. The primary measure of efficacy was the change from Baseline to Week 12 in peak TPRI during exercise assessed 3 to 6 hours after the subject's morning dose of UT-15C to obtain measurements at peak concentrations of treprostinil. The equation used to determine the Total Pulmonary Resistance Index (TPRI) (mmHg/\[L/min/m\^2\]) is Mean Pulmonary Artery Pressure (PAPm)/ Cardiac Index (CI).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

50 participants

Primary outcome timeframe

Baseline and Week 12

Results posted on

2016-05-27

Participant Flow

The recruitment period for this study was May 2010 to October 2012. Sites were located in the US only.

The 50 subjects who received a dose of study drug are presented here.

Participant milestones

Participant milestones
Measure	Dose Group 1 0.25 mg twice daily UT-15C: oral	Dose Group 2 1.25 mg twice daily UT-15C: oral	Dose Group 3 individual Maximum Tolerated Dose UT-15C: oral
Overall Study STARTED	11	19	20
Overall Study COMPLETED	10	18	18
Overall Study NOT COMPLETED	1	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Dose Group 1 0.25 mg twice daily UT-15C: oral	Dose Group 2 1.25 mg twice daily UT-15C: oral	Dose Group 3 individual Maximum Tolerated Dose UT-15C: oral
Overall Study Adverse Event	1	1	0
Overall Study Death	0	0	1
Overall Study Withdrawal by Subject	0	0	1

Baseline Characteristics

A Dose Response Study of UT-15C SR in Patients With Exercise-Induced Pulmonary Hypertension

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose Group 1 n=11 Participants 0.25 mg twice daily UT-15C: oral	Dose Group 2 n=19 Participants 1.25 mg twice daily UT-15C: oral	Dose Group 3 n=20 Participants individual Maximum Tolerated Dose UT-15C: oral	Total n=50 Participants Total of all reporting groups
Age, Continuous	53.1 years n=5 Participants	58.9 years n=7 Participants	57.6 years n=5 Participants	57.1 years n=4 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	15 Participants n=7 Participants	15 Participants n=5 Participants	41 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants	9 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	11 Participants n=5 Participants	16 Participants n=7 Participants	17 Participants n=5 Participants	44 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants	18 Participants n=7 Participants	19 Participants n=5 Participants	47 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	11 participants n=5 Participants	19 participants n=7 Participants	20 participants n=5 Participants	50 participants n=4 Participants
PAH History Idiopathic, heritable or drug or toxin-induced PAH	5 participants n=5 Participants	6 participants n=7 Participants	6 participants n=5 Participants	17 participants n=4 Participants
PAH History PAH associated with connective tissue diseases	5 participants n=5 Participants	9 participants n=7 Participants	10 participants n=5 Participants	24 participants n=4 Participants
PAH History PAH associated with HIV	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
PAH History PH associated with interstitial lung disease (ILD)	0 participants n=5 Participants	4 participants n=7 Participants	3 participants n=5 Participants	7 participants n=4 Participants
PAH History PH associated with sarcoidosis	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	2 participants n=4 Participants
Background PAH Therapy Both PDE-5i and ERA Dual Therapy	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants
Background PAH Therapy ERA	4 participants n=5 Participants	4 participants n=7 Participants	1 participants n=5 Participants	9 participants n=4 Participants
Background PAH Therapy PDE-5i	3 participants n=5 Participants	6 participants n=7 Participants	7 participants n=5 Participants	16 participants n=4 Participants
Background PAH Therapy No Background Therapy	4 participants n=5 Participants	9 participants n=7 Participants	11 participants n=5 Participants	24 participants n=4 Participants
Baseline Six-Minute Walk Distance (6MWD)	366.0 meters STANDARD_DEVIATION 79.6 • n=5 Participants	338.1 meters STANDARD_DEVIATION 55.7 • n=7 Participants	311.4 meters STANDARD_DEVIATION 67.4 • n=5 Participants	333.6 meters STANDARD_DEVIATION 68.1 • n=4 Participants
World Health Organization (WHO) Functional Class Class I	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
World Health Organization (WHO) Functional Class Class II	2 participants n=5 Participants	5 participants n=7 Participants	4 participants n=5 Participants	11 participants n=4 Participants
World Health Organization (WHO) Functional Class Class III	9 participants n=5 Participants	14 participants n=7 Participants	16 participants n=5 Participants	39 participants n=4 Participants
World Health Organization (WHO) Functional Class Class IV	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: All subjects with Baseline and Week 12 TPRI values recorded were included in the analysis.

Outcome measures

Outcome measures
Measure	Dose Group 1 n=10 Participants 0.25 mg twice daily UT-15C: oral	Dose Group 2 n=14 Participants 1.25 mg twice daily UT-15C: oral	Dose Group 3 n=17 Participants individual Maximum Tolerated Dose UT-15C: oral
Change in Peak Total Pulmonary Resistance Index (TPRI) During Exercise From Baseline to Week 12 Baseline	15.096 mmHg/(L/min/m^2) Standard Deviation 11.668	13.954 mmHg/(L/min/m^2) Standard Deviation 9.397	15.441 mmHg/(L/min/m^2) Standard Deviation 10.013
Change in Peak Total Pulmonary Resistance Index (TPRI) During Exercise From Baseline to Week 12 Week 12	14.608 mmHg/(L/min/m^2) Standard Deviation 9.274	14.509 mmHg/(L/min/m^2) Standard Deviation 9.463	13.423 mmHg/(L/min/m^2) Standard Deviation 7.257
Change in Peak Total Pulmonary Resistance Index (TPRI) During Exercise From Baseline to Week 12 Change from Baseline	-0.488 mmHg/(L/min/m^2) Standard Deviation 7.132	0.555 mmHg/(L/min/m^2) Standard Deviation 4.428	-2.019 mmHg/(L/min/m^2) Standard Deviation 5.332

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: All subjects with Baseline and Week 12 PAPm values recorded were included in the analysis.

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. The PAPm values and their respective changes from Baseline to Week 12 at peak exercise will be summarized by treatment group and measured by Swan-Ganz right heart catheterization.

Outcome measures

Outcome measures
Measure	Dose Group 1 n=10 Participants 0.25 mg twice daily UT-15C: oral	Dose Group 2 n=18 Participants 1.25 mg twice daily UT-15C: oral	Dose Group 3 n=18 Participants individual Maximum Tolerated Dose UT-15C: oral
Change in Mean Pulmonary Artery Pressure (PAPm) From Baseline to Week 12 Baseline	58.5 mmHg Standard Deviation 20.7	49.1 mmHg Standard Deviation 11.8	51.2 mmHg Standard Deviation 17.5
Change in Mean Pulmonary Artery Pressure (PAPm) From Baseline to Week 12 Week 12	58.5 mmHg Standard Deviation 21.6	49.4 mmHg Standard Deviation 13.4	50.8 mmHg Standard Deviation 14.7
Change in Mean Pulmonary Artery Pressure (PAPm) From Baseline to Week 12 Change from Baseline	0.0 mmHg Standard Deviation 6.0	0.3 mmHg Standard Deviation 5.4	-0.4 mmHg Standard Deviation 6.7

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: All subjects with Baseline and Week 12 CI values recorded were included in the analysis.

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 12 at peak exercise will be summarized by treatment group and measured by Swan-Ganz right heart catheterization.

Outcome measures

Outcome measures
Measure	Dose Group 1 n=10 Participants 0.25 mg twice daily UT-15C: oral	Dose Group 2 n=14 Participants 1.25 mg twice daily UT-15C: oral	Dose Group 3 n=17 Participants individual Maximum Tolerated Dose UT-15C: oral
Change in Cardiac Index (CI) From Baseline to Week 12 Change from Baseline	-0.024 L/min/m^2 Standard Deviation 1.209	-0.177 L/min/m^2 Standard Deviation 0.716	0.412 L/min/m^2 Standard Deviation 0.959
Change in Cardiac Index (CI) From Baseline to Week 12 Baseline	5.337 L/min/m^2 Standard Deviation 2.870	4.366 L/min/m^2 Standard Deviation 1.462	3.940 L/min/m^2 Standard Deviation 1.208
Change in Cardiac Index (CI) From Baseline to Week 12 Week 12	5.313 L/min/m^2 Standard Deviation 3.352	4.188 L/min/m^2 Standard Deviation 1.399	4.352 L/min/m^2 Standard Deviation 1.372

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: All subjects with Baseline and Week 12 6MWD values recorded were included in the analysis.

The intent of the 6MWD test is to evaluate exercise capacity associated with carrying out activities of daily living. Change in 6MWD from Baseline to Week 12, correlates with the current clinical standard for assessing patient functional status in the treatment of PH and is considered an objective measure of patient functional status by the American Thoracic Society (ATS). Subjects were instructed to walk down a corridor at a comfortable speed as far as they could manage for six minutes. 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

Outcome measures
Measure	Dose Group 1 n=10 Participants 0.25 mg twice daily UT-15C: oral	Dose Group 2 n=18 Participants 1.25 mg twice daily UT-15C: oral	Dose Group 3 n=17 Participants individual Maximum Tolerated Dose UT-15C: oral
Change in 6-minute Walk Distance (6MWD) From Baseline to Week 12 Baseline	361.5 meters Standard Deviation 82.4	338.0 meters Standard Deviation 57.3	317.8 meters Standard Deviation 55.2
Change in 6-minute Walk Distance (6MWD) From Baseline to Week 12 Week 12	407.6 meters Standard Deviation 98.2	356.7 meters Standard Deviation 89.8	349.5 meters Standard Deviation 89.8
Change in 6-minute Walk Distance (6MWD) From Baseline to Week 12 Change from Baseline	46.1 meters Standard Deviation 74.9	18.7 meters Standard Deviation 74.3	31.6 meters Standard Deviation 64.9

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: All subjects with Baseline and Week 12 Borg dyspnea scores recorded were included in the analysis.

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

Outcome measures
Measure	Dose Group 1 n=10 Participants 0.25 mg twice daily UT-15C: oral	Dose Group 2 n=18 Participants 1.25 mg twice daily UT-15C: oral	Dose Group 3 n=17 Participants individual Maximum Tolerated Dose UT-15C: oral
Change in Borg Dyspnea Score (Following 6MWT) From Baseline to Week 12 Baseline	3.0 score Interval 1.0 to 5.0	3.8 score Interval 3.0 to 5.0	3.0 score Interval 2.0 to 6.0
Change in Borg Dyspnea Score (Following 6MWT) From Baseline to Week 12 Week 12	2.5 score Interval 1.0 to 5.0	3.0 score Interval 2.0 to 6.0	3.0 score Interval 2.0 to 5.0
Change in Borg Dyspnea Score (Following 6MWT) From Baseline to Week 12 Change from Baseline	0.5 score Interval -2.0 to 2.0	0.0 score Interval -1.5 to 1.0	0.0 score Interval -1.5 to 1.0

SECONDARY outcome

Timeframe: Change from Baseline at 12 Weeks

Population: All subjects with Baseline and Week 12 values recorded for symptoms of PH were included in the analysis.

Symptoms of PH including fatigue, dyspnea, edema, dizziness, syncope, chest pain and orthopnea were assessed and severity grade values (i.e., 0, 1, 2 or 3) for each symptom were assigned for subjects. A severity of 0 indicated no symptoms, the maximum severity was 3, indicating severe symptoms. Median change in symptom severity from Baseline to Week 12 is described.

Outcome measures

Outcome measures
Measure	Dose Group 1 n=10 Participants 0.25 mg twice daily UT-15C: oral	Dose Group 2 n=18 Participants 1.25 mg twice daily UT-15C: oral	Dose Group 3 n=18 Participants individual Maximum Tolerated Dose UT-15C: oral
Change in PH Symptoms From Baseline to Week 12 Change in Fatigue Symptoms from Baseline	0.0 units on a scale Interval -1.0 to 0.0	0.0 units on a scale Interval -1.0 to 0.0	0.0 units on a scale Interval -1.0 to 0.0
Change in PH Symptoms From Baseline to Week 12 Change in Dyspnea Symptoms from Baseline	-1.0 units on a scale Interval -1.0 to 0.0	0.0 units on a scale Interval -1.0 to 0.0	-0.5 units on a scale Interval -1.0 to 0.0
Change in PH Symptoms From Baseline to Week 12 Change in Edema Symptoms from Baseline	0.0 units on a scale Interval -1.0 to 0.0	0.0 units on a scale Interval -1.0 to 1.0	0.0 units on a scale Interval -1.0 to 0.0
Change in PH Symptoms From Baseline to Week 12 Change in Dizziness Symptoms from Baseline	0.0 units on a scale Interval -1.0 to 0.0	0.0 units on a scale Interval -1.0 to 0.0	0.0 units on a scale Interval -1.0 to 0.0
Change in PH Symptoms From Baseline to Week 12 Change in Syncope Symptoms from Baseline	0.0 units on a scale Interval 0.0 to 0.0	0.0 units on a scale Interval 0.0 to 0.0	0.0 units on a scale Interval 0.0 to 0.0
Change in PH Symptoms From Baseline to Week 12 Change in Chest Pain Symptoms from Baseline	0.0 units on a scale Interval -1.0 to 0.0	0.0 units on a scale Interval -1.0 to 0.0	0.0 units on a scale Interval 0.0 to 0.0
Change in PH Symptoms From Baseline to Week 12 Change in Orthopnea Symptoms from Baseline	0.0 units on a scale Interval -1.0 to 0.0	0.0 units on a scale Interval -1.0 to 0.0	0.0 units on a scale Interval -1.0 to 0.0

SECONDARY outcome

Timeframe: Change from Baseline at Week 12

Population: All subjects with Baseline and Week 12 WHO functional classifications recorded were included in the analysis.

The WHO Functional Class of pulmonary hypertension is a physical activity rating scale as follows: 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. Only participants who experienced a change in WHO functional classification from Baseline to Week 12 are described by class change below; all other participants maintained their Baseline WHO functional classification at Week 12.

Outcome measures

Outcome measures
Measure	Dose Group 1 n=10 Participants 0.25 mg twice daily UT-15C: oral	Dose Group 2 n=18 Participants 1.25 mg twice daily UT-15C: oral	Dose Group 3 n=18 Participants individual Maximum Tolerated Dose UT-15C: oral
Number of Participants With a Change From Baseline World Health Organization (WHO) Functional Classification at Week 12 Change from Class II to Class III	0 participants	0 participants	1 participants
Number of Participants With a Change From Baseline World Health Organization (WHO) Functional Classification at Week 12 Change from Class III to Class I	1 participants	0 participants	0 participants
Number of Participants With a Change From Baseline World Health Organization (WHO) Functional Classification at Week 12 Change from Class III to Class II	2 participants	1 participants	4 participants

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: All subjects with Baseline and Week 12 NT-proBNP values recorded were included in the analysis.

The N-terminal pro-BNP (NT-proBNP) serum concentration was assessed to compare the severity of heart failure at Baseline and Week 12.

Outcome measures

Outcome measures
Measure	Dose Group 1 n=10 Participants 0.25 mg twice daily UT-15C: oral	Dose Group 2 n=15 Participants 1.25 mg twice daily UT-15C: oral	Dose Group 3 n=18 Participants individual Maximum Tolerated Dose UT-15C: oral
Change in N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) Concentrations From Baseline to Week 12 Baseline	678.7 pg/mL Standard Deviation 1530.0	565.4 pg/mL Standard Deviation 960.0	1092.1 pg/mL Standard Deviation 1768.9
Change in N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) Concentrations From Baseline to Week 12 Week 12	654.4 pg/mL Standard Deviation 1133.7	750.5 pg/mL Standard Deviation 1223.3	1571.7 pg/mL Standard Deviation 2808.6
Change in N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) Concentrations From Baseline to Week 12 Change from Baseline	-24.4 pg/mL Standard Deviation 592.1	185.1 pg/mL Standard Deviation 634.9	479.6 pg/mL Standard Deviation 2236.9

Adverse Events

Dose Group 1

Serious events: 2 serious events

Other events: 11 other events

Deaths: 0 deaths

Dose Group 2

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Dose Group 3

Serious events: 4 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Dose Group 1 n=11 participants at risk 0.25 mg twice daily UT-15C: oral	Dose Group 2 n=19 participants at risk 1.25 mg twice daily UT-15C: oral	Dose Group 3 n=20 participants at risk individual Maximum Tolerated Dose UT-15C: oral
Cardiac disorders Arrhythmia	0.00% 0/11 • Adverse events were recorded throughout the 12 week study, including the screening phase, as well as 30 days post end of study visit.	0.00% 0/19 • Adverse events were recorded throughout the 12 week study, including the screening phase, as well as 30 days post end of study visit.	10.0% 2/20 • Number of events 2 • Adverse events were recorded throughout the 12 week study, including the screening phase, as well as 30 days post end of study visit.
Cardiac disorders Cardiac failure	0.00% 0/11 • Adverse events were recorded throughout the 12 week study, including the screening phase, as well as 30 days post end of study visit.	0.00% 0/19 • Adverse events were recorded throughout the 12 week study, including the screening phase, as well as 30 days post end of study visit.	5.0% 1/20 • Number of events 1 • Adverse events were recorded throughout the 12 week study, including the screening phase, as well as 30 days post end of study visit.
Cardiac disorders Right ventricular failure	0.00% 0/11 • Adverse events were recorded throughout the 12 week study, including the screening phase, as well as 30 days post end of study visit.	0.00% 0/19 • Adverse events were recorded throughout the 12 week study, including the screening phase, as well as 30 days post end of study visit.	5.0% 1/20 • Number of events 1 • Adverse events were recorded throughout the 12 week study, including the screening phase, as well as 30 days post end of study visit.
Metabolism and nutrition disorders Hypervolaemia	0.00% 0/11 • Adverse events were recorded throughout the 12 week study, including the screening phase, as well as 30 days post end of study visit.	0.00% 0/19 • Adverse events were recorded throughout the 12 week study, including the screening phase, as well as 30 days post end of study visit.	10.0% 2/20 • Number of events 3 • Adverse events were recorded throughout the 12 week study, including the screening phase, as well as 30 days post end of study visit.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/11 • Adverse events were recorded throughout the 12 week study, including the screening phase, as well as 30 days post end of study visit.	0.00% 0/19 • Adverse events were recorded throughout the 12 week study, including the screening phase, as well as 30 days post end of study visit.	10.0% 2/20 • Number of events 2 • Adverse events were recorded throughout the 12 week study, including the screening phase, as well as 30 days post end of study visit.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/11 • Adverse events were recorded throughout the 12 week study, including the screening phase, as well as 30 days post end of study visit.	0.00% 0/19 • Adverse events were recorded throughout the 12 week study, including the screening phase, as well as 30 days post end of study visit.	5.0% 1/20 • Number of events 1 • Adverse events were recorded throughout the 12 week study, including the screening phase, as well as 30 days post end of study visit.
Gastrointestinal disorders Colitis	0.00% 0/11 • Adverse events were recorded throughout the 12 week study, including the screening phase, as well as 30 days post end of study visit.	0.00% 0/19 • Adverse events were recorded throughout the 12 week study, including the screening phase, as well as 30 days post end of study visit.	5.0% 1/20 • Number of events 1 • Adverse events were recorded throughout the 12 week study, including the screening phase, as well as 30 days post end of study visit.
Gastrointestinal disorders Vomiting	0.00% 0/11 • Adverse events were recorded throughout the 12 week study, including the screening phase, as well as 30 days post end of study visit.	0.00% 0/19 • Adverse events were recorded throughout the 12 week study, including the screening phase, as well as 30 days post end of study visit.	5.0% 1/20 • Number of events 1 • Adverse events were recorded throughout the 12 week study, including the screening phase, as well as 30 days post end of study visit.
General disorders Chest discomfort	9.1% 1/11 • Number of events 1 • Adverse events were recorded throughout the 12 week study, including the screening phase, as well as 30 days post end of study visit.	0.00% 0/19 • Adverse events were recorded throughout the 12 week study, including the screening phase, as well as 30 days post end of study visit.	0.00% 0/20 • Adverse events were recorded throughout the 12 week study, including the screening phase, as well as 30 days post end of study visit.
Infections and infestations Pneumonia	9.1% 1/11 • Number of events 1 • Adverse events were recorded throughout the 12 week study, including the screening phase, as well as 30 days post end of study visit.	0.00% 0/19 • Adverse events were recorded throughout the 12 week study, including the screening phase, as well as 30 days post end of study visit.	0.00% 0/20 • Adverse events were recorded throughout the 12 week study, including the screening phase, as well as 30 days post end of study visit.
Injury, poisoning and procedural complications Subdural haematoma	9.1% 1/11 • Number of events 1 • Adverse events were recorded throughout the 12 week study, including the screening phase, as well as 30 days post end of study visit.	0.00% 0/19 • Adverse events were recorded throughout the 12 week study, including the screening phase, as well as 30 days post end of study visit.	0.00% 0/20 • Adverse events were recorded throughout the 12 week study, including the screening phase, as well as 30 days post end of study visit.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/11 • Adverse events were recorded throughout the 12 week study, including the screening phase, as well as 30 days post end of study visit.	0.00% 0/19 • Adverse events were recorded throughout the 12 week study, including the screening phase, as well as 30 days post end of study visit.	5.0% 1/20 • Number of events 1 • Adverse events were recorded throughout the 12 week study, including the screening phase, as well as 30 days post end of study visit.
Nervous system disorders Haemorrhage intracranial	9.1% 1/11 • Number of events 1 • Adverse events were recorded throughout the 12 week study, including the screening phase, as well as 30 days post end of study visit.	0.00% 0/19 • Adverse events were recorded throughout the 12 week study, including the screening phase, as well as 30 days post end of study visit.	0.00% 0/20 • Adverse events were recorded throughout the 12 week study, including the screening phase, as well as 30 days post end of study visit.

Other adverse events

Additional Information

Kevin Laliberte, PharmD

United Therapeutics, Corp.

Phone: 919-425-8176

Email: [email protected]

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