Trial Outcomes & Findings for Iloprost Power Disc-15 in Pulmonary Arterial Hypertension (NCT NCT00723554)

NCT ID: NCT00723554

Last Updated: 2013-04-04

Results Overview

Systolic blood pressure was measured at the end of study visit

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 63 participants
• Primary outcome timeframe: an average of approximately 268 days
• Results posted on: 2013-04-04

Participant Flow

Patients were enrolled at 22 U.S. centers

Adults with pulmonary arterial hypertension (PAH) who were using Ventavis (Iloprost) Inhalation Solution Delivered by I-Neb Utilizing Power Disc-6 (PD-6) were enrolled

Participant milestones

Measure	Iloprost iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-6 (PD-6) and Power Disc-15 (PD-15).
Overall Study STARTED	63
Overall Study COMPLETED	34
Overall Study NOT COMPLETED	29

Reasons for withdrawal

Measure	Iloprost iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-6 (PD-6) and Power Disc-15 (PD-15).
Overall Study Adverse Event	12
Overall Study Investigator's judgement	5
Overall Study Inhaled medication other than iloprost	4
Overall Study Withdrawal of consent	3
Overall Study Other	3
Overall Study Lost to Follow-up	1
Overall Study Non-compliance	1

Baseline Characteristics

Iloprost Power Disc-15 in Pulmonary Arterial Hypertension

Baseline characteristics by cohort

Measure	Iloprost n=63 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-6 (PD-6) and Power Disc-15 (PD-15).
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	35 Participants n=5 Participants
Age, Categorical >=65 years	28 Participants n=5 Participants
Age Continuous	59.9 years STANDARD_DEVIATION 12.91 • n=5 Participants
Sex: Female, Male Female	58 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants
Region of Enrollment United States	63 participants n=5 Participants

PRIMARY outcome

Timeframe: From the first dose to last dose of investigational product, an average of approximately 268 days, plus 48 hours

Population: Safety population

Number of patients reporting at least one treatment-emergent AE/Serious AE

Outcome measures

Measure	Iloprost n=63 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Number of Patients Reporting Treatment-emergent Adverse Events (AEs)	53 participants

PRIMARY outcome

Timeframe: From the first dose of investigational product to study discontinuation, an average of approximately 268 days

Population: Safety population

Number of patients reporting at least one treatment-emergent AE/Serious AE leading to discontinuation of study investigational treatment

Outcome measures

Measure	Iloprost n=63 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Number of Patients Who Discontinued Iloprost PD-15 Treatment Due to an AE	8 participants

PRIMARY outcome

Timeframe: From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours

Population: Safety population

Number of patients reporting at least one treatment-emergent serious AEs

Outcome measures

Measure	Iloprost n=63 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Number of Patients Reporting Treatment-emergent Serious AEs	18 participants

PRIMARY outcome

Timeframe: Day 1

Population: Safety population

Systolic blood pressure was measured immediately prior to first dosing with Iloprost PD-15

Outcome measures

Measure	Iloprost n=63 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Systolic Blood Pressure - Iloprost PD-6 (Period 1)	117.7 mmHg Standard Deviation 15.61

PRIMARY outcome

Timeframe: Day 28

Population: Safety population - missing data were not imputed

Systolic blood pressure was measured on Day 28 of treatment with Iloprost PD-15

Outcome measures

Measure	Iloprost n=61 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Systolic Blood Pressure - Iloprost PD-15 (Period 2)	116.2 mmHg Standard Deviation 14.71

PRIMARY outcome

Timeframe: an average of approximately 268 days

Population: Safety population - missing data were not imputed

Systolic blood pressure was measured at the end of study visit

Outcome measures

Measure	Iloprost n=53 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Systolic Blood Pressure - Iloprost PD-15 (Period 3)	119.0 mmHg Standard Deviation 17.47

PRIMARY outcome

Timeframe: Day 1 and Day 28

Population: Safety population - missing data were not imputed

Systolic blood pressure was measured on Day 1 prior to treatment with Iloprost PD-15 (Period 1) and Day 28 of treatment with Iloprost PD-15 (Period 2)

Outcome measures

Measure	Iloprost n=61 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Change in Systolic Blood Pressure - (Period 1 to Period 2)	-1.9 mmHg Standard Deviation 13.07

PRIMARY outcome

Timeframe: Day 1 and End of study visit, an average of approximately 268 days

Population: Safety population - missing data were not imputed

Systolic blood pressure was measured on Day 1 prior to treatment with Iloprost PD-15 (Period 1) and at the end of treatment with Iloprost PD-15 (Period 3)

Outcome measures

Measure	Iloprost n=53 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Change in Systolic Blood Pressure - (Period 1 to Period 3)	0.8 mmHg Standard Deviation 17.82

PRIMARY outcome

Timeframe: Day 1

Diastolic blood pressure was measured immediately prior to first dosing with Iloprost PD-15

Outcome measures

Measure	Iloprost n=63 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Diastolic Blood Pressure - Iloprost PD-6 (Period 1)	67.6 mmHg Standard Deviation 10.57

PRIMARY outcome

Timeframe: Day 28

Population: Safety population - missing data were not imputed

Diastolic blood pressure was measured on Day 28 of treatment with Iloprost PD-15

Outcome measures

Measure	Iloprost n=61 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Diastolic Blood Pressure - Iloprost PD-15 (Period 2)	67.0 mmHg Standard Deviation 8.86

PRIMARY outcome

Timeframe: an average of approximately 268 days

Population: Safety population - missing data were not imputed

Diastolic blood pressure was measured at the end of study visit

Outcome measures

Measure	Iloprost n=53 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Diastolic Blood Pressure - Iloprost PD-15 (Period 3)	65.6 mmHg Standard Deviation 9.50

PRIMARY outcome

Timeframe: Day 1 and Day 28

Population: Safety population - missing data were not imputed

Diastolic blood pressure was measured on Day 1 prior to treatment with Iloprost PD-15 (Period 1) and Day 28 of treatment with Iloprost PD-15 (Period 2)

Outcome measures

Measure	Iloprost n=61 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Change in Diastolic Blood Pressure - (Period 1 to Period 2)	-0.5 mmHg Standard Deviation 9.66

PRIMARY outcome

Timeframe: Day 1 and End of study visit, an average of approximately 268 days

Population: Safety population - missing data were not imputed

Diastolic blood pressure was measured on Day 1 prior to treatment with Iloprost PD-15 (Period 1) and at the end of treatment with Iloprost PD-15 (Period 3)

Outcome measures

Measure	Iloprost n=53 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Change in Diastolic Blood Pressure - (Period 1 to Period 3)	-2.3 mmHg Standard Deviation 10.64

PRIMARY outcome

Timeframe: Day 1

Population: Safety population

Heart rate was measured immediately prior to first dosing with Iloprost PD-15

Outcome measures

Measure	Iloprost n=63 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Heart Rate - Iloprost PD-6 (Period 1)	73.8 beats per minute Standard Deviation 11.67

PRIMARY outcome

Timeframe: Day 28

Population: Safety population - missing data were not imputed

Heart rate was measured on Day 28 of treatment with Iloprost PD-15

Outcome measures

Measure	Iloprost n=61 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Heart Rate - Iloprost PD-15 (Period 2)	74.2 beats per minute Standard Deviation 11.76

PRIMARY outcome

Timeframe: an average of approximately 268 days

Population: Safety population - missing data were not imputed

Heart rate was measured at the end of study visit

Outcome measures

Measure	Iloprost n=53 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Heart Rate - Iloprost PD-15 (Period 3)	75.6 beats per minute Standard Deviation 13.66

PRIMARY outcome

Timeframe: Day 1 and Day 28

Population: Safety population - missing data were not imputed

Heart rate was measured on Day 1 prior to treatment with Iloprost PD-15 (Period 1) and Day 28 of treatment with Iloprost PD-15 (Period 2)

Outcome measures

Measure	Iloprost n=61 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Change in Heart Rate - (Period 1 to Period 2)	0.3 beats per minute Standard Deviation 12.24

PRIMARY outcome

Timeframe: Day 1 and End of study visit, an average of approximately 268 days

Population: Safety population - missing data were not imputed

Heart rate was measured on Day 1 prior to treatment with Iloprost PD-15 (Period 1) and at the end of treatment with Iloprost PD-15 (Period 3)

Outcome measures

Measure	Iloprost n=53 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Change in Heart Rate - (Period 1 to Period 3)	2.6 beats per minute Standard Deviation 13.89

SECONDARY outcome

Timeframe: average of approximately 28 days

Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.

The time and date of inhalation, inhalation time (minutes), and dose completion status (<12.5%, ≥12.5 to <100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used.

Outcome measures

Measure	Iloprost n=58 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Average Inhalation Time - Iloprost PD-6 (Period 1)	13.9 minutes Standard Deviation 5.83

SECONDARY outcome

Timeframe: average of approximately 28 days

Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.

The time and date of inhalation, inhalation time (minutes), and dose completion status (<12.5%, ≥12.5 to <100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used.

Outcome measures

Measure	Iloprost n=58 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Average Inhalation Time - Iloprost PD-15 (Period 2)	7.7 minutes Standard Deviation 4.01

SECONDARY outcome

Timeframe: average of approximately 240 days

Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.

The time and date of inhalation, inhalation time (minutes), and dose completion status (<12.5%, ≥12.5 to <100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used.

Outcome measures

Measure	Iloprost n=49 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Average Inhalation Time - Iloprost PD-15 (Period 3)	8.4 minutes Standard Deviation 4.30

SECONDARY outcome

Timeframe: average approximately 56 days

Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.

The time and date of inhalation, inhalation time (minutes), and dose completion status (<12.5%, ≥12.5 to <100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used.

Outcome measures

Measure	Iloprost n=58 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Change in Average Inhalation Time - (Period 1 to Period 2)	-6.1 minutes Standard Deviation 2.92

SECONDARY outcome

Timeframe: average of approximately 28 days

Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.

The time and date of inhalation, inhalation time (minutes), and dose completion status (<12.5%, ≥12.5 to <100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used.

Outcome measures

Measure	Iloprost n=58 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Average Number of Days of Dosing - Iloprost PD-6 (Period 1)	27.6 days Standard Deviation 1.11

SECONDARY outcome

Timeframe: average of approximately 28 days

Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.

The time and date of inhalation, inhalation time (minutes), and dose completion status (<12.5%, ≥12.5 to <100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used.

Outcome measures

Measure	Iloprost n=58 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Average Number of Days of Dosing - Iloprost PD-15 (Period 2)	27.4 days Standard Deviation 2.66

SECONDARY outcome

Timeframe: average of approximately 240 days

Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.

The time and date of inhalation, inhalation time (minutes), and dose completion status (<12.5%, ≥12.5 to <100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used.

Outcome measures

Measure	Iloprost n=49 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Average Number of Days of Dosing - Iloprost PD-15 (Period 3)	240 days Standard Deviation 139.03

SECONDARY outcome

Timeframe: average approximately 56 days

Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.

The time and date of inhalation, inhalation time (minutes), and dose completion status (<12.5%, ≥12.5 to <100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used.

Outcome measures

Measure	Iloprost n=58 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Change in Average Number of Days of Dosing - (Period 1 to Period 2)	-0.2 days Standard Deviation 2.93

SECONDARY outcome

Timeframe: average of approximately 28 days

Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.

The time and date of inhalation, inhalation time (minutes), and dose completion status (<12.5%, ≥12.5 to <100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used.

Outcome measures

Measure	Iloprost n=58 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Average Number of Daily Doses - Iloprost PD-6 (Period 1)	5.1 doses per day Standard Deviation 1.48

SECONDARY outcome

Timeframe: average of approximately 28 days

Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.

The time and date of inhalation, inhalation time (minutes), and dose completion status (<12.5%, ≥12.5 to <100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used.

Outcome measures

Measure	Iloprost n=58 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Average Number of Daily Doses - Iloprost PD-15 (Period 2)	5.6 doses per day Standard Deviation 1.14

SECONDARY outcome

Timeframe: average of approximately 240 days

Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.

The time and date of inhalation, inhalation time (minutes), and dose completion status (<12.5%, ≥12.5 to <100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used.

Outcome measures

Measure	Iloprost n=49 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Average Number of Daily Doses - Iloprost PD-15 (Period 3)	4.7 doses per day Standard Deviation 1.69

SECONDARY outcome

Timeframe: average approximately 56 days

Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.

The time and date of inhalation, inhalation time (minutes), and dose completion status (<12.5%, ≥12.5 to <100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used.

Outcome measures

Measure	Iloprost n=58 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Change in Average Number of Daily Doses - (Period 1 to Period 2)	0.5 doses per day Standard Deviation 1.00

SECONDARY outcome

Timeframe: average of approximately 28 days

Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.

The time and date of inhalation, inhalation time (minutes), and dose completion status (<12.5%, ≥12.5 to <100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used.

Outcome measures

Measure	Iloprost n=58 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Percentage of Complete Doses Delivered - Iloprost PD-6 (Period 1)	84.3 percentage of complete doses Standard Deviation 23.42

SECONDARY outcome

Timeframe: average of approximately 28 days

Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.

The time and date of inhalation, inhalation time (minutes), and dose completion status (<12.5%, ≥12.5 to <100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used.

Outcome measures

Measure	Iloprost n=58 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Percentage of Complete Doses Delivered - Iloprost PD-15 (Period 2)	95.4 percentage of complete doses Standard Deviation 14.75

SECONDARY outcome

Timeframe: average of approximately 240 days

Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.

The time and date of inhalation, inhalation time (minutes), and dose completion status (<12.5%, ≥12.5 to <100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used.

Outcome measures

Measure	Iloprost n=49 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Percentage of Complete Doses Delivered - Iloprost PD-15 (Period 3)	94.2 percentage of complete doses Standard Deviation 12.02

SECONDARY outcome

Timeframe: average approximately 56 days

Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.

The time and date of inhalation, inhalation time (minutes), and dose completion status (<12.5%, ≥12.5 to <100%, full) were recorded in the memory chip of the I-neb® AAD® each time it was used.

Outcome measures

Measure	Iloprost n=58 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Change in Percentage of Complete Doses Delivered - (Period 1 to Period 2)	11.0 percentage of complete doses Standard Deviation 17.23

SECONDARY outcome

Timeframe: average of approximately 28 days

Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.

Disease severity was assessed by NYHA classification of PAH criteria: Class I: no limitation of physical activity (PA). Ordinary PA: no undue dyspnea/fatigue, chest pain, near syncope. Class II: slight limitation of PA. Comfortable at rest. Ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class III: marked limitation of PA. Comfortable at rest. Less than ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class IV: inability to carry out PA without symptoms. Right heart failure. Dyspnea/fatigue may even have been present at rest. Discomfort increased by any PA.

Outcome measures

Measure	Iloprost n=58 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
New York Health Association (NYHA) Functional Class - Iloprost PD-6 (Period 1, Prior to First Dose With Iloprost PD-15) Class I	3 participants
New York Health Association (NYHA) Functional Class - Iloprost PD-6 (Period 1, Prior to First Dose With Iloprost PD-15) Class II	17 participants
New York Health Association (NYHA) Functional Class - Iloprost PD-6 (Period 1, Prior to First Dose With Iloprost PD-15) Class III	34 participants
New York Health Association (NYHA) Functional Class - Iloprost PD-6 (Period 1, Prior to First Dose With Iloprost PD-15) Class IV	4 participants

SECONDARY outcome

Timeframe: average of approximately 28 days

Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.

Disease severity was assessed by NYHA classification of PAH criteria: Class I: no limitation of physical activity (PA). Ordinary PA: no undue dyspnea/fatigue, chest pain, near syncope. Class II: slight limitation of PA. Comfortable at rest. Ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class III: marked limitation of PA. Comfortable at rest. Less than ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class IV: inability to carry out PA without symptoms. Right heart failure. Dyspnea/fatigue may even have been present at rest. Discomfort increased by any PA.

Outcome measures

Measure	Iloprost n=55 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
NYHA Functional Class - Iloprost PD-15 (Period 2, Day 28) Class I	3 participants
NYHA Functional Class - Iloprost PD-15 (Period 2, Day 28) Class II	17 participants
NYHA Functional Class - Iloprost PD-15 (Period 2, Day 28) Class III	33 participants
NYHA Functional Class - Iloprost PD-15 (Period 2, Day 28) Class IV	2 participants

SECONDARY outcome

Timeframe: average of approximately 268 days

Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.

Disease severity was assessed by NYHA classification of PAH criteria: Class I: no limitation of physical activity (PA). Ordinary PA: no undue dyspnea/fatigue, chest pain, near syncope. Class II: slight limitation of PA. Comfortable at rest. Ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class III: marked limitation of PA. Comfortable at rest. Less than ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class IV: inability to carry out PA without symptoms. Right heart failure. Dyspnea/fatigue may even have been present at rest. Discomfort increased by any PA.

Outcome measures

Measure	Iloprost n=48 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
NYHA Functional Class - Iloprost PD-15 (Period 3, End of Study Visit)) Class I	3 participants
NYHA Functional Class - Iloprost PD-15 (Period 3, End of Study Visit)) Class II	20 participants
NYHA Functional Class - Iloprost PD-15 (Period 3, End of Study Visit)) Class III	19 participants
NYHA Functional Class - Iloprost PD-15 (Period 3, End of Study Visit)) Class IV	6 participants

SECONDARY outcome

Timeframe: average approximately 28 days

Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.

Disease severity was assessed by NYHA classification of PAH criteria: Class I: no limitation of physical activity (PA). Ordinary PA: no undue dyspnea/fatigue, chest pain, near syncope. Class II: slight limitation of PA. Comfortable at rest. Ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class III: marked limitation of PA. Comfortable at rest. Less than ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class IV: inability to carry out PA without symptoms. Right heart failure. Dyspnea/fatigue may even have been present at rest. Discomfort increased by any PA.

Outcome measures

Measure	Iloprost n=55 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Number of Patients With Improved, no Change, or Worsening of NYHA Functional Class - (Period 1, Prior to First Dose With Iloprost PD-15 to Period 2, Day 28) Improved	4 participants
Number of Patients With Improved, no Change, or Worsening of NYHA Functional Class - (Period 1, Prior to First Dose With Iloprost PD-15 to Period 2, Day 28) No change	50 participants
Number of Patients With Improved, no Change, or Worsening of NYHA Functional Class - (Period 1, Prior to First Dose With Iloprost PD-15 to Period 2, Day 28) Worse	1 participants

SECONDARY outcome

Timeframe: average approximately 268 days

Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.

Disease severity was assessed by NYHA classification of PAH criteria: Class I: no limitation of physical activity (PA). Ordinary PA: no undue dyspnea/fatigue, chest pain, near syncope. Class II: slight limitation of PA. Comfortable at rest. Ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class III: marked limitation of PA. Comfortable at rest. Less than ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class IV: inability to carry out PA without symptoms. Right heart failure. Dyspnea/fatigue may even have been present at rest. Discomfort increased by any PA.

Outcome measures

Measure	Iloprost n=48 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Number of Patients With Improved, no Change, or Worsening of NYHA Functional Class - (Period 1, Prior to First Dose With Iloprost PD-15 to Period 3, End of Study Visit) Improved	7 participants
Number of Patients With Improved, no Change, or Worsening of NYHA Functional Class - (Period 1, Prior to First Dose With Iloprost PD-15 to Period 3, End of Study Visit) No change	37 participants
Number of Patients With Improved, no Change, or Worsening of NYHA Functional Class - (Period 1, Prior to First Dose With Iloprost PD-15 to Period 3, End of Study Visit) Worse	4 participants

SECONDARY outcome

Timeframe: average of approximately 28 days

Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.

The Patient Global Self Assessment is a 7-point scale that was presented to patients prior to conducting visit-specific study procedures. Patients were asked to compare their current PAH status to their status in the past by selecting one of the following options: markedly better; moderately better; mildly better; no change; mildly worse; moderately worse; or markedly worse.

On Day 1 prior to their first dose of iloprost with PD-15 (Baseline), patients were asked to compare their PAH status to that during Screening (if the Screening and Baseline visits were conducted on the same day, then patients were asked to compare their PAH status to that in the past 2 weeks). On Day 28 and at the end of study (EOS) visit, patients were asked to compare their PAH status to that of the previous visit.

Outcome measures

Measure	Iloprost n=58 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Patient Global Self Assessment - Iloprost PD-6 (Period 1, Prior to First Dose With Iloprost PD-15) Markedly better	8 participants
Patient Global Self Assessment - Iloprost PD-6 (Period 1, Prior to First Dose With Iloprost PD-15) Moderately better	8 participants
Patient Global Self Assessment - Iloprost PD-6 (Period 1, Prior to First Dose With Iloprost PD-15) Mildly better	9 participants
Patient Global Self Assessment - Iloprost PD-6 (Period 1, Prior to First Dose With Iloprost PD-15) No change	31 participants
Patient Global Self Assessment - Iloprost PD-6 (Period 1, Prior to First Dose With Iloprost PD-15) Mildly worse	2 participants
Patient Global Self Assessment - Iloprost PD-6 (Period 1, Prior to First Dose With Iloprost PD-15) Moderately worse	0 participants
Patient Global Self Assessment - Iloprost PD-6 (Period 1, Prior to First Dose With Iloprost PD-15) Markedly worse	0 participants

SECONDARY outcome

Timeframe: average of approximately 28 days

Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.

The Patient Global Self Assessment is a 7-point scale that was presented to patients prior to conducting visit-specific study procedures. Patients were asked to compare their current PAH status to their status in the past by selecting one of the following options: markedly better; moderately better; mildly better; no change; mildly worse; moderately worse; or markedly worse.

On Day 1 prior to their first dose of iloprost with PD-15 (Baseline), patients were asked to compare their PAH status to that during Screening (if the Screening and Baseline visits were conducted on the same day, then patients were asked to compare their PAH status to that in the past 2 weeks). On Day 28 and at the EOS visit, patients were asked to compare their PAH status to that of the previous visit.

Outcome measures

Measure	Iloprost n=56 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Patient Global Self Assessment - Iloprost PD-15 (Period 2, Day 28) Markedly better	7 participants
Patient Global Self Assessment - Iloprost PD-15 (Period 2, Day 28) Moderately better	15 participants
Patient Global Self Assessment - Iloprost PD-15 (Period 2, Day 28) Mildly better	12 participants
Patient Global Self Assessment - Iloprost PD-15 (Period 2, Day 28) No change	21 participants
Patient Global Self Assessment - Iloprost PD-15 (Period 2, Day 28) Mildly worse	0 participants
Patient Global Self Assessment - Iloprost PD-15 (Period 2, Day 28) Moderately worse	1 participants
Patient Global Self Assessment - Iloprost PD-15 (Period 2, Day 28) Markedly worse	0 participants

SECONDARY outcome

Timeframe: average of approximately 268 days

Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.

The Patient Global Self Assessment is a 7-point scale that was presented to patients prior to conducting visit-specific study procedures. Patients were asked to compare their current PAH status to their status in the past by selecting one of the following options: markedly better; moderately better; mildly better; no change; mildly worse; moderately worse; or markedly worse.

On Day 1 prior to their first dose of iloprost with PD-15 (Baseline), patients were asked to compare their PAH status to that during Screening (if the Screening and Baseline visits were conducted on the same day, then patients were asked to compare their PAH status to that in the past 2 weeks). On Day 28 and at the EOS visit, patients were asked to compare their PAH status to that of the previous visit.

Outcome measures

Measure	Iloprost n=50 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Patient Global Self Assessment - Iloprost PD-15 (Period 3, End of Study Visit)) Markedly better	6 participants
Patient Global Self Assessment - Iloprost PD-15 (Period 3, End of Study Visit)) Moderately better	10 participants
Patient Global Self Assessment - Iloprost PD-15 (Period 3, End of Study Visit)) Mildly better	11 participants
Patient Global Self Assessment - Iloprost PD-15 (Period 3, End of Study Visit)) No change	17 participants
Patient Global Self Assessment - Iloprost PD-15 (Period 3, End of Study Visit)) Mildly worse	4 participants
Patient Global Self Assessment - Iloprost PD-15 (Period 3, End of Study Visit)) Moderately worse	1 participants
Patient Global Self Assessment - Iloprost PD-15 (Period 3, End of Study Visit)) Markedly worse	1 participants

SECONDARY outcome

Timeframe: average of approximately 28 days

Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.

The Patient Global Self Assessment is a 7-point scale that was presented to patients prior to conducting visit-specific study procedures. Patients were asked to compare their current PAH status to their status in the past by selecting one of the following options: markedly better; moderately better; mildly better; no change; mildly worse; moderately worse; or markedly worse.

On Day 1 prior to their first dose of iloprost with PD-15 (Baseline), patients were asked to compare their PAH status to that during Screening (if the Screening and Baseline visits were conducted on the same day, then patients were asked to compare their PAH status to that in the past 2 weeks). On Day 28 and at the EOS visit, patients were asked to compare their PAH status to that of the previous visit.

Outcome measures

Measure	Iloprost n=56 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Number of Patients With Improved, no Change, or Worse Patient Global Self Assessment - Change From Previous Visit to Period 2, Day 28 Improved	34 participants
Number of Patients With Improved, no Change, or Worse Patient Global Self Assessment - Change From Previous Visit to Period 2, Day 28 No change	21 participants
Number of Patients With Improved, no Change, or Worse Patient Global Self Assessment - Change From Previous Visit to Period 2, Day 28 Worse	1 participants

SECONDARY outcome

Timeframe: average of approximately 268 days

Population: Modified intent-to-treat (MITT) population - includes all enrolled patients without major protocol violations, who received at least one dose of iloprost with PD-15, and had one or more post-baseline evaluations for pharmacodynamic endpoints.

The Patient Global Self Assessment is a 7-point scale that was presented to patients prior to conducting visit-specific study procedures. Patients were asked to compare their current PAH status to their status in the past by selecting one of the following options: markedly better; moderately better; mildly better; no change; mildly worse; moderately worse; or markedly worse.

On Day 1 prior to their first dose of iloprost with PD-15 (Baseline), patients were asked to compare their PAH status to that during Screening (if the Screening and Baseline visits were conducted on the same day, then patients were asked to compare their PAH status to that in the past 2 weeks). On Day 28 and at the EOS visit, patients were asked to compare their PAH status to that of the previous visit.

Outcome measures

Measure	Iloprost n=50 Participants iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Number of Patients With Improved, no Change, or Worse Patient Global Self Assessment - Change From Previous Visit to Period 3, End of Study Visit Improved	27 participants
Number of Patients With Improved, no Change, or Worse Patient Global Self Assessment - Change From Previous Visit to Period 3, End of Study Visit No change	17 participants
Number of Patients With Improved, no Change, or Worse Patient Global Self Assessment - Change From Previous Visit to Period 3, End of Study Visit Worse	6 participants

Adverse Events

Iloprost

Serious events: 18 serious events

Other events: 50 other events

Deaths: 0 deaths

Serious adverse events

Measure	Iloprost n=63 participants at risk iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Respiratory, thoracic and mediastinal disorders Pulmonary arterial hypertension	7.9% 5/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Respiratory, thoracic and mediastinal disorders Epistaxis	1.6% 1/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Respiratory, thoracic and mediastinal disorders Hypoxia	1.6% 1/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.6% 1/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Cardiac disorders Atrial fibrillation	3.2% 2/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Cardiac disorders Atrioventricular block complete	1.6% 1/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Cardiac disorders Cardiac arrest	1.6% 1/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Cardiac disorders Cardiac failure acute	1.6% 1/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Cardiac disorders Cardiac failure congestive	1.6% 1/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Cardiac disorders Cardio-respiratory arrest	1.6% 1/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Infections and infestations Pneumonia	3.2% 2/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Infections and infestations Gastroenteritis	1.6% 1/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Infections and infestations Kidney infection	1.6% 1/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Infections and infestations Sepsis	1.6% 1/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Infections and infestations Septic shock	1.6% 1/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Infections and infestations Urinary tract infection	1.6% 1/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Infections and infestations Urosepsis	1.6% 1/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Gastrointestinal disorders Gastrointestinal hemorrhage	3.2% 2/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Gastrointestinal disorders Nausea	1.6% 1/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Gastrointestinal disorders Esophagitis	1.6% 1/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Gastrointestinal disorders Vomiting	1.6% 1/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Nervous system disorders Carotid artery disease	1.6% 1/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Nervous system disorders Cerebral hemorrhage	1.6% 1/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Nervous system disorders Transient ischemic attack	1.6% 1/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
General disorders Chest pain	3.2% 2/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Blood and lymphatic system disorders Anemia	1.6% 1/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Hepatobiliary disorders Hepatic hemorrhage	1.6% 1/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Injury, poisoning and procedural complications Femur fracture	1.6% 1/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Investigations Transaminases increased	1.6% 1/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Musculoskeletal and connective tissue disorders Mixed connective tissue disease	1.6% 1/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Teratoma	1.6% 1/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	1.6% 1/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Psychiatric disorders Mental status changes	1.6% 1/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Vascular disorders Hypotension	1.6% 1/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events

Other adverse events

Measure	Iloprost n=63 participants at risk iloprost (10 µg/mL) standard dose (5 µg) delivered by I-neb® Adaptive Aerosol Delivery System (AAD) using Power Disc-15 (PD-15).
Blood and lymphatic system disorders ANAEMIA	6.3% 4/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Cardiac disorders PALPITATIONS	7.9% 5/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Ear and labyrinth disorders VERTIGO	4.8% 3/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Gastrointestinal disorders ABDOMINAL DISTENSION	6.3% 4/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Gastrointestinal disorders DIARRHOEA	14.3% 9/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Gastrointestinal disorders NAUSEA	14.3% 9/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
General disorders CHEST PAIN	6.3% 4/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
General disorders FATIGUE	15.9% 10/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
General disorders OEDEMA	6.3% 4/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Infections and infestations ACUTE SINUSITIS	4.8% 3/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Infections and infestations BRONCHITIS	7.9% 5/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Infections and infestations SINUSITIS	6.3% 4/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	14.3% 9/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Infections and infestations URINARY TRACT INFECTION	9.5% 6/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Investigations INTERNATIONAL NORMALISED RATIO INCREASED	4.8% 3/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Metabolism and nutrition disorders GOUT	4.8% 3/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	7.9% 5/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Musculoskeletal and connective tissue disorders PAIN IN JAW	6.3% 4/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Nervous system disorders DIZZINESS	12.7% 8/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Nervous system disorders HEADACHE	17.5% 11/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Psychiatric disorders ANXIETY	6.3% 4/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Psychiatric disorders INSOMNIA	9.5% 6/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Respiratory, thoracic and mediastinal disorders COUGH	11.1% 7/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Respiratory, thoracic and mediastinal disorders DYSPNOEA	9.5% 6/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Respiratory, thoracic and mediastinal disorders EPISTAXIS	6.3% 4/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Respiratory, thoracic and mediastinal disorders NASAL CONGESTION	6.3% 4/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Respiratory, thoracic and mediastinal disorders PULMONARY ARTERIAL HYPERTENSION	4.8% 3/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Vascular disorders HAEMATOMA	6.3% 4/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events
Vascular disorders HYPERTENSION	4.8% 3/63 • From the first to last dose of investigational product, an average of approximately 268 days, plus 48 hours Serious treatment-emergent adverse events

Additional Information

Wade Benton, PharmD/ Director, Medical Affairs Veletri and Ventavis

Actelion Pharmaceuticals, US, Inc.

Phone: (650) 624-6900

Email: wade.benton@actelion.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place