Trial Outcomes & Findings for Clinical Study of Macitentan in Patients With Pulmonary Arterial Hypertension to Psychometrically Validate the PAH-SYMPACT Instrument (NCT NCT01841762)

Last Updated: 2019-02-26

Results Overview

Content validity of the PAH-SYMPACT was assessed using item performance, exploratory and confirmatory factor analysis. The final item content and domain structure of PAH-SYMPACT was determined based on these analyses from the Steering Committee (expert clinicians) and findings from the qualitative research done with patients previously.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

284 participants

Primary outcome timeframe

From Screening Visit (Day -14) to End of Treatment (EOT) Visit (Visit 4, Week 16)

Results posted on

2019-02-26

Participant Flow

Seventy-nine sites recruited subjects to reach a total of 284 total enrolled, with 335 subjects entered screening. Institution-based and community clinic sites, with pulmonary arterial hypertension expertise, were included in the study. The first subject, first visit occurred on 25 APR 2013 and last subject, last visit occurred on 05 OCT 2015

Screen failures total 51 subjects. Six subjects were removed from the full analysis set of 284 due to exclusion. The per protocol set includes 278 subjects total (97.9% of enrollment), utilized for all validation and exploratory ePRO analyses. The safety set, encompassing all enrolled subjects receiving study treatment, includes 284 subjects.

Participant milestones

Participant milestones
Measure	Macitentan Macitentan tablet, dose of 10 mg, once daily
Screening Period STARTED	335
Screening Period COMPLETED	284
Screening Period NOT COMPLETED	51
Treatment Period STARTED	284
Treatment Period COMPLETED	252
Treatment Period NOT COMPLETED	32
Post-Treatment Safety Follow-Up Period STARTED	284
Post-Treatment Safety Follow-Up Period COMPLETED	269
Post-Treatment Safety Follow-Up Period NOT COMPLETED	15

Reasons for withdrawal

Reasons for withdrawal
Measure	Macitentan Macitentan tablet, dose of 10 mg, once daily
Screening Period Other, 2 PAH-SYMPACT cycles not complete	51
Treatment Period Adverse Event	16
Treatment Period Death	1
Treatment Period Withdrawal by Subject	7
Treatment Period Lost to Follow-up	1
Treatment Period Physician Decision	2
Treatment Period Other, including non-compliance	5
Post-Treatment Safety Follow-Up Period Death	1
Post-Treatment Safety Follow-Up Period Withdrawal by Subject	7
Post-Treatment Safety Follow-Up Period Lost to Follow-up	6
Post-Treatment Safety Follow-Up Period Other, administrative error	1

Baseline Characteristics

Each respective row population complies with overall number of patients.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Macitentan n=284 Participants Macitentan tablet, dose of 10 mg, once daily
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	167 Participants n=5 Participants
Age, Categorical >=65 years	117 Participants n=5 Participants
Age, Continuous	59.7 Years n=5 Participants • Each respective row population complies with overall number of patients.
Sex: Female, Male Female	223 Participants n=5 Participants
Sex: Female, Male Male	61 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	27 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	257 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants
Race (NIH/OMB) Asian	8 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	35 Participants n=5 Participants
Race (NIH/OMB) White	228 Participants n=5 Participants
Race (NIH/OMB) More than one race	10 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: From Screening Visit (Day -14) to End of Treatment (EOT) Visit (Visit 4, Week 16)

Population: Per Protocol Set (PPS) comprised all patients included in the Full Analysis Set (FAS) who had no major protocol violations.

Outcome measures

Outcome measures
Measure	Macitentan n=278 Participants Macitentan tablet, dose of 10 mg, once daily
Development and Refinement of the Patient-reported Outcome Measure of Symptoms and Their Impact in PAH (the PAH-SYMPACT) Item number in symptoms part of baseline	16 Items
Development and Refinement of the Patient-reported Outcome Measure of Symptoms and Their Impact in PAH (the PAH-SYMPACT) Item number in symptoms part at Week 16	11 Items
Development and Refinement of the Patient-reported Outcome Measure of Symptoms and Their Impact in PAH (the PAH-SYMPACT) Item number in impacts part at baseline	25 Items
Development and Refinement of the Patient-reported Outcome Measure of Symptoms and Their Impact in PAH (the PAH-SYMPACT) Item number in impacts part at Week 16	11 Items

PRIMARY outcome

Timeframe: From ePRO period 1 (Days -14 to -8) to ePRO period 2 (Days -7 to -1) in screening period.

Population: Per Protocol Set of 278 patients.

The reliability of the PAH-SYMPACT is assessed by test-retest reliability. Intra-class correlation coefficients (ICCs) assess test-retest reliability for the symptom and impact part scores as well as domains. ICCs equal to or greater than 0.70 are considered to demonstrate good test-retest reliability for total and domain scores.

Outcome measures

Outcome measures
Measure	Macitentan n=278 Participants Macitentan tablet, dose of 10 mg, once daily
Validation of the Patient-reported Outcome Measure of Symptoms and Their Impact in PAH (the PAH-SYMPACT), With Reliability Assessed Via Test-retest Reliability. ICCs of Cognitive/Emotional Impacts domain	0.84 Intra-class correlation coefficient
Validation of the Patient-reported Outcome Measure of Symptoms and Their Impact in PAH (the PAH-SYMPACT), With Reliability Assessed Via Test-retest Reliability. ICCs of Cardiopulmonary Symptoms domain	0.94 Intra-class correlation coefficient
Validation of the Patient-reported Outcome Measure of Symptoms and Their Impact in PAH (the PAH-SYMPACT), With Reliability Assessed Via Test-retest Reliability. ICCs of Cardiovascular Symptoms domain	0.93 Intra-class correlation coefficient
Validation of the Patient-reported Outcome Measure of Symptoms and Their Impact in PAH (the PAH-SYMPACT), With Reliability Assessed Via Test-retest Reliability. ICCs of Physical Impacts domain	0.91 Intra-class correlation coefficient

PRIMARY outcome

Timeframe: From ePRO period 1 (Days -14 to -8) to ePRO period 2 (Days -7 to -1) in screening period.

Population: Per protocol set of 278.

The reliability of the PAH-SYMPACT is assessed by internal consistency reliability. This was determined using Cronbach's alpha-a value on an internal level scale from 0 to 1.0 with higher scores indicating a more-reliable (precise) instrument.

Outcome measures

Outcome measures
Measure	Macitentan n=278 Participants Macitentan tablet, dose of 10 mg, once daily
Validation of the Patient-reported Outcome Measure of Symptoms and Their Impact in PAH (the PAH-SYMPACT), Assessing Internal Consistency Reliability. Cronbach's Alpha for Cardiopulmonary Symptoms	0.81 Ratio of variance
Validation of the Patient-reported Outcome Measure of Symptoms and Their Impact in PAH (the PAH-SYMPACT), Assessing Internal Consistency Reliability. Cronbach's Alpha for Cardiovascular Symptoms	0.88 Ratio of variance
Validation of the Patient-reported Outcome Measure of Symptoms and Their Impact in PAH (the PAH-SYMPACT), Assessing Internal Consistency Reliability. Cronbach's Alpha for Physical Impacts Domain	0.92 Ratio of variance
Validation of the Patient-reported Outcome Measure of Symptoms and Their Impact in PAH (the PAH-SYMPACT), Assessing Internal Consistency Reliability. Cronbach's Alpha for Cognitive/Emotional Impacts	0.87 Ratio of variance

SECONDARY outcome

Timeframe: From Day 1 (Baseline Visit) to End of Study visit (EoS).

Population: Safety set of 284 subjects.

Safety events are reported and documented as defined in study protocol.

Outcome measures

Outcome measures
Measure	Macitentan n=284 Participants Macitentan tablet, dose of 10 mg, once daily
Number of Participants With Treatment-emergent Adverse Events, Serious Adverse Events, and Adverse Events Resulting in Patient Study Drug Discontinuation Between Time Periods, BL to End of Study Visit (EoS, Week 16+30 Days for Follow-up Safety Visits) Participants with AEs	228 Participants
Number of Participants With Treatment-emergent Adverse Events, Serious Adverse Events, and Adverse Events Resulting in Patient Study Drug Discontinuation Between Time Periods, BL to End of Study Visit (EoS, Week 16+30 Days for Follow-up Safety Visits) Participants with severe intensity AEs	36 Participants
Number of Participants With Treatment-emergent Adverse Events, Serious Adverse Events, and Adverse Events Resulting in Patient Study Drug Discontinuation Between Time Periods, BL to End of Study Visit (EoS, Week 16+30 Days for Follow-up Safety Visits) Participants with SAEs	49 Participants
Number of Participants With Treatment-emergent Adverse Events, Serious Adverse Events, and Adverse Events Resulting in Patient Study Drug Discontinuation Between Time Periods, BL to End of Study Visit (EoS, Week 16+30 Days for Follow-up Safety Visits) Participants prematurely discontinued study drug	17 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: From Screening period (Days -7 to -1) to Week 16 (7-day period prior to Week 16 visit).

Population: Per Protocol Set of 278 subjects.

Sensitivity to change is an aspect of construct validity and represents the instrument's ability to detect underlying change. Sensitivity to change was examined to compare the difference in mean score in each domain of the PAH-SYMPACT. The symptoms and impacts domains consisted of 11 items each reported on a 7-point Likert Scale (from 0=no symptom/with no difficulty at all/not at all to 6=very severe symptoms/very much/extremely/not able at all). An average symptoms domain score is determined based on the daily scores of the containing items. An average impacts domain score is determined based on the items in the domain.

Outcome measures

Outcome measures
Measure	Macitentan n=278 Participants Macitentan tablet, dose of 10 mg, once daily
Assessment of the Sensitivity to Detect Change in the Symptoms and Impacts Domain Scores of the PAH-SYMPACT From Baseline to Week 16. Cardiopulmonary Symptoms domain score at baseline	1.0 Score on a scale Interval 0.5 to 1.3
Assessment of the Sensitivity to Detect Change in the Symptoms and Impacts Domain Scores of the PAH-SYMPACT From Baseline to Week 16. Cardiopulmonary Symptoms domain score at Week 8	0.8 Score on a scale Interval 0.4 to 1.2
Assessment of the Sensitivity to Detect Change in the Symptoms and Impacts Domain Scores of the PAH-SYMPACT From Baseline to Week 16. Cardiopulmonary Symptoms domain score at Week 16	0.7 Score on a scale Interval 0.4 to 1.2
Assessment of the Sensitivity to Detect Change in the Symptoms and Impacts Domain Scores of the PAH-SYMPACT From Baseline to Week 16. Cardiovascular Symptoms domain score at baseline	0.4 Score on a scale Interval 0.1 to 0.7
Assessment of the Sensitivity to Detect Change in the Symptoms and Impacts Domain Scores of the PAH-SYMPACT From Baseline to Week 16. Cardiovascular Symptoms domain score at Week 8	0.2 Score on a scale Interval 0.0 to 0.5
Assessment of the Sensitivity to Detect Change in the Symptoms and Impacts Domain Scores of the PAH-SYMPACT From Baseline to Week 16. Cardiovascular Symptoms domain score at Week 16	0.2 Score on a scale Interval 0.0 to 0.5
Assessment of the Sensitivity to Detect Change in the Symptoms and Impacts Domain Scores of the PAH-SYMPACT From Baseline to Week 16. Physical Impacts domain score at baseline	1.3 Score on a scale Interval 0.6 to 2.0
Assessment of the Sensitivity to Detect Change in the Symptoms and Impacts Domain Scores of the PAH-SYMPACT From Baseline to Week 16. Physical Impacts domain score at Week 8	1.0 Score on a scale Interval 0.4 to 1.7
Assessment of the Sensitivity to Detect Change in the Symptoms and Impacts Domain Scores of the PAH-SYMPACT From Baseline to Week 16. Physical Impacts domain score at Week 16	0.9 Score on a scale Interval 0.4 to 1.6
Assessment of the Sensitivity to Detect Change in the Symptoms and Impacts Domain Scores of the PAH-SYMPACT From Baseline to Week 16. Cogn./Emotional Impacts domain score at baseline	0.8 Score on a scale Interval 0.3 to 1.5
Assessment of the Sensitivity to Detect Change in the Symptoms and Impacts Domain Scores of the PAH-SYMPACT From Baseline to Week 16. Cogn./Emotional Impacts domain score at Week 8	0.8 Score on a scale Interval 0.3 to 1.3
Assessment of the Sensitivity to Detect Change in the Symptoms and Impacts Domain Scores of the PAH-SYMPACT From Baseline to Week 16. Cogn./Emotional Impacts domain score at Week 16	0.5 Score on a scale Interval 0.5 to 1.3

Adverse Events

Macitentan

Serious events: 49 serious events

Other events: 228 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Macitentan n=284 participants at risk Macitentan tablet, dose of 10 mg, once daily
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.8% 5/284 • Treatment-emergent adverse events were collected from study drug initiation until Day 30 after study drug discontinuation. Study sites were instructed to document any adverse change from the patient's baseline condition, i.e., any unfavorable and unintended sign, including an abnormal laboratory finding, symptom, or disease that occurs during the course of the study, whether or not considered related to the study drug. Counts and percentages of subjects who experienced adverse events were tabulated by system organ class and preferred term within each system organ class, as well as by individual preferred term.
General disorders Chest Pain	1.4% 4/284 • Treatment-emergent adverse events were collected from study drug initiation until Day 30 after study drug discontinuation. Study sites were instructed to document any adverse change from the patient's baseline condition, i.e., any unfavorable and unintended sign, including an abnormal laboratory finding, symptom, or disease that occurs during the course of the study, whether or not considered related to the study drug. Counts and percentages of subjects who experienced adverse events were tabulated by system organ class and preferred term within each system organ class, as well as by individual preferred term.
Respiratory, thoracic and mediastinal disorders Pneumonia	1.4% 4/284 • Treatment-emergent adverse events were collected from study drug initiation until Day 30 after study drug discontinuation. Study sites were instructed to document any adverse change from the patient's baseline condition, i.e., any unfavorable and unintended sign, including an abnormal laboratory finding, symptom, or disease that occurs during the course of the study, whether or not considered related to the study drug. Counts and percentages of subjects who experienced adverse events were tabulated by system organ class and preferred term within each system organ class, as well as by individual preferred term.
Blood and lymphatic system disorders Anaemia	1.1% 3/284 • Treatment-emergent adverse events were collected from study drug initiation until Day 30 after study drug discontinuation. Study sites were instructed to document any adverse change from the patient's baseline condition, i.e., any unfavorable and unintended sign, including an abnormal laboratory finding, symptom, or disease that occurs during the course of the study, whether or not considered related to the study drug. Counts and percentages of subjects who experienced adverse events were tabulated by system organ class and preferred term within each system organ class, as well as by individual preferred term.
Cardiac disorders Cardiac Failure	1.1% 3/284 • Treatment-emergent adverse events were collected from study drug initiation until Day 30 after study drug discontinuation. Study sites were instructed to document any adverse change from the patient's baseline condition, i.e., any unfavorable and unintended sign, including an abnormal laboratory finding, symptom, or disease that occurs during the course of the study, whether or not considered related to the study drug. Counts and percentages of subjects who experienced adverse events were tabulated by system organ class and preferred term within each system organ class, as well as by individual preferred term.
Cardiac disorders Cardiac Failure Congestive	1.1% 3/284 • Treatment-emergent adverse events were collected from study drug initiation until Day 30 after study drug discontinuation. Study sites were instructed to document any adverse change from the patient's baseline condition, i.e., any unfavorable and unintended sign, including an abnormal laboratory finding, symptom, or disease that occurs during the course of the study, whether or not considered related to the study drug. Counts and percentages of subjects who experienced adverse events were tabulated by system organ class and preferred term within each system organ class, as well as by individual preferred term.
General disorders Fluid Overload	1.1% 3/284 • Treatment-emergent adverse events were collected from study drug initiation until Day 30 after study drug discontinuation. Study sites were instructed to document any adverse change from the patient's baseline condition, i.e., any unfavorable and unintended sign, including an abnormal laboratory finding, symptom, or disease that occurs during the course of the study, whether or not considered related to the study drug. Counts and percentages of subjects who experienced adverse events were tabulated by system organ class and preferred term within each system organ class, as well as by individual preferred term.
Respiratory, thoracic and mediastinal disorders Hypoxia	1.1% 3/284 • Treatment-emergent adverse events were collected from study drug initiation until Day 30 after study drug discontinuation. Study sites were instructed to document any adverse change from the patient's baseline condition, i.e., any unfavorable and unintended sign, including an abnormal laboratory finding, symptom, or disease that occurs during the course of the study, whether or not considered related to the study drug. Counts and percentages of subjects who experienced adverse events were tabulated by system organ class and preferred term within each system organ class, as well as by individual preferred term.
Renal and urinary disorders Renal Failure Acute	1.1% 3/284 • Treatment-emergent adverse events were collected from study drug initiation until Day 30 after study drug discontinuation. Study sites were instructed to document any adverse change from the patient's baseline condition, i.e., any unfavorable and unintended sign, including an abnormal laboratory finding, symptom, or disease that occurs during the course of the study, whether or not considered related to the study drug. Counts and percentages of subjects who experienced adverse events were tabulated by system organ class and preferred term within each system organ class, as well as by individual preferred term.
Gastrointestinal disorders Small Intestinal Obstruction	1.1% 3/284 • Treatment-emergent adverse events were collected from study drug initiation until Day 30 after study drug discontinuation. Study sites were instructed to document any adverse change from the patient's baseline condition, i.e., any unfavorable and unintended sign, including an abnormal laboratory finding, symptom, or disease that occurs during the course of the study, whether or not considered related to the study drug. Counts and percentages of subjects who experienced adverse events were tabulated by system organ class and preferred term within each system organ class, as well as by individual preferred term.
Respiratory, thoracic and mediastinal disorders Acute Respiratory Disorder	0.70% 2/284 • Treatment-emergent adverse events were collected from study drug initiation until Day 30 after study drug discontinuation. Study sites were instructed to document any adverse change from the patient's baseline condition, i.e., any unfavorable and unintended sign, including an abnormal laboratory finding, symptom, or disease that occurs during the course of the study, whether or not considered related to the study drug. Counts and percentages of subjects who experienced adverse events were tabulated by system organ class and preferred term within each system organ class, as well as by individual preferred term.
Gastrointestinal disorders Diverticulitis	0.70% 2/284 • Treatment-emergent adverse events were collected from study drug initiation until Day 30 after study drug discontinuation. Study sites were instructed to document any adverse change from the patient's baseline condition, i.e., any unfavorable and unintended sign, including an abnormal laboratory finding, symptom, or disease that occurs during the course of the study, whether or not considered related to the study drug. Counts and percentages of subjects who experienced adverse events were tabulated by system organ class and preferred term within each system organ class, as well as by individual preferred term.
Blood and lymphatic system disorders Hypoglycaemia	0.70% 2/284 • Treatment-emergent adverse events were collected from study drug initiation until Day 30 after study drug discontinuation. Study sites were instructed to document any adverse change from the patient's baseline condition, i.e., any unfavorable and unintended sign, including an abnormal laboratory finding, symptom, or disease that occurs during the course of the study, whether or not considered related to the study drug. Counts and percentages of subjects who experienced adverse events were tabulated by system organ class and preferred term within each system organ class, as well as by individual preferred term.
Surgical and medical procedures Transfusion	0.70% 2/284 • Treatment-emergent adverse events were collected from study drug initiation until Day 30 after study drug discontinuation. Study sites were instructed to document any adverse change from the patient's baseline condition, i.e., any unfavorable and unintended sign, including an abnormal laboratory finding, symptom, or disease that occurs during the course of the study, whether or not considered related to the study drug. Counts and percentages of subjects who experienced adverse events were tabulated by system organ class and preferred term within each system organ class, as well as by individual preferred term.
Nervous system disorders Vertigo	0.70% 2/284 • Treatment-emergent adverse events were collected from study drug initiation until Day 30 after study drug discontinuation. Study sites were instructed to document any adverse change from the patient's baseline condition, i.e., any unfavorable and unintended sign, including an abnormal laboratory finding, symptom, or disease that occurs during the course of the study, whether or not considered related to the study drug. Counts and percentages of subjects who experienced adverse events were tabulated by system organ class and preferred term within each system organ class, as well as by individual preferred term.
Blood and lymphatic system disorders Angina Unstable	0.35% 1/284 • Treatment-emergent adverse events were collected from study drug initiation until Day 30 after study drug discontinuation. Study sites were instructed to document any adverse change from the patient's baseline condition, i.e., any unfavorable and unintended sign, including an abnormal laboratory finding, symptom, or disease that occurs during the course of the study, whether or not considered related to the study drug. Counts and percentages of subjects who experienced adverse events were tabulated by system organ class and preferred term within each system organ class, as well as by individual preferred term.
Cardiac disorders Atrial Fibrillation	0.35% 1/284 • Treatment-emergent adverse events were collected from study drug initiation until Day 30 after study drug discontinuation. Study sites were instructed to document any adverse change from the patient's baseline condition, i.e., any unfavorable and unintended sign, including an abnormal laboratory finding, symptom, or disease that occurs during the course of the study, whether or not considered related to the study drug. Counts and percentages of subjects who experienced adverse events were tabulated by system organ class and preferred term within each system organ class, as well as by individual preferred term.
Cardiac disorders Atrial Flutter	0.35% 1/284 • Treatment-emergent adverse events were collected from study drug initiation until Day 30 after study drug discontinuation. Study sites were instructed to document any adverse change from the patient's baseline condition, i.e., any unfavorable and unintended sign, including an abnormal laboratory finding, symptom, or disease that occurs during the course of the study, whether or not considered related to the study drug. Counts and percentages of subjects who experienced adverse events were tabulated by system organ class and preferred term within each system organ class, as well as by individual preferred term.
Renal and urinary disorders Bladder Transitional Cell Carcinoma	0.35% 1/284 • Treatment-emergent adverse events were collected from study drug initiation until Day 30 after study drug discontinuation. Study sites were instructed to document any adverse change from the patient's baseline condition, i.e., any unfavorable and unintended sign, including an abnormal laboratory finding, symptom, or disease that occurs during the course of the study, whether or not considered related to the study drug. Counts and percentages of subjects who experienced adverse events were tabulated by system organ class and preferred term within each system organ class, as well as by individual preferred term.
Nervous system disorders Cerebrovascular Accident	0.35% 1/284 • Treatment-emergent adverse events were collected from study drug initiation until Day 30 after study drug discontinuation. Study sites were instructed to document any adverse change from the patient's baseline condition, i.e., any unfavorable and unintended sign, including an abnormal laboratory finding, symptom, or disease that occurs during the course of the study, whether or not considered related to the study drug. Counts and percentages of subjects who experienced adverse events were tabulated by system organ class and preferred term within each system organ class, as well as by individual preferred term.

Other adverse events

Other adverse events
Measure	Macitentan n=284 participants at risk Macitentan tablet, dose of 10 mg, once daily
Blood and lymphatic system disorders Oedema peripheral	17.6% 50/284 • Treatment-emergent adverse events were collected from study drug initiation until Day 30 after study drug discontinuation. Study sites were instructed to document any adverse change from the patient's baseline condition, i.e., any unfavorable and unintended sign, including an abnormal laboratory finding, symptom, or disease that occurs during the course of the study, whether or not considered related to the study drug. Counts and percentages of subjects who experienced adverse events were tabulated by system organ class and preferred term within each system organ class, as well as by individual preferred term.
Nervous system disorders Headache	12.7% 36/284 • Treatment-emergent adverse events were collected from study drug initiation until Day 30 after study drug discontinuation. Study sites were instructed to document any adverse change from the patient's baseline condition, i.e., any unfavorable and unintended sign, including an abnormal laboratory finding, symptom, or disease that occurs during the course of the study, whether or not considered related to the study drug. Counts and percentages of subjects who experienced adverse events were tabulated by system organ class and preferred term within each system organ class, as well as by individual preferred term.
Respiratory, thoracic and mediastinal disorders Dyspnoea	12.0% 34/284 • Treatment-emergent adverse events were collected from study drug initiation until Day 30 after study drug discontinuation. Study sites were instructed to document any adverse change from the patient's baseline condition, i.e., any unfavorable and unintended sign, including an abnormal laboratory finding, symptom, or disease that occurs during the course of the study, whether or not considered related to the study drug. Counts and percentages of subjects who experienced adverse events were tabulated by system organ class and preferred term within each system organ class, as well as by individual preferred term.
Respiratory, thoracic and mediastinal disorders Cough	9.2% 26/284 • Treatment-emergent adverse events were collected from study drug initiation until Day 30 after study drug discontinuation. Study sites were instructed to document any adverse change from the patient's baseline condition, i.e., any unfavorable and unintended sign, including an abnormal laboratory finding, symptom, or disease that occurs during the course of the study, whether or not considered related to the study drug. Counts and percentages of subjects who experienced adverse events were tabulated by system organ class and preferred term within each system organ class, as well as by individual preferred term.
Respiratory, thoracic and mediastinal disorders Nasal congestion	8.1% 23/284 • Treatment-emergent adverse events were collected from study drug initiation until Day 30 after study drug discontinuation. Study sites were instructed to document any adverse change from the patient's baseline condition, i.e., any unfavorable and unintended sign, including an abnormal laboratory finding, symptom, or disease that occurs during the course of the study, whether or not considered related to the study drug. Counts and percentages of subjects who experienced adverse events were tabulated by system organ class and preferred term within each system organ class, as well as by individual preferred term.
General disorders Fatigue	7.7% 22/284 • Treatment-emergent adverse events were collected from study drug initiation until Day 30 after study drug discontinuation. Study sites were instructed to document any adverse change from the patient's baseline condition, i.e., any unfavorable and unintended sign, including an abnormal laboratory finding, symptom, or disease that occurs during the course of the study, whether or not considered related to the study drug. Counts and percentages of subjects who experienced adverse events were tabulated by system organ class and preferred term within each system organ class, as well as by individual preferred term.
Ear and labyrinth disorders Dizziness	6.7% 19/284 • Treatment-emergent adverse events were collected from study drug initiation until Day 30 after study drug discontinuation. Study sites were instructed to document any adverse change from the patient's baseline condition, i.e., any unfavorable and unintended sign, including an abnormal laboratory finding, symptom, or disease that occurs during the course of the study, whether or not considered related to the study drug. Counts and percentages of subjects who experienced adverse events were tabulated by system organ class and preferred term within each system organ class, as well as by individual preferred term.
Respiratory, thoracic and mediastinal disorders Upper Respiratory Tract Infection	6.7% 19/284 • Treatment-emergent adverse events were collected from study drug initiation until Day 30 after study drug discontinuation. Study sites were instructed to document any adverse change from the patient's baseline condition, i.e., any unfavorable and unintended sign, including an abnormal laboratory finding, symptom, or disease that occurs during the course of the study, whether or not considered related to the study drug. Counts and percentages of subjects who experienced adverse events were tabulated by system organ class and preferred term within each system organ class, as well as by individual preferred term.
General disorders Nausea	6.0% 17/284 • Treatment-emergent adverse events were collected from study drug initiation until Day 30 after study drug discontinuation. Study sites were instructed to document any adverse change from the patient's baseline condition, i.e., any unfavorable and unintended sign, including an abnormal laboratory finding, symptom, or disease that occurs during the course of the study, whether or not considered related to the study drug. Counts and percentages of subjects who experienced adverse events were tabulated by system organ class and preferred term within each system organ class, as well as by individual preferred term.
Blood and lymphatic system disorders Anaemia	5.6% 16/284 • Treatment-emergent adverse events were collected from study drug initiation until Day 30 after study drug discontinuation. Study sites were instructed to document any adverse change from the patient's baseline condition, i.e., any unfavorable and unintended sign, including an abnormal laboratory finding, symptom, or disease that occurs during the course of the study, whether or not considered related to the study drug. Counts and percentages of subjects who experienced adverse events were tabulated by system organ class and preferred term within each system organ class, as well as by individual preferred term.

Additional Information

Scott Tsurutani / Associate Director, Clinical Operations

Actelion Pharmaceuticals US, Inc.

Phone: 6508086586

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Any study-related publication written independently by investigators must be submitted to Actelion for review at least 30 days prior to submission for publication or presentation. Upon review, Actelion may provide comments, and may also request alterations and/or deletions for the sole purpose of protecting its confidential information and/or patent rights. Neither the institution nor the investigator should permit publication during such a review period.
Publication restrictions are in place

Restriction type: OTHER