Trial Outcomes & Findings for Phase 2 Extension Study of Ambrisentan in Pulmonary Arterial Hypertension (NCT NCT00424021)

Last Updated: 2012-01-27

Results Overview

The number of participants in the AMB-220-E analysis set who experienced AEs (including serious AEs) of severe severity (ie, made it impossible to perform routine activities and the subject may have experienced intolerable discomfort or pain) that began after entering AMB-220-E (treatment-emergent AEs) and that occurred in more than 1 participant are summarized by dose group. The AMB-220-E analysis set consisted of all participants who received at least 1 dose of study drug during the AMB-220-E study.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

54 participants

Primary outcome timeframe

Week 24 (AMB-220-E baseline) to Week 334

Results posted on

2012-01-27

Participant Flow

Participants who completed Week 24 of NCT00046319 and responded to ambrisentan were eligible for enrollment. Response to ambrisentan treatment was determined by the investigator at Week 24 of NCT00046319 based on improvement in efficacy, acceptable safety profile, and \>= 4 weeks of stable, conventional pulmonary arterial hypertension (PAH) therapy.

No subjects failed screening. Subjects who completed an optional down-titration period at the end of NCT00046319 were re-titrated if their final dose was 5 mg or 10 mg.

Participant milestones

Participant milestones
Measure	1 mg The optimized final dose from the open-label period of AMB 220 (given once daily \[QD\] by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	2.5 mg The optimized final dose from the open-label period of AMB 220 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	5 mg The optimized final dose from the open-label period of AMB 220 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.	10 mg The optimized final dose from the open-label period of AMB 220 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.
NCT00046319 Study Period STARTED	16	19	16	13
NCT00046319 Study Period COMPLETED	15	16	15	12
NCT00046319 Study Period NOT COMPLETED	1	3	1	1
AMB-220-E Study Period STARTED	2	7	19	26
AMB-220-E Study Period COMPLETED	1	5	14	16
AMB-220-E Study Period NOT COMPLETED	1	2	5	10

Reasons for withdrawal

Reasons for withdrawal
Measure	1 mg The optimized final dose from the open-label period of AMB 220 (given once daily \[QD\] by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	2.5 mg The optimized final dose from the open-label period of AMB 220 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	5 mg The optimized final dose from the open-label period of AMB 220 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.	10 mg The optimized final dose from the open-label period of AMB 220 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.
NCT00046319 Study Period Adverse Event	1	0	1	1
NCT00046319 Study Period Withdrawal by Subject	0	1	0	0
NCT00046319 Study Period Sponsor discretion	0	1	0	0
NCT00046319 Study Period Lost to Follow-up	0	1	0	0
AMB-220-E Study Period Adverse Event	1	1	3	7
AMB-220-E Study Period Death	0	0	1	1
AMB-220-E Study Period Lost to Follow-up	0	1	1	1
AMB-220-E Study Period Physician Decision	0	0	0	1

Baseline Characteristics

Phase 2 Extension Study of Ambrisentan in Pulmonary Arterial Hypertension

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	1 mg n=2 Participants The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	2.5 mg n=7 Participants The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	5 mg n=19 Participants The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.	10 mg n=26 Participants The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.	Total n=54 Participants Total of all reporting groups
Age Continuous	54.0 years STANDARD_DEVIATION 12.73 • n=5 Participants	43.0 years STANDARD_DEVIATION 17.18 • n=7 Participants	56.7 years STANDARD_DEVIATION 13.48 • n=5 Participants	49.0 years STANDARD_DEVIATION 15.59 • n=4 Participants	51.1 years STANDARD_DEVIATION 15.33 • n=21 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	6 Participants n=7 Participants	17 Participants n=5 Participants	22 Participants n=4 Participants	46 Participants n=21 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants	8 Participants n=21 Participants
Race/Ethnicity, Customized Caucasian	1 Participants n=5 Participants	5 Participants n=7 Participants	13 Participants n=5 Participants	20 Participants n=4 Participants	39 Participants n=21 Participants
Race/Ethnicity, Customized Black	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	4 Participants n=21 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants
Race/Ethnicity, Customized Hispanic	0 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	5 Participants n=4 Participants	8 Participants n=21 Participants
Years Pulmonary Arterial Hypertension (PAH) Present	2.0 Years STANDARD_DEVIATION 0.00 • n=5 Participants	4.4 Years STANDARD_DEVIATION 3.87 • n=7 Participants	2.7 Years STANDARD_DEVIATION 2.91 • n=5 Participants	4.8 Years STANDARD_DEVIATION 4.81 • n=4 Participants	3.9 Years STANDARD_DEVIATION 4.07 • n=21 Participants
6-minute Walk Distance	462.0 Meters STANDARD_DEVIATION 132.94 • n=5 Participants	400.4 Meters STANDARD_DEVIATION 85.13 • n=7 Participants	398.8 Meters STANDARD_DEVIATION 111.56 • n=5 Participants	410.7 Meters STANDARD_DEVIATION 93.79 • n=4 Participants	406.9 Meters STANDARD_DEVIATION 98.56 • n=21 Participants
Borg Dyspnea Index	2.5 Score STANDARD_DEVIATION 0.71 • n=5 Participants	1.6 Score STANDARD_DEVIATION 1.65 • n=7 Participants	2.8 Score STANDARD_DEVIATION 1.77 • n=5 Participants	2.9 Score STANDARD_DEVIATION 1.81 • n=4 Participants	2.7 Score STANDARD_DEVIATION 1.76 • n=21 Participants
World Health Organization Class I	1 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants	8 Participants n=21 Participants
World Health Organization Class II	0 Participants n=5 Participants	3 Participants n=7 Participants	11 Participants n=5 Participants	13 Participants n=4 Participants	27 Participants n=21 Participants
World Health Organization Class III	1 Participants n=5 Participants	1 Participants n=7 Participants	8 Participants n=5 Participants	9 Participants n=4 Participants	19 Participants n=21 Participants
Primary Diagnosis Idiopathic Pulmonary Arterial Hypertension	0 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants	15 Participants n=4 Participants	32 Participants n=21 Participants
Primary Diagnosis Mixed Connective Tissue Disease	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants	7 Participants n=21 Participants
Primary Diagnosis Systemic Lupus Erythematosus	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants	2 Participants n=21 Participants
Primary Diagnosis Systemic Sclerosis	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants
Primary Diagnosis Overlap Syndrome	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Primary Diagnosis Anorexigen Use	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	4 Participants n=21 Participants
Primary Diagnosis Human immunodeficiency virus (HIV) Infection	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Primary Diagnosis Other	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	3 Participants n=21 Participants
Height	169.8 Centimeters STANDARD_DEVIATION 3.11 • n=5 Participants	160.6 Centimeters STANDARD_DEVIATION 11.84 • n=7 Participants	163.1 Centimeters STANDARD_DEVIATION 8.07 • n=5 Participants	164.5 Centimeters STANDARD_DEVIATION 10.03 • n=4 Participants	163.7 Centimeters STANDARD_DEVIATION 9.42 • n=21 Participants
Weight	66.0 Kilograms STANDARD_DEVIATION 8.49 • n=5 Participants	68.1 Kilograms STANDARD_DEVIATION 14.97 • n=7 Participants	74.6 Kilograms STANDARD_DEVIATION 21.32 • n=5 Participants	76.1 Kilograms STANDARD_DEVIATION 17.96 • n=4 Participants	74.2 Kilograms STANDARD_DEVIATION 18.51 • n=21 Participants

PRIMARY outcome

Timeframe: Week 24 (AMB-220-E baseline) to Week 334

Population: The AMB-220-E population consisted of all subjects who received at least 1 dose of study drug during the AMB-220-E study.

Outcome measures

Outcome measures
Measure	1 mg n=2 Participants The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	2.5 mg n=7 Participants The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	5 mg n=19 Participants The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.	10 mg n=26 Participants The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.
Number of Participants With Pulmonary Arterial Hypertension (PAH) Who Completed the Phase II NCT00046319 Study and Who Experienced Severe Adverse Events (AEs) During Long-term Ambrisentan Exposure Abdominal Pain NOS	0 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Pulmonary Arterial Hypertension (PAH) Who Completed the Phase II NCT00046319 Study and Who Experienced Severe Adverse Events (AEs) During Long-term Ambrisentan Exposure Alanine Aminotransferase Increased	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With Pulmonary Arterial Hypertension (PAH) Who Completed the Phase II NCT00046319 Study and Who Experienced Severe Adverse Events (AEs) During Long-term Ambrisentan Exposure Anaemia NOS	0 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Pulmonary Arterial Hypertension (PAH) Who Completed the Phase II NCT00046319 Study and Who Experienced Severe Adverse Events (AEs) During Long-term Ambrisentan Exposure Angina Pectoris	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Pulmonary Arterial Hypertension (PAH) Who Completed the Phase II NCT00046319 Study and Who Experienced Severe Adverse Events (AEs) During Long-term Ambrisentan Exposure Aspartate Aminotransferase Increased	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With Pulmonary Arterial Hypertension (PAH) Who Completed the Phase II NCT00046319 Study and Who Experienced Severe Adverse Events (AEs) During Long-term Ambrisentan Exposure Gastrointestinal Arteriovenous Malformation	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With Pulmonary Arterial Hypertension (PAH) Who Completed the Phase II NCT00046319 Study and Who Experienced Severe Adverse Events (AEs) During Long-term Ambrisentan Exposure Gastrointestinal Hemorrhage NOS	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With Pulmonary Arterial Hypertension (PAH) Who Completed the Phase II NCT00046319 Study and Who Experienced Severe Adverse Events (AEs) During Long-term Ambrisentan Exposure Infection NOS	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Pulmonary Arterial Hypertension (PAH) Who Completed the Phase II NCT00046319 Study and Who Experienced Severe Adverse Events (AEs) During Long-term Ambrisentan Exposure Oedema Peripheral	0 Participants	0 Participants	1 Participants	2 Participants
Number of Participants With Pulmonary Arterial Hypertension (PAH) Who Completed the Phase II NCT00046319 Study and Who Experienced Severe Adverse Events (AEs) During Long-term Ambrisentan Exposure Ovarian Cyst	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Pulmonary Arterial Hypertension (PAH) Who Completed the Phase II NCT00046319 Study and Who Experienced Severe Adverse Events (AEs) During Long-term Ambrisentan Exposure Pulmonary Hypertension NOS Aggravated	0 Participants	0 Participants	0 Participants	4 Participants
Number of Participants With Pulmonary Arterial Hypertension (PAH) Who Completed the Phase II NCT00046319 Study and Who Experienced Severe Adverse Events (AEs) During Long-term Ambrisentan Exposure Right Ventricular Failure	0 Participants	0 Participants	1 Participants	6 Participants
Number of Participants With Pulmonary Arterial Hypertension (PAH) Who Completed the Phase II NCT00046319 Study and Who Experienced Severe Adverse Events (AEs) During Long-term Ambrisentan Exposure Syncope	0 Participants	0 Participants	0 Participants	4 Participants

PRIMARY outcome

Timeframe: Week 24 (AMB-220-E baseline) to Week 329.3

Population: The AMB-220-E population consisted of all subjects who received at least 1 dose of study drug during the AMB-220-E study.

The number of participants in the AMB-220-E analysis set who experienced AEs (including serious AEs) of moderate severity (ie, interfered with routine activities and subject may have experienced significant discomfort) that began after entering AMB-220-E (treatment-emergent AEs) and that occurred in more than 1 participant are summarized by dose group. The AMB-220-E analysis set consisted of all participants who received at least 1 dose of study drug during the AMB-220-E study.

Outcome measures

Outcome measures
Measure	1 mg n=2 Participants The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	2.5 mg n=7 Participants The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	5 mg n=19 Participants The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.	10 mg n=26 Participants The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Bronchitis NOS	1 Participants	3 Participants	1 Participants	4 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Back Pain	0 Participants	0 Participants	2 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Anaemia NOS	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Angina Pectoris	1 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Anxiety	0 Participants	0 Participants	1 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Arthralgia	1 Participants	0 Participants	3 Participants	5 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Arrhythmia NOS	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Aspartate Aminotransferase Increased	2 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Atrial Fibrillation	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Basal Cell Carcinoma	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Bronchospasm NOS	1 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Bursitis	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Calcinosis	0 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Cataract	1 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Cellulitis	0 Participants	0 Participants	2 Participants	0 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Chest Pain	0 Participants	3 Participants	2 Participants	0 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Constipation	0 Participants	0 Participants	3 Participants	3 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Contusion	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Cough	1 Participants	1 Participants	2 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Cyanosis NOS	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Depression	0 Participants	0 Participants	2 Participants	5 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Diarrhoea NOS	0 Participants	0 Participants	3 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Dizziness	0 Participants	1 Participants	2 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Dyspepsia	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Dyspnoea NOS	0 Participants	1 Participants	0 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Ear Infection NOS	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Epistaxis	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Fatigue	0 Participants	0 Participants	2 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Fatigue Aggravated	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Flushing	0 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Gastroenteritis NOS	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Gastroenteritis Viral NOS	0 Participants	0 Participants	1 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Gastrooesophageal Reflux Disease	0 Participants	1 Participants	1 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Headache	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Hypoxia	0 Participants	1 Participants	1 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Influenza	0 Participants	1 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure International Normalised Ratio Increased	0 Participants	1 Participants	2 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Iron Deficiency Anaemia	0 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Localised Infection	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Localised Osteoarthritis	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Nasopharyngitis	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Nausea	0 Participants	0 Participants	1 Participants	5 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Otitis Media NOS	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Palpitations	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Pruritus	0 Participants	0 Participants	3 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Syncope	0 Participants	1 Participants	3 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Dyspnoea Exacerbated	0 Participants	2 Participants	5 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Erythema	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Foot Fracture	0 Participants	0 Participants	2 Participants	0 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Gamma-glutamyltransferase Increased	1 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Abdominal Distension	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Activated Partial Thromboplastin Time Prolonged	0 Participants	0 Participants	2 Participants	0 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Alanine Aminotransferase Increased	2 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Gingival Infection	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Gout	0 Participants	0 Participants	2 Participants	0 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Hepatobiliary Disorders	0 Participants	0 Participants	1 Participants	4 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Herpes Zoster	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Hypertension NOS	0 Participants	0 Participants	2 Participants	0 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Hypokalaemia	0 Participants	0 Participants	1 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Hypotension NOS	1 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Insomnia	0 Participants	0 Participants	2 Participants	4 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Intervertebral Disc Herniation	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Limb Injury NOS	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Lower Respiratory Tract Infection NOS	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Menorrhagia	0 Participants	0 Participants	0 Participants	3 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Migraine NOS	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Nasal Congestion	0 Participants	0 Participants	2 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Nausea Postoperative	0 Participants	0 Participants	1 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Neck Pain	0 Participants	0 Participants	2 Participants	0 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Oedema Peripheral	0 Participants	0 Participants	1 Participants	4 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Oesophageal Candidiasis	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Osteoporosis NOS	0 Participants	0 Participants	2 Participants	0 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Pain in Limb	0 Participants	0 Participants	1 Participants	3 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Pneumonia NOS	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Post Procedural Pain	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Prothrombin Time Prolonged	0 Participants	0 Participants	2 Participants	0 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Pulmonary Hypertension NOS Aggravated	0 Participants	1 Participants	3 Participants	3 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Pyrexia	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Right Ventricular Failure	0 Participants	1 Participants	1 Participants	3 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Sinusitis Chronic NOS	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Sinusitis NOS	0 Participants	0 Participants	0 Participants	5 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Skin Infection	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Tooth Infection	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Tooth Injury	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Upper Respiratory Tract Infection NOS	1 Participants	1 Participants	3 Participants	8 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Upper Respiratory Tract Infection Viral NOS	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Urinary Tract Infection NOS	0 Participants	0 Participants	4 Participants	3 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Visual Disturbance NOS	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure Vomiting NOS	0 Participants	1 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Week 24 (AMB-220-E baseline) to Week 329.3

Population: The AMB-220-E population consisted of all subjects who received at least 1 dose of study drug during the AMB-220-E study.

The number of participants in the AMB-220-E analysis set who experienced AEs (including serious AEs) of mild severity (ie, did not interfere with routine activities and the subject may have experienced slight discomfort) that began after entering AMB-220-E (treatment-emergent AEs) and that occurred in more than 1 participant are summarized by dose group. The AMB-220-E analysis set consisted of all participants who received at least 1 dose of study drug during the AMB-220-E study.

Outcome measures

Outcome measures
Measure	1 mg n=2 Participants The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	2.5 mg n=7 Participants The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	5 mg n=19 Participants The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.	10 mg n=26 Participants The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Palpitations	0 Participants	1 Participants	3 Participants	4 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Anorexia	0 Participants	0 Participants	2 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Arthralgia	0 Participants	2 Participants	0 Participants	4 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Blood Alkaline Phosphatase NOS Increased	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Bronchitis NOS	0 Participants	1 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Colonic Polyp	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Constipation	0 Participants	1 Participants	1 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Diarrhoea NOS	0 Participants	1 Participants	4 Participants	4 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Dry Skin	0 Participants	0 Participants	2 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Erythema	0 Participants	0 Participants	3 Participants	0 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Eye redness	0 Participants	0 Participants	1 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Flatulence	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Flushing	0 Participants	0 Participants	2 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Influenza	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Influenza Like Illness	0 Participants	0 Participants	2 Participants	0 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Lymphadenopathy	0 Participants	0 Participants	2 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Nasal Congestion	1 Participants	0 Participants	4 Participants	5 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Nocturia	0 Participants	0 Participants	2 Participants	0 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Oxygen Saturation Decreased	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Pericardial Effusion	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Pharyngitis	1 Participants	0 Participants	1 Participants	3 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Pneumonia NOS	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Productive Cough	0 Participants	2 Participants	0 Participants	0 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Pruritus	0 Participants	0 Participants	2 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Pyrexia	0 Participants	1 Participants	3 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Renal Cyst NOS	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Scleroderma	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Seasonal Allergy	1 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Skin Ulcer	0 Participants	0 Participants	2 Participants	0 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Sleep Apnoea Syndrome	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Tachycardia NOS	0 Participants	0 Participants	1 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Transient Ischaemic Attack	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Vein Distended	0 Participants	0 Participants	1 Participants	3 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Vertigo	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Vision Blurred	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Vomiting NOS	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Gastrooesophageal Reflux Disease	1 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Haemorrhoids	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Headache	1 Participants	0 Participants	3 Participants	6 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Heart Sounds Abnormal	0 Participants	1 Participants	2 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Hepatomegaly	0 Participants	2 Participants	0 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Herpes Simplex	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Hypercholesterolaemia	1 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Hypertension NOS	0 Participants	0 Participants	1 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Hyperuricaemia	0 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Hypokalaemia	1 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Hypotension NOS	0 Participants	0 Participants	3 Participants	0 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Insomnia	0 Participants	1 Participants	1 Participants	4 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure International Normalised Ratio Increased	0 Participants	0 Participants	2 Participants	0 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Abdominal Distension	0 Participants	0 Participants	1 Participants	3 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Abdominal Pain Upper	0 Participants	0 Participants	2 Participants	0 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Acquired Hypothyroidism	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Anaemia NOS	0 Participants	1 Participants	1 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Anxiety	0 Participants	2 Participants	2 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Arrhythmia NOS	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Asthenia	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Blood Potassium Decreased	1 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Bradycardia NOS	1 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Bundle Branch Block Right	0 Participants	0 Participants	2 Participants	0 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Cardiac Murmur NOS	0 Participants	0 Participants	3 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Chest Pain	0 Participants	1 Participants	1 Participants	4 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Clubbing	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Cough	0 Participants	2 Participants	6 Participants	6 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Crackles Lung	0 Participants	0 Participants	1 Participants	3 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Cyanosis NOS	0 Participants	0 Participants	0 Participants	3 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Depression	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Diverticulum NOS	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Dizziness	1 Participants	0 Participants	3 Participants	3 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Dizziness Postural	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Dry Mouth	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Dyspnoea Exacerbated	0 Participants	1 Participants	3 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Enanthema	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Epistaxis	1 Participants	0 Participants	4 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Muscle Cramp	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Nail Fungal Infection NOS	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Nasopharyngitis	0 Participants	1 Participants	2 Participants	5 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Nausea	0 Participants	0 Participants	2 Participants	5 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Fatigue	0 Participants	1 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Fatigue Aggravated	0 Participants	0 Participants	0 Participants	4 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Neck Pain	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Oedema Peripheral	1 Participants	3 Participants	10 Participants	9 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Pain in Jaw	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Rash NOS	0 Participants	0 Participants	1 Participants	3 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Respiratory Tract Infection NOS	0 Participants	0 Participants	1 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Sinusitis NOS	0 Participants	0 Participants	1 Participants	3 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Somnolence	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Squamous Cell Carcinoma	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Syncope	0 Participants	1 Participants	2 Participants	0 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Thyroid Disorder	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Upper Respiratory Tract Infection NOS	0 Participants	3 Participants	2 Participants	6 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Feeling Cold	0 Participants	1 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Gastroenteritis NOS	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Venous Stasis	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Gastrointestinal Upset	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Viral Infection NOS	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure Weight Decreased	1 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure White Blood Cell Count Increased	1 Participants	1 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Week 24 (AMB-220-E baseline)

Population: Primary efficacy analyses were performed for the AMB-220-E analysis set (all subjects who received at least 1 dose of study drug during the AMB-220-E study). Results are presented using the last-observation-carried-forward (LOCF) imputation.

The 6MWT was conducted according to the American Thoracic Society guidelines (ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002; 166(1):111-117.) Primary efficacy analyses were performed for the AMB-220-E analysis set (all subjects who received at least 1 dose of study drug during the AMB-220-E study).

Outcome measures

Outcome measures
Measure	1 mg n=54 Participants The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	2.5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.	10 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.
Baseline Measurement in Exercise Capacity as Measured by the 6-minute Walk Test (6MWT) Distance (Baseline [Week 24])	406.1 Meters Standard Deviation 97.78	—	—	—

SECONDARY outcome

Timeframe: 24 weeks (Week 24 to Week 48)

Outcome measures

Outcome measures
Measure	1 mg n=54 Participants The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	2.5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.	10 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.
Change From Baseline (Week 24 of NCT00046319) in Exercise Capacity as Measured by the 6-minute Walk Test (6MWT) Distance (Last Observation Carried Forward [LOCF]) (Week 48)	4.5 Meters Standard Deviation 46.93	—	—	—

SECONDARY outcome

Timeframe: 84 weeks (Week 24 to Week 108)

Outcome measures

Outcome measures
Measure	1 mg n=54 Participants The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	2.5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.	10 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.
Change From Baseline (Week 24 of NCT00046319) in Exercise Capacity as Measured by the 6-minute Walk Test (6MWT) Distance (LOCF) (Week 108)	-10.3 Meters Standard Deviation 73.16	—	—	—

SECONDARY outcome

Timeframe: 132 weeks (Week 24 to Week 156)

Outcome measures

Outcome measures
Measure	1 mg n=54 Participants The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	2.5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.	10 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.
Change From Baseline (Week 24 of NCT00046319) in Exercise Capacity as Measured by the 6-minute Walk Test (6MWT) Distance (LOCF) (Week 156)	-4.7 Meters Standard Deviation 83.08	—	—	—

SECONDARY outcome

Timeframe: 180 weeks (Week 24 to Week 204)

Outcome measures

Outcome measures
Measure	1 mg n=54 Participants The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	2.5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.	10 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.
Change From Baseline (Week 24 of NCT00046319) in Exercise Capacity as Measured by the 6-minute Walk Test (6MWT) Distance (LOCF) (Week 204)	-13.9 Meters Standard Deviation 77.04	—	—	—

SECONDARY outcome

Timeframe: Week 24 (AMB-220-E baseline)

Change from baseline evaluated after 24 (baseline), 48, 108, 156, and 204 weeks of ambrisentan therapy in BDI (measured as units on a scale) immediately following exercise. Borg Dyspnea Index, a measure of perceived shortness of breath: 0 units on a scale (none) to 10 units on a scale (maximum breathlessness).

Outcome measures

Outcome measures
Measure	1 mg n=54 Participants The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	2.5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.	10 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.
Baseline Measurement in Exercise Capacity as Measured by the Borg Dyspnea Index (BDI) (Baseline [Week 24])	2.69 Units on a Scale Standard Deviation 1.728	—	—	—

SECONDARY outcome

Timeframe: 24 weeks (Week 24 to Week 48)

Outcome measures

Outcome measures
Measure	1 mg n=54 Participants The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	2.5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.	10 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.
Change From Baseline (Week 24 of NCT00046319) in Exercise Capacity as Measured by the BDI (LOCF) (Week 48)	0.21 Units on a Scale Standard Deviation 1.323	—	—	—

SECONDARY outcome

Timeframe: 84 weeks (Week 24 to Week 108)

Outcome measures

Outcome measures
Measure	1 mg n=54 Participants The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	2.5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.	10 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.
Change From Baseline (Week 24 of NCT00046319) in Exercise Capacity as Measured by the BDI (LOCF) (Week 108)	0.46 Units on a Scale Standard Deviation 1.659	—	—	—

SECONDARY outcome

Timeframe: 132 weeks (Week 24 to Week 156)

Outcome measures

Outcome measures
Measure	1 mg n=54 Participants The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	2.5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.	10 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.
Change From Baseline (Week 24 of NCT00046319) in Exercise Capacity as Measured by the BDI (LOCF) (Week 156)	0.50 Units on a Scale Standard Deviation 1.888	—	—	—

SECONDARY outcome

Timeframe: 180 weeks (Week 24 to Week 204)

Outcome measures

Outcome measures
Measure	1 mg n=54 Participants The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	2.5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.	10 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.
Change From Baseline (Week 24 of NCT00046319) in Exercise Capacity as Measured by the BDI (LOCF) (Week 204)	0.46 Units on a Scale Standard Deviation 1.721	—	—	—

SECONDARY outcome

Timeframe: Week 24 (AMB-220-E baseline)

Classes: I) pulmonary hypertension (PH); ordinary physical activity not limited or causes increased dyspnea, fatigue, chest pain, or presyncope. II) PH; ordinary physical activity mildly limited and causes increased dyspnea, fatigue, chest pain, or presyncope; comfortable at rest. III) PH; physical activity markedly limited and less than ordinary physical activity causes increased dyspnea, fatigue, chest pain, or presyncope; comfortable at rest. IV) PH; physical activity causes symptoms; signs of right heart failure; dyspnea/fatigue possibly at rest.

Outcome measures

Outcome measures
Measure	1 mg n=54 Participants The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	2.5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.	10 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.
Baseline Measurement in Exercise Capacity as Measured by the World Health Organization (WHO) Functional Classification (Baseline [Week 24]) WHO Classification I	8 Participants	—	—	—
Baseline Measurement in Exercise Capacity as Measured by the World Health Organization (WHO) Functional Classification (Baseline [Week 24]) WHO Classification II	27 Participants	—	—	—
Baseline Measurement in Exercise Capacity as Measured by the World Health Organization (WHO) Functional Classification (Baseline [Week 24]) WHO Classification III	19 Participants	—	—	—
Baseline Measurement in Exercise Capacity as Measured by the World Health Organization (WHO) Functional Classification (Baseline [Week 24]) WHO Classification IV	0 Participants	—	—	—

SECONDARY outcome

Timeframe: 24 weeks (Week 24 [baseline of AMB-220-E] to Week 48)

Classes: I) PH; ordinary physical activity not limited or causes increased dyspnea, fatigue, chest pain, or presyncope. II) PH; ordinary physical activity mildly limited and causes increased dyspnea, fatigue, chest pain, or presyncope; comfortable at rest. III) PH; physical activity markedly limited and less than ordinary physical activity causes increased dyspnea, fatigue, chest pain, or presyncope; comfortable at rest. IV) PH; physical activity causes symptoms; signs of right heart failure; dyspnea/fatigue possibly at rest.

Outcome measures

Outcome measures
Measure	1 mg n=54 Participants The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	2.5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.	10 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.
Exercise Capacity as Measured by the WHO Functional Classification (LOCF) After 24 Weeks of Treatment in AMB-220-E WHO Classification I	7 Participants	—	—	—
Exercise Capacity as Measured by the WHO Functional Classification (LOCF) After 24 Weeks of Treatment in AMB-220-E WHO Classification II	29 Participants	—	—	—
Exercise Capacity as Measured by the WHO Functional Classification (LOCF) After 24 Weeks of Treatment in AMB-220-E WHO Classification III	18 Participants	—	—	—
Exercise Capacity as Measured by the WHO Functional Classification (LOCF) After 24 Weeks of Treatment in AMB-220-E WHO Classification IV	0 Participants	—	—	—

SECONDARY outcome

Timeframe: 84 weeks (Week 24 of NCT00046319 to Week 108)

Outcome measures

Outcome measures
Measure	1 mg n=54 Participants The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	2.5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.	10 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.
Exercise Capacity as Measured by the WHO Functional Classification (LOCF) After 84 Weeks of Treatment in AMB-220-E WHO Classification I	5 Participants	—	—	—
Exercise Capacity as Measured by the WHO Functional Classification (LOCF) After 84 Weeks of Treatment in AMB-220-E WHO Classification II	25 Participants	—	—	—
Exercise Capacity as Measured by the WHO Functional Classification (LOCF) After 84 Weeks of Treatment in AMB-220-E WHO Classification III	21 Participants	—	—	—
Exercise Capacity as Measured by the WHO Functional Classification (LOCF) After 84 Weeks of Treatment in AMB-220-E WHO Classification IV	3 Participants	—	—	—

SECONDARY outcome

Timeframe: 132 weeks (Week 24 of NCT00046319 to Week 156)

Outcome measures

Outcome measures
Measure	1 mg n=54 Participants The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	2.5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.	10 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.
Exercise Capacity as Measured by the WHO Functional Classification (LOCF) After 132 Weeks of Treatment in AMB-220-E WHO Classification I	10 Participants	—	—	—
Exercise Capacity as Measured by the WHO Functional Classification (LOCF) After 132 Weeks of Treatment in AMB-220-E WHO Classification II	18 Participants	—	—	—
Exercise Capacity as Measured by the WHO Functional Classification (LOCF) After 132 Weeks of Treatment in AMB-220-E WHO Classification III	24 Participants	—	—	—
Exercise Capacity as Measured by the WHO Functional Classification (LOCF) After 132 Weeks of Treatment in AMB-220-E WHO Classification IV	2 Participants	—	—	—

SECONDARY outcome

Timeframe: 180 weeks (Week 24 of NCT00046319 to Week 204)

Outcome measures

Outcome measures
Measure	1 mg n=54 Participants The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	2.5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.	10 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.
Exercise Capacity as Measured by the WHO Functional Classification (LOCF) After 180 Weeks of Treatment in AMB-220-E WHO Classification I	10 Participants	—	—	—
Exercise Capacity as Measured by the WHO Functional Classification (LOCF) After 180 Weeks of Treatment in AMB-220-E WHO Classification II	19 Participants	—	—	—
Exercise Capacity as Measured by the WHO Functional Classification (LOCF) After 180 Weeks of Treatment in AMB-220-E WHO Classification III	23 Participants	—	—	—
Exercise Capacity as Measured by the WHO Functional Classification (LOCF) After 180 Weeks of Treatment in AMB-220-E WHO Classification IV	2 Participants	—	—	—

SECONDARY outcome

Timeframe: Week 24 (AMB-220-E baseline)

Population: Primary efficacy analyses were performed for the AMB-220-E analysis set (all subjects who received at least 1 dose of study drug during the AMB-220-E study).

The SGA was determined using a visual-analog scale. Subjects were asked the question, "How are you feeling today?" and were asked to draw a vertical mark on a 100-mm horizontal line in which zero represented "very poor" and 100 represented "excellent."

Outcome measures

Outcome measures
Measure	1 mg n=54 Participants The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	2.5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.	10 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.
Baseline Measurement in Exercise Capacity as Measured by the Subject Global Assessment (SGA) (Baseline [Week 24])	69.5 Units on a Scale Standard Deviation 20.49	—	—	—

SECONDARY outcome

Timeframe: 24 weeks (Week 24 to Week 48)

Outcome measures

Outcome measures
Measure	1 mg n=54 Participants The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	2.5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.	10 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.
Change From Baseline (Week 24 of NCT00046319) in Exercise Capacity as Measured by the SGA (LOCF) (Week 48)	-0.6 Units on a Scale Standard Deviation 19.41	—	—	—

SECONDARY outcome

Timeframe: 84 weeks (Week 24 to Week 108)

Outcome measures

Outcome measures
Measure	1 mg n=54 Participants The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	2.5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.	10 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.
Change From Baseline (Week 24 of NCT00046319) in Exercise Capacity as Measured by the SGA (LOCF) (Week 108)	-7.4 Units on a Scale Standard Deviation 25.79	—	—	—

SECONDARY outcome

Timeframe: 132 weeks (Week 24 to Week 156)

Outcome measures

Outcome measures
Measure	1 mg n=54 Participants The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	2.5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.	10 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.
Change From Baseline (Week 24 of NCT00046319) in Exercise Capacity as Measured by the SGA (LOCF) (Week 156)	-5.1 Units on a Scale Standard Deviation 25.31	—	—	—

SECONDARY outcome

Timeframe: 180 weeks (Week 24 to Week 204)

Outcome measures

Outcome measures
Measure	1 mg n=54 Participants The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	2.5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.	10 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.
Change From Baseline (Week 24 of NCT00046319) in Exercise Capacity as Measured by the SGA (LOCF) (Week 204)	-1.9 Units on a Scale Standard Deviation 23.69	—	—	—

SECONDARY outcome

Timeframe: Week 0 (NCT00046319 baseline) to Week 360

Population: The NCT00046319 analysis set (all subjects who received at least 1 dose of study drug during the AMB-220 study) was evaluated during the NCT00046319 and AMB-220-E study periods.

Clinical worsening of PAH was defined as death, lung transplantation, hospitalization for PAH, atrial septostomy, the addition of approved prostanoid therapy, or study withdrawal due to the addition of other clinically approved PAH therapeutic agents. Sildenafil, a type 5 phosphodiesterase (PDE-5) inhibitor, had not received regulatory approval for the treatment of PAH until late in the conduct of AMB 220 and AMB 220-E, and did not count toward clinical worsening. Results are presented as the Kaplan-Meier estimate (% probability) of not having clinical worsening after a given time.

Outcome measures

Outcome measures
Measure	1 mg n=64 Participants The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	2.5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.	10 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.
Time to Clinical Worsening of PAH No clinical worsening after 1 year of treatment	78 Probability (%) 116.662	—	—	—
Time to Clinical Worsening of PAH No clinical worsening after 2 years of treatment	69 Probability (%)	—	—	—
Time to Clinical Worsening of PAH No clinical worsening after 3 years of treatment	60 Probability (%)	—	—	—
Time to Clinical Worsening of PAH No clinical worsening after 4 years of treatment	55 Probability (%)	—	—	—

SECONDARY outcome

Timeframe: Week 0 (NCT00046319 baseline) to Week 360

Population: The NCT00046319 analysis set (all subjects who received at least 1 dose of study drug during the NCT00046319 study) was evaluated during the NCT00046319 and AMB-220-E study periods.

Failure-free treatment status was defined as the time from initiation of active treatment to the first occurrence of death, lung transplantation, the addition of approved prostanoid therapy, or study withdrawal due to the addition of other clinically approved PAH therapeutic agents. Results are presented as the Kaplan-Meier estimate (% probability) of not having treatment failure after a given time.

Outcome measures

Outcome measures
Measure	1 mg n=64 Participants The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	2.5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.	10 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.
Failure-free Treatment Status No treatment failure after 1 year of treatment	89 Probability (%) 110.672	—	—	—
Failure-free Treatment Status No treatment failure after 2 years of treatment	77 Probability (%)	—	—	—
Failure-free Treatment Status No treatment failure after 3 years of treatment	74 Probability (%)	—	—	—
Failure-free Treatment Status No treatment failure after 4 years of treatment	70 Probability (%)	—	—	—

SECONDARY outcome

Timeframe: Week 24 (AMB-220-E baseline) to Week 329.3

Population: The AMB-220-E analysis set (all subjects who received at least 1 dose of study drug during the AMB-220-E study) was evaluated during the AMB-220-E study period.

Long-term survival was defined as the time from initiation of active treatment to death. Results are presented as the Kaplan-Meier estimate (% probability) of survival after a given time.

Outcome measures

Outcome measures
Measure	1 mg n=64 Participants The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	2.5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	5 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.	10 mg The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.
Long-term Survival Survival after 1 year of treatment	94 Probability (%) 111.873	—	—	—
Long-term Survival Survival after 2 years of treatment	87 Probability (%)	—	—	—
Long-term Survival Survival after 3 years of treatment	87 Probability (%)	—	—	—
Long-term Survival Survival after 4 years of treatment	87 Probability (%)	—	—	—

Adverse Events

1 mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

2.5 mg

Serious events: 2 serious events

Other events: 7 other events

Deaths: 0 deaths

5 mg

Serious events: 12 serious events

Other events: 19 other events

Deaths: 0 deaths

10 mg

Serious events: 18 serious events

Other events: 26 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	1 mg n=2 participants at risk The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	2.5 mg n=7 participants at risk The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	5 mg n=19 participants at risk The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.	10 mg n=26 participants at risk The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.
Blood and lymphatic system disorders Anaemia NOS	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	0.00% 0/26
Blood and lymphatic system disorders Coagulopathy	0.00% 0/2	0.00% 0/7	0.00% 0/19	3.8% 1/26 • Number of events 1
Blood and lymphatic system disorders Neutropenia	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Blood and lymphatic system disorders Secondary anaemia	0.00% 0/2	0.00% 0/7	0.00% 0/19	7.7% 2/26 • Number of events 2
Cardiac disorders Angina pectoris	0.00% 0/2	0.00% 0/7	0.00% 0/19	7.7% 2/26 • Number of events 2
Cardiac disorders Atrial fibrillation	0.00% 0/2	0.00% 0/7	0.00% 0/19	3.8% 1/26 • Number of events 1
Cardiac disorders Atrial flutter	0.00% 0/2	0.00% 0/7	0.00% 0/19	3.8% 1/26 • Number of events 1
Cardiac disorders Atrial tachycardia	0.00% 0/2	0.00% 0/7	0.00% 0/19	3.8% 1/26 • Number of events 1
Cardiac disorders Bradycardia NOS	0.00% 0/2	0.00% 0/7	0.00% 0/19	3.8% 1/26 • Number of events 1
Cardiac disorders Cardiac arrest	0.00% 0/2	0.00% 0/7	0.00% 0/19	3.8% 1/26 • Number of events 1
Cardiac disorders Right ventricular failure	0.00% 0/2	0.00% 0/7	10.5% 2/19 • Number of events 3	30.8% 8/26 • Number of events 11
Congenital, familial and genetic disorders Gastrointestinal arteriovenous malformation	0.00% 0/2	0.00% 0/7	0.00% 0/19	7.7% 2/26 • Number of events 2
Gastrointestinal disorders Abdominal pain NOS	0.00% 0/2	0.00% 0/7	0.00% 0/19	3.8% 1/26 • Number of events 1
Gastrointestinal disorders Abdominal symptom NOS	0.00% 0/2	0.00% 0/7	0.00% 0/19	3.8% 1/26 • Number of events 1
Gastrointestinal disorders Constipation	0.00% 0/2	0.00% 0/7	0.00% 0/19	3.8% 1/26 • Number of events 1
Gastrointestinal disorders Gastrointestinal haemorrhage NOS	0.00% 0/2	0.00% 0/7	0.00% 0/19	7.7% 2/26 • Number of events 2
Gastrointestinal disorders Inguinal hernia NOS	0.00% 0/2	0.00% 0/7	0.00% 0/19	3.8% 1/26 • Number of events 1
Gastrointestinal disorders Intestinal ischemia	0.00% 0/2	0.00% 0/7	0.00% 0/19	3.8% 1/26 • Number of events 1
Gastrointestinal disorders Intestinal obstruction NOS	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	0.00% 0/26
Gastrointestinal disorders Pancreatitis NOS	0.00% 0/2	0.00% 0/7	0.00% 0/19	3.8% 1/26 • Number of events 1
General disorders Calcinosis	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
General disorders Chest pain	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
General disorders Drug withdrawal syndrome	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Hepatobiliary disorders Cholecystitis acute NOS	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Infections and infestations Abdominal wall infection	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Infections and infestations Bronchopneumonia NOS	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Infections and infestations Infection NOS	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	3.8% 1/26 • Number of events 1
Infections and infestations Lobar pneumonia NOS	0.00% 0/2	0.00% 0/7	0.00% 0/19	3.8% 1/26 • Number of events 1
Infections and infestations Lower respiratory tract infection NOS	0.00% 0/2	0.00% 0/7	0.00% 0/19	3.8% 1/26 • Number of events 1
Infections and infestations Pneumonia NOS	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	3.8% 1/26 • Number of events 1
Infections and infestations Pneumonia chlamydial	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Infections and infestations Pneumonia viral NOS	0.00% 0/2	0.00% 0/7	0.00% 0/19	3.8% 1/26 • Number of events 1
Infections and infestations Septic shock	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Infections and infestations Urinary tract infection NOS	0.00% 0/2	0.00% 0/7	0.00% 0/19	3.8% 1/26 • Number of events 1
Infections and infestations Viral infection NOS	0.00% 0/2	0.00% 0/7	0.00% 0/19	3.8% 1/26 • Number of events 1
Investigations Alanine aminotransferase increased	0.00% 0/2	0.00% 0/7	0.00% 0/19	7.7% 2/26 • Number of events 2
Investigations Aspartate aminotransferase increased	0.00% 0/2	0.00% 0/7	0.00% 0/19	7.7% 2/26 • Number of events 2
Investigations C-reactive protein increased	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Investigations Liver function tests NOS abnormal	0.00% 0/2	0.00% 0/7	0.00% 0/19	3.8% 1/26 • Number of events 1
Metabolism and nutrition disorders Dehydration	0.00% 0/2	0.00% 0/7	0.00% 0/19	3.8% 1/26 • Number of events 1
Metabolism and nutrition disorders Fluid retention	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	0.00% 0/26
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/2	0.00% 0/7	0.00% 0/19	3.8% 1/26 • Number of events 1
Musculoskeletal and connective tissue disorders Haemarthrosis	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	0.00% 0/26
Musculoskeletal and connective tissue disorders Localised osteoarthritis	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 2	0.00% 0/26
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/2	0.00% 0/7	0.00% 0/19	3.8% 1/26 • Number of events 1
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer NOS	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Multiple myeloma	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	0.00% 0/26
Nervous system disorders Cerebral arterial aneurysm	0.00% 0/2	0.00% 0/7	0.00% 0/19	3.8% 1/26 • Number of events 1
Nervous system disorders Lumbar radiculopathy	0.00% 0/2	0.00% 0/7	0.00% 0/19	3.8% 1/26 • Number of events 1
Nervous system disorders Lumbar spinal stenosis	0.00% 0/2	0.00% 0/7	0.00% 0/19	3.8% 1/26 • Number of events 1
Nervous system disorders Syncope	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	11.5% 3/26 • Number of events 4
Nervous system disorders Transient ischaemic attack	0.00% 0/2	0.00% 0/7	0.00% 0/19	3.8% 1/26 • Number of events 1
Nervous system disorders Vasovagal attack	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Renal and urinary disorders Hydronephrosis	0.00% 0/2	0.00% 0/7	0.00% 0/19	3.8% 1/26 • Number of events 1
Renal and urinary disorders Nephrolithiasis	0.00% 0/2	0.00% 0/7	0.00% 0/19	3.8% 1/26 • Number of events 1
Renal and urinary disorders Renal failure acute	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	0.00% 0/26
Renal and urinary disorders Urinary tract obstruction NOS	0.00% 0/2	0.00% 0/7	0.00% 0/19	3.8% 1/26 • Number of events 1
Reproductive system and breast disorders Menometrorrhagia	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Reproductive system and breast disorders Ovarian cyst	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	3.8% 1/26 • Number of events 1
Reproductive system and breast disorders Pelvic haematoma	0.00% 0/2	0.00% 0/7	0.00% 0/19	3.8% 1/26 • Number of events 1
Reproductive system and breast disorders Vaginal haemorrhage	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	0.00% 0/26
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/2	0.00% 0/7	0.00% 0/19	3.8% 1/26 • Number of events 1
Respiratory, thoracic and mediastinal disorders Brain hypoxia	0.00% 0/2	0.00% 0/7	0.00% 0/19	3.8% 1/26 • Number of events 1
Respiratory, thoracic and mediastinal disorders Bronchitis NOS	0.00% 0/2	0.00% 0/7	0.00% 0/19	3.8% 1/26 • Number of events 1
Respiratory, thoracic and mediastinal disorders Dyspnoea exacerbated	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/2	0.00% 0/7	0.00% 0/19	3.8% 1/26 • Number of events 1
Respiratory, thoracic and mediastinal disorders Pneumonitis NOS	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	0.00% 0/26
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension NOS aggravated	0.00% 0/2	14.3% 1/7 • Number of events 1	10.5% 2/19 • Number of events 2	15.4% 4/26 • Number of events 4
Vascular disorders Haemodynamic instability	0.00% 0/2	0.00% 0/7	0.00% 0/19	3.8% 1/26 • Number of events 1
Vascular disorders Peripheral occlusion	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Vascular disorders Venous ulcer NOS	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26

Other adverse events

Other adverse events
Measure	1 mg n=2 participants at risk The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	2.5 mg n=7 participants at risk The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion.	5 mg n=19 participants at risk The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.	10 mg n=26 participants at risk The optimized final dose from the open-label period of NCT00046319 (given QD by oral administration) was used in this study, with further dose refinement at the investigator's discretion. Subjects who completed an optional down-titration period at the end of AMB 220 were re-titrated if their final dose was 5 or 10 mg.
Blood and lymphatic system disorders Anaemia NOS	0.00% 0/2	28.6% 2/7 • Number of events 5	10.5% 2/19 • Number of events 5	15.4% 4/26 • Number of events 5
Blood and lymphatic system disorders Iron deficiency anaemia	0.00% 0/2	14.3% 1/7 • Number of events 1	5.3% 1/19 • Number of events 1	0.00% 0/26
Blood and lymphatic system disorders Leukopenia NOS	0.00% 0/2	14.3% 1/7 • Number of events 1	5.3% 1/19 • Number of events 1	0.00% 0/26
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/2	0.00% 0/7	10.5% 2/19 • Number of events 2	7.7% 2/26 • Number of events 3
Blood and lymphatic system disorders Splenomegaly	0.00% 0/2	0.00% 0/7	0.00% 0/19	7.7% 2/26 • Number of events 2
Cardiac disorders Angina pectoris	50.0% 1/2 • Number of events 2	0.00% 0/7	5.3% 1/19 • Number of events 2	3.8% 1/26 • Number of events 1
Cardiac disorders Arrhythmia NOS	0.00% 0/2	0.00% 0/7	10.5% 2/19 • Number of events 2	7.7% 2/26 • Number of events 2
Cardiac disorders Bradycardia NOS	50.0% 1/2 • Number of events 2	14.3% 1/7 • Number of events 1	0.00% 0/19	3.8% 1/26 • Number of events 1
Cardiac disorders Bundle branch block right	0.00% 0/2	0.00% 0/7	10.5% 2/19 • Number of events 2	0.00% 0/26
Cardiac disorders Clubbing	0.00% 0/2	0.00% 0/7	0.00% 0/19	7.7% 2/26 • Number of events 2
Cardiac disorders Cyanosis NOS	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	15.4% 4/26 • Number of events 5
Cardiac disorders Palpitations	0.00% 0/2	14.3% 1/7 • Number of events 2	15.8% 3/19 • Number of events 7	23.1% 6/26 • Number of events 8
Cardiac disorders Palpitations aggravated	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Cardiac disorders Pericardial effusion	0.00% 0/2	0.00% 0/7	0.00% 0/19	7.7% 2/26 • Number of events 2
Cardiac disorders Right ventricular failure	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	19.2% 5/26 • Number of events 6
Cardiac disorders Tachycardia NOS	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	7.7% 2/26 • Number of events 2
Congenital, familial and genetic disorders Pigmented naevus	0.00% 0/2	0.00% 0/7	0.00% 0/19	7.7% 2/26 • Number of events 2
Ear and labyrinth disorders Ear congestion	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Ear and labyrinth disorders Hypoacusis	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Ear and labyrinth disorders Sensation of block in ear	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Ear and labyrinth disorders Tinnitus	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Ear and labyrinth disorders Vertigo	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 2	3.8% 1/26 • Number of events 1
Endocrine disorders Acquired hypothyroidism	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	3.8% 1/26 • Number of events 1
Endocrine disorders Thyroid disorder NOS	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	7.7% 2/26 • Number of events 2
Eye disorders Blepharitis	0.00% 0/2	0.00% 0/7	0.00% 0/19	7.7% 2/26 • Number of events 2
Eye disorders Cataract	50.0% 1/2 • Number of events 1	0.00% 0/7	0.00% 0/19	7.7% 2/26 • Number of events 2
Eye disorders Cataract bilateral NOS	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Eye disorders Eye irritation	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Eye disorders Eye pruritis	50.0% 1/2 • Number of events 1	0.00% 0/7	0.00% 0/19	3.8% 1/26 • Number of events 1
Eye disorders Eye redness	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	7.7% 2/26 • Number of events 3
Eye disorders Lacrimation increased	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Eye disorders Vision blurred	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	3.8% 1/26 • Number of events 1
Eye disorders Visual acuity reduced	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Eye disorders Visual disturbance NOS	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	7.7% 2/26 • Number of events 2
Gastrointestinal disorders Abdominal distension	0.00% 0/2	14.3% 1/7 • Number of events 1	5.3% 1/19 • Number of events 1	15.4% 4/26 • Number of events 5
Gastrointestinal disorders Abdominal pain NOS	0.00% 0/2	14.3% 1/7 • Number of events 1	5.3% 1/19 • Number of events 1	3.8% 1/26 • Number of events 1
Gastrointestinal disorders Abdominal pain upper	0.00% 0/2	0.00% 0/7	10.5% 2/19 • Number of events 2	3.8% 1/26 • Number of events 1
Gastrointestinal disorders Ascites	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	3.8% 1/26 • Number of events 1
Gastrointestinal disorders Colonic polyp	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	7.7% 2/26 • Number of events 2
Gastrointestinal disorders Constipation	0.00% 0/2	14.3% 1/7 • Number of events 1	21.1% 4/19 • Number of events 5	19.2% 5/26 • Number of events 8
Gastrointestinal disorders Dental discomfort	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	0.00% 0/26
Gastrointestinal disorders Diarrhoea NOS	0.00% 0/2	14.3% 1/7 • Number of events 1	36.8% 7/19 • Number of events 13	23.1% 6/26 • Number of events 6
Gastrointestinal disorders Diverticulum NOS	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	3.8% 1/26 • Number of events 1
Gastrointestinal disorders Dry mouth	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	3.8% 1/26 • Number of events 1
Gastrointestinal disorders Duodenal ulcer	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Gastrointestinal disorders Dyspepsia	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	11.5% 3/26 • Number of events 4
Gastrointestinal disorders Dysphagia	50.0% 1/2 • Number of events 1	0.00% 0/7	0.00% 0/19	0.00% 0/26
Gastrointestinal disorders Faecal incontinence	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	0.00% 0/26
Gastrointestinal disorders Flatulence	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	3.8% 1/26 • Number of events 1
Gastrointestinal disorders Gastroenteritis NOS	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	11.5% 3/26 • Number of events 3
Gastrointestinal disorders Gastrointestinal upset	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	3.8% 1/26 • Number of events 1
Gastrointestinal disorders Gastrooesophageal reflux disease	50.0% 1/2 • Number of events 1	28.6% 2/7 • Number of events 2	5.3% 1/19 • Number of events 3	7.7% 2/26 • Number of events 5
Gastrointestinal disorders Gingival bleeding	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Gastrointestinal disorders Gingival pain	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	3.8% 1/26 • Number of events 1
Gastrointestinal disorders Gingival swelling	50.0% 1/2 • Number of events 1	0.00% 0/7	5.3% 1/19 • Number of events 2	0.00% 0/26
Gastrointestinal disorders Haemorrhoids	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	7.7% 2/26 • Number of events 2
Gastrointestinal disorders Hiatus hernia	0.00% 0/2	0.00% 0/7	0.00% 0/19	7.7% 2/26 • Number of events 2
Gastrointestinal disorders Ileus paralytic	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	3.8% 1/26 • Number of events 2
Gastrointestinal disorders Intestinal polyp	50.0% 1/2 • Number of events 1	0.00% 0/7	0.00% 0/19	0.00% 0/26
Gastrointestinal disorders Melanosis coli	50.0% 1/2 • Number of events 1	0.00% 0/7	0.00% 0/19	0.00% 0/26
Gastrointestinal disorders Nausea	0.00% 0/2	14.3% 1/7 • Number of events 1	15.8% 3/19 • Number of events 4	38.5% 10/26 • Number of events 12
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Gastrointestinal disorders Stomatitis	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Gastrointestinal disorders Vomiting NOS	0.00% 0/2	28.6% 2/7 • Number of events 3	0.00% 0/19	11.5% 3/26 • Number of events 3
General disorders Asthenia	0.00% 0/2	0.00% 0/7	10.5% 2/19 • Number of events 2	3.8% 1/26 • Number of events 1
General disorders Calcinosis	0.00% 0/2	14.3% 1/7 • Number of events 1	5.3% 1/19 • Number of events 2	0.00% 0/26
General disorders Chest discomfort	50.0% 1/2 • Number of events 1	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
General disorders Chest pain	0.00% 0/2	57.1% 4/7 • Number of events 8	10.5% 2/19 • Number of events 3	15.4% 4/26 • Number of events 5
General disorders Chest pressure sensation	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 2	0.00% 0/26
General disorders Enanthema	0.00% 0/2	0.00% 0/7	0.00% 0/19	7.7% 2/26 • Number of events 3
General disorders Fall	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	7.7% 2/26 • Number of events 2
General disorders Fatigue	0.00% 0/2	14.3% 1/7 • Number of events 2	15.8% 3/19 • Number of events 5	7.7% 2/26 • Number of events 2
General disorders Fatigue aggravated	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	23.1% 6/26 • Number of events 6
General disorders Feeling cold	0.00% 0/2	14.3% 1/7 • Number of events 1	5.3% 1/19 • Number of events 1	3.8% 1/26 • Number of events 1
General disorders Feeling hot	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
General disorders Influenza like illness	0.00% 0/2	0.00% 0/7	10.5% 2/19 • Number of events 2	3.8% 1/26 • Number of events 1
General disorders Lethargy	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	3.8% 1/26 • Number of events 1
General disorders Malaise	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
General disorders Mucosal oedema NOS	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
General disorders Oedema peripheral	50.0% 1/2 • Number of events 1	42.9% 3/7 • Number of events 8	63.2% 12/19 • Number of events 20	57.7% 15/26 • Number of events 26
General disorders Pain NOS	50.0% 1/2 • Number of events 1	0.00% 0/7	0.00% 0/19	3.8% 1/26 • Number of events 1
General disorders Pyrexia	0.00% 0/2	28.6% 2/7 • Number of events 3	15.8% 3/19 • Number of events 4	7.7% 2/26 • Number of events 2
General disorders Rigors	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	3.8% 1/26 • Number of events 1
Hepatobiliary disorders Hepatic pain	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	0.00% 0/26
Hepatobiliary disorders Hepatomegaly	0.00% 0/2	28.6% 2/7 • Number of events 2	0.00% 0/19	11.5% 3/26 • Number of events 3
Immune system disorders Seasonal allergy	50.0% 1/2 • Number of events 1	0.00% 0/7	5.3% 1/19 • Number of events 1	3.8% 1/26 • Number of events 1
Infections and infestations Abscess limb	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Infections and infestations Cellulitis	0.00% 0/2	0.00% 0/7	10.5% 2/19 • Number of events 2	0.00% 0/26
Infections and infestations Erysipelas	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Infections and infestations Gastroenteritis viral NOS	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	7.7% 2/26 • Number of events 2
Infections and infestations Gingival infection	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	3.8% 1/26 • Number of events 1
Infections and infestations Herpes simplex	0.00% 0/2	0.00% 0/7	0.00% 0/19	7.7% 2/26 • Number of events 3
Infections and infestations Herpes zoster	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 2	11.5% 3/26 • Number of events 4
Infections and infestations Influenza	0.00% 0/2	28.6% 2/7 • Number of events 4	5.3% 1/19 • Number of events 1	7.7% 2/26 • Number of events 3
Infections and infestations Localised infection	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 5	3.8% 1/26 • Number of events 1
Infections and infestations Nail fungal infection NOS	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	3.8% 1/26 • Number of events 1
Infections and infestations Oesphageal candidiasis	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	3.8% 1/26 • Number of events 1
Infections and infestations Oral candidiasis	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	3.8% 1/26 • Number of events 1
Infections and infestations Otitis media NOS	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	3.8% 1/26 • Number of events 1
Infections and infestations Pneumonia NOS	0.00% 0/2	0.00% 0/7	10.5% 2/19 • Number of events 2	3.8% 1/26 • Number of events 2
Infections and infestations Respiratory tract infection NOS	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	11.5% 3/26 • Number of events 3
Infections and infestations Respiratory tract infection viral NOS	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Infections and infestations Sinusitis NOS	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	30.8% 8/26 • Number of events 9
Infections and infestations Sinusitis chronic NOS	0.00% 0/2	0.00% 0/7	0.00% 0/19	7.7% 2/26 • Number of events 2
Infections and infestations Skin fungal infection NOS	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Infections and infestations Skin infection	0.00% 0/2	0.00% 0/7	10.5% 2/19 • Number of events 2	3.8% 1/26 • Number of events 1
Infections and infestations Tinea pedis	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Infections and infestations Tooth abscess	0.00% 0/2	14.3% 1/7 • Number of events 1	5.3% 1/19 • Number of events 1	0.00% 0/26
Infections and infestations Tooth infection	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	7.7% 2/26 • Number of events 2
Infections and infestations Upper respiratory tract infection NOS	50.0% 1/2 • Number of events 2	57.1% 4/7 • Number of events 9	26.3% 5/19 • Number of events 7	53.8% 14/26 • Number of events 23
Infections and infestations Upper respiratory tract infection viral NOS	0.00% 0/2	0.00% 0/7	0.00% 0/19	7.7% 2/26 • Number of events 2
Infections and infestations Urinary tract infection NOS	0.00% 0/2	14.3% 1/7 • Number of events 2	21.1% 4/19 • Number of events 10	15.4% 4/26 • Number of events 6
Infections and infestations Viral diarrhoea	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	0.00% 0/26
Infections and infestations Viral infection NOS	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	3.8% 1/26 • Number of events 2
Injury, poisoning and procedural complications Abrasion NOS	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Injury, poisoning and procedural complications Anaemia postoperative	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Injury, poisoning and procedural complications Blister	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Injury, poisoning and procedural complications Foot fracture	0.00% 0/2	0.00% 0/7	15.8% 3/19 • Number of events 3	0.00% 0/26
Injury, poisoning and procedural complications Joint sprain	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	3.8% 1/26 • Number of events 1
Injury, poisoning and procedural complications Limb injury NOS	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 3	7.7% 2/26 • Number of events 2
Injury, poisoning and procedural complications Nausea postoperative	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	7.7% 2/26 • Number of events 2
Injury, poisoning and procedural complications Open wound	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Injury, poisoning and procedural complications Post procedural discomfort	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Injury, poisoning and procedural complications Post procedural pain	0.00% 0/2	0.00% 0/7	0.00% 0/19	7.7% 2/26 • Number of events 3
Injury, poisoning and procedural complications Spinal compression fracture	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Injury, poisoning and procedural complications Tooth injury	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	3.8% 1/26 • Number of events 1
Investigations Activated partial thromboplastin time	0.00% 0/2	0.00% 0/7	10.5% 2/19 • Number of events 2	0.00% 0/26
Investigations Alanine aminotransferase increased	100.0% 2/2 • Number of events 2	14.3% 1/7 • Number of events 1	0.00% 0/19	3.8% 1/26 • Number of events 2
Investigations Aspartate aminotransferase increased	100.0% 2/2 • Number of events 2	14.3% 1/7 • Number of events 1	0.00% 0/19	3.8% 1/26 • Number of events 2
Investigations Blood alkaline phosphatase NOS increased	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	7.7% 2/26 • Number of events 2
Investigations Blood amylase increased	50.0% 1/2 • Number of events 4	0.00% 0/7	0.00% 0/19	3.8% 1/26 • Number of events 1
Investigations Blood chloride decreased	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	0.00% 0/26
Investigations Blood glucose increased	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Investigations Blood potassium decreased	50.0% 1/2 • Number of events 1	14.3% 1/7 • Number of events 1	5.3% 1/19 • Number of events 1	3.8% 1/26 • Number of events 1
Investigations Blood potassium increased	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Investigations Blood sodium decreased	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	0.00% 0/26
Investigations C-reactive protein increased	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 3	0.00% 0/26
Investigations Cardiac murmur NOS	0.00% 0/2	0.00% 0/7	15.8% 3/19 • Number of events 3	7.7% 2/26 • Number of events 2
Investigations Carotid bruit	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Investigations Gamma-glutamyltransferase increased	50.0% 1/2 • Number of events 1	0.00% 0/7	5.3% 1/19 • Number of events 1	7.7% 2/26 • Number of events 2
Investigations Heart rate irregular	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	3.8% 1/26 • Number of events 1
Investigations Heart sounds abnormal	0.00% 0/2	14.3% 1/7 • Number of events 4	10.5% 2/19 • Number of events 2	7.7% 2/26 • Number of events 2
Investigations International normalised ratio increased	0.00% 0/2	14.3% 1/7 • Number of events 1	21.1% 4/19 • Number of events 7	7.7% 2/26 • Number of events 2
Investigations Lipase increased	50.0% 1/2 • Number of events 4	0.00% 0/7	0.00% 0/19	3.8% 1/26 • Number of events 1
Investigations Mean cell haemoglobin increased	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 2	0.00% 0/26
Investigations Mean cell volume increased	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 2	0.00% 0/26
Investigations Oxygen saturation decreased	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	3.8% 1/26 • Number of events 1
Investigations Platelet count decreased	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Investigations Prothrombin time prolonged	0.00% 0/2	0.00% 0/7	10.5% 2/19 • Number of events 2	0.00% 0/26
Investigations Pulmonary arterial wedge pressure increased	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Investigations QRS axis abnormal	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Investigations Venous pressure jugular increased	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Investigations Weight decreased	50.0% 1/2 • Number of events 1	0.00% 0/7	5.3% 1/19 • Number of events 1	3.8% 1/26 • Number of events 1
Investigations White blood cell count increased	50.0% 1/2 • Number of events 1	14.3% 1/7 • Number of events 1	0.00% 0/19	0.00% 0/26
Metabolism and nutrition disorders Anorexia	0.00% 0/2	0.00% 0/7	10.5% 2/19 • Number of events 2	3.8% 1/26 • Number of events 1
Metabolism and nutrition disorders Appetite decreased NOS	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	3.8% 1/26 • Number of events 1
Metabolism and nutrition disorders Diabetes mellitus NOS	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Metabolism and nutrition disorders Gout	0.00% 0/2	0.00% 0/7	10.5% 2/19 • Number of events 2	0.00% 0/26
Metabolism and nutrition disorders Hypercholesterolaemia	50.0% 1/2 • Number of events 1	0.00% 0/7	10.5% 2/19 • Number of events 3	0.00% 0/26
Metabolism and nutrition disorders Hyperuricaemia	0.00% 0/2	14.3% 1/7 • Number of events 1	5.3% 1/19 • Number of events 1	0.00% 0/26
Metabolism and nutrition disorders Hypokalaemia	50.0% 1/2 • Number of events 3	0.00% 0/7	10.5% 2/19 • Number of events 2	11.5% 3/26 • Number of events 4
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	3.8% 1/26 • Number of events 1
Metabolism and nutrition disorders Obesity	50.0% 1/2 • Number of events 1	0.00% 0/7	0.00% 0/19	0.00% 0/26
Musculoskeletal and connective tissue disorders Arthralgia	50.0% 1/2 • Number of events 1	28.6% 2/7 • Number of events 2	21.1% 4/19 • Number of events 5	34.6% 9/26 • Number of events 13
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/2	0.00% 0/7	15.8% 3/19 • Number of events 3	11.5% 3/26 • Number of events 4
Musculoskeletal and connective tissue disorders Bursitis	0.00% 0/2	0.00% 0/7	0.00% 0/19	7.7% 2/26 • Number of events 2
Musculoskeletal and connective tissue disorders Haemarthrosis	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	0.00% 0/26
Musculoskeletal and connective tissue disorders Intervertebral disc herniation	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	3.8% 1/26 • Number of events 1
Musculoskeletal and connective tissue disorders Knee deformity NOS	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Musculoskeletal and connective tissue disorders Localised osteoarthritis	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 3	3.8% 1/26 • Number of events 1
Musculoskeletal and connective tissue disorders Monoarthritis	0.00% 0/2	14.3% 1/7 • Number of events 2	0.00% 0/19	3.8% 1/26 • Number of events 1
Metabolism and nutrition disorders Muscle cramp	50.0% 1/2 • Number of events 1	0.00% 0/7	5.3% 1/19 • Number of events 1	3.8% 1/26 • Number of events 1
Musculoskeletal and connective tissue disorders Musculoskeletal discomfort	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	0.00% 0/2	0.00% 0/7	0.00% 0/19	7.7% 2/26 • Number of events 2
Metabolism and nutrition disorders Myalgia	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Metabolism and nutrition disorders Neck pain	0.00% 0/2	0.00% 0/7	10.5% 2/19 • Number of events 2	3.8% 1/26 • Number of events 2
Musculoskeletal and connective tissue disorders Osteoarthritis NOS	0.00% 0/2	14.3% 1/7 • Number of events 1	5.3% 1/19 • Number of events 3	0.00% 0/26
Musculoskeletal and connective tissue disorders Osteopenia	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Musculoskeletal and connective tissue disorders Osteoporosis NOS	0.00% 0/2	0.00% 0/7	10.5% 2/19 • Number of events 2	3.8% 1/26 • Number of events 1
Musculoskeletal and connective tissue disorders Pain in jaw	0.00% 0/2	0.00% 0/7	0.00% 0/19	11.5% 3/26 • Number of events 3
Musculoskeletal and connective tissue disorders Pain in limb	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	15.4% 4/26 • Number of events 4
Musculoskeletal and connective tissue disorders Polymyalgia	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Musculoskeletal and connective tissue disorders Scleroderma	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	7.7% 2/26 • Number of events 2
Musculoskeletal and connective tissue disorders Tendonitis	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/2	0.00% 0/7	0.00% 0/19	7.7% 2/26 • Number of events 2
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer NOS	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	3.8% 1/26 • Number of events 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine fibroids	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Nervous system disorders Balance impaired NOS	50.0% 1/2 • Number of events 1	0.00% 0/7	0.00% 0/19	0.00% 0/26
Nervous system disorders Burning sensation NOS	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Nervous system disorders Dizziness	50.0% 1/2 • Number of events 1	14.3% 1/7 • Number of events 4	26.3% 5/19 • Number of events 9	19.2% 5/26 • Number of events 6
Nervous system disorders Dizziness postural	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	3.8% 1/26 • Number of events 1
Nervous system disorders Headache	50.0% 1/2 • Number of events 1	14.3% 1/7 • Number of events 3	15.8% 3/19 • Number of events 3	30.8% 8/26 • Number of events 9
Nervous system disorders Hypoaesthesia	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Nervous system disorders Memory impairment	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	3.8% 1/26 • Number of events 1
Nervous system disorders Migraine NOS	0.00% 0/2	0.00% 0/7	0.00% 0/19	7.7% 2/26 • Number of events 2
Nervous system disorders Sinus headache	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	3.8% 1/26 • Number of events 1
Nervous system disorders Sleep apnoea syndrome	0.00% 0/2	0.00% 0/7	0.00% 0/19	7.7% 2/26 • Number of events 2
Nervous system disorders Syncope	0.00% 0/2	28.6% 2/7 • Number of events 2	21.1% 4/19 • Number of events 5	11.5% 3/26 • Number of events 5
Nervous system disorders Vasovagal attack	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Psychiatric disorders Acute psychosis	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Psychiatric disorders Anxiety	0.00% 0/2	28.6% 2/7 • Number of events 2	15.8% 3/19 • Number of events 4	11.5% 3/26 • Number of events 3
Psychiatric disorders Confusional state	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Psychiatric disorders Delirium	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Psychiatric disorders Depression	0.00% 0/2	0.00% 0/7	15.8% 3/19 • Number of events 3	26.9% 7/26 • Number of events 7
Psychiatric disorders Depression aggravated	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 2	0.00% 0/26
Psychiatric disorders Insomnia	0.00% 0/2	14.3% 1/7 • Number of events 1	15.8% 3/19 • Number of events 3	30.8% 8/26 • Number of events 11
Psychiatric disorders Insomnia exacerbated	0.00% 0/2	0.00% 0/7	0.00% 0/19	7.7% 2/26 • Number of events 2
Renal and urinary disorders Cystitis NOS	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Renal and urinary disorders Nephrolithiasis	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	3.8% 1/26 • Number of events 1
Renal and urinary disorders Nocturia	0.00% 0/2	0.00% 0/7	10.5% 2/19 • Number of events 2	0.00% 0/26
Renal and urinary disorders Renal cyst NOS	0.00% 0/2	0.00% 0/7	0.00% 0/19	7.7% 2/26 • Number of events 2
Renal and urinary disorders Urine odour abnormal	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	0.00% 0/26
Reproductive system and breast disorders Amenorrhoea NOS	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Reproductive system and breast disorders Breast mass NOS	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	3.8% 1/26 • Number of events 1
Reproductive system and breast disorders Menometrorrhagia	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Reproductive system and breast disorders Menorrhagia	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	11.5% 3/26 • Number of events 4
Reproductive system and breast disorders Ovarian cyst	0.00% 0/2	0.00% 0/7	0.00% 0/19	7.7% 2/26 • Number of events 2
Reproductive system and breast disorders Pelvic pain NOS	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	3.8% 1/26 • Number of events 1
Reproductive system and breast disorders Prostatic hypertrophy	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Reproductive system and breast disorders Vaginal haemorrage	0.00% 0/2	14.3% 1/7 • Number of events 2	0.00% 0/19	0.00% 0/26
Respiratory, thoracic and mediastinal disorders Bronchial obstruction	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Respiratory, thoracic and mediastinal disorders Bronchitis NOS	50.0% 1/2 • Number of events 1	57.1% 4/7 • Number of events 7	10.5% 2/19 • Number of events 2	19.2% 5/26 • Number of events 5
Respiratory, thoracic and mediastinal disorders Bronchospasm NOS	50.0% 1/2 • Number of events 1	0.00% 0/7	0.00% 0/19	3.8% 1/26 • Number of events 1
Respiratory, thoracic and mediastinal disorders Cough	50.0% 1/2 • Number of events 3	42.9% 3/7 • Number of events 5	47.4% 9/19 • Number of events 10	30.8% 8/26 • Number of events 11
Respiratory, thoracic and mediastinal disorders Crackles lung	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	11.5% 3/26 • Number of events 3
Respiratory, thoracic and mediastinal disorders Dyspnoea NOS	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	7.7% 2/26 • Number of events 2
Respiratory, thoracic and mediastinal disorders Dyspnoea exacerbated	0.00% 0/2	42.9% 3/7 • Number of events 6	47.4% 9/19 • Number of events 12	7.7% 2/26 • Number of events 2
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/2	14.3% 1/7 • Number of events 1	5.3% 1/19 • Number of events 1	0.00% 0/26
Respiratory, thoracic and mediastinal disorders Epistaxis	50.0% 1/2 • Number of events 1	0.00% 0/7	21.1% 4/19 • Number of events 4	11.5% 3/26 • Number of events 4
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/2	0.00% 0/7	0.00% 0/19	7.7% 2/26 • Number of events 4
Respiratory, thoracic and mediastinal disorders Hoarseness	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	3.8% 1/26 • Number of events 1
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/2	14.3% 1/7 • Number of events 2	5.3% 1/19 • Number of events 1	11.5% 3/26 • Number of events 3
Respiratory, thoracic and mediastinal disorders Lung infiltration NOS	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	0.00% 0/26
Respiratory, thoracic and mediastinal disorders Nasal congestion	50.0% 1/2 • Number of events 2	0.00% 0/7	31.6% 6/19 • Number of events 8	23.1% 6/26 • Number of events 7
Respiratory, thoracic and mediastinal disorders Nasal mucosal disorder NOS	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Respiratory, thoracic and mediastinal disorders Nasopharyngitis	0.00% 0/2	14.3% 1/7 • Number of events 5	15.8% 3/19 • Number of events 4	23.1% 6/26 • Number of events 13
Respiratory, thoracic and mediastinal disorders Pharyngitis	50.0% 1/2 • Number of events 2	14.3% 1/7 • Number of events 1	5.3% 1/19 • Number of events 3	11.5% 3/26 • Number of events 5
Reproductive system and breast disorders Productive cough	0.00% 0/2	28.6% 2/7 • Number of events 2	5.3% 1/19 • Number of events 1	0.00% 0/26
Reproductive system and breast disorders Pulmonary congestion	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Reproductive system and breast disorders Pulmonary hypertension NOS aggravated	0.00% 0/2	0.00% 0/7	15.8% 3/19 • Number of events 5	26.9% 7/26 • Number of events 8
Respiratory, thoracic and mediastinal disorders Pulmonary vascular disorder NOS	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	0.00% 0/26
Respiratory, thoracic and mediastinal disorders Respiratory fremitus	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	0.00% 0/26
Reproductive system and breast disorders Rhinitis allergic NOS	0.00% 0/2	0.00% 0/7	0.00% 0/19	7.7% 2/26 • Number of events 2
Reproductive system and breast disorders Ronchi	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	0.00% 0/26
Respiratory, thoracic and mediastinal disorders Sneezing	50.0% 1/2 • Number of events 1	0.00% 0/7	0.00% 0/19	0.00% 0/26
Reproductive system and breast disorders Wheezing	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Respiratory, thoracic and mediastinal disorders Wheezing aggravated	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	0.00% 0/26
Skin and subcutaneous tissue disorders Acne NOS	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Skin and subcutaneous tissue disorders Contusion	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	3.8% 1/26 • Number of events 1
Skin and subcutaneous tissue disorders Dermatitis NOS	0.00% 0/2	0.00% 0/7	10.5% 2/19 • Number of events 2	0.00% 0/26
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/2	0.00% 0/7	10.5% 2/19 • Number of events 2	3.8% 1/26 • Number of events 1
Skin and subcutaneous tissue disorders Eczema	0.00% 0/2	0.00% 0/7	0.00% 0/19	7.7% 2/26 • Number of events 4
Skin and subcutaneous tissue disorders Eczema weeping	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Skin and subcutaneous tissue disorders Erythema	0.00% 0/2	0.00% 0/7	21.1% 4/19 • Number of events 4	3.8% 1/26 • Number of events 2
Skin and subcutaneous tissue disorders Hair disorder NOS	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Skin and subcutaneous tissue disorders Hyperkeratosis	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	3.8% 1/26 • Number of events 2
Skin and subcutaneous tissue disorders Nail disorder NOS	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Skin and subcutaneous tissue disorders Panniculitis	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Skin and subcutaneous tissue disorders Pruritis	0.00% 0/2	0.00% 0/7	26.3% 5/19 • Number of events 6	11.5% 3/26 • Number of events 3
Skin and subcutaneous tissue disorders Rash NOS	0.00% 0/2	0.00% 0/7	10.5% 2/19 • Number of events 2	11.5% 3/26 • Number of events 4
Skin and subcutaneous tissue disorders Skin lesion NOS	0.00% 0/2	0.00% 0/7	0.00% 0/19	11.5% 3/26 • Number of events 6
Skin and subcutaneous tissue disorders Skin ulcer	0.00% 0/2	0.00% 0/7	15.8% 3/19 • Number of events 3	0.00% 0/26
Skin and subcutaneous tissue disorders Solar keratosis	0.00% 0/2	0.00% 0/7	0.00% 0/19	7.7% 2/26 • Number of events 4
Skin and subcutaneous tissue disorders Sweating increased	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Skin and subcutaneous tissue disorders Swelling face	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Skin and subcutaneous tissue disorders Telangiectasia	0.00% 0/2	14.3% 1/7 • Number of events 1	10.5% 2/19 • Number of events 2	0.00% 0/26
Skin and subcutaneous tissue disorders Urticaria NOS	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Vascular disorders Aortic stenosis	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Vascular disorders Flushing	0.00% 0/2	14.3% 1/7 • Number of events 2	15.8% 3/19 • Number of events 3	7.7% 2/26 • Number of events 2
Vascular disorders Haematoma NOS	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 2	3.8% 1/26 • Number of events 1
Vascular disorders Hot flushes NOS	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Vascular disorders Hypertension NOS	0.00% 0/2	0.00% 0/7	15.8% 3/19 • Number of events 3	7.7% 2/26 • Number of events 2
Vascular disorders Hypertensive crisis	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 2	0.00% 0/26
Vascular disorders Hypotension NOS	50.0% 1/2 • Number of events 1	0.00% 0/7	21.1% 4/19 • Number of events 4	3.8% 1/26 • Number of events 3
Vascular disorders Orthostatic hypotension	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	3.8% 1/26 • Number of events 1
Vascular disorders Peripheral coldness	0.00% 0/2	14.3% 1/7 • Number of events 1	0.00% 0/19	0.00% 0/26
Vascular disorders Peripheral occlusion	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
Vascular disorders Vein distended	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	15.4% 4/26 • Number of events 8
Vascular disorders Venous stasis	0.00% 0/2	0.00% 0/7	0.00% 0/19	7.7% 2/26 • Number of events 2
Vascular disorders Venous ulcer NOS	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	0.00% 0/26
General disorders Chest tightness	0.00% 0/2	14.3% 1/7 • Number of events 2	0.00% 0/19	0.00% 0/26
Nervous system disorders Somnolence	0.00% 0/2	0.00% 0/7	5.3% 1/19 • Number of events 1	3.8% 1/26 • Number of events 1

Additional Information

Karen L Miller, PhD

Gilead Sciences, Inc.

Phone: 650-524-3892

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place