Trial Outcomes & Findings for (ARTEMIS-IPF) Randomized, Placebo-Controlled Study to Evaluate Safety and Effectiveness of Ambrisentan in IPF (NCT NCT00768300)
NCT ID: NCT00768300
Last Updated: 2014-04-08
Results Overview
The median time to death or disease progression was based on Kaplan-Meier (KM) estimates of pooling over strata, and was defined as the first occurrence of any of the following: * Either 1) a decrease of ≥ 10% in FVC (L) and a decrease of ≥ 5% in diffuse lung capacity for carbon monoxide (DLCO) (ml/min/mmHg), or 2) a decrease of ≥ 5% in FVC (L) and a decrease of ≥ 15% in DLCO (ml/min/mmHg); deterioration in FVC and DLCO must be confirmed at the subsequent visit within 28 (± 14) days * Respiratory hospitalization (hospitalization involving worsening of, or deterioration in respiratory symptoms, gas exchange/hypoxemia, or radiographic findings on chest x-ray or high-resolution computerised tomography (HRCT) scan * All-cause mortality
Recruitment status
TERMINATED
Study phase
PHASE3
Target enrollment
494 participants
Primary outcome timeframe
Up to 48 months
Results posted on
2014-04-08
Participant Flow
Participants were enrolled in a total of 136 study sites in North and South America, Europe, and Australia. The first participant was screened on 10 December 2008. The last participant observation was on 28 February 2011.
494 participants were randomized; 492 participants were treated, and comprise the Safety Analysis Set and the Full Analysis Set.
Participant milestones
| Measure |
Ambrisentan
Ambrisentan (5 mg or 10 mg tablet) administered orally once daily
|
Placebo
Placebo to match ambrisentan administered orally once daily
|
|---|---|---|
|
Overall Study
STARTED
|
330
|
164
|
|
Overall Study
Randomized and Treated
|
329
|
163
|
|
Overall Study
COMPLETED
|
1
|
1
|
|
Overall Study
NOT COMPLETED
|
329
|
163
|
Reasons for withdrawal
| Measure |
Ambrisentan
Ambrisentan (5 mg or 10 mg tablet) administered orally once daily
|
Placebo
Placebo to match ambrisentan administered orally once daily
|
|---|---|---|
|
Overall Study
Randomized but not treated
|
1
|
1
|
|
Overall Study
Adverse Event
|
10
|
2
|
|
Overall Study
Protocol Violation
|
6
|
1
|
|
Overall Study
Withdrawal by Subject
|
13
|
7
|
|
Overall Study
Physician Decision
|
2
|
3
|
|
Overall Study
Study discontinued by Sponsor
|
271
|
140
|
|
Overall Study
Death
|
21
|
5
|
|
Overall Study
Subject moved to pursue lung transplant
|
1
|
1
|
|
Overall Study
Screen failure following randomization
|
1
|
0
|
|
Overall Study
Received lung transplant
|
1
|
1
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
|
Overall Study
Began prohibited concomitant medication
|
0
|
1
|
|
Overall Study
Treated but never dosed with Study drug
|
1
|
0
|
|
Overall Study
Missing data
|
1
|
0
|
Baseline Characteristics
(ARTEMIS-IPF) Randomized, Placebo-Controlled Study to Evaluate Safety and Effectiveness of Ambrisentan in IPF
Baseline characteristics by cohort
| Measure |
Ambrisentan
n=329 Participants
Ambrisentan (5 mg or 10 mg tablet) administered orally once daily
|
Placebo
n=163 Participants
Placebo to match ambrisentan administered orally once daily
|
Total
n=492 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
65.8 years
STANDARD_DEVIATION 7.4 • n=5 Participants
|
66.1 years
STANDARD_DEVIATION 7.1 • n=7 Participants
|
65.9 years
STANDARD_DEVIATION 7.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
85 Participants
n=5 Participants
|
52 Participants
n=7 Participants
|
137 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
244 Participants
n=5 Participants
|
111 Participants
n=7 Participants
|
355 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African Heritage
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
293 participants
n=5 Participants
|
145 participants
n=7 Participants
|
438 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
4 participants
n=5 Participants
|
1 participants
n=7 Participants
|
5 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaskan Native
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
27 participants
n=5 Participants
|
16 participants
n=7 Participants
|
43 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not Permitted
|
3 participants
n=5 Participants
|
0 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
141 participants
n=5 Participants
|
62 participants
n=7 Participants
|
203 participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
25 participants
n=5 Participants
|
14 participants
n=7 Participants
|
39 participants
n=5 Participants
|
|
Region of Enrollment
Australia
|
22 participants
n=5 Participants
|
12 participants
n=7 Participants
|
34 participants
n=5 Participants
|
|
Region of Enrollment
France
|
21 participants
n=5 Participants
|
10 participants
n=7 Participants
|
31 participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
17 participants
n=5 Participants
|
9 participants
n=7 Participants
|
26 participants
n=5 Participants
|
|
Region of Enrollment
Brazil
|
18 participants
n=5 Participants
|
6 participants
n=7 Participants
|
24 participants
n=5 Participants
|
|
Region of Enrollment
Peru
|
12 participants
n=5 Participants
|
6 participants
n=7 Participants
|
18 participants
n=5 Participants
|
|
Region of Enrollment
Czech Republic
|
10 participants
n=5 Participants
|
6 participants
n=7 Participants
|
16 participants
n=5 Participants
|
|
Region of Enrollment
Israel
|
8 participants
n=5 Participants
|
7 participants
n=7 Participants
|
15 participants
n=5 Participants
|
|
Region of Enrollment
Italy
|
11 participants
n=5 Participants
|
3 participants
n=7 Participants
|
14 participants
n=5 Participants
|
|
Region of Enrollment
Belgium
|
7 participants
n=5 Participants
|
6 participants
n=7 Participants
|
13 participants
n=5 Participants
|
|
Region of Enrollment
Colombia
|
8 participants
n=5 Participants
|
3 participants
n=7 Participants
|
11 participants
n=5 Participants
|
|
Region of Enrollment
Mexico
|
5 participants
n=5 Participants
|
4 participants
n=7 Participants
|
9 participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
3 participants
n=5 Participants
|
6 participants
n=7 Participants
|
9 participants
n=5 Participants
|
|
Region of Enrollment
Spain
|
7 participants
n=5 Participants
|
1 participants
n=7 Participants
|
8 participants
n=5 Participants
|
|
Region of Enrollment
Poland
|
3 participants
n=5 Participants
|
3 participants
n=7 Participants
|
6 participants
n=5 Participants
|
|
Region of Enrollment
Switzerland
|
5 participants
n=5 Participants
|
1 participants
n=7 Participants
|
6 participants
n=5 Participants
|
|
Region of Enrollment
Austria
|
2 participants
n=5 Participants
|
2 participants
n=7 Participants
|
4 participants
n=5 Participants
|
|
Region of Enrollment
Chile
|
3 participants
n=5 Participants
|
1 participants
n=7 Participants
|
4 participants
n=5 Participants
|
|
Region of Enrollment
Argentina
|
1 participants
n=5 Participants
|
2 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Region of Enrollment
Ireland
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Baseline Pulmonary Hypertension (PH) per interactive voice response system (IVRS)
No
|
293 participants
n=5 Participants
|
145 participants
n=7 Participants
|
438 participants
n=5 Participants
|
|
Baseline Pulmonary Hypertension (PH) per interactive voice response system (IVRS)
Yes
|
36 participants
n=5 Participants
|
18 participants
n=7 Participants
|
54 participants
n=5 Participants
|
|
Smoking status
Never
|
105 participants
n=5 Participants
|
53 participants
n=7 Participants
|
158 participants
n=5 Participants
|
|
Smoking status
Current
|
7 participants
n=5 Participants
|
5 participants
n=7 Participants
|
12 participants
n=5 Participants
|
|
Smoking status
Former
|
217 participants
n=5 Participants
|
104 participants
n=7 Participants
|
321 participants
n=5 Participants
|
|
Surgical lung biopsy (SLB) to Confirm Diagnosis of IPF (per IVRS)
No
|
175 participants
n=5 Participants
|
87 participants
n=7 Participants
|
262 participants
n=5 Participants
|
|
Surgical lung biopsy (SLB) to Confirm Diagnosis of IPF (per IVRS)
Yes
|
154 participants
n=5 Participants
|
76 participants
n=7 Participants
|
230 participants
n=5 Participants
|
|
Disease duration
|
1.13 years
STANDARD_DEVIATION 1.39 • n=5 Participants
|
0.91 years
STANDARD_DEVIATION 1.19 • n=7 Participants
|
1.06 years
STANDARD_DEVIATION 1.33 • n=5 Participants
|
|
Forced vital capacity (FVC) percent predicted
|
68.74 percentage of FVC % predicted
STANDARD_DEVIATION 13.12 • n=5 Participants
|
69.86 percentage of FVC % predicted
STANDARD_DEVIATION 13.75 • n=7 Participants
|
69.11 percentage of FVC % predicted
STANDARD_DEVIATION 13.33 • n=5 Participants
|
|
Six mile walk test (6MWT)
|
410.4 meters
STANDARD_DEVIATION 118.7 • n=5 Participants
|
420.5 meters
STANDARD_DEVIATION 121.4 • n=7 Participants
|
413.7 meters
STANDARD_DEVIATION 119.6 • n=5 Participants
|
|
Hemoglobin Adjusted Diffusing lung capacity for carbon monoxide (DLCO) percent predicted
|
42.04 percentage of DLCO % predicted
STANDARD_DEVIATION 13.77 • n=5 Participants
|
45.57 percentage of DLCO % predicted
STANDARD_DEVIATION 13.25 • n=7 Participants
|
43.20 percentage of DLCO % predicted
STANDARD_DEVIATION 13.69 • n=5 Participants
|
|
Prior IPF Medications
No
|
205 participants
n=5 Participants
|
97 participants
n=7 Participants
|
302 participants
n=5 Participants
|
|
Prior IPF Medications
Yes
|
124 participants
n=5 Participants
|
65 participants
n=7 Participants
|
189 participants
n=5 Participants
|
|
N-acetylcysteine (NAC) Use
No
|
310 participants
n=5 Participants
|
153 participants
n=7 Participants
|
463 participants
n=5 Participants
|
|
N-acetylcysteine (NAC) Use
Yes
|
19 participants
n=5 Participants
|
8 participants
n=7 Participants
|
27 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 48 monthsPopulation: Full Analysis Set: participants who were randomized and treated
The median time to death or disease progression was based on Kaplan-Meier (KM) estimates of pooling over strata, and was defined as the first occurrence of any of the following: * Either 1) a decrease of ≥ 10% in FVC (L) and a decrease of ≥ 5% in diffuse lung capacity for carbon monoxide (DLCO) (ml/min/mmHg), or 2) a decrease of ≥ 5% in FVC (L) and a decrease of ≥ 15% in DLCO (ml/min/mmHg); deterioration in FVC and DLCO must be confirmed at the subsequent visit within 28 (± 14) days * Respiratory hospitalization (hospitalization involving worsening of, or deterioration in respiratory symptoms, gas exchange/hypoxemia, or radiographic findings on chest x-ray or high-resolution computerised tomography (HRCT) scan * All-cause mortality
Outcome measures
| Measure |
Ambrisentan
n=329 Participants
Ambrisentan (5 mg or 10 mg tablet) administered orally once daily
|
Placebo
n=163 Participants
Placebo to match ambrisentan administered orally once daily
|
|---|---|---|
|
Time to Death or Disease (IPF) Progression.
|
84.14 weeks
Interval 36.0 to
Insufficient data for estimation due to study termination
|
NA weeks
Interval 60.0 to
Insufficient data for estimation due to study termination
|
SECONDARY outcome
Timeframe: Baseline and Week 48Population: Full Analysis Set
The proportion of participants with no disease progression or death is presented as a percentage using a Kaplan-Meier (KM) estimate of survival or not experiencing disease progression.
Outcome measures
| Measure |
Ambrisentan
n=329 Participants
Ambrisentan (5 mg or 10 mg tablet) administered orally once daily
|
Placebo
n=163 Participants
Placebo to match ambrisentan administered orally once daily
|
|---|---|---|
|
Proportion of Participants With No Disease Progression or Death at 48 Weeks
|
65 percentage of participants
|
80 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline and Week 48Population: Participants in the Full Analysis Set with evaluable change data were analyzed.
FVC is defined as the volume of air (liters) that can forcibly be blown out after taking a full breath. FVC % predicted is defined as FVC % of the participant divided by the average FVC % in the population for any person of similar age, sex, and body composition.
Outcome measures
| Measure |
Ambrisentan
n=163 Participants
Ambrisentan (5 mg or 10 mg tablet) administered orally once daily
|
Placebo
n=80 Participants
Placebo to match ambrisentan administered orally once daily
|
|---|---|---|
|
Change in FVC % Predicted at Week 48
|
-10.24 percent change in FVC % predicted
Standard Deviation 25.95
|
-5.28 percent change in FVC % predicted
Standard Deviation 15.68
|
SECONDARY outcome
Timeframe: Baseline and Week 48Population: Participants in the Full Analysis Set with evaluable change data were analyzed.
DLCO is the extent to which oxygen passes from the air sacs of the lungs into the blood. DLCO % predicted is defined as DLCO % of the participant divided by the average DLCO % in the population for any person of similar age, sex and body composition.
Outcome measures
| Measure |
Ambrisentan
n=163 Participants
Ambrisentan (5 mg or 10 mg tablet) administered orally once daily
|
Placebo
n=80 Participants
Placebo to match ambrisentan administered orally once daily
|
|---|---|---|
|
Change in DLCO % Predicted at Week 48
|
-2.68 percent change in DLCO % predicted
Standard Deviation 27.60
|
-11.28 percent change in DLCO % predicted
Standard Deviation 32.06
|
SECONDARY outcome
Timeframe: Baseline and Week 48Population: Participants in the Full Analysis Set with evaluable change data were analyzed.
The 6MWT is a measure of exercise tolerance, and measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface.
Outcome measures
| Measure |
Ambrisentan
n=162 Participants
Ambrisentan (5 mg or 10 mg tablet) administered orally once daily
|
Placebo
n=80 Participants
Placebo to match ambrisentan administered orally once daily
|
|---|---|---|
|
Change in 6MWT at Week 48
|
-52.5 meters
Standard Deviation 148.7
|
-10.6 meters
Standard Deviation 89.8
|
SECONDARY outcome
Timeframe: Baseline and Week 48Population: Participants in the Full Analysis Set with evaluable change data were analyzed.
The range of each health domain score is 0-100, with 0 indicating a poorer health state and 100 indicating a better health state. An increase in score indicates an improvement in health state.
Outcome measures
| Measure |
Ambrisentan
n=158 Participants
Ambrisentan (5 mg or 10 mg tablet) administered orally once daily
|
Placebo
n=78 Participants
Placebo to match ambrisentan administered orally once daily
|
|---|---|---|
|
Change in Quality of Life (QOL) Score at Week 48 as Assessed by the Short-Form 36® (SF-36)
Physical function
|
-1.65 units on a scale
Standard Deviation 10.86
|
-2.60 units on a scale
Standard Deviation 7.25
|
|
Change in Quality of Life (QOL) Score at Week 48 as Assessed by the Short-Form 36® (SF-36)
General Health
|
-2.81 units on a scale
Standard Deviation 9.77
|
-1.95 units on a scale
Standard Deviation 8.63
|
|
Change in Quality of Life (QOL) Score at Week 48 as Assessed by the Short-Form 36® (SF-36)
Vitality
|
-1.67 units on a scale
Standard Deviation 12.67
|
-0.12 units on a scale
Standard Deviation 7.69
|
SECONDARY outcome
Timeframe: Baseline and Week 48Population: Participants in the Full Analysis Set with evaluable change data were analyzed.
The SGRQ is designed to measure impact on overall health, daily life, and perceived well-being in participants with obstructive airways disease. The range of each score is 0-100, with 0 indicating fewer limitations and 100 indicating more limitations; an increase in score indicates an increase in limitations.
Outcome measures
| Measure |
Ambrisentan
n=159 Participants
Ambrisentan (5 mg or 10 mg tablet) administered orally once daily
|
Placebo
n=78 Participants
Placebo to match ambrisentan administered orally once daily
|
|---|---|---|
|
Change in Quality of Life (QOL) Score at Week 48 as Assessed by the St. George's Respiratory Questionnaire (SGRQ)
Total Score
|
4.70 units on a scale
Standard Deviation 19.92
|
3.04 units on a scale
Standard Deviation 13.80
|
|
Change in Quality of Life (QOL) Score at Week 48 as Assessed by the St. George's Respiratory Questionnaire (SGRQ)
Symptoms Score
|
3.30 units on a scale
Standard Deviation 22.11
|
2.84 units on a scale
Standard Deviation 20.43
|
|
Change in Quality of Life (QOL) Score at Week 48 as Assessed by the St. George's Respiratory Questionnaire (SGRQ)
Activity Score
|
5.54 units on a scale
Standard Deviation 19.38
|
2.05 units on a scale
Standard Deviation 16.47
|
|
Change in Quality of Life (QOL) Score at Week 48 as Assessed by the St. George's Respiratory Questionnaire (SGRQ)
Impacts Score
|
4.68 units on a scale
Standard Deviation 24.07
|
3.09 units on a scale
Standard Deviation 15.80
|
SECONDARY outcome
Timeframe: Baseline and Week 48Population: Participants in the Full Analysis Set with evaluable change data were analyzed.
The transitional focal score (-9 to 9) is the sum of relative change from baseline for the Functional Impairment, Magnitude of Task, and Magnitude of Effort scores (each -3 to 3 scale). A TDI score of -9 represents a maximum degradation of all three tests; a score of 9 represents a maximum improvement of all three tests.
Outcome measures
| Measure |
Ambrisentan
n=163 Participants
Ambrisentan (5 mg or 10 mg tablet) administered orally once daily
|
Placebo
n=80 Participants
Placebo to match ambrisentan administered orally once daily
|
|---|---|---|
|
Change in Dyspnea Score at Week 48 as Assessed by the Transitional Dyspnea Index (TDI)
|
-1.23 units on a scale
Standard Deviation 3.74
|
-0.84 units on a scale
Standard Deviation 2.99
|
SECONDARY outcome
Timeframe: Up to 48 weeksPopulation: Participants in the Full Analysis Set without PH at baseline were analyzed.
The percentage of participants known to have developed pulmonary hypertension on study documented by right heart catheterization (RHC) was analyzed. RHC was done at baseline and 48 weeks, or at the early termination visit.
Outcome measures
| Measure |
Ambrisentan
n=293 Participants
Ambrisentan (5 mg or 10 mg tablet) administered orally once daily
|
Placebo
n=145 Participants
Placebo to match ambrisentan administered orally once daily
|
|---|---|---|
|
Percentage of Participants Who Developed PH on Study
|
0.7 percentage of participants
|
2.1 percentage of participants
|
Adverse Events
Ambrisentan
Serious events: 73 serious events
Other events: 227 other events
Deaths: 0 deaths
Placebo
Serious events: 25 serious events
Other events: 104 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Ambrisentan
n=329 participants at risk
Ambrisentan (5 mg or 10 mg tablet) administered orally once daily
|
Placebo
n=163 participants at risk
Placebo to match ambrisentan administered orally once daily
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
Pain in jaw
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.00%
0/329 • Up to 48 months
|
0.61%
1/163 • Up to 48 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer metastatic
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma
|
0.00%
0/329 • Up to 48 months
|
0.61%
1/163 • Up to 48 months
|
|
Nervous system disorders
Headache
|
1.5%
5/329 • Up to 48 months
|
0.61%
1/163 • Up to 48 months
|
|
Nervous system disorders
Cerebrovascular accident
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Nervous system disorders
Ischaemic stroke
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Nervous system disorders
Syncope
|
0.30%
1/329 • Up to 48 months
|
0.61%
1/163 • Up to 48 months
|
|
Nervous system disorders
Somnolence
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Nervous system disorders
Carotid artery stenosis
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Nervous system disorders
Coma
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Nervous system disorders
Grand mal convulsion
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Nervous system disorders
Nerve compression
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Nervous system disorders
Hypoaesthesia
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Psychiatric disorders
Anxiety
|
0.91%
3/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Psychiatric disorders
Delirium
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Blood and lymphatic system disorders
Anaemia
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Cardiac disorders
Acute myocardial infarction
|
0.91%
3/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Cardiac disorders
Angina pectoris
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Cardiac disorders
Angina unstable
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Cardiac disorders
Atrial fibrillation
|
0.61%
2/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Cardiac disorders
Sinus tachycardia
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Cardiac disorders
Cardiac failure congestive
|
1.2%
4/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Cardiac disorders
Cardiomegaly
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Cardiac disorders
Dilatation atrial
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Cardiac disorders
Tricuspid valve incompetence
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Cardiac disorders
Palpitations
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Cardiac disorders
Extrasystoles
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Cardiac disorders
Electromechanical dissociation
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Ear and labyrinth disorders
Acute vestibular syndrome
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Eye disorders
Cataract
|
0.00%
0/329 • Up to 48 months
|
0.61%
1/163 • Up to 48 months
|
|
Eye disorders
Choroidal haemorrage
|
0.00%
0/329 • Up to 48 months
|
0.61%
1/163 • Up to 48 months
|
|
Eye disorders
Visual impairment
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Gastrointestinal disorders
Constipation
|
1.2%
4/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.61%
2/329 • Up to 48 months
|
1.2%
2/163 • Up to 48 months
|
|
Gastrointestinal disorders
Diarrhoea
|
0.30%
1/329 • Up to 48 months
|
0.61%
1/163 • Up to 48 months
|
|
Gastrointestinal disorders
Colitis
|
0.30%
1/329 • Up to 48 months
|
0.61%
1/163 • Up to 48 months
|
|
Gastrointestinal disorders
Nausea
|
0.61%
2/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Gastrointestinal disorders
Colonic polyp
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/329 • Up to 48 months
|
0.61%
1/163 • Up to 48 months
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Gastrointestinal disorders
Aptyalism
|
0.00%
0/329 • Up to 48 months
|
0.61%
1/163 • Up to 48 months
|
|
General disorders
Oedema peripheral
|
1.2%
4/329 • Up to 48 months
|
0.61%
1/163 • Up to 48 months
|
|
General disorders
Oedema
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
General disorders
Chest pain
|
0.61%
2/329 • Up to 48 months
|
0.61%
1/163 • Up to 48 months
|
|
General disorders
Pain
|
0.61%
2/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
General disorders
Pyrexia
|
0.61%
2/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
General disorders
Fatigue
|
0.61%
2/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
General disorders
Catheter site haemorrhage
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
General disorders
Influenza like illness
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
General disorders
Hyperthermia
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Infections and infestations
Nasopharyngitis
|
0.61%
2/329 • Up to 48 months
|
1.2%
2/163 • Up to 48 months
|
|
Infections and infestations
Upper respiratory tract infection
|
0.30%
1/329 • Up to 48 months
|
0.61%
1/163 • Up to 48 months
|
|
Infections and infestations
Pharyngitis
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Infections and infestations
Sinusitis
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Infections and infestations
Pneumonia
|
2.7%
9/329 • Up to 48 months
|
1.2%
2/163 • Up to 48 months
|
|
Infections and infestations
Bronchitis
|
0.91%
3/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Infections and infestations
Lobar pneumonia
|
0.30%
1/329 • Up to 48 months
|
0.61%
1/163 • Up to 48 months
|
|
Infections and infestations
Bronchopneumonia
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Infections and infestations
Lower respiratory tract infection
|
0.00%
0/329 • Up to 48 months
|
0.61%
1/163 • Up to 48 months
|
|
Infections and infestations
Respiratory tract infection
|
0.61%
2/329 • Up to 48 months
|
0.61%
1/163 • Up to 48 months
|
|
Infections and infestations
Infection
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Infections and infestations
Cellulitis
|
0.61%
2/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Infections and infestations
Endocarditis bacterial
|
0.30%
1/329 • Up to 48 months
|
0.61%
1/163 • Up to 48 months
|
|
Infections and infestations
Sepsis
|
0.61%
2/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Infections and infestations
Bacteraemia
|
0.00%
0/329 • Up to 48 months
|
0.61%
1/163 • Up to 48 months
|
|
Infections and infestations
Appendicitis
|
0.00%
0/329 • Up to 48 months
|
0.61%
1/163 • Up to 48 months
|
|
Infections and infestations
Influenza
|
0.61%
2/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Infections and infestations
Urinary tract infection
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Infections and infestations
Oral candidiasis
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Infections and infestations
Conjunctivitis viral
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/329 • Up to 48 months
|
1.2%
2/163 • Up to 48 months
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/329 • Up to 48 months
|
0.61%
1/163 • Up to 48 months
|
|
Investigations
Hepatic enzyme increased
|
0.00%
0/329 • Up to 48 months
|
0.61%
1/163 • Up to 48 months
|
|
Investigations
Electrocardiogram ST-T segment abnormal
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Investigations
Electrocardiogram T wave inversion
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Investigations
Computerised tomogram thorax abnormal
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
1.2%
4/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.61%
2/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.61%
2/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Metabolism and nutrition disorders
Anorexia
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Metabolism and nutrition disorders
Diabetic ketoacidosis
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.61%
2/329 • Up to 48 months
|
0.61%
1/163 • Up to 48 months
|
|
Musculoskeletal and connective tissue disorders
Clubbing
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
0.00%
0/329 • Up to 48 months
|
0.61%
1/163 • Up to 48 months
|
|
Psychiatric disorders
Insomnia
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Renal and urinary disorders
Renal failure acute
|
0.61%
2/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Renal and urinary disorders
Renal failure
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Reproductive system and breast disorders
Prostatomegaly
|
0.00%
0/329 • Up to 48 months
|
0.61%
1/163 • Up to 48 months
|
|
Reproductive system and breast disorders
Benign prostatic hyperplasia
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Respiratory, thoracic and mediastinal disorders
Idiopathic pulmonary fibrosis
|
6.1%
20/329 • Up to 48 months
|
2.5%
4/163 • Up to 48 months
|
|
Respiratory, thoracic and mediastinal disorders
Emphysema
|
0.61%
2/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary fibrosis
|
0.61%
2/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary alveolar haemorrhage
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
5.2%
17/329 • Up to 48 months
|
1.2%
2/163 • Up to 48 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory arrest
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
1.2%
4/329 • Up to 48 months
|
0.61%
1/163 • Up to 48 months
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
1.2%
4/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
1.5%
5/329 • Up to 48 months
|
0.61%
1/163 • Up to 48 months
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
1.2%
4/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
1.2%
4/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Respiratory, thoracic and mediastinal disorders
Choking
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/329 • Up to 48 months
|
0.61%
1/163 • Up to 48 months
|
|
Respiratory, thoracic and mediastinal disorders
Pleurisy
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/329 • Up to 48 months
|
0.61%
1/163 • Up to 48 months
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/329 • Up to 48 months
|
0.61%
1/163 • Up to 48 months
|
|
Vascular disorders
Hypotension
|
1.2%
4/329 • Up to 48 months
|
0.61%
1/163 • Up to 48 months
|
|
Vascular disorders
Hypertension
|
0.91%
3/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Vascular disorders
Subclavian vein thrombosis
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Vascular disorders
Flushing
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Vascular disorders
Hot flush
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Cardiac disorders
Cardiac ventricular disorder
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
|
Vascular disorders
Peripheral ischaemia
|
0.30%
1/329 • Up to 48 months
|
0.00%
0/163 • Up to 48 months
|
Other adverse events
| Measure |
Ambrisentan
n=329 participants at risk
Ambrisentan (5 mg or 10 mg tablet) administered orally once daily
|
Placebo
n=163 participants at risk
Placebo to match ambrisentan administered orally once daily
|
|---|---|---|
|
General disorders
Oedema peripheral
|
22.2%
73/329 • Up to 48 months
|
8.6%
14/163 • Up to 48 months
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract infection
|
14.3%
47/329 • Up to 48 months
|
11.0%
18/163 • Up to 48 months
|
|
Nervous system disorders
Headache
|
14.3%
47/329 • Up to 48 months
|
10.4%
17/163 • Up to 48 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
12.2%
40/329 • Up to 48 months
|
6.7%
11/163 • Up to 48 months
|
|
Infections and infestations
Nasopharyngitis
|
11.2%
37/329 • Up to 48 months
|
11.0%
18/163 • Up to 48 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
10.3%
34/329 • Up to 48 months
|
12.3%
20/163 • Up to 48 months
|
|
Respiratory, thoracic and mediastinal disorders
Idiopathic pulmonary fibrosis
|
5.8%
19/329 • Up to 48 months
|
1.2%
2/163 • Up to 48 months
|
|
Infections and infestations
Bronchitis
|
7.0%
23/329 • Up to 48 months
|
9.2%
15/163 • Up to 48 months
|
|
General disorders
Fatigue
|
6.7%
22/329 • Up to 48 months
|
8.6%
14/163 • Up to 48 months
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
8.2%
27/329 • Up to 48 months
|
3.7%
6/163 • Up to 48 months
|
|
Gastrointestinal disorders
Constipation
|
5.8%
19/329 • Up to 48 months
|
6.1%
10/163 • Up to 48 months
|
|
Gastrointestinal disorders
Diarrhoea
|
6.1%
20/329 • Up to 48 months
|
4.9%
8/163 • Up to 48 months
|
|
Infections and infestations
Sinusitis
|
6.1%
20/329 • Up to 48 months
|
3.7%
6/163 • Up to 48 months
|
|
Infections and infestations
Respiratory tract infection
|
2.7%
9/329 • Up to 48 months
|
7.4%
12/163 • Up to 48 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.5%
18/329 • Up to 48 months
|
3.1%
5/163 • Up to 48 months
|
|
Nervous system disorders
Dizziness
|
6.1%
20/329 • Up to 48 months
|
1.2%
2/163 • Up to 48 months
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
2.4%
8/329 • Up to 48 months
|
5.5%
9/163 • Up to 48 months
|
|
Gastrointestinal disorders
Nausea
|
4.6%
15/329 • Up to 48 months
|
5.5%
9/163 • Up to 48 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: * The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or * The study has been completed at all study sites for at least 2 years
- Publication restrictions are in place
Restriction type: OTHER