(ARTEMIS-IPF) Randomized, Placebo-Controlled Study to Evaluate Safety and Effectiveness of Ambrisentan in IPF (ARTEMIS-IPF)

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ClinicalTrials.gov Identifier: NCT00768300

Recruitment Status : Terminated (Lack of efficacy)

First Posted : October 8, 2008

Results First Posted : April 8, 2014

Last Update Posted : April 8, 2014

Sponsor:

Information provided by (Responsible Party):

Gilead Sciences

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
Condition	Idiopathic Pulmonary Fibrosis
Interventions	Drug: Ambrisentan Drug: Placebo
Enrollment	494

Participant Flow

Recruitment Details	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.
Pre-assignment Details	494 participants were randomized; 492 participants were treated, and comprise the Safety Analysis Set and the Full Analysis Set.


Arm/Group Title	Ambrisentan	Placebo
Arm/Group Description	Ambrisentan (5 mg or 10 mg tablet) ...	Placebo to match ambrisentan admini...
Arm/Group Description	Ambrisentan (5 mg or 10 mg tablet) administered orally once daily	Placebo to match ambrisentan administered orally once daily
Period Title: Overall Study
Started	330	164
Randomized and Treated	329	163
Completed	1	1
Not Completed	329	163
Reason Not Completed
Randomized but not treated	1	1
Adverse Event	10	2
Protocol Violation	6	1
Withdrawal by Subject	13	7
Physician Decision	2	3
Study discontinued by Sponsor	271	140
Death	21	5
Subject moved to pursue lung transplant	1	1
Screen failure following randomization	1	0
Received lung transplant	1	1
Lost to Follow-up	0	1
Began prohibited concomitant medication	0	1
Treated but never dosed with Study drug	1	0
Missing data	1	0

Baseline Characteristics

Arm/Group Title		Ambrisentan	Placebo	Total
Arm/Group Description		Ambrisentan (5 mg or 10 mg tablet) ...	Placebo to match ambrisentan admini...	Total of all reporting groups
Arm/Group Description		Ambrisentan (5 mg or 10 mg tablet) administered orally once daily	Placebo to match ambrisentan administered orally once daily	Total of all reporting groups
Overall Number of Baseline Participants		329	163	492
Baseline Analysis Population Description		...
Baseline Analysis Population Description		Full Analysis Set: participants who were randomized and treated
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	329 participants	163 participants	492 participants
		65.8 (7.4)	66.1 (7.1)	65.9 (7.3)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	329 participants	163 participants	492 participants
	Female	85 25.8%	52 31.9%	137 27.8%
	Male	244 74.2%	111 68.1%	355 72.2%
Race/Ethnicity, Customized Measure Type: Number Unit of measure: Participants	Number Analyzed	329 participants	163 participants	492 participants
Black or African Heritage		1	0	1
White		293	145	438
Asian		4	1	5
American Indian or Alaskan Native		1	1	2
Other		27	16	43
Not Permitted		3	0	3
Region of Enrollment ^[1] Measure Type: Number Unit of measure: Participants	Number Analyzed	329 participants	163 participants	492 participants
United States		141	62	203
Canada		25	14	39
Australia		22	12	34
France		21	10	31
Germany		17	9	26
Brazil		18	6	24
Peru		12	6	18
Czech Republic		10	6	16
Israel		8	7	15
Italy		11	3	14
Belgium		7	6	13
Colombia		8	3	11
Mexico		5	4	9
United Kingdom		3	6	9
Spain		7	1	8
Poland		3	3	6
Switzerland		5	1	6
Austria		2	2	4
Chile		3	1	4
Argentina		1	2	3
Ireland		1	0	1
		[1] Measure Description: All participants who were randomized are presented in Region of Enrollment (ambrisentan = 330; placebo = 164)
Baseline Pulmonary Hypertension (PH) per interactive voice response system (IVRS) Measure Type: Number Unit of measure: Participants	Number Analyzed	329 participants	163 participants	492 participants
No		293	145	438
Yes		36	18	54
Smoking status ^[1] Measure Type: Number Unit of measure: Participants	Number Analyzed	329 participants	163 participants	492 participants
Never		105	53	158
Current		7	5	12
Former		217	104	321
		[1] Measure Description: Smoking status data is missing for one participant randomized to placebo.
Surgical lung biopsy (SLB) to Confirm Diagnosis of IPF (per IVRS) Measure Type: Number Unit of measure: Participants	Number Analyzed	329 participants	163 participants	492 participants
No		175	87	262
Yes		154	76	230
Disease duration Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	329 participants	163 participants	492 participants
		1.13 (1.39)	0.91 (1.19)	1.06 (1.33)
Forced vital capacity (FVC) percent predicted Least Squares Mean (Standard Deviation) Unit of measure: Percentage of FVC % predicted
	Number Analyzed	329 participants	163 participants	492 participants
		68.74 (13.12)	69.86 (13.75)	69.11 (13.33)
Six mile walk test (6MWT) Mean (Standard Deviation) Unit of measure: Meters
	Number Analyzed	329 participants	163 participants	492 participants
		410.4 (118.7)	420.5 (121.4)	413.7 (119.6)
Hemoglobin Adjusted Diffusing lung capacity for carbon monoxide (DLCO) percent predicted Least Squares Mean (Standard Deviation) Unit of measure: Percentage of DLCO % predicted
	Number Analyzed	329 participants	163 participants	492 participants
		42.04 (13.77)	45.57 (13.25)	43.20 (13.69)
Prior IPF Medications ^[1] Measure Type: Number Unit of measure: Participants	Number Analyzed	329 participants	163 participants	492 participants
No		205	97	302
Yes		124	65	189
		[1] Measure Description: Prior IPF Medications data is missing for one participant randomized to placebo.
N-acetylcysteine (NAC) Use ^[1] Measure Type: Number Unit of measure: Participants	Number Analyzed	329 participants	163 participants	492 participants
No		310	153	463
Yes		19	8	27
		[1] Measure Description: NAC is a therapy commonly used in the treatment of IPF. NAC use data is missing for two participants randomized to placebo.

Outcome Measures

1.Primary Outcome


Title	Time to Death or Disease (IPF) Progression.
Description	The median time to death or disease progression was based on Kaplan-Me...
Description	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
Time Frame	Up to 48 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set: participants who were randomized and treated


Arm/Group Title	Ambrisentan	Placebo
Arm/Group Description:	Ambrisentan (5 mg or 10 mg tablet) ...	Placebo to match ambrisentan admini...
Arm/Group Description:	Ambrisentan (5 mg or 10 mg tablet) administered orally once daily	Placebo to match ambrisentan administered orally once daily
Overall Number of Participants Analyzed	329	163
Median (Inter-Quartile Range) Unit of Measure: weeks
	84.14 ^[1] (36.00 to NA)	NA ^[1] (60.00 to NA)

[1]

Insufficient data for estimation due to study termination

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ambrisentan, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.010
	Comments	P-value was based on a stratified log-rank test with strata of baseline presence of pulmonary hypertension and whether a surgical lung biopsy was performed with definite or probable usual interstitial pneumonia (UIP) based on core pathology review.
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.74
	Confidence Interval	(2-Sided) 95% 1.14 to 2.66
	Estimation Comments	The hazard ratio was based on a stratified Cox proportional hazards model with strata of baseline presence of pulmonary hypertension and whether a surgical lung biopsy was performed with definite or probable UIP based on core pathology review.

2.Secondary Outcome


Title	Proportion of Participants With No Disease Progression or Death at 48 Weeks
Description	The proportion of participants with no disease progression or death is...
Description	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.
Time Frame	Baseline and Week 48

Outcome Measure Data

Analysis Population Description

Full Analysis Set


Arm/Group Title	Ambrisentan	Placebo
Arm/Group Description:	Ambrisentan (5 mg or 10 mg tablet) ...	Placebo to match ambrisentan admini...
Arm/Group Description:	Ambrisentan (5 mg or 10 mg tablet) administered orally once daily	Placebo to match ambrisentan administered orally once daily
Overall Number of Participants Analyzed	329	163
Measure Type: Number Unit of Measure: percentage of participants
	65	80

3.Secondary Outcome


Title	Change in FVC % Predicted at Week 48
Description	FVC is defined as the volume of air (liters) that can forcibly be blow...
Description	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.
Time Frame	Baseline and Week 48

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set with evaluable change data were analyzed.


Arm/Group Title	Ambrisentan	Placebo
Arm/Group Description:	Ambrisentan (5 mg or 10 mg tablet) ...	Placebo to match ambrisentan admini...
Arm/Group Description:	Ambrisentan (5 mg or 10 mg tablet) administered orally once daily	Placebo to match ambrisentan administered orally once daily
Overall Number of Participants Analyzed	163	80
Mean (Standard Deviation) Unit of Measure: percent change in FVC % predicted
	-10.24 (25.95)	-5.28 (15.68)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ambrisentan, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.086
	Comments	P-value was calculated using the Van Elteren test with strata of baseline presence of PH and whether a SLB was performed with definite or probable UIP based on core pathology review.
	Method	Van Elteren test
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Point estimate
	Estimated Value	4.29
	Confidence Interval	(2-Sided) 95% -0.805 to 9.376
	Estimation Comments	The point estimate and 95% confidence interval (CI) were based on the Hodges-Lehmann Estimate of treatment effect for percent change from baseline.

4.Secondary Outcome


Title	Change in DLCO % Predicted at Week 48
Description	DLCO is the extent to which oxygen passes from the air sacs of the lun...
Description	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.
Time Frame	Baseline and Week 48

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set with evaluable change data were analyzed.


Arm/Group Title	Ambrisentan	Placebo
Arm/Group Description:	Ambrisentan (5 mg or 10 mg tablet) ...	Placebo to match ambrisentan admini...
Arm/Group Description:	Ambrisentan (5 mg or 10 mg tablet) administered orally once daily	Placebo to match ambrisentan administered orally once daily
Overall Number of Participants Analyzed	163	80
Mean (Standard Deviation) Unit of Measure: percent change in DLCO % predicted
	-2.68 (27.60)	-11.28 (32.06)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ambrisentan, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.250
	Comments	P-value was calculated using the Van Elteren test with strata of baseline presence of PH and whether a SLB was performed with definite or probable UIP based on core pathology review.
	Method	Van Elteren test
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Point estimate
	Estimated Value	2.85
	Confidence Interval	(2-Sided) 95% -2.20 to 7.90
	Estimation Comments	The point estimate and its 95% CI were based on the Hodges-Lehmann Estimate of treatment effect for percent change from baseline.

5.Secondary Outcome


Title	Change in 6MWT at Week 48
Description	The 6MWT is a measure of exercise tolerance, and measures the distance...
Description	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.
Time Frame	Baseline and Week 48

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set with evaluable change data were analyzed.


Arm/Group Title	Ambrisentan	Placebo
Arm/Group Description:	Ambrisentan (5 mg or 10 mg tablet) ...	Placebo to match ambrisentan admini...
Arm/Group Description:	Ambrisentan (5 mg or 10 mg tablet) administered orally once daily	Placebo to match ambrisentan administered orally once daily
Overall Number of Participants Analyzed	162	80
Mean (Standard Deviation) Unit of Measure: meters
	-52.5 (148.7)	-10.6 (89.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ambrisentan, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.150
	Comments	P-value was calculated using the Van Elteren test with strata of baseline presence of PH and whether a SLB was performed with definite or probable UIP based on core pathology review.
	Method	Van Elteren test
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Point estimate
	Estimated Value	16.00
	Confidence Interval	(2-Sided) 95% -5.00 to 37.00
	Estimation Comments	The point estimate and 95% CI were based on the Hodges-Lehmann Estimate of treatment effect for percent change from baseline.

6.Secondary Outcome


Title	Change in Quality of Life (QOL) Score at Week 48 as Assessed by the Short-Form 36® (SF-36)
Description	The range of each health domain score is 0-100, with 0 indicating a po...
Description	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.
Time Frame	Baseline and Week 48

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set with evaluable change data were analyzed.


Arm/Group Title	Ambrisentan	Placebo
Arm/Group Description:	Ambrisentan (5 mg or 10 mg tablet) ...	Placebo to match ambrisentan admini...
Arm/Group Description:	Ambrisentan (5 mg or 10 mg tablet) administered orally once daily	Placebo to match ambrisentan administered orally once daily
Overall Number of Participants Analyzed	158	78
Mean (Standard Deviation) Unit of Measure: units on a scale
Physical function	-1.65 (10.86)	-2.60 (7.25)
General Health	-2.81 (9.77)	-1.95 (8.63)
Vitality	-1.67 (12.67)	-0.12 (7.69)

7.Secondary Outcome


Title	Change in Quality of Life (QOL) Score at Week 48 as Assessed by the St. George's Respiratory Questionnaire (SGRQ)
Description	The SGRQ is designed to measure impact on overall health, daily life, ...
Description	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.
Time Frame	Baseline and Week 48

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set with evaluable change data were analyzed.


Arm/Group Title	Ambrisentan	Placebo
Arm/Group Description:	Ambrisentan (5 mg or 10 mg tablet) ...	Placebo to match ambrisentan admini...
Arm/Group Description:	Ambrisentan (5 mg or 10 mg tablet) administered orally once daily	Placebo to match ambrisentan administered orally once daily
Overall Number of Participants Analyzed	159	78
Mean (Standard Deviation) Unit of Measure: units on a scale
Symptoms Score	3.30 (22.11)	2.84 (20.43)
Activity Score	5.54 (19.38)	2.05 (16.47)
Impacts Score	4.68 (24.07)	3.09 (15.80)
Total Score	4.70 (19.92)	3.04 (13.80)

8.Secondary Outcome


Title	Change in Dyspnea Score at Week 48 as Assessed by the Transitional Dyspnea Index (TDI)
Description	The transitional focal score (-9 to 9) is the sum of relative change f...
Description	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.
Time Frame	Baseline and Week 48

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set with evaluable change data were analyzed.


Arm/Group Title	Ambrisentan	Placebo
Arm/Group Description:	Ambrisentan (5 mg or 10 mg tablet) ...	Placebo to match ambrisentan admini...
Arm/Group Description:	Ambrisentan (5 mg or 10 mg tablet) administered orally once daily	Placebo to match ambrisentan administered orally once daily
Overall Number of Participants Analyzed	163	80
Mean (Standard Deviation) Unit of Measure: units on a scale
	-1.23 (3.74)	-0.84 (2.99)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ambrisentan, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.793
	Comments	The p-value was based on a Wilcoxon rank sum test stratified by baseline pulmonary hypertension (Yes/No) and surgical lung biopsy was performed with definite or probable UIP based on core pathology review (Yes/No).
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Point estimate
	Estimated Value	0.50
	Confidence Interval	(2-Sided) 95% 0.00 to 1.00
	Estimation Comments	The point estimate and 95% confidence interval were based on the Hodges-Lehmann Estimate of treatment effect

9.Secondary Outcome


Title	Percentage of Participants Who Developed PH on Study
Description	The percentage of participants known to have developed pulmonary hyper...
Description	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.
Time Frame	Up to 48 weeks

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set without PH at baseline were analyzed.


Arm/Group Title	Ambrisentan	Placebo
Arm/Group Description:	Ambrisentan (5 mg or 10 mg tablet) ...	Placebo to match ambrisentan admini...
Arm/Group Description:	Ambrisentan (5 mg or 10 mg tablet) administered orally once daily	Placebo to match ambrisentan administered orally once daily
Overall Number of Participants Analyzed	293	145
Measure Type: Number Unit of Measure: percentage of participants
	0.7	2.1

Adverse Events

Time Frame	Up to 48 months
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Ambrisentan	Placebo
Arm/Group Description	Ambrisentan (5 mg or 10 mg tablet) ...	Placebo to match ambrisentan admini...
Arm/Group Description	Ambrisentan (5 mg or 10 mg tablet) administered orally once daily	Placebo to match ambrisentan administered orally once daily
All-Cause Mortality
	Ambrisentan	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events Serious Adverse Events
	Ambrisentan	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	73/329 (22.19%)	25/163 (15.34%)
Blood and lymphatic system disorders
Anaemia ^† 1	1/329 (0.30%)	0/163 (0.00%)
Cardiac disorders
Acute myocardial infarction ^† 1	3/329 (0.91%)	0/163 (0.00%)
Angina pectoris ^† 1	1/329 (0.30%)	0/163 (0.00%)
Angina unstable ^† 1	1/329 (0.30%)	0/163 (0.00%)
Atrial fibrillation ^† 1	2/329 (0.61%)	0/163 (0.00%)
Sinus tachycardia ^† 1	1/329 (0.30%)	0/163 (0.00%)
Cardiac failure congestive ^† 1	4/329 (1.22%)	0/163 (0.00%)
Cardiomegaly ^† 1	1/329 (0.30%)	0/163 (0.00%)
Dilatation atrial ^† 1	1/329 (0.30%)	0/163 (0.00%)
Tricuspid valve incompetence ^† 1	1/329 (0.30%)	0/163 (0.00%)
Palpitations ^† 1	1/329 (0.30%)	0/163 (0.00%)
Extrasystoles ^† 1	1/329 (0.30%)	0/163 (0.00%)
Electromechanical dissociation ^† 1	1/329 (0.30%)	0/163 (0.00%)
Cardiac ventricular disorder ^† 1	1/329 (0.30%)	0/163 (0.00%)
Ear and labyrinth disorders
Acute vestibular syndrome ^† 1	1/329 (0.30%)	0/163 (0.00%)
Eye disorders
Cataract ^† 1	0/329 (0.00%)	1/163 (0.61%)
Choroidal haemorrage ^† 1	0/329 (0.00%)	1/163 (0.61%)
Visual impairment ^† 1	1/329 (0.30%)	0/163 (0.00%)
Gastrointestinal disorders
Constipation ^† 1	4/329 (1.22%)	0/163 (0.00%)
Gastrooesophageal reflux disease ^† 1	2/329 (0.61%)	2/163 (1.23%)
Diarrhoea ^† 1	1/329 (0.30%)	1/163 (0.61%)
Colitis ^† 1	1/329 (0.30%)	1/163 (0.61%)
Nausea ^† 1	2/329 (0.61%)	0/163 (0.00%)
Colonic polyp ^† 1	1/329 (0.30%)	0/163 (0.00%)
Small intestinal obstruction ^† 1	1/329 (0.30%)	0/163 (0.00%)
Abdominal pain upper ^† 1	0/329 (0.00%)	1/163 (0.61%)
Upper gastrointestinal haemorrhage ^† 1	1/329 (0.30%)	0/163 (0.00%)
Aptyalism ^† 1	0/329 (0.00%)	1/163 (0.61%)
General disorders
Oedema peripheral ^† 1	4/329 (1.22%)	1/163 (0.61%)
Oedema ^† 1	1/329 (0.30%)	0/163 (0.00%)
Chest pain ^† 1	2/329 (0.61%)	1/163 (0.61%)
Pain ^† 1	2/329 (0.61%)	0/163 (0.00%)
Pyrexia ^† 1	2/329 (0.61%)	0/163 (0.00%)
Fatigue ^† 1	2/329 (0.61%)	0/163 (0.00%)
Catheter site haemorrhage ^† 1	1/329 (0.30%)	0/163 (0.00%)
Influenza like illness ^† 1	1/329 (0.30%)	0/163 (0.00%)
Hyperthermia ^† 1	1/329 (0.30%)	0/163 (0.00%)
Infections and infestations
Nasopharyngitis ^† 1	2/329 (0.61%)	2/163 (1.23%)
Upper respiratory tract infection ^† 1	1/329 (0.30%)	1/163 (0.61%)
Pharyngitis ^† 1	1/329 (0.30%)	0/163 (0.00%)
Sinusitis ^† 1	1/329 (0.30%)	0/163 (0.00%)
Pneumonia ^† 1	9/329 (2.74%)	2/163 (1.23%)
Bronchitis ^† 1	3/329 (0.91%)	0/163 (0.00%)
Lobar pneumonia ^† 1	1/329 (0.30%)	1/163 (0.61%)
Bronchopneumonia ^† 1	1/329 (0.30%)	0/163 (0.00%)
Lower respiratory tract infection ^† 1	0/329 (0.00%)	1/163 (0.61%)
Respiratory tract infection ^† 1	2/329 (0.61%)	1/163 (0.61%)
Infection ^† 1	1/329 (0.30%)	0/163 (0.00%)
Cellulitis ^† 1	2/329 (0.61%)	0/163 (0.00%)
Endocarditis bacterial ^† 1	1/329 (0.30%)	1/163 (0.61%)
Sepsis ^† 1	2/329 (0.61%)	0/163 (0.00%)
Bacteraemia ^† 1	0/329 (0.00%)	1/163 (0.61%)
Appendicitis ^† 1	0/329 (0.00%)	1/163 (0.61%)
Influenza ^† 1	2/329 (0.61%)	0/163 (0.00%)
Urinary tract infection ^† 1	1/329 (0.30%)	0/163 (0.00%)
Oral candidiasis ^† 1	1/329 (0.30%)	0/163 (0.00%)
Conjunctivitis viral ^† 1	1/329 (0.30%)	0/163 (0.00%)
Injury, poisoning and procedural complications
Road traffic accident ^† 1	1/329 (0.30%)	0/163 (0.00%)
Rib fracture ^† 1	1/329 (0.30%)	0/163 (0.00%)
Investigations
Alanine aminotransferase increased ^† 1	0/329 (0.00%)	2/163 (1.23%)
Aspartate aminotransferase increased ^† 1	0/329 (0.00%)	1/163 (0.61%)
Hepatic enzyme increased ^† 1	0/329 (0.00%)	1/163 (0.61%)
Electrocardiogram ST-T segment abnormal ^† 1	1/329 (0.30%)	0/163 (0.00%)
Electrocardiogram T wave inversion ^† 1	1/329 (0.30%)	0/163 (0.00%)
Computerised tomogram thorax abnormal ^† 1	1/329 (0.30%)	0/163 (0.00%)
Metabolism and nutrition disorders
Hyperkalaemia ^† 1	4/329 (1.22%)	0/163 (0.00%)
Hypokalaemia ^† 1	2/329 (0.61%)	0/163 (0.00%)
Hyperglycaemia ^† 1	2/329 (0.61%)	0/163 (0.00%)
Anorexia ^† 1	1/329 (0.30%)	0/163 (0.00%)
Diabetic ketoacidosis ^† 1	1/329 (0.30%)	0/163 (0.00%)
Hypophosphataemia ^† 1	1/329 (0.30%)	0/163 (0.00%)
Musculoskeletal and connective tissue disorders
Back pain ^† 1	1/329 (0.30%)	0/163 (0.00%)
Musculoskeletal pain ^† 1	1/329 (0.30%)	0/163 (0.00%)
Osteoarthritis ^† 1	2/329 (0.61%)	1/163 (0.61%)
Clubbing ^† 1	1/329 (0.30%)	0/163 (0.00%)
Joint swelling ^† 1	0/329 (0.00%)	1/163 (0.61%)
Pain in jaw ^† 1	1/329 (0.30%)	0/163 (0.00%)
Myalgia ^† 1	1/329 (0.30%)	0/163 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma ^† 1	0/329 (0.00%)	1/163 (0.61%)
Squamous cell carcinoma ^† 1	1/329 (0.30%)	0/163 (0.00%)
Prostate cancer ^† 1	1/329 (0.30%)	0/163 (0.00%)
Prostate cancer metastatic ^† 1	1/329 (0.30%)	0/163 (0.00%)
Lung neoplasm malignant ^† 1	1/329 (0.30%)	0/163 (0.00%)
Malignant melanoma ^† 1	0/329 (0.00%)	1/163 (0.61%)
Nervous system disorders
Headache ^† 1	5/329 (1.52%)	1/163 (0.61%)
Cerebrovascular accident ^† 1	1/329 (0.30%)	0/163 (0.00%)
Ischaemic stroke ^† 1	1/329 (0.30%)	0/163 (0.00%)
Syncope ^† 1	1/329 (0.30%)	1/163 (0.61%)
Somnolence ^† 1	1/329 (0.30%)	0/163 (0.00%)
Carotid artery stenosis ^† 1	1/329 (0.30%)	0/163 (0.00%)
Coma ^† 1	1/329 (0.30%)	0/163 (0.00%)
Grand mal convulsion ^† 1	1/329 (0.30%)	0/163 (0.00%)
Nerve compression ^† 1	1/329 (0.30%)	0/163 (0.00%)
Hypoaesthesia ^† 1	1/329 (0.30%)	0/163 (0.00%)
Psychiatric disorders
Anxiety ^† 1	3/329 (0.91%)	0/163 (0.00%)
Delirium ^† 1	1/329 (0.30%)	0/163 (0.00%)
Insomnia ^† 1	1/329 (0.30%)	0/163 (0.00%)
Renal and urinary disorders
Renal failure acute ^† 1	2/329 (0.61%)	0/163 (0.00%)
Renal failure ^† 1	1/329 (0.30%)	0/163 (0.00%)
Reproductive system and breast disorders
Prostatomegaly ^† 1	0/329 (0.00%)	1/163 (0.61%)
Benign prostatic hyperplasia ^† 1	1/329 (0.30%)	0/163 (0.00%)
Respiratory, thoracic and mediastinal disorders
Idiopathic pulmonary fibrosis ^† 1	20/329 (6.08%)	4/163 (2.45%)
Emphysema ^† 1	2/329 (0.61%)	0/163 (0.00%)
Pulmonary fibrosis ^† 1	2/329 (0.61%)	0/163 (0.00%)
Pulmonary alveolar haemorrhage ^† 1	1/329 (0.30%)	0/163 (0.00%)
Dyspnoea ^† 1	17/329 (5.17%)	2/163 (1.23%)
Respiratory arrest ^† 1	1/329 (0.30%)	0/163 (0.00%)
Cough ^† 1	4/329 (1.22%)	1/163 (0.61%)
Haemoptysis ^† 1	4/329 (1.22%)	0/163 (0.00%)
Productive cough ^† 1	1/329 (0.30%)	0/163 (0.00%)
Acute respiratory failure ^† 1	5/329 (1.52%)	1/163 (0.61%)
Respiratory failure ^† 1	4/329 (1.22%)	0/163 (0.00%)
Nasal congestion ^† 1	4/329 (1.22%)	0/163 (0.00%)
Rhinitis allergic ^† 1	1/329 (0.30%)	0/163 (0.00%)
Choking ^† 1	1/329 (0.30%)	0/163 (0.00%)
Rhinorrhoea ^† 1	1/329 (0.30%)	0/163 (0.00%)
Hypoxia ^† 1	1/329 (0.30%)	0/163 (0.00%)
Pneumothorax ^† 1	1/329 (0.30%)	0/163 (0.00%)
Pneumonitis ^† 1	1/329 (0.30%)	0/163 (0.00%)
Hiccups ^† 1	1/329 (0.30%)	0/163 (0.00%)
Epistaxis ^† 1	0/329 (0.00%)	1/163 (0.61%)
Pleurisy ^† 1	1/329 (0.30%)	0/163 (0.00%)
Pulmonary embolism ^† 1	0/329 (0.00%)	1/163 (0.61%)
Skin and subcutaneous tissue disorders
Rash ^† 1	0/329 (0.00%)	1/163 (0.61%)
Vascular disorders
Hypotension ^† 1	4/329 (1.22%)	1/163 (0.61%)
Hypertension ^† 1	3/329 (0.91%)	0/163 (0.00%)
Subclavian vein thrombosis ^† 1	1/329 (0.30%)	0/163 (0.00%)
Flushing ^† 1	1/329 (0.30%)	0/163 (0.00%)
Hot flush ^† 1	1/329 (0.30%)	0/163 (0.00%)
Peripheral ischaemia ^† 1	1/329 (0.30%)	0/163 (0.00%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA (11.1)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Ambrisentan	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	227/329 (69.00%)	104/163 (63.80%)
Gastrointestinal disorders
Constipation ^† 1	19/329 (5.78%)	10/163 (6.13%)
Diarrhoea ^† 1	20/329 (6.08%)	8/163 (4.91%)
Nausea ^† 1	15/329 (4.56%)	9/163 (5.52%)
General disorders
Oedema peripheral ^† 1	73/329 (22.19%)	14/163 (8.59%)
Fatigue ^† 1	22/329 (6.69%)	14/163 (8.59%)
Infections and infestations
Nasopharyngitis ^† 1	37/329 (11.25%)	18/163 (11.04%)
Bronchitis ^† 1	23/329 (6.99%)	15/163 (9.20%)
Sinusitis ^† 1	20/329 (6.08%)	6/163 (3.68%)
Respiratory tract infection ^† 1	9/329 (2.74%)	12/163 (7.36%)
Musculoskeletal and connective tissue disorders
Back pain ^† 1	18/329 (5.47%)	5/163 (3.07%)
Nervous system disorders
Headache ^† 1	47/329 (14.29%)	17/163 (10.43%)
Dizziness ^† 1	20/329 (6.08%)	2/163 (1.23%)
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract infection ^† 1	47/329 (14.29%)	18/163 (11.04%)
Dyspnoea ^† 1	40/329 (12.16%)	11/163 (6.75%)
Cough ^† 1	34/329 (10.33%)	20/163 (12.27%)
Idiopathic pulmonary fibrosis ^† 1	19/329 (5.78%)	2/163 (1.23%)
Nasal congestion ^† 1	27/329 (8.21%)	6/163 (3.68%)
Productive cough ^† 1	8/329 (2.43%)	9/163 (5.52%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA (11.1)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Clinical Trial Disclosures
Organization:	Gilead Sciences, Inc.
EMail:	ClinicalTrialDisclosures@gilead.com

Publications of Results:

Raghu G, Behr J, Brown KK, Egan JJ, Kawut SM, Flaherty KR, Martinez FJ, Nathan SD, Wells AU, Collard HR, Costabel U, Richeldi L, de Andrade J, Khalil N, Morrison LD, Lederer DJ, Shao L, Li X, Pedersen PS, Montgomery AB, Chien JW, O'Riordan TG; ARTEMIS-IPF Investigators*. Treatment of idiopathic pulmonary fibrosis with ambrisentan: a parallel, randomized trial. Ann Intern Med. 2013 May 7;158(9):641-9. doi: 10.7326/0003-4819-158-9-201305070-00003. Erratum in: Ann Intern Med. 2014 May 6;160(9):658.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Raghu G, Lynch D, Godwin JD, Webb R, Colby TV, Leslie KO, Behr J, Brown KK, Egan JJ, Flaherty KR, Martinez FJ, Wells AU, Shao L, Zhou H, Pedersen PS, Sood R, Montgomery AB, O'Riordan TG. Diagnosis of idiopathic pulmonary fibrosis with high-resolution CT in patients with little or no radiological evidence of honeycombing: secondary analysis of a randomised, controlled trial. Lancet Respir Med. 2014 Apr;2(4):277-84. doi: 10.1016/S2213-2600(14)70011-6. Epub 2014 Feb 18.

Chien JW, Richards TJ, Gibson KF, Zhang Y, Lindell KO, Shao L, Lyman SK, Adamkewicz JI, Smith V, Kaminski N, O'Riordan T. Serum lysyl oxidase-like 2 levels and idiopathic pulmonary fibrosis disease progression. Eur Respir J. 2014 May;43(5):1430-8. doi: 10.1183/09031936.00141013. Epub 2013 Oct 31.

Layout table for additonal information

Responsible Party:	Gilead Sciences
ClinicalTrials.gov Identifier:	NCT00768300
Other Study ID Numbers:	GS-US-231-0101
First Submitted:	October 7, 2008
First Posted:	October 8, 2008
Results First Submitted:	July 15, 2013
Results First Posted:	April 8, 2014
Last Update Posted:	April 8, 2014

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