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ARTEMIS-PH - Study of Ambrisentan in Subjects With Pulmonary Hypertension Associated With Idiopathic Pulmonary Fibrosis (ARTEMIS-PH)

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ClinicalTrials.gov Identifier: NCT00879229
Recruitment Status : Terminated
First Posted : April 9, 2009
Results First Posted : April 22, 2014
Last Update Posted : May 15, 2014
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Idiopathic Pulmonary Fibrosis
Pulmonary Hypertension
Interventions Drug: Ambrisentan
Drug: Placebo
Enrollment 40

Recruitment Details Subjects were enrolled in a total of 29 study sites in Australia, Europe, and North America. The first participant was screened on 21 October 2009. The last participant observation was on 22 February 2011.
Pre-assignment Details 96 participants were screened; 40 participants were randomized and treated, and comprise the Safety Analysis Set and the Full Analysis Set.
Arm/Group Title Ambrisentan Placebo
Hide Arm/Group Description Participants were randomized to receive ambrisentan treatment for 56 weeks Participants were randomized to receive placebo for 48 weeks, followed by ambrisentan treatment for 8 weeks.
Period Title: Overall Study
Started 25 15
Completed 3 1
Not Completed 22 14
Reason Not Completed
Study terminated by Sponsor             13             12
Death             4             2
Adverse Event             2             0
Withdrawal by Subject             1             0
Clinical status did not improve             1             0
Other             1             0
Arm/Group Title Ambrisentan Placebo Total
Hide Arm/Group Description Participants were randomized to receive ambrisentan treatment for 56 weeks Participants were randomized to receive placebo for 48 weeks, followed by ambrisentan treatment for 8 weeks. Total of all reporting groups
Overall Number of Baseline Participants 25 15 40
Hide Baseline Analysis Population Description
Full Analysis Set: participants who were randomized and received at least one dose of study drug
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 25 participants 15 participants 40 participants
68  (7.7) 68  (5.2) 68  (6.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants 15 participants 40 participants
Female
5
  20.0%
5
  33.3%
10
  25.0%
Male
20
  80.0%
10
  66.7%
30
  75.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 25 participants 15 participants 40 participants
White 25 14 39
Asian 0 1 1
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 25 participants 15 participants 40 participants
United States 14 9 23
Australia 3 2 5
Italy 4 1 5
Canada 3 1 4
Germany 1 2 3
Baseline Dyspnea Index (BDI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 25 participants 15 participants 40 participants
5.0  (2.15) 4.4  (2.10) 4.8  (2.13)
[1]
Measure Description: BDI range is 0 to 12 (worst to best).
1.Primary Outcome
Title Change From Baseline in Six-minute Walk Distance (6MWD).
Hide Description The change from baseline in 6MWD at Week 16 (end of blinded treatment) was evaluated.
Time Frame Baseline to Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set (randomized and received at least one dose of study medication) with evaluable data were analyzed.
Arm/Group Title Ambrisentan Placebo
Hide Arm/Group Description:
Participants were randomized to receive ambrisentan treatment for 56 weeks
Participants were randomized to receive placebo for 48 weeks, followed by ambrisentan treatment for 8 weeks.
Overall Number of Participants Analyzed 21 9
Mean (Standard Error)
Unit of Measure: meters
-96  (38) -67  (51)
Show Statistical Analysis 1 Hide 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 0.696
Comments This is an exact Wilcoxon rank sum test p-value for testing equality of ambrisentan and placebo distributions.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -29
Confidence Interval (2-Sided) 95%
-54 to 17
Parameter Dispersion
Type: Standard Error of the mean
Value: 67
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Long-term Survival
Hide Description Long-term survival was assessed as a Kaplan-Meier (KM) estimate of the percent probability of survival, with censoring at Week 48.
Time Frame Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Ambrisentan Placebo
Hide Arm/Group Description:
Participants were randomized to receive ambrisentan treatment for 56 weeks
Participants were randomized to receive placebo for 48 weeks, followed by ambrisentan treatment for 8 weeks.
Overall Number of Participants Analyzed 25 15
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percent probability (KM% estimate)
22
(2.6 to 41.0)
23
(0.0 to 52.5)
3.Secondary Outcome
Title Transition Dyspnea Index (TDI)
Hide Description The change in TDI at Week 16 (end of blinded treatment) was evaluated. TDI measures the change from the baseline characteristic "Baseline Dyspnea Index." The TDI range is -9 to +9 (worst to best; 0 = no change).
Time Frame Baseline to Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set with evaluable data were analyzed.
Arm/Group Title Ambrisentan Placebo
Hide Arm/Group Description:
Participants were randomized to receive ambrisentan treatment for 56 weeks
Participants were randomized to receive placebo for 48 weeks, followed by ambrisentan treatment for 8 weeks.
Overall Number of Participants Analyzed 14 8
Mean (Standard Deviation)
Unit of Measure: units on a scale
-1.5  (3.08) -1.4  (3.78)
4.Secondary Outcome
Title Change From Baseline in WHO Functional Class
Hide Description WHO functional class rates severity of pulmonary hypertension, with 4 categories on a scale of 1 to 4 with the worst category being 4. Change is represented as an increase ("+1: Improved"), decrease ("-1: Deteriorated"), or no change ("0: No change") on the scale.
Time Frame Baseline to Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set with evaluable data were analyzed.
Arm/Group Title Ambrisentan Placebo
Hide Arm/Group Description:
Participants were randomized to receive ambrisentan treatment for 56 weeks
Participants were randomized to receive placebo for 48 weeks, followed by ambrisentan treatment for 8 weeks.
Overall Number of Participants Analyzed 14 8
Measure Type: Number
Unit of Measure: units on a scale
-1: Deteriorated 0 1
0: No change 11 5
+1: Improved 3 2
5.Secondary Outcome
Title Change From Baseline in Forced Vital Capacity (FVC) Percent Predicted
Hide Description FVC is a pulmonary function test, and is defined as the volume of air that can forcibly be blown out after taking a full breath. FVC% predicted is defined as FVC% of the patient divided by the average FVC% in the population for any person of similar age, sex and body composition.
Time Frame Baseline to Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Insufficient data due to study termination
Arm/Group Title Ambrisentan Placebo
Hide Arm/Group Description:
Participants were randomized to receive ambrisentan treatment for 56 weeks
Participants were randomized to receive placebo for 48 weeks, followed by ambrisentan treatment for 8 weeks.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title Change From Baseline in N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP)
Hide Description Assessment of the the level of the amino acid fragment NT-proBNP is used to establish prognosis in cardiovascular disease.
Time Frame Baseline to Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Insufficient data due to study termination
Arm/Group Title Ambrisentan Placebo
Hide Arm/Group Description:
Participants were randomized to receive ambrisentan treatment for 56 weeks
Participants were randomized to receive placebo for 48 weeks, followed by ambrisentan treatment for 8 weeks.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
7.Secondary Outcome
Title Change From Baseline in the Borg Dyspnea Index (BORG) Immediately Following Exercise
Hide Description Borg Dyspnea Index is a measure of perceived shortness of breath: 0 units on a scale (none) to 10 units on a scale (maximum breathlessness).
Time Frame Baseline to Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Insufficient data due to study termination
Arm/Group Title Ambrisentan Placebo
Hide Arm/Group Description:
Participants were randomized to receive ambrisentan treatment for 56 weeks
Participants were randomized to receive placebo for 48 weeks, followed by ambrisentan treatment for 8 weeks.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
8.Secondary Outcome
Title Hemoglobin-corrected Diffusing Capacity for Carbon Monoxide (DLCO) Percent Predicted
Hide Description DLCO is a pulmonary function test, and measures the partial pressure difference between inspired and expired carbon monoxide. DLCO% predicted is defined as DLCO% of the patient divided by the average DLCO% in the population for any person of similar age, sex and body composition.
Time Frame Baseline to Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Insufficient data due to study termination
Arm/Group Title Ambrisentan Placebo
Hide Arm/Group Description:
Participants were randomized to receive ambrisentan treatment for 56 weeks
Participants were randomized to receive placebo for 48 weeks, followed by ambrisentan treatment for 8 weeks.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
9.Secondary Outcome
Title Change in Quality of Life (QOL) Score as Assessed by the Short-Form 36® (SF-36)
Hide Description Each SF-36 score is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. An increase in score indicates an improvement in health state.
Time Frame Baseline to Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Insufficient data due to study termination
Arm/Group Title Ambrisentan Placebo
Hide Arm/Group Description:
Participants were randomized to receive ambrisentan treatment for 56 weeks
Participants were randomized to receive placebo for 48 weeks, followed by ambrisentan treatment for 8 weeks.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
10.Secondary Outcome
Title Change in QOL Score as Assessed by the St. George’s Respiratory Questionnaire (SRGQ)
Hide Description The SRGQ is designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. Patients respond to questions about symptoms (frequency & severity) and impact components (social functioning and psychological disturbances resulting from airways disease). Scores range from 0 to 100, with higher scores indicating more limitations.
Time Frame Baseline to Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Insufficient data due to study termination
Arm/Group Title Ambrisentan Placebo
Hide Arm/Group Description:
Participants were randomized to receive ambrisentan treatment for 56 weeks
Participants were randomized to receive placebo for 48 weeks, followed by ambrisentan treatment for 8 weeks.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Baseline to end of treatment
Adverse Event Reporting Description Adverse events were collected based on the randomization group and not with regards to the specific treatment received.
 
Arm/Group Title Ambrisentan Placebo
Hide Arm/Group Description Participants were randomized to receive ambrisentan treatment for 56 weeks Participants were randomized to receive placebo for 48 weeks, followed by ambrisentan treatment for 8 weeks.
All-Cause Mortality
Ambrisentan Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Ambrisentan Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   12/25 (48.00%)   3/15 (20.00%) 
Blood and lymphatic system disorders     
Anaemia  1  1/25 (4.00%)  0/15 (0.00%) 
Cardiac disorders     
Atrioventricular block complete  1  1/25 (4.00%)  0/15 (0.00%) 
Bradycardia  1  1/25 (4.00%)  0/15 (0.00%) 
Gastrointestinal disorders     
Abdominal pain lower  1  1/25 (4.00%)  0/15 (0.00%) 
Infections and infestations     
Pneumonia  1  2/25 (8.00%)  0/15 (0.00%) 
Respiratory tract infection  1  0/25 (0.00%)  1/15 (6.67%) 
Injury, poisoning and procedural complications     
Procedural complication  1  0/25 (0.00%)  1/15 (6.67%) 
Investigations     
Electrocardiogram T wave inversion  1  1/25 (4.00%)  0/15 (0.00%) 
Metabolism and nutrition disorders     
Hyperkalaemia  1  1/25 (4.00%)  0/15 (0.00%) 
Musculoskeletal and connective tissue disorders     
Groin pain  1  1/25 (4.00%)  0/15 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Breast cancer  1  1/25 (4.00%)  0/15 (0.00%) 
Renal and urinary disorders     
Renal failure  1  1/25 (4.00%)  0/15 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Idiopathic pulmonary fibrosis  1  3/25 (12.00%)  1/15 (6.67%) 
Dyspnoea  1  2/25 (8.00%)  0/15 (0.00%) 
Hypoxia  1  2/25 (8.00%)  0/15 (0.00%) 
Acute respiratory failure  1  1/25 (4.00%)  0/15 (0.00%) 
Haemoptysis  1  1/25 (4.00%)  0/15 (0.00%) 
Interstitial lung disease  1  1/25 (4.00%)  0/15 (0.00%) 
Pulmonary fibrosis  1  1/25 (4.00%)  0/15 (0.00%) 
Respiratory failure  1  1/25 (4.00%)  0/15 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (13.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ambrisentan Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   18/25 (72.00%)   12/15 (80.00%) 
Blood and lymphatic system disorders     
Anaemia  1  1/25 (4.00%)  1/15 (6.67%) 
Cardiac disorders     
Myocardial infarction  1  0/25 (0.00%)  1/15 (6.67%) 
Palpitations  1  0/25 (0.00%)  1/15 (6.67%) 
Endocrine disorders     
Hyperparathyroidism secondary  1  0/25 (0.00%)  1/15 (6.67%) 
Gastrointestinal disorders     
Constipation  1  4/25 (16.00%)  1/15 (6.67%) 
Abdominal distension  1  2/25 (8.00%)  0/15 (0.00%) 
Abdominal pain upper  1  1/25 (4.00%)  1/15 (6.67%) 
Abdominal discomfort  1  0/25 (0.00%)  1/15 (6.67%) 
Abdominal pain  1  0/25 (0.00%)  1/15 (6.67%) 
Diarrhoea  1  0/25 (0.00%)  2/15 (13.33%) 
Dry mouth  1  0/25 (0.00%)  1/15 (6.67%) 
Dyspepsia  1  0/25 (0.00%)  1/15 (6.67%) 
Nausea  1  0/25 (0.00%)  2/15 (13.33%) 
Vomiting  1  0/25 (0.00%)  1/15 (6.67%) 
General disorders     
Oedema peripheral  1  5/25 (20.00%)  3/15 (20.00%) 
Pyrexia  1  2/25 (8.00%)  0/15 (0.00%) 
Fatigue  1  1/25 (4.00%)  4/15 (26.67%) 
Chest discomfort  1  0/25 (0.00%)  1/15 (6.67%) 
Chest pain  1  0/25 (0.00%)  1/15 (6.67%) 
Malaise  1  0/25 (0.00%)  1/15 (6.67%) 
Infections and infestations     
Upper respiratory tract infection  1  4/25 (16.00%)  1/15 (6.67%) 
Pneumonia  1  1/25 (4.00%)  1/15 (6.67%) 
Respiratory tract infection  1  1/25 (4.00%)  1/15 (6.67%) 
Sinusitis  1  1/25 (4.00%)  1/15 (6.67%) 
Bronchitis  1  0/25 (0.00%)  1/15 (6.67%) 
Diverticulitis  1  0/25 (0.00%)  2/15 (13.33%) 
Influenza  1  0/25 (0.00%)  1/15 (6.67%) 
Lower respiratory tract infection  1  0/25 (0.00%)  2/15 (13.33%) 
Nasopharyngitis  1  0/25 (0.00%)  1/15 (6.67%) 
Rhinitis  1  0/25 (0.00%)  1/15 (6.67%) 
Urinary tract infection  1  0/25 (0.00%)  3/15 (20.00%) 
Viral infection  1  0/25 (0.00%)  1/15 (6.67%) 
Injury, poisoning and procedural complications     
Joint sprain  1  0/25 (0.00%)  1/15 (6.67%) 
Investigations     
Cardiac murmur  1  2/25 (8.00%)  0/15 (0.00%) 
Eosinophil count increased  1  0/25 (0.00%)  1/15 (6.67%) 
Metabolism and nutrition disorders     
Decreased appetite  1  0/25 (0.00%)  1/15 (6.67%) 
Hypercalcaemia  1  0/25 (0.00%)  1/15 (6.67%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  2/25 (8.00%)  3/15 (20.00%) 
Muscle spasms  1  1/25 (4.00%)  1/15 (6.67%) 
Musculoskeletal chest pain  1  0/25 (0.00%)  1/15 (6.67%) 
Neck pain  1  0/25 (0.00%)  1/15 (6.67%) 
Pain in extremity  1  0/25 (0.00%)  1/15 (6.67%) 
Nervous system disorders     
Headache  1  5/25 (20.00%)  3/15 (20.00%) 
Dizziness  1  0/25 (0.00%)  2/15 (13.33%) 
Neuropathy peripheral  1  0/25 (0.00%)  1/15 (6.67%) 
Syncope  1  0/25 (0.00%)  1/15 (6.67%) 
Psychiatric disorders     
Anxiety  1  0/25 (0.00%)  1/15 (6.67%) 
Renal and urinary disorders     
Proteinuria  1  0/25 (0.00%)  1/15 (6.67%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  6/25 (24.00%)  5/15 (33.33%) 
Nasal congestion  1  6/25 (24.00%)  1/15 (6.67%) 
Cough  1  3/25 (12.00%)  2/15 (13.33%) 
Hypoxia  1  2/25 (8.00%)  1/15 (6.67%) 
Orthopnoea  1  0/25 (0.00%)  1/15 (6.67%) 
Skin and subcutaneous tissue disorders     
Hyperhidrosis  1  2/25 (8.00%)  0/15 (0.00%) 
Alopecia  1  0/25 (0.00%)  1/15 (6.67%) 
Ecchymosis  1  0/25 (0.00%)  1/15 (6.67%) 
Vascular disorders     
Flushing  1  1/25 (4.00%)  2/15 (13.33%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (13.1)
Study GS-US-300-0128 was terminated early with enrollment of 40 of 225 planned subjects.
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
Name/Title: Clinical Trial Disclosures
Organization: Gilead Sciences, Inc.
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT00879229     History of Changes
Other Study ID Numbers: GS-US-300-0128
First Submitted: April 8, 2009
First Posted: April 9, 2009
Results First Submitted: August 9, 2013
Results First Posted: April 22, 2014
Last Update Posted: May 15, 2014