Trial Outcomes & Findings for ARTEMIS-PH - Study of Ambrisentan in Subjects With Pulmonary Hypertension Associated With Idiopathic Pulmonary Fibrosis (NCT NCT00879229)

NCT ID: NCT00879229

Last Updated: 2014-05-15

Results Overview

The change from baseline in 6MWD at Week 16 (end of blinded treatment) was evaluated.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

40 participants

Primary outcome timeframe

Baseline to Week 16

Results posted on

2014-05-15

Participant Flow

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.

96 participants were screened; 40 participants were randomized and treated, and comprise the Safety Analysis Set and the Full Analysis Set.

Participant milestones

Participant milestones
Measure	Ambrisentan Participants were randomized to receive ambrisentan treatment for 56 weeks	Placebo Participants were randomized to receive placebo for 48 weeks, followed by ambrisentan treatment for 8 weeks.
Overall Study STARTED	25	15
Overall Study COMPLETED	3	1
Overall Study NOT COMPLETED	22	14

Reasons for withdrawal

Reasons for withdrawal
Measure	Ambrisentan Participants were randomized to receive ambrisentan treatment for 56 weeks	Placebo Participants were randomized to receive placebo for 48 weeks, followed by ambrisentan treatment for 8 weeks.
Overall Study Study terminated by Sponsor	13	12
Overall Study Death	4	2
Overall Study Adverse Event	2	0
Overall Study Withdrawal by Subject	1	0
Overall Study Clinical status did not improve	1	0
Overall Study Other	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ambrisentan n=25 Participants Participants were randomized to receive ambrisentan treatment for 56 weeks	Placebo n=15 Participants Participants were randomized to receive placebo for 48 weeks, followed by ambrisentan treatment for 8 weeks.	Total n=40 Participants Total of all reporting groups
Age, Continuous	68 years STANDARD_DEVIATION 7.7 • n=93 Participants	68 years STANDARD_DEVIATION 5.2 • n=4 Participants	68 years STANDARD_DEVIATION 6.8 • n=27 Participants
Sex: Female, Male Female	5 Participants n=93 Participants	5 Participants n=4 Participants	10 Participants n=27 Participants
Sex: Female, Male Male	20 Participants n=93 Participants	10 Participants n=4 Participants	30 Participants n=27 Participants
Race/Ethnicity, Customized White	25 participants n=93 Participants	14 participants n=4 Participants	39 participants n=27 Participants
Race/Ethnicity, Customized Asian	0 participants n=93 Participants	1 participants n=4 Participants	1 participants n=27 Participants
Region of Enrollment United States	14 participants n=93 Participants	9 participants n=4 Participants	23 participants n=27 Participants
Region of Enrollment Australia	3 participants n=93 Participants	2 participants n=4 Participants	5 participants n=27 Participants
Region of Enrollment Italy	4 participants n=93 Participants	1 participants n=4 Participants	5 participants n=27 Participants
Region of Enrollment Canada	3 participants n=93 Participants	1 participants n=4 Participants	4 participants n=27 Participants
Region of Enrollment Germany	1 participants n=93 Participants	2 participants n=4 Participants	3 participants n=27 Participants
Baseline Dyspnea Index (BDI)	5.0 units on a scale STANDARD_DEVIATION 2.15 • n=93 Participants	4.4 units on a scale STANDARD_DEVIATION 2.10 • n=4 Participants	4.8 units on a scale STANDARD_DEVIATION 2.13 • n=27 Participants

PRIMARY outcome

Timeframe: Baseline to Week 16

Population: Participants in the Full Analysis Set (randomized and received at least one dose of study medication) with evaluable data were analyzed.

The change from baseline in 6MWD at Week 16 (end of blinded treatment) was evaluated.

Outcome measures

Outcome measures
Measure	Ambrisentan n=21 Participants Participants were randomized to receive ambrisentan treatment for 56 weeks	Placebo n=9 Participants Participants were randomized to receive placebo for 48 weeks, followed by ambrisentan treatment for 8 weeks.
Change From Baseline in Six-minute Walk Distance (6MWD).	-96 meters Standard Error 38	-67 meters Standard Error 51

SECONDARY outcome

Timeframe: Week 48

Population: Full Analysis Set

Long-term survival was assessed as a Kaplan-Meier (KM) estimate of the percent probability of survival, with censoring at Week 48.

Outcome measures

Outcome measures
Measure	Ambrisentan n=25 Participants Participants were randomized to receive ambrisentan treatment for 56 weeks	Placebo n=15 Participants Participants were randomized to receive placebo for 48 weeks, followed by ambrisentan treatment for 8 weeks.
Long-term Survival	22 percent probability (KM% estimate) Interval 2.6 to 41.0	23 percent probability (KM% estimate) Interval 0.0 to 52.5

SECONDARY outcome

Timeframe: Baseline to Week 16

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

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).

Outcome measures

Outcome measures
Measure	Ambrisentan n=14 Participants Participants were randomized to receive ambrisentan treatment for 56 weeks	Placebo n=8 Participants Participants were randomized to receive placebo for 48 weeks, followed by ambrisentan treatment for 8 weeks.
Transition Dyspnea Index (TDI)	-1.5 units on a scale Standard Deviation 3.08	-1.4 units on a scale Standard Deviation 3.78

SECONDARY outcome

Timeframe: Baseline to Week 16

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

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.

Outcome measures

Outcome measures
Measure	Ambrisentan n=14 Participants Participants were randomized to receive ambrisentan treatment for 56 weeks	Placebo n=8 Participants Participants were randomized to receive placebo for 48 weeks, followed by ambrisentan treatment for 8 weeks.
Change From Baseline in WHO Functional Class -1: Deteriorated	0 units on a scale	1 units on a scale
Change From Baseline in WHO Functional Class 0: No change	11 units on a scale	5 units on a scale
Change From Baseline in WHO Functional Class +1: Improved	3 units on a scale	2 units on a scale

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: Insufficient data due to study termination

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: Insufficient data due to study termination

Assessment of the the level of the amino acid fragment NT-proBNP is used to establish prognosis in cardiovascular disease.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: Insufficient data due to study termination

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).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: Insufficient data due to study termination

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: Insufficient data due to study termination

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: Insufficient data due to study termination

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.

Outcome measures

Outcome data not reported

Adverse Events

Ambrisentan

Serious events: 12 serious events

Other events: 18 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Trial Disclosures

Gilead Sciences, Inc.

Email: [email protected]

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

Measure	Ambrisentan n=25 participants at risk Participants were randomized to receive ambrisentan treatment for 56 weeks	Placebo n=15 participants at risk Participants were randomized to receive placebo for 48 weeks, followed by ambrisentan treatment for 8 weeks.
Blood and lymphatic system disorders Anaemia	4.0% 1/25 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.	0.00% 0/15 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.
Cardiac disorders Atrioventricular block complete	4.0% 1/25 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.	0.00% 0/15 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.
Cardiac disorders Bradycardia	4.0% 1/25 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.	0.00% 0/15 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.
Gastrointestinal disorders Abdominal pain lower	4.0% 1/25 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.	0.00% 0/15 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.
Infections and infestations Pneumonia	8.0% 2/25 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.	0.00% 0/15 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.
Infections and infestations Respiratory tract infection	0.00% 0/25 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.	6.7% 1/15 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.
Injury, poisoning and procedural complications Procedural complication	0.00% 0/25 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.	6.7% 1/15 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.
Investigations Electrocardiogram T wave inversion	4.0% 1/25 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.	0.00% 0/15 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.
Metabolism and nutrition disorders Hyperkalaemia	4.0% 1/25 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.	0.00% 0/15 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.
Musculoskeletal and connective tissue disorders Groin pain	4.0% 1/25 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.	0.00% 0/15 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	4.0% 1/25 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.	0.00% 0/15 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.
Renal and urinary disorders Renal failure	4.0% 1/25 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.	0.00% 0/15 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.
Respiratory, thoracic and mediastinal disorders Idiopathic pulmonary fibrosis	12.0% 3/25 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.	6.7% 1/15 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.
Respiratory, thoracic and mediastinal disorders Dyspnoea	8.0% 2/25 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.	0.00% 0/15 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.
Respiratory, thoracic and mediastinal disorders Hypoxia	8.0% 2/25 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.	0.00% 0/15 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	4.0% 1/25 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.	0.00% 0/15 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.
Respiratory, thoracic and mediastinal disorders Haemoptysis	4.0% 1/25 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.	0.00% 0/15 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	4.0% 1/25 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.	0.00% 0/15 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	4.0% 1/25 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.	0.00% 0/15 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.
Respiratory, thoracic and mediastinal disorders Respiratory failure	4.0% 1/25 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.	0.00% 0/15 • Baseline to end of treatment Adverse events were collected based on the randomization group and not with regards to the specific treatment received.