ARTEMIS-PH: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Parallel-Group Study to Evaluate the Efficacy and Safety of Ambrisentan in Subjects with Idiopathic Pulmonary Fibrosis and Pulmonary Hypertension - ARTEMIS-PH

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2009-011169-98-DE
• Date of registration: 06/08/2009
• Prospective Registration: Yes
• Primary sponsor: Gilead Sciences, Inc
• Public title: ARTEMIS-PH: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Parallel-Group Study to Evaluate the Efficacy and Safety of Ambrisentan in Subjects with Idiopathic Pulmonary Fibrosis and Pulmonary Hypertension - ARTEMIS-PH
• Scientific title: ARTEMIS-PH: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Parallel-Group Study to Evaluate the Efficacy and Safety of Ambrisentan in Subjects with Idiopathic Pulmonary Fibrosis and Pulmonary Hypertension - ARTEMIS-PH
• Date of first enrolment: 03/11/2009
• Target sample size: 225
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-011169-98
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Austria, Czech Republic, Germany, Italy, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
- Must be between 35 and 80 years of age, inclusive, at the Screening Visit.
- Weigh =40 kg at the Screening Visit
- Confident diagnosis of IPF including the following criteria:
HRCT scan findings of definite or consistent of IPF, combined with the following:
i. Insidious onset of otherwise unexplained dyspnea on exertion
ii. Duration of illness =3 months
iii. Bibasilar, inspiratory crackles
Subjects with a HRCT scan with findings of definite or consistent IPF do not require a confirmatory SLB (if performed it must show evidence of definite or probable IPF)
Subjects with a HRCT consistent with IPF do not require a confirmatory SLB (if performed it must show evidence of definite or probable IPF) but must have their HRCT scan reviewed and confirmed by a core radiologist
Subjects between 35 and 39 years are eligible if they have definite IPF on HRCT and IPF on SLB (i.e. definite or probable)
- Confirmed diagnosis of PH on RHC, defined by the following hemodynamic criteria:
a. mPAP of =25 mmHg
b. PVR >240 dyne.sec/cm5
c. PCWP or LVEDP of =15 mmHg
RHC performed within 24 weeks prior to the Screening are acceptable, if longer than 24 weeks, the RHC must be repeated. Section 7.6 provides a guideline of evidence to suggest the presence of PH
- Willingness to undergo a RHC during the screening period if no prior RHC or if prior RHC performed more than 24 weeks prior to Screening
- %FVC =40% at Screening
- Able to walk a distance of at least 50 m during two 6MWT performed during the Screening Period. These two tests must meet each of the following criteria:
a. The distance walked in these two tests cannot vary by more than 15%. The second 6MWT distance must be between 85% and 115% of the first distance
b. Resting SpO2 =88% (with or without supplemental O2) prior to initiating the 6MWT
c. If a subject is receiving supplemental O2, the O2 flow rate must be the same for these two tests. Supplemental O2 requirements will be determined by a resting O2 titration procedure (ROTP) prior to the first 6MWT performed
A maximum of 6 tests may be conducted during the Screening Period per subject to generate two tests that meet the above criteria. The first of the two qualifying tests will be considered the Screening Visit 6MWT; the second of the two qualifying tests will be considered the Randomization Visit 6MWT. A maximum of two tests can be performed per day and tests must be separated by at least two hours.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
- SLB-based diagnosis other than UIP
- Known causes of interstitial lung diseases (e.g., drug toxicities, environmental exposures, collagen vascular diseases, or sarcoidosis)
- Evidence of significant obstructive lung disease as determined by at least 1 of the following:
a. Forced expiratory volume in 1 second (FEV1)/FVC ratio <0.6 determined at the Screening Visit
b. Significant emphysema on HRCT, defined as HRCT findings in which the extent of emphysema exceeds the extent of fibrosis
- Hospitalized for an acute exacerbation of IPF within 8 weeks prior to the Screening Visit
- Pulmonary or upper respiratory tract infection needing hospitalization within 8 weeks prior to the Screening Visit
- Diagnosis of PH primarily due to an etiology other than IPF, including IPAH, or PAH-CTD
- Left ventricular ejection fraction (LVEF) <40% as determined by echocardiography at the time of the Screening Visit or within 30 days of the screening visit



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Pulmonary Hypertension associated with Idiopathic Pulmonary Fibrosis
MedDRA version: 12.0 Level: LLT Classification code 10021240 Term: Idiopathic pulmonary fibrosis
MedDRA version: 12.0 Level: LLT Classification code 10037400 Term: Pulmonary hypertension

Intervention(s)

Trade Name: Letairis
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Ambrisentan
CAS Number: 177036-94-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Letairis
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Ambrisentan
CAS Number: 177036-94-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: The primary objective of this study is to compare the change in 6-minute walk distance (6MWD) after initiating ambrisentan or placebo treatment in subjects with pulmonary hypertension (PH) associated with idiopathic pulmonary fibrosis (IPF).

Primary end point(s): The primary efficacy endpoint is the change from baseline in 6MWD evaluated after 16 weeks of blinded treatment.
Additional analyses supportive of the primary endpoint will be conducted and are specified in the statistical analysis plan (SAP)

Secondary Objective: The secondary objectives of this study are to evaluate changes in other clinical measures of PH and IPF, including long-term survival, a composite morbidity/mortality endpoint, dyspnea symptoms, SpO2min, distance-saturation product (6MWD*SpO2min), World Health Organization (WHO) functional class, pulmonary function tests (PFT), quality of life (QoL), and serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations.

Secondary ID(s)

GS-US-300-0128