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

This study has been terminated.
(Lack of efficacy)
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT00768300
First received: October 7, 2008
Last updated: February 27, 2014
Last verified: February 2014
Results First Received: July 15, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Idiopathic Pulmonary Fibrosis
Interventions: Drug: Ambrisentan
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
494 participants were randomized; 492 participants were treated, and comprise the Safety Analysis Set and the Full Analysis Set.

Reporting Groups
  Description
Ambrisentan Ambrisentan (5 mg or 10 mg tablet) administered orally once daily
Placebo Placebo to match ambrisentan administered orally once daily

Participant Flow:   Overall Study
    Ambrisentan     Placebo  
STARTED     330     164  
Randomized and Treated     329     163  
COMPLETED     1     1  
NOT COMPLETED     329     163  
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
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set: participants who were randomized and treated

Reporting Groups
  Description
Ambrisentan Ambrisentan (5 mg or 10 mg tablet) administered orally once daily
Placebo Placebo to match ambrisentan administered orally once daily
Total Total of all reporting groups

Baseline Measures
    Ambrisentan     Placebo     Total  
Number of Participants  
[units: participants]
  329     163     492  
Age  
[units: years]
Mean ± Standard Deviation
  65.8  ± 7.4     66.1  ± 7.1     65.9  ± 7.3  
Gender  
[units: participants]
     
Female     85     52     137  
Male     244     111     355  
Race/Ethnicity, Customized  
[units: 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]
[units: 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  
Baseline Pulmonary Hypertension (PH) per interactive voice response system (IVRS)  
[units: participants]
     
No     293     145     438  
Yes     36     18     54  
Smoking status [2]
[units: participants]
     
Never     105     53     158  
Current     7     5     12  
Former     217     104     321  
Surgical lung biopsy (SLB) to Confirm Diagnosis of IPF (per IVRS)  
[units: participants]
     
No     175     87     262  
Yes     154     76     230  
Disease duration  
[units: years]
Mean ± Standard Deviation
  1.13  ± 1.39     0.91  ± 1.19     1.06  ± 1.33  
Forced vital capacity (FVC) percent predicted  
[units: percentage of FVC % predicted]
Least Squares Mean ± Standard Deviation
  68.74  ± 13.12     69.86  ± 13.75     69.11  ± 13.33  
Six mile walk test (6MWT)  
[units: meters]
Mean ± Standard Deviation
  410.4  ± 118.7     420.5  ± 121.4     413.7  ± 119.6  
Hemoglobin Adjusted Diffusing lung capacity for carbon monoxide (DLCO) percent predicted  
[units: percentage of DLCO % predicted]
Least Squares Mean ± Standard Deviation
  42.04  ± 13.77     45.57  ± 13.25     43.20  ± 13.69  
Prior IPF Medications [3]
[units: participants]
     
No     205     97     302  
Yes     124     65     189  
N-acetylcysteine (NAC) Use [4]
[units: participants]
     
No     310     153     463  
Yes     19     8     27  
[1] All participants who were randomized are presented in Region of Enrollment (ambrisentan = 330; placebo = 164)
[2] Smoking status data is missing for one participant randomized to placebo.
[3] Prior IPF Medications data is missing for one participant randomized to placebo.
[4] NAC is a therapy commonly used in the treatment of IPF. NAC use data is missing for two participants randomized to placebo.



  Outcome Measures
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1.  Primary:   Time to Death or Disease (IPF) Progression.   [ Time Frame: Up to 48 months ]

2.  Secondary:   Proportion of Participants With No Disease Progression or Death at 48 Weeks   [ Time Frame: Baseline and Week 48 ]

3.  Secondary:   Change in FVC % Predicted at Week 48   [ Time Frame: Baseline and Week 48 ]

4.  Secondary:   Change in DLCO % Predicted at Week 48   [ Time Frame: Baseline and Week 48 ]

5.  Secondary:   Change in 6MWT at Week 48   [ Time Frame: Baseline and Week 48 ]

6.  Secondary:   Change in Quality of Life (QOL) Score at Week 48 as Assessed by the Short-Form 36® (SF-36)   [ Time Frame: Baseline and Week 48 ]

7.  Secondary:   Change in Quality of Life (QOL) Score at Week 48 as Assessed by the St. George’s Respiratory Questionnaire (SGRQ)   [ Time Frame: Baseline and Week 48 ]

8.  Secondary:   Change in Dyspnea Score at Week 48 as Assessed by the Transitional Dyspnea Index (TDI)   [ Time Frame: Baseline and Week 48 ]

9.  Secondary:   Percentage of Participants Who Developed PH on Study   [ Time Frame: Up to 48 weeks ]


  Serious Adverse Events


  Other Adverse Events


  More Information
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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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Clinical Trial Disclosures
Organization: Gilead Sciences, Inc.
e-mail: ClinicalTrialDisclosures@gilead.com


Publications of Results:

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT00768300     History of Changes
Other Study ID Numbers: GS-US-231-0101
Study First Received: October 7, 2008
Results First Received: July 15, 2013
Last Updated: February 27, 2014
Health Authority: United States: Food and Drug Administration