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A Open Label Study to Assess the Long-term Safety, Tolerability and Efficacy of Ambrisentan in Subjects With Inoperable Chronic Thromboembolic Pulmonary Hypertension (CTEPH) (AMBER II)

This study has been terminated.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01894022
First Posted: July 9, 2013
Last Update Posted: September 11, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
GlaxoSmithKline
Results First Submitted: July 15, 2016  
Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition: Hypertension
Intervention: Drug: Ambrisentan 5 mg

  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
This was an open label, long-term extension study to the double-blind, placebo-controlled study AMB115811 (NCT01884675). Only those participants (par.) in study AMB115811 were eligible for enrollment in this study. The planned duration was a minimum of 18 months, but the study was terminated due to futility of enrollment in study AMB115811.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Out of the 33 participants randomized (16 participants in the Placebo arm and 17 in the Ambrisentan arm) in study AMB115811, a total of 19 participants were enrolled in this extension study.

Reporting Groups
  Description
Previous Placebo Participants received placebo tablet once daily (OD) for 16 weeks in study AMB115811. Upon enrollment in the extension study AMB116457, participants received ambrisentan 5 milligrams (mg) tablet OD. The dose could be up-titrated to ambrisentan 10 mg OD or adjusted back to ambrisentan 5 mg OD.
Previous Ambrisentan Participants received ambrisentan 5 mg tablet OD for 16 weeks in study AMB115811. Upon enrollment in the extension study AMB116457, participants continued to receive ambrisentan 5 mg OD. The dose could be up-titrated to ambrisentan 10 mg OD or adjusted back to ambrisentan 5 mg OD.

Participant Flow:   Overall Study
    Previous Placebo   Previous Ambrisentan
STARTED   9   10 
COMPLETED   0   0 
NOT COMPLETED   9   10 
Death                1                0 
Adverse Event, non-fatal                1                0 
Study Closed/terminated                7                10 



  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.
Participant characteristics at the start of the extension study.

Reporting Groups
  Description
Previous Placebo Participants received placebo tablet once daily (OD) for 16 weeks in study AMB115811. Upon enrollment in the extension study AMB116457, participants received ambrisentan 5 milligrams (mg) tablet OD. The dose could be up-titrated to ambrisentan 10 mg OD or adjusted back to ambrisentan 5 mg OD.
Previous Ambrisentan Participants received ambrisentan 5 mg tablet OD for 16 weeks in study AMB115811. Upon enrollment in the extension study AMB116457, participants continued to receive ambrisentan 5 mg OD. The dose could be up-titrated to ambrisentan 10 mg OD or adjusted back to ambrisentan 5 mg OD.
Total Total of all reporting groups

Baseline Measures
   Previous Placebo   Previous Ambrisentan   Total 
Overall Participants Analyzed 
[Units: Participants]
 9   10   19 
Age 
[Units: Years]
Median (Inter-Quartile Range)
 63.0 
 (58.0 to 69.0) 
 61.0 
 (47.0 to 66.0) 
 63.0 
 (54.0 to 69.0) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      6  66.7%      4  40.0%      10  52.6% 
Male      3  33.3%      6  60.0%      9  47.4% 
Race/Ethnicity, Customized 
[Units: Participants]
     
Asian - East Asian Heritage   2   1   3 
Asian - Japanese Heritage   2   1   3 
White - White/Caucasian/European Heritage   5   8   13 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)   [ Time Frame: From entry visit of the extension study up to approximately 16 months ]

2.  Primary:   Change From Study AMB115811 Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Absolute Neutrophil Count [ANC]), Platelet Count, and White Blood Cell (WBC) Count at the Indicated Time Points   [ Time Frame: Baseline from study AMB115811; Entry visit of the extension study; Months 1, 3, 6, 9, 12, 15; and End of Study (assessed up to approximately 16 months) ]

3.  Primary:   Change From Study AMB115811 Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points   [ Time Frame: Baseline from study AMB115811; Entry visit of the extension study; Months 1, 3, 6, 9, 12, 15; and End of Study (assessed up to approximately 16 months) ]

4.  Primary:   Change From Study AMB115811 Baseline in Hematocrit at the Indicated Time Points   [ Time Frame: Baseline from study AMB115811; Entry visit of the extension study; Months 1, 3, 6, 9, 12, 15; and End of Study (assessed up to approximately 16 months) ]

5.  Primary:   Change From Study AMB115811 Baseline in Mean Corpuscle Volume at the Indicated Time Points   [ Time Frame: Baseline from study AMB115811; Entry visit of the extension study; Months 1, 3, 6, 9, 12, 15; and End of Study (assessed up to approximately 16 months) ]

6.  Primary:   Change From Study AMB115811 Baseline in Red Blood Cell Count and Reticulocytes at the Indicated Time Points   [ Time Frame: Baseline from study AMB115811; Entry visit of the extension study; Months 1, 3, 6, 9, 12, 15; and End of Study (assessed up to approximately 16 months) ]

7.  Primary:   Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern at Any Time Post Entry Visit   [ Time Frame: Post entry visit of the extension study and up to End of Study (assessed up to approximately 16 months) ]

8.  Primary:   Number of Participants With Creatinine Values of Potential Clinical Concern at Any Time Post Entry Visit   [ Time Frame: Entry visit of the extension study; Months 1, 3, 6, 9, 12, 15; and End of Study plus any unscheduled lab tests (assessed up to approximately 16 months) ]

9.  Primary:   Change From Study AMB115811 Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Assessed at the Indicated Time Points   [ Time Frame: Baseline from study AMB115811; Entry visit of the extension study; Months 1, 3, 6, 9, 12, 15; and End of Study (assessed up to approximately 16 months) ]

10.  Primary:   Change From Study AMB115811 Baseline in Heart Rate at the Indicated Time Points   [ Time Frame: Baseline from study AMB115811; Entry visit of the extension study; Months 1, 3, 6, 9, 12, 15; and End of Study (assessed up to approximately 16 months) ]

11.  Primary:   Change From Study AMB115811 Baseline in Weight at the Indicated Time Points   [ Time Frame: Baseline from study AMB115811; Entry visit of the extension study; Months 1, 3, 6, 9, 12, 15; and End of Study (assessed up to approximately 16 months) ]

12.  Primary:   Time to First Change in Dose of Open-label Ambrisentan Due to Tolerability Issues in Any Participant   [ Time Frame: From the Entry visit of the extension study up to approximately 16 months ]

13.  Secondary:   Change From Study AMB115811 Baseline in the 6 Minutes Walking Distance (6MWD) at the Indicated Time Points   [ Time Frame: During Study AMB115811: Months 0 (Baseline), 1, 2, 3, 4, Early Withdrawal (EW); During Extension Study: Months 1, 3, 6, 9, 12, 15 and at End of Study (assessed up to approximately 20 months) ]

14.  Secondary:   Change From Study AMB115811 Baseline (BL) in World Health Organization (WHO) Functional Class (FC) at the Indicated Time Points   [ Time Frame: During Study AMB115811: Months (M) 0 (Baseline), 1, 2, 3, 4, Early Withdrawal (EW); During Extension (ext) Study: Months 1, 3, 6, 9, 12, 15 and at End of Study (assessed up to approximately 20 months) ]

15.  Secondary:   Change From Study AMB115811 Baseline in Borg CR10 Scale (BCR10S) Immediately Following Exercise at the Indicated Time Points   [ Time Frame: During Study AMB115811: Months (M) 0 (Baseline), 1, 2, 3, 4, Early Withdrawal (EW); During Extension (Ext) Study: Months 1, 3, 6, 9, 12, 15 and at End of Study (assessed up to approximately 20 months) ]

16.  Secondary:   Number of Participants With Clinical Worsening of Chronic Thromboembolic Pulmonary Hypertension (CTEPH)   [ Time Frame: From randomization up to End of Study for the extension study (assessed up to approximately 20 months) ]

17.  Secondary:   Change From Study AMB115811 Baseline in Quality of Life as Measured by Short Form 36 Health Survey (SF-36)   [ Time Frame: Baseline from study AMB115811 up to End of Study for the extension study (assessed up to approximately 20 months) ]

18.  Secondary:   Percent Change From Study AMB115811 Baseline in Plasma N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP)   [ Time Frame: During Study AMB115811: Months 0 (Baseline), 1, 2, 3, 4, Early Withdrawal (EW); During Extension Study: Months 1, 3, 6, 9, 12, 15 and at End of Study (assessed up to approximately 20 months) ]

19.  Secondary:   Change From Start of Ambrisentan Treatment in 6 Minutes Walking Distance at the Indicated Time Points   [ Time Frame: Previous Placebo: Months 0 (Entry visit of the extension), 1, 3, 6, 9, 12; Previous Ambrisentan: Month 0 (Baseline of study AMB115811), 1, 2, 3, 4, Early Withdrawal (EW) (AMB115811), 5, 7, 10, 13, 16, 19; and at End of Study ]

20.  Secondary:   Change From Start of Ambrisentan Treatment in World Health Organization (WHO) Functional Class (FC) at the Indicated Time Points   [ Time Frame: Previous Placebo: Months 0 (Entry visit of the extension), 1, 3, 6, 9, 12; Previous Ambrisentan: Month 0 (Baseline of study AMB115811), 1, 2, 3, 4, Early Withdrawal (EW) (AMB115811), 5, 7, 10, 13, 16, 19; and at End of Study ]

21.  Secondary:   Change From Start of Ambrisentan Treatment in Borg CR10 Scale (BCR10S) Immediately Following Exercise at the Indicated Time Points   [ Time Frame: Previous Placebo: Months 0 (Entry visit of the extension), 1, 3, 6, 9, 12; Previous Ambrisentan: Month 0 (Baseline of study AMB115811), 1, 2, 3, 4, Early Withdrawal (EW) (AMB115811), 5, 7, 10, 13, 16, 19; and at End of Study ]

22.  Secondary:   Percent Change From Start of Ambrisentan Treatment in Plasma N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP)   [ Time Frame: Previous Placebo: Months 0 (Entry visit of the extension), 1, 3, 6, 9, 12; Previous Ambrisentan: Month 0 (Baseline of study AMB115811), 1, 2, 3, 4, Early Withdrawal (EW) (AMB115811), 5, 7, 10, 13, 16, 19; and at End of Study ]

23.  Secondary:   Time to First Change in Dose of Open-label Ambrisentan Due to Deterioration of Clinical Conditions in Any Participant   [ Time Frame: From Entry visit of the extension study up to End of Study (assessed up to approximately 16 months) ]

24.  Secondary:   Time to First Addition of Another Targeted PAH Therapeutic Agent Due to Deterioration of Clinical Condition or Lack of Beneficial Effect With Previous Therapy in Any Participant   [ Time Frame: From Entry visit of the extension study up to End of Study (assessed up to approximately 16 months) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
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  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.


Results Point of Contact:  
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343



Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01894022     History of Changes
Other Study ID Numbers: 116457
First Submitted: July 3, 2013
First Posted: July 9, 2013
Results First Submitted: July 15, 2016
Results First Posted: June 8, 2017
Last Update Posted: September 11, 2017