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 is an open label, long term extension to Study AMB115811. All subjects may remain in the extension study for a minimum of 18 months. Beyond the 18-month period, subjects may continue in the extension study until one of the following:
- The product is approved locally for use in inoperable CTEPH patients;
- Development for use in the CTEPH population is discontinued or product is not approved by the local regulatory authorities
- The investigator decides to discontinue the subject or subject decides to discontinue from the study.
The primary purpose of this study is to provide clinically relevant information on the long term safety of ambrisentan in subjects with inoperable CTEPH.
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open-label Extension Study of the Long-term Safety, Tolerability and Efficacy of Ambrisentan in Subjects With Inoperable Chronic Thromboembolic Pulmonary Hypertension (CTEPH)|
- Number of subjects with adverse events and serious adverse events [ Time Frame: Up to 3.5 years ]
- Safety as assessed by clinical laboratory measurements (including liver safety and haematological parameters) [ Time Frame: Up to 3.5 years ]Clinical laboratory measurements will include liver safety and haematological parameters
- Safety as assessed by physical examination [ Time Frame: Up to 3.5 years ]Physical examination will be done to assess weight, jugular venous pressure, liver size, peripheral oedema, ascites and signs of deep vein thrombosis
- Safety as assessed by vital Signs measurements [ Time Frame: Up to 3.5 years ]Vital signs including heart rate and supine blood pressure, and weight will be collected at each clinic visit.
- The time to change in dosing of Ambrisentan or other PAH therapeutic agent [ Time Frame: Up to 3.5 years ]Other targeted Pulmonary arterial hypertension (PAH) therapeutic agents include prostanoids, Phosphodiesterase type 5 (PDE-5) inhibitors; and tolerability issues include e.g. adverse events.
- 6 minute walking distance (6MWD) test [ Time Frame: Up to 3.5 years ]The 6MWD measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface.
- World Health Organisation (WHO) functional class [ Time Frame: Up to 3.5 years ]WHO functional class will be determined every three months for the first 18 months, and at the time the subject exits the study.
- Borg CR10 Scale (BCR10S) [ Time Frame: Up to 3.5 years ]The BCR10S is a method for measuring perceived exertion and effort in physical work. The BCR10S will be performed straight after every 6MWD test for the first 18 months (every three months during the first 18 months, and at the time the subject exits the study).
- Clinical worsening of CTEPH [ Time Frame: First 18 months of the study ]Clinical worsening of CTEPH is defined as defined by the time from randomization to the first occurrence of death, lung transplantation, hospitalization for worsening CTEPH, atrial septostomy, addition of parenteral prostanoids and appearance of two or more CTEPH worsening events
- Time to addition of another targeted PAH therapeutic agents [ Time Frame: Up to 3.5 years ]Addition of another targeted PAH therapeutics agents is defined as addition of other PAH agents due to deterioration of clinical condition and lack of beneficial effect with previous therapy (not reaching set treatment goals).
- Change in dose of ambrisentan or other targeted PAH therapeutic agents [ Time Frame: Up to 3.5 years ]Change in dose of ambrisentan or other targeted PAH therapeutic agents (prostanoids, PDE-5 inhibitors) is defined as a dose change due to deterioration of clinical condition.
- Subject Global Assessment using the Short Form 36 Health Survey (SF-36) [ Time Frame: Up to 3.5 years ]Subject Global assessments (SF-36 short form) will be performed every three months for the first 18 months, and at the time the subject exits the study. The SF-36 Health Survey asks 36 questions to measure functional health and well-being from the subject's point of view.
- N-terminal pro-B-type natriuretic peptide (NT-Pro BNP) concentration [ Time Frame: first 18 months or early withdrawal ]Blood samples for determination of NT-Pro BNP plasma concentrations will be collected every three months for the first 18 months or early withdrawal.
|Study Start Date:||January 2014|
|Study Completion Date:||November 2015|
|Primary Completion Date:||November 2015 (Final data collection date for primary outcome measure)|
Experimental: Ambrisentan Arm
All subjects will receive ambrisentan initially at a dose of 5 mg once daily (OD). Based on the investigator's best judgment, the subject may continue on 5 mg OD, or be up-titrated to 10 mg OD. The dose may also be adjusted back to 5 mg OD at investigator discretion.
Drug: Ambrisentan 5 mg
Round, white, film-coated, immediate-release tablets, containing 5 mg ambrisentan. Subjects will be dosed orally once daily. Subjects may receive 5mg, or 10 mg of ambrisentan OD.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01894022
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|Study Director:||GSK Clinical Trials||GlaxoSmithKline|