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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:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01894022
First received: July 3, 2013
Last updated: August 9, 2017
Last verified: August 2017
July 3, 2013
August 9, 2017
January 23, 2014
November 18, 2015   (Final data collection date for primary outcome measure)
  • 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 ]
    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect. Refer to the general AE/SAE module for a list of AEs and SAEs. Participant's final visit in Study AMB115811 was used as the entry visit of this open-label extension study. Safety (Extension) Population: all participants who enrolled and took at least one dose of study treatment during the extension study.
  • 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) ]
    Hematology parameters were assessed at Entry visit of the extension study, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15, and end of study. Change from study AMB115811 Baseline in basophils, eosinophils, lymphocytes, monocytes, total neutrophils (ANC), platelet count, and WBC count are summarized. AMB115811 Baseline is the last value recorded on or prior to start of study treatment in that study. Change from AMB115811 Baseline was calculated as the value at the indicated visit minus the Baseline value. Participant's final visit in Study AMB115811 was used as the entry visit of this open-label extension study. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). NA indicates that data were not available.
  • 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) ]
    Hematology parameters were assessed at Entry visit of the extension study, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15, and end of study. Change from study AMB115811 Baseline in hemoglobin and MCHC is summarized. AMB115811 Baseline is the last value recorded on or prior to start of study treatment in that study. Change from AMB115811 Baseline was calculated as the value at the indicated visit minus the Baseline value. Participant's final visit in Study AMB115811 was used as the entry visit of this open-label extension study. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). NA indicates that data were not available.
  • 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) ]
    Hematology parameters were assessed at Entry visit of the extension study, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15, and end of study. Change from study AMB115811 Baseline in hematocrit is summarized. AMB115811 Baseline is the last value recorded on or prior to start of study treatment in that study. Change from AMB115811 Baseline was calculated as the value at the indicated visit minus the Baseline value. Participant's final visit in study AMB115811 was used as the entry visit of this open-label extension study. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). NA indicates that data were not available.
  • 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) ]
    Hematology parameters were assessed at Entry visit of the extension study, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15, and end of study. Change from study AMB115811 Baseline in mean corpuscle volume is summarized. AMB115811 Baseline is the last value recorded on or prior to start of study treatment in that study. Change from AMB115811 Baseline was calculated as the value at the indicated visit minus the Baseline value. Participant's final visit in study AMB115811 was used as the entry visit of this open-label extension study. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). NA indicates that data were not available.
  • 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) ]
    Hematology parameters were assessed at Entry visit of the extension study, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15, and end of study. Change from study AMB115811 Baseline in red blood cell count and reticulocytes is summarized. AMB115811 Baseline is the last value recorded on or prior to start of study treatment in that study. Change from AMB115811 Baseline was calculated as the value at the indicated visit minus the Baseline value. Participant's final visit in study AMB115811 was used as the entry visit of this open-label extension study. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). NA indicates that data were not available.
  • 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) ]
    Blood samples were collected post Entry visit of the extension study and up to end of study for evaluation of the clinical chemistry parameters of alanine amino transferase (ALT), aspartate amino transferase (AST), gamma glutamyl transferase (GGT), and total bilirubin. The clinical chemistry parameters of potential clinical concern high were defined as follows: ALT, AST, GGT >=3 times upper limit of normal (ULN); total bilirubin >=2 times ULN. Participants with both normal and high values were counted once under their worst case (high). Participant's final visit in study AMB115811 was used as the entry visit of this open-label extension study.
  • 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) ]
    Blood samples were collected at Entry visit of the extension study, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15, and end of study plus any unscheduled lab tests for creatinine. A creatinine value of potential clinical concern high was defined as >=176.8 micromoles per Liter. Participants with both normal and high values were counted once under their worst case (high). Participant's final visit in study AMB115811 was used as the entry visit of this open-label extension study.
  • 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) ]
    Vital signs including SBP and DBP were assessed at Entry visit of the extension study, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15, and end of study. Change from study AMB115811 Baseline in SBP and DBP is summarized. AMB115811 Baseline is the last value recorded on or prior to start of study treatment in that study. Change from AMB115811 Baseline was calculated as the value at the indicated visit minus the Baseline value. Participant's final visit in study AMB115811 was used as the entry visit of this open-label extension study. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). NA indicates that data were not available.
  • 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) ]
    Vital signs including heart rate were assessed at Entry visit of the extension study, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15, and end of study. Change from study AMB115811 Baseline in heart rate is summarized. AMB115811 Baseline is the last value recorded on or prior to start of study treatment in that study. Change from AMB115811 Baseline was calculated as the value at the indicated visit minus the Baseline value. Participant's final visit in study AMB115811 was used as the entry visit of this open-label extension study. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). NA indicates that data were not available
  • 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) ]
    Weight was measured at Entry visit of the extension study, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15, and at end of study. Change from study AMB115811 Baseline in weight is summarized. AMB115811 Baseline is the last value recorded on or prior to start of study treatment in that study. Change from AMB115811 Baseline was calculated as the value at the indicated visit minus the Baseline value. Participant's final visit in study AMB115811 was used as the entry visit of this open-label extension study. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). NA indicates that data were not available.
  • 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 ]
    The time to change in dose of ambrisentan or other targeted PAH (pulmonary arterial hypertension) therapeutic agents (prostanoids, PDE-5 inhibitors) due to tolerability issues (e.g. adverse events). Dosing data were collected, but after the study was terminated, not all endpoints listed in the protocol were analyzed, including time to first change in dose of open-label ambrisentan. This decision was documented in the reporting and analysis plan prior to database lock.
  • 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.
Complete list of historical versions of study NCT01894022 on ClinicalTrials.gov Archive Site
  • 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) ]
    The 6-minute walk test was conducted according to the American Thoracic Society guidelines in accordance with local standard operating procedures. 6MWD was measured by a 6-minute walk test. This test measures the distance that a par. can walk in a period of 6 minutes. AMB115811 Baseline was the Week 0 value in that study. Change from study AMB115811 Baseline was calculated as the value at the indicated visit minus the Baseline value. Par.'s final visit in study AMB115811 was used as the entry visit of this extension study. For the Extension study, the visit schedule (Months 1, 3, 6, 9, 12 and 15) was mapped to the visit schedule (Months 5, 7, 10, 13, 16 and 19) for continuity with study AMB115811. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Intent-to-treat (ITT) Population: all par. who were randomized and took at least one dose of study medication in the double-blind phase (placebo or ambrisentan).
  • 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) ]
    WHO FC indicates severity of pulmonary arterial hypertension (PAH) and is an adaptation of the New York Heart Association classification, assessed by the investigator. There are 4 grades for WHO FC based on severity of symptoms (Class I = none, Class IV = most severe). Grades mapped to numeric scale 1-4 (i.e. Class IV = 4). WHO FC system links symptoms with activity limitations, allowing clinicians to predict disease progression and prognosis. AMB115811 BL is the last value recorded on or prior to start of study treatment in that study. Change from AMB115811 BL was calculated as the value at the indicated visit minus the BL value (positive change = worsening). Par.'s final visit in AMB115811 was used as entry visit of this ext study. For Ext study, the visit schedule (M1,3,6,9,12 and 15) was mapped to the visit schedule (M5,7,10,13,16 and 19) for continuity with study AMB115811. Only par. available at the specified TP were analyzed (represented by n=X,X in the category title).
  • 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) ]
    BCR10S score, a rating of perceived exertion, was collected immediately following completion of the 6-minute walk test. Scores range from 0 to 10 (0=nothing at all, 10=extremely strong). If par.'s perception or feeling was stronger than "10", that is "extremely strong", "Maximal" -a larger number could be used, for example 12 or still higher, that is "Absolute maximum"). AMB115811 BL data was calculated as average of 2 BCR10S values obtained following the 2 6MWD tests used in determining the BL 6MWD in that study. If only 1 measurement was available, it was used. Change from AMB115811 BL was calculated as the value at the indicated visit minus the BL value. Par.'s final visit in AMB115811 was used as the entry visit of ext study. For the Ext study, the visit schedule (M1,3,6,9,12 and 15) mapped to the visit schedule (M5,7,10,13,16 and 19) for continuity with AMB115811. Only those par. available at the specified time points were analyzed (represented by n=X,X in the category titles).
  • 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) ]
    Time to clinical worsening of CTEPH was defined as the time from randomization in study AMB115811 to the first occurrence of any of the following events: death (all cause), lung transplantation, hospitalization for CTEPH deterioration, atrial septostomy, addition of parenteral prostanoids, appearance of two or more CTEPH worsening events. Worsening events included: >=20% of decrease in 6MWD; >=1 increase of WHO Functional Classes; worsening right ventricular failure; rapidly progressing cardiogenic, hepatic, or renal failure; refractory systolic hypotension (SBP <85 mmHg).
  • 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) ]
    The SF-36 version 2 is a self-administered, health-related quality of life (QoL) metric. It is a 36-item questionnaire designed to measure 8 domains of functional health status and well-being: physical functioning, role-physical, bodily pain, general health perceptions, vitality, social functioning, role-emotional, and mental health as well as 2 summary measures (Physical Health and Mental Health). Each domain is scored from 0 (poorer health) to 100 (better health). Baseline of study AMB115811 was to be used. Change from study AMB115811 Baseline was to be calculated as the value at the indicated visit minus the Baseline value. The SF-36 data were collected, but after the study was terminated, not all endpoints listed in the protocol were analyzed, including the SF-36. This decision was documented in the reporting and analysis plan prior to database lock.
  • 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) ]
    The ratio to Baseline in NT-proBNP was calculated as the ratio of the value at the specified time-point to the AMB115811 Baseline value and was expressed as a percent change from AMB115811 Baseline. This was done by taking the mean change on the log scale, exponentiating, subtracting 1 and multiplying by 100. Standard deviation (SD) of the logged values (log[SD]) have been presented. AMB115811 Baseline is the last value recorded on or prior to start of study treatment in that study. Participant's final visit in study AMB115811 was used as the entry visit of this open-label extension study. For the Extension study, the visit schedule (Months 1, 3, 6, 9, 12 and 15) was mapped to the visit schedule (Months 5, 7, 10, 13, 16 and 19) for continuity with study AMB115811. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). NA indicates that data were not available.
  • 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 ]
    The 6 minute walk distance data in a previous outcome measure were also analyzed as change from start of ambrisentan treatment. As participants started to receive ambrisentan treatment in two studies, two different time points for start of ambrisentan treatment were used for this analysis. For participants who received ambrisentan treatment in Study AMB115811, the Baseline for that study was used. For participants who received placebo in Study AMB115811, entry visit of the Extension study was defined as Baseline. Change from start of ambrisentan was calculated as the value at the indicated visit minus the start of ambrisentan value. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category title).
  • 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 ]
    The WHO functional class data in a previous outcome measure were also analyzed as change from start of ambrisentan treatment. There are 4 grades for WHO FC based on severity of symptoms of pulmonary arterial hypertension (Class I = none, Class IV = most severe). Grades mapped to numeric scale 1-4 (i.e. Class IV = 4). As participants started to receive ambrisentan treatment in two studies, two different time points for start of ambrisentan treatment were used for this analysis. For participants who received ambrisentan treatment in Study AMB115811, the Baseline for that study was used. For participants who received placebo in Study AMB115811, entry visit of the Extension study was defined as Baseline. Change from start of ambrisentan was calculated as the value at the indicated visit minus the start of ambrisentan value (positive change = worsening). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
  • 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 ]
    The BCR10S data in a previous outcome measure were also analyzed as change from start of ambrisentan treatment. BCR10S score, a rating of perceived exertion, ranges from 0 to 10 (0=nothing at all, 10 extremely strong). If par.'s perception or feeling was stronger than "10", a larger number could be used. As participants started to receive ambrisentan treatment in two studies, two different time points for start of ambrisentan treatment were used for this analysis. For participants who received ambrisentan treatment in Study AMB115811, the Baseline for that study was used. For participants who received placebo in Study AMB115811, entry visit of the Extension study was defined as Baseline. Change from start of ambrisentan was calculated as the value at the indicated visit minus the start of ambrisentan value. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category title).
  • 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 ]
    The NT-proBNP data in a previous outcome measure were also analyzed as change from start of ambrisentan treatment. The ratio to start of ambrisentan in NT-proBNP was calculated as the ratio of the value at the specified time-point to the start of ambrisentan value and was expressed as a percent change from start of ambrisentan. This was done by taking the mean change on the log scale, exponentiating, subtracting 1 and multiplying by 100. Standard deviation (SD) of the logged values (log[SD]) have been presented. As par. started to receive ambrisentan treatment in 2 studies, 2 different time points for start of ambrisentan treatment were used for this analysis. For par. who received ambrisentan treatment in study AMB115811, the Baseline for that study was used. For par. who received placebo in Study AMB115811, entry visit of the Extension study was defined as Baseline. Only those par. available at the specified time points were analyzed (represented by n=X, X in the category title).
  • 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) ]
    The time to change in dose of ambrisentan or other targeted PAH therapeutic agents (prostanoids, PDE-5 inhibitors) due to deterioration of clinical condition. Dosing data were collected, but after the study was terminated, not all endpoints listed in the protocol were analyzed, including time to first change in dose of open-label ambrisentan. This decision was documented in the reporting and analysis plan prior to database lock.
  • 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) ]

    The time to addition of another targeted PAH therapeutic agents (prostanoids, PDE-5 inhibitors) due to the following reasons:

    Deterioration of clinical condition; Lack of beneficial effect with previous therapy (not reaching set treatment goals). PAH therapies were collected, but after the study was terminated, not all endpoints listed in the protocol were analyzed, including time to first addition of another targeted PAH therapeutic agent. This decision was documented in the reporting and analysis plan prior to database lock.

  • 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.
Not Provided
Not Provided
 
A Open Label Study to Assess the Long-term Safety, Tolerability and Efficacy of Ambrisentan in Subjects With Inoperable Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
An Open-label Extension Study of the Long-term Safety, Tolerability and Efficacy of Ambrisentan in Subjects With Inoperable Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
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; or 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.
Not Provided
Interventional
Phase 3
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Hypertension
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.
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.
Intervention: Drug: Ambrisentan 5 mg
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
19
November 18, 2015
November 18, 2015   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Have been randomized to the protocol for AMB115811 and have met one of the following: Completed the Week 16 visit in AMB115811; Or Prematurely withdrew from AMB115811 for whatever reason (where investigational product [IP] has been stopped due to safety or efficacy reasons, the subject may still enter into the open label study regardless of what treatment they are receiving [other treatments will not be supplied by the sponsor]. The investigator will decide whether or not the subject will receive the IP
  • Subject is able and willing to give written informed consent. As part of the consent, female subjects of childbearing potential will be informed of the risk of teratogenicity and will need to be counseled in a developmentally appropriate manner on the importance of pregnancy prevention; and male subjects will need to be informed of potential risk of testicular tubular atrophy and aspermia.
  • Specific information regarding warnings, precautions, contraindications, adverse events, and other pertinent information on the GSK investigational product or other study treatment that may impact subject eligibility is provided in the Investigators Brochure and product label for PAH indication.
  • In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category

Exclusion Criteria:

  • Subject meeting any of the following criteria must not receive ambrisentan, however may still be followed-up as part of the study and be treated according to best clinical practice as decided by the investigator:
  • Subject has a known hypersensitivity to the Investigational Products, the metabolites, or formulation excipients
  • Female subjects who are pregnant or breastfeeding or no-longer agree to comply with using effective contraception as defined in the protocol.
  • Subjects with alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >= 3x Upper limit of normal (ULN)
  • Subjects with bilirubin >= 2xULN (>35% direct bilirubin)
  • Subjects with severe renal impairment (estimated creatinine clearance <30 millilitre per minute (mL/min) assessed within the previous 45 days) at the point of transition from Study AMB115811
  • Subject has moderate - severe hepatic impairment (Child-Pugh class B-C with or without cirrhosis) at the point of transition from study AMB115811
  • Subject with clinically significant fluid retention in the opinion of the investigator
  • Subject with clinically significant anemia in the opinion of the investigator
  • Subjects who are to enter another clinical trial or be treated with another investigational product after exiting Study AMB115811.
Sexes Eligible for Study: All
18 Years to 80 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Argentina,   Austria,   Canada,   China,   Czechia,   Germany,   Israel,   Japan,   Korea, Republic of,   Mexico,   Netherlands,   Russian Federation,   Saudi Arabia,   Spain,   United Kingdom,   United States
Czech Republic
 
NCT01894022
116457
Yes
Not Provided
Not Provided
GlaxoSmithKline
GlaxoSmithKline
Not Provided
Study Director: GSK Clinical Trials GlaxoSmithKline
GlaxoSmithKline
August 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP