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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)

Primary Purpose

Hypertension

Status

Terminated

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Ambrisentan 5 mg

About this trial

This is an interventional treatment trial for Hypertension focused on measuring Inoperable chronic thromboembolic pulmonary hypertension, endothelin receptor antagonist

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Ambrisentan Arm

Arm Description

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.

Outcomes

Primary Outcome Measures

Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)

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

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

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

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

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

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

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

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

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

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

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

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.

Secondary Outcome Measures

Change From Study AMB115811 Baseline in the 6 Minutes Walking Distance (6MWD) at the Indicated Time Points

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

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

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 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)

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)

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

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

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

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)

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

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

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.

Full Information

NCT ID

NCT01894022

First Posted

July 3, 2013

Last Updated

August 9, 2017

Sponsor

GlaxoSmithKline

1. Study Identification

Unique Protocol Identification Number

NCT01894022

Brief Title

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

Acronym

AMBER II

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)

Study Type

Interventional

2. Study Status

Record Verification Date

August 2017

Overall Recruitment Status

Terminated

Study Start Date

January 23, 2014 (Actual)

Primary Completion Date

November 18, 2015 (Actual)

Study Completion Date

November 18, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

GlaxoSmithKline

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hypertension

Keywords

Inoperable chronic thromboembolic pulmonary hypertension, endothelin receptor antagonist

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

19 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ambrisentan Arm

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Ambrisentan 5 mg

Intervention Description

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.

Primary Outcome Measure Information:

Title

Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)

Description

Time Frame

From entry visit of the extension study up to approximately 16 months

Title

Description

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)

Title

Change From Study AMB115811 Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points

Description

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.

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)

Title

Change From Study AMB115811 Baseline in Hematocrit at the Indicated Time Points

Description

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.

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)

Title

Change From Study AMB115811 Baseline in Mean Corpuscle Volume at the Indicated Time Points

Description

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.

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)

Title

Change From Study AMB115811 Baseline in Red Blood Cell Count and Reticulocytes at the Indicated Time Points

Description

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.

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)

Title

Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern at Any Time Post Entry Visit

Description

Time Frame

Post entry visit of the extension study and up to End of Study (assessed up to approximately 16 months)

Title

Number of Participants With Creatinine Values of Potential Clinical Concern at Any Time Post Entry Visit

Description

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)

Title

Change From Study AMB115811 Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Assessed at the Indicated Time Points

Description

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)

Title

Change From Study AMB115811 Baseline in Heart Rate at the Indicated Time Points

Description

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)

Title

Change From Study AMB115811 Baseline in Weight at the Indicated Time Points

Description

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)

Title

Time to First Change in Dose of Open-label Ambrisentan Due to Tolerability Issues in Any Participant

Description

Time Frame

From the Entry visit of the extension study up to approximately 16 months

Secondary Outcome Measure Information:

Title

Change From Study AMB115811 Baseline in the 6 Minutes Walking Distance (6MWD) at the Indicated Time Points

Description

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)

Title

Change From Study AMB115811 Baseline (BL) in World Health Organization (WHO) Functional Class (FC) at the Indicated Time Points

Description

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)

Title

Change From Study AMB115811 Baseline in Borg CR10 Scale (BCR10S) Immediately Following Exercise at the Indicated Time Points

Description

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)

Title

Number of Participants With Clinical Worsening of Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

Description

Time Frame

From randomization up to End of Study for the extension study (assessed up to approximately 20 months)

Title

Change From Study AMB115811 Baseline in Quality of Life as Measured by Short Form 36 Health Survey (SF-36)

Description

Time Frame

Baseline from study AMB115811 up to End of Study for the extension study (assessed up to approximately 20 months)

Title

Percent Change From Study AMB115811 Baseline in Plasma N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP)

Description

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)

Title

Change From Start of Ambrisentan Treatment in 6 Minutes Walking Distance at the Indicated Time Points

Description

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

Title

Change From Start of Ambrisentan Treatment in World Health Organization (WHO) Functional Class (FC) at the Indicated Time Points

Description

Time Frame

Title

Change From Start of Ambrisentan Treatment in Borg CR10 Scale (BCR10S) Immediately Following Exercise at the Indicated Time Points

Description

Time Frame

Title

Percent Change From Start of Ambrisentan Treatment in Plasma N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP)

Description

Time Frame

Title

Time to First Change in Dose of Open-label Ambrisentan Due to Deterioration of Clinical Conditions in Any Participant

Description

Time Frame

From Entry visit of the extension study up to End of Study (assessed up to approximately 16 months)

Title

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

Description

Time Frame

From Entry visit of the extension study up to End of Study (assessed up to approximately 16 months)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

GSK Clinical Trials

Organizational Affiliation

GlaxoSmithKline

Official's Role

Study Director

Facility Information:

Facility Name

GSK Investigational Site

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02118

Country

United States

Facility Name

GSK Investigational Site

City

Dallas

State/Province

Texas

ZIP/Postal Code

75390-8550

Country

United States

Facility Name

GSK Investigational Site

City

Rosario

State/Province

Santa Fe

ZIP/Postal Code

S2000ODA

Country

Argentina

Facility Name

GSK Investigational Site

City

Ciudad Autonoma de Buenos Aires

ZIP/Postal Code

C1181ACH

Country

Argentina

Facility Name

GSK Investigational Site

City

Corrientes

ZIP/Postal Code

W3400AMZ

Country

Argentina

Facility Name

GSK Investigational Site

City

Santa Fe

ZIP/Postal Code

S3000AZG

Country

Argentina

Facility Name

GSK Investigational Site

City

Graz

ZIP/Postal Code

A-8036

Country

Austria

Facility Name

GSK Investigational Site

City

Innsbruck

ZIP/Postal Code

A-6020

Country

Austria

Facility Name

GSK Investigational Site

City

Vienna

ZIP/Postal Code

1090

Country

Austria

Facility Name

GSK Investigational Site

City

Edmonton

State/Province

Alberta

ZIP/Postal Code

T6G 2G3

Country

Canada

Facility Name

GSK Investigational Site

City

London

State/Province

Ontario

ZIP/Postal Code

N6A 5W9

Country

Canada

Facility Name

GSK Investigational Site

City

Wuhan

State/Province

Hubei

ZIP/Postal Code

430022

Country

China

Facility Name

GSK Investigational Site

City

Xian

State/Province

Shaanxi

ZIP/Postal Code

710061

Country

China

Facility Name

GSK Investigational Site

City

Beijing

ZIP/Postal Code

100020

Country

China

Facility Name

GSK Investigational Site

City

Beijing

ZIP/Postal Code

100037

Country

China

Facility Name

GSK Investigational Site

City

Beijing

ZIP/Postal Code

100038

Country

China

Facility Name

GSK Investigational Site

City

Shanghai

ZIP/Postal Code

200433

Country

China

Facility Name

GSK Investigational Site

City

Praha 2

ZIP/Postal Code

128 08

Country

Czechia

Facility Name

GSK Investigational Site

City

Heidelberg

State/Province

Baden-Wuerttemberg

ZIP/Postal Code

69126

Country

Germany

Facility Name

GSK Investigational Site

City

Regensburg

State/Province

Bayern

ZIP/Postal Code

93053

Country

Germany

Facility Name

GSK Investigational Site

City

Wuerzburg

State/Province

Bayern

ZIP/Postal Code

97074

Country

Germany

Facility Name

GSK Investigational Site

City

Hannover

State/Province

Niedersachsen

ZIP/Postal Code

30625

Country

Germany

Facility Name

GSK Investigational Site

City

Homburg

State/Province

Saarland

ZIP/Postal Code

66421

Country

Germany

Facility Name

GSK Investigational Site

City

Dresden

State/Province

Sachsen

ZIP/Postal Code

01307

Country

Germany

Facility Name

GSK Investigational Site

City

Leipzig

State/Province

Sachsen

ZIP/Postal Code

04103

Country

Germany

Facility Name

GSK Investigational Site

City

Ashkelon

ZIP/Postal Code

78360

Country

Israel

Facility Name

GSK Investigational Site

City

Zrifin

ZIP/Postal Code

70300

Country

Israel

Facility Name

GSK Investigational Site

City

Aichi

ZIP/Postal Code

466-8560

Country

Japan

Facility Name

GSK Investigational Site

City

Fukuoka

ZIP/Postal Code

812-8582

Country

Japan

Facility Name

GSK Investigational Site

City

Hokkaido

ZIP/Postal Code

060-8648

Country

Japan

Facility Name

GSK Investigational Site

City

Hyogo

ZIP/Postal Code

650-0017

Country

Japan

Facility Name

GSK Investigational Site

City

Miyagi

ZIP/Postal Code

980-8574

Country

Japan

Facility Name

GSK Investigational Site

City

Tochigi

ZIP/Postal Code

329-0498

Country

Japan

Facility Name

GSK Investigational Site

City

Tokyo

ZIP/Postal Code

113-8655

Country

Japan

Facility Name

GSK Investigational Site

City

Tokyo

ZIP/Postal Code

181-8611

Country

Japan

Facility Name

GSK Investigational Site

City

Seoul

ZIP/Postal Code

110-744

Country

Korea, Republic of

Facility Name

GSK Investigational Site

City

Seoul

ZIP/Postal Code

120-752

Country

Korea, Republic of

Facility Name

GSK Investigational Site

City

Seoul

ZIP/Postal Code

135-710

Country

Korea, Republic of

Facility Name

GSK Investigational Site

City

Monterrey NL

State/Province

Nuevo León

ZIP/Postal Code

64718

Country

Mexico

Facility Name

GSK Investigational Site

City

Amsterdam

ZIP/Postal Code

1081 HV

Country

Netherlands

Facility Name

GSK Investigational Site

City

Kemerovo

ZIP/Postal Code

650002

Country

Russian Federation

Facility Name

GSK Investigational Site

City

Tomsk

ZIP/Postal Code

634012

Country

Russian Federation

Facility Name

GSK Investigational Site

City

Riyadh

Country

Saudi Arabia

Facility Name

GSK Investigational Site

City

Barcelona

ZIP/Postal Code

08036

Country

Spain

Facility Name

GSK Investigational Site

City

Madrid

ZIP/Postal Code

28041

Country

Spain

Facility Name

GSK Investigational Site

City

Majadahonda (Madrid)

ZIP/Postal Code

28222

Country

Spain

Facility Name

GSK Investigational Site

City

Sevilla

ZIP/Postal Code

41013

Country

Spain

Facility Name

GSK Investigational Site

City

Cambridge

ZIP/Postal Code

CB23 3RE

Country

United Kingdom

Facility Name

GSK Investigational Site

City

Clydebank

ZIP/Postal Code

G81 4DY

Country

United Kingdom

Facility Name

GSK Investigational Site

City

London

ZIP/Postal Code

NW3 2QH

Country

United Kingdom

12. IPD Sharing Statement

Learn more about this trial

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

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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)

Hypertension

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial