Last updated: 07/17/2024 16:46:57

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

GSK study ID

116457

See study documents

Clinicaltrials.gov ID

See results summary

EudraCT ID

EU CT Number

Not applicable

Trial status

Terminated (halted prematurely)

Terminated (halted prematurely)

Overview

Eligibility

Locations

Study documents

Results summary

Plain language summaries

Additional information

Trial overview

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)

Trial description: 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.

Primary purpose:

Treatment

Trial design:

Single Group Assignment

Masking:

None (Open Label)

Allocation:

Not applicable

Primary outcomes:

Number of participants with any adverse event (AE) or serious adverse event (SAE)

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

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

Timeframe: 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)

Change from study AMB115811 Baseline in hemoglobin and mean corpuscle hemoglobin concentration (MCHC) at the indicated time points

Timeframe: 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)

Change from study AMB115811 Baseline in hematocrit at the indicated time points

Timeframe: 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)

Change from study AMB115811 Baseline in mean corpuscle volume at the indicated time points

Timeframe: 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)

Change from study AMB115811 Baseline in red blood cell count and reticulocytes at the indicated time points

Timeframe: 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)

Number of participants with clinical chemistry parameters of potential clinical concern at any time post entry visit

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

Number of participants with creatinine values of potential clinical concern at any time post entry visit

Timeframe: 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)

Change from study AMB115811 Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) assessed at the indicated time points

Timeframe: 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)

Change from study AMB115811 Baseline in heart rate at the indicated time points

Timeframe: 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)

Change from study AMB115811 Baseline in weight at the indicated time points

Timeframe: 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)

Time to first change in dose of open-label ambrisentan due to tolerability issues in any participant

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

Secondary outcomes:

Change from study AMB115811 Baseline in the 6 minutes walking distance (6MWD) at the indicated time points

Timeframe: 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)

Change from study AMB115811 Baseline (BL) in World Health Organization (WHO) functional class (FC) at the indicated time points

Timeframe: 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)

Change from study AMB115811 Baseline in Borg CR10 Scale (BCR10S) immediately following exercise at the indicated time points

Timeframe: 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)

Number of participants with clinical worsening of chronic thromboembolic pulmonary hypertension (CTEPH)

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

Change from study AMB115811 Baseline in Quality of Life as measured by Short Form 36 Health Survey (SF-36)

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

Percent change from study AMB115811 Baseline in plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP)

Timeframe: 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)

Change from Start of Ambrisentan Treatment in 6 minutes walking distance at the indicated time points

Timeframe: 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

Change from Start of Ambrisentan Treatment in World Health Organization (WHO) functional class (FC) at the indicated time points

Timeframe: 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

Change from Start of Ambrisentan Treatment in Borg CR10 Scale (BCR10S) immediately following exercise at the indicated time points

Timeframe: 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

Percent change from Start of Ambrisentan Treatment in plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP)

Timeframe: 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

Time to first change in dose of open-label ambrisentan due to deterioration of clinical conditions in any participant

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

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

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

Interventions:

Drug: Ambrisentan 5 mg

Enrollment:

19

Observational study model:

Not applicable

Primary completion date:

2015-18-11

Time perspective:

Not applicable

Clinical publications:

Pilar Escribano-Subias, Hakim Bendjenana, Paula Curtis, Irene Lang, Anton Vonk Noordegraaf.Ambrisentan for treatment of inoperable chronic thromboembolic pulmonary hypertension (CTEPH) .Pulm Circ.2019;9(2):1-3 DOI: 10.1177/2045894019846433 PMID: 30957635

Medical condition

Hypertension

Product

ambrisentan

Collaborators

Not applicable

Study date(s)

January 2014 to November 2015

Type

Interventional

Phase

3

Participation criteria

Sex

Female & Male

Age

18 - 80 years

Accepts healthy volunteers

No

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.

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

Inclusion and exclusion 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.

Trial location(s)

Location

Status

Contact us

Location

GSK Investigational Site

AMSTERDAM, Netherlands, 1081 HV

Status

Study Complete

Location

GSK Investigational Site

Aichi, Japan, 466-8560

Status

Study Complete

Location

GSK Investigational Site

Barcelona, Spain, 08036

Status

Study Complete

Location

GSK Investigational Site

Beijing, China, 100020

Status

Study Complete

Location

GSK Investigational Site

Beijing, China, 100037

Status

Study Complete

Location

GSK Investigational Site

Dresden, Sachsen, Germany, 01307

Status

Study Complete

Location

GSK Investigational Site

Kemerovo, Russia, 650002

Status

Study Complete

Location

GSK Investigational Site

London, United Kingdom, NW3 2QH

Status

Study Complete

Location

GSK Investigational Site

Madrid, Spain, 28041

Status

Study Complete

Location

GSK Investigational Site

Majadahonda (Madrid), Spain, 28222

Status

Study Complete

Location

GSK Investigational Site

Miyagi, Japan, 980-8574

Status

Study Complete

Location

GSK Investigational Site

Monterrey NL, Nuevo León, Mexico, 64718

Status

Study Complete

Location

GSK Investigational Site

Praha 2, Czech Republic, 128 08

Status

Study Complete

Location

GSK Investigational Site

Sevilla, Spain, 41013

Status

Study Complete

Location

GSK Investigational Site

Shanghai, China, 200433

Status

Study Complete

Location

GSK Investigational Site

Tochigi, Japan, 329-0498

Status

Study Complete

Location

GSK Investigational Site

Wuerzburg, Bayern, Germany, 97074

Status

Study Complete

Study documents

Protocol

Available language(s): English

Download document(s)

Scientific result summary

Available language(s): English

Download document(s)

If you wish to request for full study report, please contact - [email protected]

Results overview

Results posted on ClinicalTrials.gov

Recruitment status

Terminated (halted prematurely)

Actual primary completion date

2015-18-11

Actual study completion date

2015-18-11

Plain language summaries

Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

Additional information about the trial

Additional information

Not applicable

Participate in clinical trial

Access to clinical trial data by researchers