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
NCT01894022
See results summary
EudraCT ID
2012-001642-17
EU CT Number
Not applicable
Trial status
Other
Other
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
    Primary completion date:
    2015-18-11
    Observational study model:
    Not applicable
    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
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    Location
    GSK Investigational Site
    AMSTERDAM, Netherlands, 1081 HV
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Aichi, Japan, 466-8560
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Barcelona, Spain, 08036
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Beijing, China, 100020
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Beijing, China, 100037
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Dresden, Sachsen, Germany, 01307
    Status
    Study Complete
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    Showing 1 - 6 of 17 Results

    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
    Other
    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
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