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 is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by GlaxoSmithKline
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01894022
First received: July 3, 2013
Last updated: September 11, 2014
Last verified: September 2014
  Purpose

This is an open label, long term extension to Study AMB115811. All subjects may remain in the extension study for a minimum of 18 months. Beyond the 18-month period, subjects may continue in the extension study until one of the following:

  • The product is approved locally for use in inoperable CTEPH patients;
  • Development for use in the CTEPH population is discontinued or product is not approved by the local regulatory authorities
  • The investigator decides to discontinue the subject or subject decides to discontinue from the study.

The primary purpose of this study is to provide clinically relevant information on the long term safety of ambrisentan in subjects with inoperable CTEPH.


Condition Intervention Phase
Hypertension
Drug: Ambrisentan 5 mg
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label Extension Study of the Long-term Safety, Tolerability and Efficacy of Ambrisentan in Subjects With Inoperable Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of subjects with adverse events and serious adverse events [ Time Frame: Up to 3.5 years ] [ Designated as safety issue: No ]
  • Safety as assessed by clinical laboratory measurements (including liver safety and haematological parameters) [ Time Frame: Up to 3.5 years ] [ Designated as safety issue: No ]
    Clinical laboratory measurements will include liver safety and haematological parameters

  • Safety as assessed by physical examination [ Time Frame: Up to 3.5 years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Other targeted Pulmonary arterial hypertension (PAH) therapeutic agents include prostanoids, Phosphodiesterase type 5 (PDE-5) inhibitors; and tolerability issues include e.g. adverse events.


Secondary Outcome Measures:
  • 6 minute walking distance (6MWD) test [ Time Frame: Up to 3.5 years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Blood samples for determination of NT-Pro BNP plasma concentrations will be collected every three months for the first 18 months or early withdrawal.


Estimated Enrollment: 160
Study Start Date: January 2014
Estimated Study Completion Date: February 2019
Estimated Primary Completion Date: February 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ambrisentan Arm
All subjects will receive ambrisentan initially at a dose of 5 mg once daily (OD). Based on the investigator's best judgment, the subject may continue on 5 mg OD, or be up-titrated to 10 mg OD. The dose may also be adjusted back to 5 mg OD at investigator discretion.
Drug: Ambrisentan 5 mg
Round, white, film-coated, immediate-release tablets, containing 5 mg ambrisentan. Subjects will be dosed orally once daily. Subjects may receive 5mg, or 10 mg of ambrisentan OD.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01894022

Contacts
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com

  Show 40 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01894022     History of Changes
Other Study ID Numbers: 116457
Study First Received: July 3, 2013
Last Updated: September 11, 2014
Health Authority: Russia: Federal Service for Drug Control of the Russian Federation (FSKN)
Argentina: ANMAT: The National Administration of Drugs, Foodstuffs and Medical Technology
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Austria: Agency for Health and Food Safety
Italy: Italian Medicines Agency
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Mexico: Federal Comission For The Protection Against Sanitary Risks (COFEPRIS)
Germany: Federal Institute for Drugs and Medical Devices
Brazil: ANVISA
South Korea: Korea Food and Drug Administration (KFDA)
China: Food and Drug Administration
France: National Agency for the Safety of Medicine and Health Products
Netherlands: Medicines Evaluation Board (MEB)
Japan: Pharmaceuticals and Medical Devices Agency
Spain: Spanish Agency for Medicines and Health Products
Canada: Health Canada
Czech Republic: State Institute for Drug Control

Keywords provided by GlaxoSmithKline:
Inoperable chronic thromboembolic pulmonary hypertension, endothelin receptor antagonist

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on September 22, 2014