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

Hypertension Clinical Trial

— 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01894022
• Other study ID #: 116457
• Status: Completed
• Phase: Phase 3
• First received: July 3, 2013
• Last updated: February 18, 2016
• Start date: January 2014
• Est. completion date: November 2015

Study information

• Verified date: February 2016
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

• 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: November 2015
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Pulmonary

Intervention

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.

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires
Argentina	GSK Investigational Site	Corrientes
Argentina	GSK Investigational Site	Rosario	Santa Fe
Argentina	GSK Investigational Site	Santa Fe
Austria	GSK Investigational Site	Graz
Austria	GSK Investigational Site	Innsbruck
Austria	GSK Investigational Site	Vienna
Canada	GSK Investigational Site	Edmonton	Alberta
Canada	GSK Investigational Site	London	Ontario
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Wuhan	Hubei
China	GSK Investigational Site	Xian	Shaanxi
Czech Republic	GSK Investigational Site	Praha 2
Germany	GSK Investigational Site	Dresden	Sachsen
Germany	GSK Investigational Site	Hannover	Niedersachsen
Germany	GSK Investigational Site	Heidelberg	Baden-Wuerttemberg
Germany	GSK Investigational Site	Homburg	Saarland
Germany	GSK Investigational Site	Leipzig	Sachsen
Germany	GSK Investigational Site	Regensburg	Bayern
Germany	GSK Investigational Site	Wuerzburg	Bayern
Israel	GSK Investigational Site	Ashkelon
Israel	GSK Investigational Site	Zrifin
Japan	GSK Investigational Site	Aichi
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Hyogo
Japan	GSK Investigational Site	Miyagi
Japan	GSK Investigational Site	Tochigi
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Mexico	GSK Investigational Site	Monterrey NL	Nuevo León
Netherlands	GSK Investigational Site	Amsterdam
Russian Federation	GSK Investigational Site	Kemerovo
Russian Federation	GSK Investigational Site	Tomsk
Saudi Arabia	GSK Investigational Site	Riyadh
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Majadahonda (Madrid)
Spain	GSK Investigational Site	Sevilla
United Kingdom	GSK Investigational Site	Cambridge
United Kingdom	GSK Investigational Site	Clydebank
United Kingdom	GSK Investigational Site	London
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Dallas	Texas

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Canada,  China,  Czech Republic,  Germany,  Israel,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  Russian Federation,  Saudi Arabia,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of subjects with adverse events and serious adverse events		Up to 3.5 years	No
Primary	Safety as assessed by clinical laboratory measurements (including liver safety and haematological parameters)	Clinical laboratory measurements will include liver safety and haematological parameters	Up to 3.5 years	No
Primary	Safety as assessed by physical examination	Physical examination will be done to assess weight, jugular venous pressure, liver size, peripheral oedema, ascites and signs of deep vein thrombosis	Up to 3.5 years	No
Primary	Safety as assessed by vital Signs measurements	Vital signs including heart rate and supine blood pressure, and weight will be collected at each clinic visit.	Up to 3.5 years	No
Primary	The time to change in dosing of Ambrisentan or other PAH therapeutic agent	Other targeted Pulmonary arterial hypertension (PAH) therapeutic agents include prostanoids, Phosphodiesterase type 5 (PDE-5) inhibitors; and tolerability issues include e.g. adverse events.	Up to 3.5 years	No
Secondary	6 minute walking distance (6MWD) test	The 6MWD measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface.	Up to 3.5 years	No
Secondary	World Health Organisation (WHO) functional class	WHO functional class will be determined every three months for the first 18 months, and at the time the subject exits the study.	Up to 3.5 years	No
Secondary	Borg CR10 Scale (BCR10S)	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).	Up to 3.5 years	No
Secondary	Clinical worsening of CTEPH	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	First 18 months of the study	No
Secondary	Time to addition of another targeted PAH therapeutic agents	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).	Up to 3.5 years	No
Secondary	Change in dose of ambrisentan or other targeted PAH therapeutic agents	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.	Up to 3.5 years	No
Secondary	Subject Global Assessment using the Short Form 36 Health Survey (SF-36)	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.	Up to 3.5 years	No
Secondary	N-terminal pro-B-type natriuretic peptide (NT-Pro BNP) concentration	Blood samples for determination of NT-Pro BNP plasma concentrations will be collected every three months for the first 18 months or early withdrawal.	first 18 months or early withdrawal	No