Ambrisentan for Inoperable Chronic Thromboembolic Pulmonary Hypertension.

NCT ID: NCT01884675

Last Updated: 2017-03-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-30
• Study Completion Date: 2015-03-31

Brief Summary

It is hypothesised that ambrisentan may provide benefit to subjects with inoperable chronic thromboembolic pulmonary hypertension (CTEPH), where currently no proven or licensed treatment options exist. This Phase III, randomized, double-blind placebo controlled parallel group, 16 week study will compare the safety and efficacy of ambrisentan 5 milligrams (mg) versus placebo in subjects with inoperable CTEPH. The study will enrol 160 subjects, to assure at least 72 evaluable subjects per treatment arm, based on 10% drop-out rate.

Conditions

Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Ambrisentan

Subjects in this arm will receive ambrisentan 5 mg tablet once daily during the treatment period.

Group Type: EXPERIMENTAL

Ambrisentan 5 mg

Intervention Type: DRUG

White, film-coated, immediate-release tablets, containing 5 mg ambrisentan for single dose oral.

Placebo

Subjects in this arm will receive ambrisentan-matching placebo tablet once daily during the treatment period.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

White, film-coated, ambrisentan-matching placebo tablet for single oral dose

Interventions

Ambrisentan 5 mg

White, film-coated, immediate-release tablets, containing 5 mg ambrisentan for single dose oral.

Intervention Type: DRUG

Placebo

White, film-coated, ambrisentan-matching placebo tablet for single oral dose

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Signed written informed consent prior to beginning study-related procedures.
• Subject must be between 18-80 years of age, inclusive, at the Screening Visit.
• Subjects must have a diagnosis of CTEPH at an expert centre with a positive V/Q and CT angiogram and a pulmonary angiogram if available within 6 months prior to screening.
• Subject must meet all of the following haemodynamic criteria by means of a RHC within 3 months prior to screening: Mean pulmonary artery pressure (mPAP) of >25 millimeters of mercury (mmHg), Pulmonary vascular resistance (PVR) >400 dynes.sec/centimetre (cm)^5, Pulmonary capillary wedge pressure (PCWP) or Left ventricle end diastolic pressure (LVEDP) of <15 mmHg.
• Subjects must have previously been judged inoperable due to the obstruction being surgically inaccessible (i.e. distal disease) by an expert multidisciplinary team which must include at least one cardiology or respiratory consultant, and one consultant PEA surgeon. For countries with CTEPH expert centers [including at least a surgeon with sound experience performing Pulmonary Endarterectomy (PEAs)] the expert team will be the local expert centre. For countries without a CTEPH surgical expert center a central adjudication committee will assess the operability of the subjects during the screening period.
• Subject must walk a distance of >150 Meters (m) and < 475 m at the screening visit.
• Subject must have a current diagnosis of being in WHO Functional Class II or III.
• Subject, with or without supplemental oxygen, must have a resting arterial oxygen saturation (SaO2) > 92% as measured by pulse oximetry at the Screening Visit.
• Subjects must have received anticoagulation for a minimum of 3 months prior to Screening
• Female subject of childbearing potential must agree to use 2 reliable methods of contraception from the Screening Visit until study completion and for at least 30 days following the last dose of Investigational Product
• Subject must agree not to participate in a clinical study involving another investigational drug or device throughout this study.
• Subject must be competent to understand the information given in the Institutional Review Board (IRB) or Independent Ethics Committee (IEC) approved informed consent form (ICF) and must sign the form prior to the initiation of any study procedures.

Exclusion Criteria

• Subject received previous Pulmonary arterial hypertension (PAH) therapy (Phosphodiesterase type 5 [PDE5i], Endothelin receptor antagonist [ERA], chronic prostanoid use)
• Subject has previously discontinued other ERA in either another clinical study or commercial product for safety or tolerability reasons other than for liver function abnormalities.
• Subject has a known hypersensitivity to the Investigational Products, the metabolites, or formulation excipients
• Subject has previously undergone a pulmonary endarterectomy or a balloon pulmonary angioplasty
• Subject receiving intravenous inotropes within 2 weeks prior to the Screening Visit (e.g. dopamine, dobutamine)
• Subjects receiving Calcium Channel Blockers or 5-hydroxy-3-methylglutaryl-coenzyme A 5-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (i.e., statins) on an unstable dose 4 weeks prior to the Screening Visit (to be eligible subjects must not have changed their dose <4 weeks prior to the screening visit)
• Subject has not enrolled in an exercise training program for cardiopulmonary rehabilitation within 12 weeks prior to the Screening Visit and must agree not to enroll in an exercise training program for pulmonary rehabilitation during the Screening Period and the first 16 weeks of the study. Subjects enrolled in an exercise program for pulmonary rehabilitation 12 weeks prior to screening may enter the study if they agree to maintain their current level of rehabilitation for the first 16 weeks of the study.
• Alanine aminotransferase (ALT) and/or Aspartate aminotransferase (AST) > 3x Upper limit of normal (ULN)
• Bilirubin > 1.5xULN (>35% direct bilirubin)
• Subject has severe renal impairment [estimated creatinine clearance <30 millilitre/minute (mL/min)] at the Screening Visit
• Subject has moderate - severe hepatic impairment (Child-Pugh class B-C with or without cirrhosis) at the Screening Visit
• Subject has clinically significant anaemia: Hemoglobin (Hb) < 10 grams/decilitre (g/dL)
• Subjects with bleeding disorders or significant active peptic ulceration in the opinion of the investigator
• Subject has uncontrolled hypertension (>180/110 mmHg) at screening
• Subject has severe hypotension (<90/50 mmHg) at screening
• Subject has had an acute myocardial infarction within the last 90 days prior to screening
• Subject has, in the opinion of the investigator, clinically significant aortic or mitral valve disease; pericardial constriction; restrictive or congestive cardiomyopathy; life-threatening cardiac arrhythmias; significant left ventricular dysfunction (ejection fraction <50% of normal); left ventricular outflow obstruction; symptomatic coronary artery disease; autonomic hypotension; fluid depletion.
• Subject with significant pulmonary disease Forced expiratory volume in 1 second (FEV1) <70% of predicted): Chronic obstructive pulmonary disease (COPD), Emphysema, evidence of fibrotic lung disease on imaging
• Subject has clinically significant fluid retention in the opinion of the investigator
• Subject with significant obesity [Body mass index (BMI) ≥35], cardiovascular, musculoskeletal or any other condition that in the opinion of the investigator may involve an impairment of exercise capacity or the performance of the 6MWD test (e.g. previous history of hip/knee surgery, lower limb ulcers associated with autoimmune diseases)
• Subject with cardiovascular, liver, renal, haematologic, gastrointestinal, immunologic, endocrine, metabolic, or central nervous system disease that, in the opinion of the Investigator, may adversely affect the safety of the subject and/or efficacy of the investigational product or severely limit the lifespan of the subject other than the condition being studied
• Subjects with a prior malignancy whose cancer is expected to require additional active treatment in the next 2 years and whose prior malignancy would prevent them from fully participating in the study
• Female subject who is pregnant or breastfeeding
• Subject has demonstrated noncompliance with previous medical regimens
• Subject has a recent (within 1 year) history of abusing alcohol or illicit drugs
• Subject has participated in a clinical study involving another investigational drug or device within 4 weeks before the Screening Visit.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Boston, Massachusetts, United States

GSK Investigational Site

Dallas, Texas, United States

GSK Investigational Site

Corrientes, Corrientes Province, Argentina

GSK Investigational Site

Rosario, Santa Fe Province, Argentina

GSK Investigational Site

Santa Fe, Santa Fe Province, Argentina

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

Graz, , Austria

GSK Investigational Site

Innsbruck, , Austria

GSK Investigational Site

Vienna, , Austria

GSK Investigational Site

Edmonton, Alberta, Canada

GSK Investigational Site

London, Ontario, Canada

GSK Investigational Site

Wuhan, Hubei, China

GSK Investigational Site

Xi'an, Shaanxi, China

GSK Investigational Site

Beijing, , China

GSK Investigational Site

Beijing, , China

GSK Investigational Site

Beijing, , China

GSK Investigational Site

Shanghai, , China

GSK Investigational Site

Prague, , Czechia

GSK Investigational Site

Heidelberg, Baden-Wurttemberg, Germany

GSK Investigational Site

Regensburg, Bavaria, Germany

GSK Investigational Site

Würzburg, Bavaria, Germany

GSK Investigational Site

Hanover, Lower Saxony, Germany

GSK Investigational Site

Homburg, Saarland, Germany

GSK Investigational Site

Dresden, Saxony, Germany

GSK Investigational Site

Leipzig, Saxony, Germany

GSK Investigational Site

Ashkelon, , Israel

GSK Investigational Site

Zrifin, , Israel

GSK Investigational Site

Aichi, , Japan

GSK Investigational Site

Fukuoka, , Japan

GSK Investigational Site

Hokkaido, , Japan

GSK Investigational Site

Hyōgo, , Japan

GSK Investigational Site

Miyagi, , Japan

GSK Investigational Site

Tochigi, , Japan

GSK Investigational Site

Tokyo, , Japan

GSK Investigational Site

Tokyo, , Japan

GSK Investigational Site

Monterrey NL, Nuevo León, Mexico

GSK Investigational Site

Amsterdam, , Netherlands

GSK Investigational Site

Kemerovo, , Russia

GSK Investigational Site

Novosibirsk, , Russia

GSK Investigational Site

Tomsk, , Russia

GSK Investigational Site

Riyadh, , Saudi Arabia

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Barcelona, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Majadahonda (Madrid), , Spain

GSK Investigational Site

Seville, , Spain

GSK Investigational Site

Cambridge, , United Kingdom

GSK Investigational Site

Clydebank, , United Kingdom

GSK Investigational Site

London, , United Kingdom

Countries

United States; Argentina; Austria; Canada; China; Czechia; Germany; Israel; Japan; Mexico; Netherlands; Russia; Saudi Arabia; South Korea; Spain; United Kingdom

Other Identifiers

115811

Identifier Type: -

Identifier Source: org_study_id