Subjects with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). MedDRA version: 14.1 Level: LLT Classification code 10068739 Term: Chronic thromboembolic pulmonary hypertension System Organ Class: 100000004855
Conditions
Sponsors
GlaxoSmithKline, S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Demographics 1. Subject must be between 18 and 75 years of age, inclusive, at the Screening Visit CTEPH Diagnosis and Classification 2. 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 3 months prior to screening *Expert centre is an expert multidisciplinary team which must include at least one cardiology or respiratory consultant, and one consultant PEA surgeon 3. Subject must meet all of the following haemodynamic criteria by means of a RHC within 4 weeks prior to screening: i. mPAP of >25 mmHg ii. PVR > 400 dynes.sec/cm5 iii. PCWP or LVEDP of =150m and 92% as measured by pulse oximetry at the Screening Visit. 8. Subjects must have received anticoagulation for a minimum of 3 months prior to Screening. General 9. 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 (reliable methods of contraception are described in Appendix 1 of the protocol. 10. Subject must agree not to participate in a clinical study involving another investigational drug or device throughout this study. 11. 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. Specific information regarding warnings, precautions, contraindications, adverse events, and other pertinent information on the investigational product that may impact subject eligibility is provided in the IB and product label. Deviations from inclusion criteria are not allowed because they can potentially jeopardize the scientific integrity of the study, regulatory acceptability or subject safety. Therefore, adherence to the criteria as specified in the protocol is essential. French subjects: 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 137 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 138
Exclusion criteria
Exclusion criteria: CTEPH Treatments 1. Subject received previous PAH therapy (PDE5i, ERA, chronic prostanoid use*) within 12 weeks prior to the screening visit *Chronic prostanoid use is considered >7 days of treatment 2. 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. 3. Subject has a known hypersensitivity to the Investigational Products, the metabolites, or formulation excipients. Other Therapies 4. Subject has previously undergone a pulmonary endartorectamy. 5. Subject receiving intravenous inotropes within 2 weeks prior to the Screening Visit (e.g. dopamine, dobutamine) 6. Subjects receiving Calcium Channel Blockers or 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 35% direct bilirubin) 10. Subject has severe renal impairment (creatinine clearance 180/110 mmHg) at screening 15. Subject has severe hypotension (<90/50 mmHg) at screening 16. Subject has had an acute myocardial infarction within the last 90 days prior to screening 17. 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. General Medical Conditions 18. Subject with significant pulmonary disease (FEV1<70% of predicted): COPD, Emphysema, evidence of fibrotic lung disease on imaging 19. Subject has clinically significant fluid retention in the opinion of the investigator 20. Subject with significant obesity (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) 21. Subject with cardiovascular, liver, renal, haematologic, gastrointestinal,
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to assess the efficacy of ambrisentan 5mg after treatment period of 16 weeks, in subjects with inoperable CTEPH.;Secondary Objective: The secondary objectives are safety and tolerability of ambrisentan 5mg.;Primary end point(s): Change from baseline in 6MWD measured at week 16.;Timepoint(s) of evaluation of this end point: Week 16 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints include change from baseline to week 16 in: ? Pulmonary Vascular Resistance (PVR) ? WHO Functional Class (FC) ? Borg CR10 Scale (BCR10S) immediately following exercise ? Clinical worsening of CTEPH, as defined by the time from randomization to the first occurrence of death, lung transplantation, hospitalization for CTEPH, atrial septostomy, addition of parenteral prostanoids, or study withdrawal due to two or more early escape criteria* *Early escape criteria to consider: 1. A decrease from baseline of at least 20 percent in the distance walked during the six-minute walk test; 2. An increase of one or more WHO Functional Class; 3. Worsening right ventricular failure (e.g., as indicated by increased jugular venous pressure; new/worsening hepatomegaly, ascites, or peripheral edema; worsening echocardiographic parameters such as tricuspid annulus plane systolic excursion (TAPSE) and TDI of the tricuspid annulus);Rapidly progressing cardiogenic, hepatic, or renal failure; 4. Refractory systolic hypotension (systolic blood pressure less than 85 mmHg). ? Other haemodynamics: Right atrial pressure (mm Hg), pulmonary artery pressure (mm Hg) and cardiac index (L/min/m2) ? N-terminal pro-B-type natriuretic peptide (NT-proBNP) Health outcomes endpoints include: ? Change from baseline to week 16 in Quality of Life as measured by the Short Form 36 Health Survey (SF-36) Safety endpoints include: ? Incidence of Adverse events and Serious Adverse events ? Change from baseline in haemoglobin or haematocrit levels ? Liver Testing abnormalities ? Vital signs (i.e. supine blood pressure and heart rate) ? Laboratory test: clinical chemistry, haematology, testicular function (males only);Timepoint(s) of evaluation of this end point: Baseline and week 16 | — |
Countries
Argentina, Austria, Brazil, Canada, China, Czech Republic, France, Germany, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Russian Federation, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactClinical Trials HelpDesk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed