Study of a drug to treat chronic thromboembolic pulmonary hypertension (CTEPH)
- Conditions
- subjects with inoperable chronic thromboembolic pulmonary hypertension (CTEPH)Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]MedDRA version: 16.0Level: LLTClassification code 10068739Term: Chronic thromboembolic pulmonary hypertensionSystem Organ Class: 100000004855
- Registration Number
- EUCTR2012-001646-18-IT
- Lead Sponsor
- GlaxoSmithKline Research & Developement Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Not Recruiting
- Sex
- All
- Target Recruitment
- 160
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 <15 mmHg
4. 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 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. See Section 6.1.1 of the protocol.
5. Subject must walk a distance of =150m and =475m at the screening visit. See Section 6.2.1.
6. Subject must have a current diagnosis of being in WHO Functional Class II or III.
7. Subject, with or without supplemental oxygen, must have a resting arterial oxygen saturation (SaO2) =>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 80
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 80
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 <4 weeks prior to the screening visit)
Exercise Programmes
7. 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.
Laboratory Values at Screening
8. ALT and/or AST = 3xULN
9. Bilirubin = 1.5xULN (>35% direct bilirubin)
10. Subject has severe renal impairment (estimated creatinine clearance <30 mL/min) at the Screening Visit
NOTE: if serum bilirubin is elevated at screening it will need to be fractionated to exclude liver injury and determine if the patient is able to be included in the trial.
Liver
11. Subject has moderate - severe hepatic impairment (Child-Pugh class B-C with or without cirrhosis) at the Screening Visit
Haematology and bleeding disorders
12. Subject has clinically significant anaemia: Hb < 10g/dL
13. Subjects with bleeding disorders or significant active peptic ulceration in the opinion of the investigator
Cardiovascular
14. Subject has uncontrolled hypertension (>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 cardiovascul
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method