An extension study of a drug to treat Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

• Register: EUCTR
• Last refreshed on: 12 September 2016
• Main ID: EUCTR2012-001642-17-CZ
• Date of registration: 01/08/2013
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Research & Developement Ltd
• Public title: An extension study of a drug to treat Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
• Scientific 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)
• Date of first enrolment: 18/09/2013
• Target sample size: 160
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-001642-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Austria, Brazil, Canada, China, Czech Republic, France, Germany, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Russian Federation, Spain, United Kingdom

Contacts

• Name: Clinical Trials HelpDesk
• Affiliation: GlaxoSmithKline Research & Development Ltd

• Name: Clinical Trials HelpDesk
• Affiliation: GlaxoSmithKline Research & Development Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects eligible for enrolment in the study must meet all of the following criteria:
Have been randomized to the protocol for AMB115811 and have met one of the following:
a) Completed the Week 16 visit in AMB115811;
b) Prematurely withdrew from AMB115811 for whatever reason*
*where 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) but will not be permitted to receive 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 counselled 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.
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

Exclusion criteria:
Exclusion from IP
Subjects 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:
1. Subject has a known hypersensitivity to the Investigational Products, the metabolites, or formulation excipients
2. Female subjects who are pregnant or breastfeeding or no-longer agree to comply with using effective contraception as defined in Appendix 2
3. Subjects with ALT and/or AST = 3xULN
4. Subjects with bilirubin = 2xULN (>35% direct bilirubin)
5. Subjects with severe renal impairment (estimated creatinine clearance <30 mL/min assessed within the previous 45 days) at the point of transition from Study AMB115811
6. Subject has moderate - severe hepatic impairment (Child-Pugh class B-C with or without cirrhosis) at the point of transition from study AMB115811
7. Subject with clinically significant fluid retention in the opinion of the investigator
8. Subject with clinically significant anemia in the opinion of the investigator
9. Subjects who are to enter another clinical trial or be treated with another investigational product after exiting Study AMB115811.

Deviations from exclusion 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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

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

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Intervention(s)

Trade Name: Volibris
Product Name: GSK1325760
Product Code: GSK1325760
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: AMBRISENTAN
CAS Number: 177036-94-1
Current Sponsor code: GSK1325760
Other descriptive name: ambrisentan
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Primary Outcome(s)

Secondary Objective: Efficacy assessments
? 6 minute walking distance (6MWD) test evaluated every three months;
? WHO functional class every three months;
? Borg CR10 Scale (BCR10S) immediately following exercise, every three months;
? Clinical worsening of CTEPH as defined by the time from randomization to the first occurrence of
? Death
? lung transplantation
? hospitalization for worsening CTEPH
? atrial septostomy
? addition parenteral prostanois
? appearance of two or more CTEPH worsening events*] (TTCW);

For further information please view section 2.2.1 of the protocol

Primary end point(s): The primary objective is the long-term safety and tolerability of ambrisentan in the CTEPH population.

Main Objective: The primary objective is the long-term safety and tolerability of ambrisentan in the CTEPH population (see Safety).

Safety assessments
? Adverse Events;
? Serious Adverse Events;
? Clinical laboratory parameters (including liver safety and haematological parameters);
? Physical examination (including jugular venous pressure, liver size, peripheral oedema, ascites and signs of deep vein thrombosis);
? Vital Signs (including body mass index at the entry visit only);
? The time to change in dose of ambrisentan or other targeted PAH therapeutic agents (prostanoids, PDE-5 inhibitors) due to tolerability issues (e.g. adverse events).

Timepoint(s) of evaluation of this end point: Entry in the study, monthly, every 3 months, every 6 months and follow-up visits

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Monthly, every 3 months, every 6 months and follow-up visits

Secondary end point(s): Efficacy

• The change from Study AMB115811 baseline and week 16 visits in the 6 minute walking distance (6MWD) test evaluated every three months;
• The change from Study AMB115811 baseline and week 16 visits in WHO functional class every three months;
• The change from Study AMB115811 baseline and week 16 visits in Borg CR10 Scale (BCR10S) immediately following exercise, every three months;
• Clinical worsening of CTEPH 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
• appearance of two or more CTEPH worsening events*;
*Worsening events 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);
4. Rapidly progressing cardiogenic, hepatic, or renal failure;
5. Refractory systolic hypotension (systolic blood pressure less than 85 mmHg).
Clinical Worsening events will be independently adjudicated.

• The time to addition of another targeted PAH therapeutic agents (prostanoids, PDE-5 inhibitors) due to the following reasons:
­ - Deterioration of clinical condition;
­ - Lack of beneficial effect with previous therapy (not reaching set treatment goals);
• The time to change in dose of ambrisentan or other targeted PAH therapeutic agents (prostanoids, PDE-5 inhibitors) due to deterioration of clinical condition;
• The change from Study AMB115811 baseline and week 16 visits in Subject Global Assessment every three months using the Short Form 36 Health
Survey (SF-36)
• Change from Study AMB115811 baseline and week 16 visits in N-terminal pro-B-type natriuretic peptide (NT-Pro BNP) concentration every three months.
Other
• The change from Study AMB115811 baseline and week 16 visits cardiopulmonary hemodynamic assessments data in subjects in whom hemodynamic data is considered part of the standard of care

Secondary ID(s)

2012-001642-17-ES

AMB116457

Source(s) of Monetary Support

GSK Pharma and R&D