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

GlaxoSmithKline (GSK)

Status and phase: Terminated; Phase 3

Conditions: Hypertension

Treatments: Drug: Ambrisentan 5 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT01894022

116457

Details and patient eligibility

About

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; or 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.

Enrollment: 19 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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19 participants in 1 patient group

Ambrisentan Arm

Experimental group

Description:

All subjects will receive ambrisentan initially at a dose of 5 mg once daily (OD). Based on the investigator's best judgment, the subject may continue on 5 mg OD, or be up-titrated to 10 mg OD. The dose may also be adjusted back to 5 mg OD at investigator discretion.

Treatment:

Drug: Ambrisentan 5 mg