Clinical trial NCT01894022: A Open Label Study to Assess the Long-term Safety, Tolerability and Efficacy of Ambrisentan in Subjects With Inoperable Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
Official 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Hypertension
Keywords: Inoperable chronic thromboembolic pulmonary hypertension, endothelin receptor antagonist
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2013-07-09
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)
timeFrame: From entry visit of the extension study up to approximately 16 months
measure: Change From Study AMB115811 Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Absolute Neutrophil Count [ANC]), Platelet Count, and White Blood Cell (WBC) Count at the Indicated Time Points
timeFrame: Baseline from study AMB115811; Entry visit of the extension study; Months 1, 3, 6, 9, 12, 15; and End of Study (assessed up to approximately 16 months)
measure: Change From Study AMB115811 Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points
timeFrame: Baseline from study AMB115811; Entry visit of the extension study; Months 1, 3, 6, 9, 12, 15; and End of Study (assessed up to approximately 16 months)
measure: Change From Study AMB115811 Baseline in Hematocrit at the Indicated Time Points
timeFrame: Baseline from study AMB115811; Entry visit of the extension study; Months 1, 3, 6, 9, 12, 15; and End of Study (assessed up to approximately 16 months)
measure: Change From Study AMB115811 Baseline in Mean Corpuscle Volume at the Indicated Time Points
timeFrame: Baseline from study AMB115811; Entry visit of the extension study; Months 1, 3, 6, 9, 12, 15; and End of Study (assessed up to approximately 16 months)
measure: Change From Study AMB115811 Baseline in Red Blood Cell Count and Reticulocytes at the Indicated Time Points
timeFrame: Baseline from study AMB115811; Entry visit of the extension study; Months 1, 3, 6, 9, 12, 15; and End of Study (assessed up to approximately 16 months)
measure: Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern at Any Time Post Entry Visit
timeFrame: Post entry visit of the extension study and up to End of Study (assessed up to approximately 16 months)
measure: Number of Participants With Creatinine Values of Potential Clinical Concern at Any Time Post Entry Visit
timeFrame: Entry visit of the extension study; Months 1, 3, 6, 9, 12, 15; and End of Study plus any unscheduled lab tests (assessed up to approximately 16 months)
measure: Change From Study AMB115811 Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Assessed at the Indicated Time Points
timeFrame: Baseline from study AMB115811; Entry visit of the extension study; Months 1, 3, 6, 9, 12, 15; and End of Study (assessed up to approximately 16 months)
measure: Change From Study AMB115811 Baseline in Heart Rate at the Indicated Time Points
timeFrame: Baseline from study AMB115811; Entry visit of the extension study; Months 1, 3, 6, 9, 12, 15; and End of Study (assessed up to approximately 16 months)
measure: Change From Study AMB115811 Baseline in Weight at the Indicated Time Points
timeFrame: Baseline from study AMB115811; Entry visit of the extension study; Months 1, 3, 6, 9, 12, 15; and End of Study (assessed up to approximately 16 months)
measure: Time to First Change in Dose of Open-label Ambrisentan Due to Tolerability Issues in Any Participant
timeFrame: From the Entry visit of the extension study up to approximately 16 months
Secondary outcomes:
measure: Change From Study AMB115811 Baseline in the 6 Minutes Walking Distance (6MWD) at the Indicated Time Points
timeFrame: During Study AMB115811: Months 0 (Baseline), 1, 2, 3, 4, Early Withdrawal (EW); During Extension Study: Months 1, 3, 6, 9, 12, 15 and at End of Study (assessed up to approximately 20 months)
measure: Change From Study AMB115811 Baseline (BL) in World Health Organization (WHO) Functional Class (FC) at the Indicated Time Points
timeFrame: During Study AMB115811: Months (M) 0 (Baseline), 1, 2, 3, 4, Early Withdrawal (EW); During Extension (ext) Study: Months 1, 3, 6, 9, 12, 15 and at End of Study (assessed up to approximately 20 months)
measure: Change From Study AMB115811 Baseline in Borg CR10 Scale (BCR10S) Immediately Following Exercise at the Indicated Time Points
timeFrame: During Study AMB115811: Months (M) 0 (Baseline), 1, 2, 3, 4, Early Withdrawal (EW); During Extension (Ext) Study: Months 1, 3, 6, 9, 12, 15 and at End of Study (assessed up to approximately 20 months)
measure: Number of Participants With Clinical Worsening of Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
timeFrame: From randomization up to End of Study for the extension study (assessed up to approximately 20 months)
measure: Change From Study AMB115811 Baseline in Quality of Life as Measured by Short Form 36 Health Survey (SF-36)
timeFrame: Baseline from study AMB115811 up to End of Study for the extension study (assessed up to approximately 20 months)
measure: Percent Change From Study AMB115811 Baseline in Plasma N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP)
timeFrame: During Study AMB115811: Months 0 (Baseline), 1, 2, 3, 4, Early Withdrawal (EW); During Extension Study: Months 1, 3, 6, 9, 12, 15 and at End of Study (assessed up to approximately 20 months)
measure: Change From Start of Ambrisentan Treatment in 6 Minutes Walking Distance at the Indicated Time Points
timeFrame: Previous Placebo: Months 0 (Entry visit of the extension), 1, 3, 6, 9, 12; Previous Ambrisentan: Month 0 (Baseline of study AMB115811), 1, 2, 3, 4, Early Withdrawal (EW) (AMB115811), 5, 7, 10, 13, 16, 19; and at End of Study
measure: Change From Start of Ambrisentan Treatment in World Health Organization (WHO) Functional Class (FC) at the Indicated Time Points
timeFrame: Previous Placebo: Months 0 (Entry visit of the extension), 1, 3, 6, 9, 12; Previous Ambrisentan: Month 0 (Baseline of study AMB115811), 1, 2, 3, 4, Early Withdrawal (EW) (AMB115811), 5, 7, 10, 13, 16, 19; and at End of Study
measure: Change From Start of Ambrisentan Treatment in Borg CR10 Scale (BCR10S) Immediately Following Exercise at the Indicated Time Points
timeFrame: Previous Placebo: Months 0 (Entry visit of the extension), 1, 3, 6, 9, 12; Previous Ambrisentan: Month 0 (Baseline of study AMB115811), 1, 2, 3, 4, Early Withdrawal (EW) (AMB115811), 5, 7, 10, 13, 16, 19; and at End of Study
measure: Percent Change From Start of Ambrisentan Treatment in Plasma N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP)
timeFrame: Previous Placebo: Months 0 (Entry visit of the extension), 1, 3, 6, 9, 12; Previous Ambrisentan: Month 0 (Baseline of study AMB115811), 1, 2, 3, 4, Early Withdrawal (EW) (AMB115811), 5, 7, 10, 13, 16, 19; and at End of Study
measure: Time to First Change in Dose of Open-label Ambrisentan Due to Deterioration of Clinical Conditions in Any Participant
timeFrame: From Entry visit of the extension study up to End of Study (assessed up to approximately 16 months)
measure: Time to First Addition of Another Targeted PAH Therapeutic Agent Due to Deterioration of Clinical Condition or Lack of Beneficial Effect With Previous Therapy in Any Participant
timeFrame: From Entry visit of the extension study up to End of Study (assessed up to approximately 16 months)
Other outcomes:
Locations:
city: Boston
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Rosario
country: Argentina
facility: GSK Investigational Site
state: Santa Fe
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Corrientes
country: Argentina
facility: GSK Investigational Site
city: Santa Fe
country: Argentina
facility: GSK Investigational Site
city: Graz
country: Austria
facility: GSK Investigational Site
city: Innsbruck
country: Austria
facility: GSK Investigational Site
city: Vienna
country: Austria
facility: GSK Investigational Site
city: Edmonton
country: Canada
facility: GSK Investigational Site
state: Alberta
city: London
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Wuhan
country: China
facility: GSK Investigational Site
state: Hubei
city: Xian
country: China
facility: GSK Investigational Site
state: Shaanxi
city: Beijing
country: China
facility: GSK Investigational Site
city: Beijing
country: China
facility: GSK Investigational Site
city: Beijing
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Praha 2
country: Czechia
facility: GSK Investigational Site
city: Heidelberg
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Regensburg
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Wuerzburg
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Hannover
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Homburg
country: Germany
facility: GSK Investigational Site
state: Saarland
city: Dresden
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Leipzig
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Ashkelon
country: Israel
facility: GSK Investigational Site
city: Zrifin
country: Israel
facility: GSK Investigational Site
city: Aichi
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Hyogo
country: Japan
facility: GSK Investigational Site
city: Miyagi
country: Japan
facility: GSK Investigational Site
city: Tochigi
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Monterrey NL
country: Mexico
facility: GSK Investigational Site
state: Nuevo León
city: Amsterdam
country: Netherlands
facility: GSK Investigational Site
city: Kemerovo
country: Russian Federation
facility: GSK Investigational Site
city: Tomsk
country: Russian Federation
facility: GSK Investigational Site
city: Riyadh
country: Saudi Arabia
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Majadahonda (Madrid)
country: Spain
facility: GSK Investigational Site
city: Sevilla
country: Spain
facility: GSK Investigational Site
city: Cambridge
country: United Kingdom
facility: GSK Investigational Site
city: Clydebank
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: