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

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT01894022
• Date of registration: 03/07/2013
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline
• Public title: 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
• 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: January 23, 2014
• Target sample size: 19
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT01894022
• Study type: Interventional
• Study design: Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Argentina, Austria, Canada, China, Czech Republic, Czechia, Germany, Israel, Japan, Korea, Republic of, Mexico, Netherlands, Russian Federation, Saudi Arabia, Spain, United Kingdom, United States

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Hypertension

Intervention(s)

Drug: Ambrisentan 5 mg

Primary Outcome(s)

Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern at Any Time Post Entry Visit [Time Frame: Post entry visit of the extension study and up to End of Study (assessed up to approximately 16 months)]

Number of Participants With Creatinine Values of Potential Clinical Concern at Any Time Post Entry Visit [Time Frame: 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)]

Change From Study AMB115811 Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Assessed at the Indicated Time Points [Time Frame: 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)]

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 [Time Frame: 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)]

Change From Study AMB115811 Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points [Time Frame: 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)]

Change From Study AMB115811 Baseline in Red Blood Cell Count and Reticulocytes at the Indicated Time Points [Time Frame: 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)]

Change From Study AMB115811 Baseline in Weight at the Indicated Time Points [Time Frame: 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)]

Time to First Change in Dose of Open-label Ambrisentan Due to Tolerability Issues in Any Participant [Time Frame: From the Entry visit of the extension study up to approximately 16 months]

Change From Study AMB115811 Baseline in Hematocrit at the Indicated Time Points [Time Frame: 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)]

Change From Study AMB115811 Baseline in Heart Rate at the Indicated Time Points [Time Frame: 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)]

Change From Study AMB115811 Baseline in Mean Corpuscle Volume at the Indicated Time Points [Time Frame: 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)]

Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) [Time Frame: From entry visit of the extension study up to approximately 16 months]

Secondary Outcome(s)

Change From Study AMB115811 Baseline in Borg CR10 Scale (BCR10S) Immediately Following Exercise at the Indicated Time Points [Time Frame: 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)]

Change From Study AMB115811 Baseline in Quality of Life as Measured by Short Form 36 Health Survey (SF-36) [Time Frame: Baseline from study AMB115811 up to End of Study for the extension study (assessed up to approximately 20 months)]

Percent Change From Study AMB115811 Baseline in Plasma N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) [Time Frame: 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)]

Change From Study AMB115811 Baseline (BL) in World Health Organization (WHO) Functional Class (FC) at the Indicated Time Points [Time Frame: 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)]

Time to First Change in Dose of Open-label Ambrisentan Due to Deterioration of Clinical Conditions in Any Participant [Time Frame: From Entry visit of the extension study up to End of Study (assessed up to approximately 16 months)]

Change From Start of Ambrisentan Treatment in Borg CR10 Scale (BCR10S) Immediately Following Exercise at the Indicated Time Points [Time Frame: 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]

Change From Start of Ambrisentan Treatment in World Health Organization (WHO) Functional Class (FC) at the Indicated Time Points [Time Frame: 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]

Change From Start of Ambrisentan Treatment in 6 Minutes Walking Distance at the Indicated Time Points [Time Frame: 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]

Change From Study AMB115811 Baseline in the 6 Minutes Walking Distance (6MWD) at the Indicated Time Points [Time Frame: 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)]

Number of Participants With Clinical Worsening of Chronic Thromboembolic Pulmonary Hypertension (CTEPH) [Time Frame: From randomization up to End of Study for the extension study (assessed up to approximately 20 months)]

Percent Change From Start of Ambrisentan Treatment in Plasma N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) [Time Frame: 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]

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 [Time Frame: From Entry visit of the extension study up to End of Study (assessed up to approximately 16 months)]

Secondary ID(s)

116457

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 08/06/2017
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01894022