Efficacy Study of Ambrisentan in Chinese Patients With Pulmonary Arterial Hypertension (PAH)

NCT01808313 | Completed Phase 3 Results

• 1 other identifier: 115812
• Study Type: interventional
• Target: 134
• Locations: 1 country
• Sites: 12

Brief Summary

This open label, single-arm, non-controlled, multicentre study will determine the effect of ambrisentan on exercise capacity (6MWT) in Chinese subjects with PAH. The study consists of a screening period of 4 weeks, a 12-week primary evaluation period (PEP) and a 12-week dose-adjustment period (DAP). Ambrisentan 5 mg will be administered to eligible subjects for 12 weeks (PEP).

Conditions

Vascular Disease

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in 6-minutes Walk Test (6MWT) at Week 12

  The 6MWT measures the distance that a participant can walk in a period of 6 minutes. Change from Baseline was calculated as the Week 12 value minus the Baseline value. Baseline 6MWT comprised of an average of the last two consecutive measurements prior to dosing that varied by not greater than 10 percent (%). If only one measurement was available, that measurement was used as the Baseline value. The last observation carried forward method was used to impute missing values.

  Baseline and Week 12

Secondary Outcomes (24)

• Change From Baseline in 6MWT at Week 24

  Baseline and Week 24

• Number of Participants With a Change From Baseline in Their World Health Organization (WHO) Functional Classification (FC) at Weeks 12 and 24

  Baseline, Week 12 and Week 24

• Change From Baseline in the Borg Dyspnea Index (BDI) at Weeks 12 and 24

  Baseline, Week 12 and Week 24

• Change From Baseline in the N-Terminal Pro-B-Type Natriuretic Peptide at Weeks 12 and 24

  Baseline, Week 12 and Week 24

• Number of Participants With the Indicated Event, as an Assessment of Time to Clinical Worsening of Pulmonary Arterial Hypertension (PAH) up to Week 24, Assessed as the First Occurrence of a Particular Event

  Baseline up to Week 24

Study Arms (1)

ambrisentan

EXPERIMENTAL

ambrisentan 5 mg will be administered to eligible subjects for 12 weeks

Drug: ambrisentan

Interventions

ambrisentan DRUG

Ambrisentan 5 mg will be administered to eligible subjects for 12 weeks

ambrisentan

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent prior to beginning study-related procedures.
• Subject must be between 18-75 years of age, inclusive, at the Screening Visit.
• Subjects must weight ≥40 kg at the Screening Visit.
• Subjects must have symptomatic or severe PAH (WHO functional class II or III) and be categorised as class 1 PAH (defined by the Updated Clinical Classification of Pulmonary Hypertension 2009), due to iPAH, congenital heart disease-congenital heart defects repaired greater than 1 year prior to screening (i.e., atrial septal defects, ventricular septal defects or patent ductus arteriosus) or CTD-related PAH (e.g., limited scleroderma, diffuse scleroderma, mixed CTD, systemic lupus erythematosus or overlap syndrome).
• NOTE: subjects with portopulmonary hypertension and pulmonary venoocclusive disease are NOT eligible for the study.
• Subjects must have had a right heart catheterisation within 6 months prior to screening and meet all of the following haemodynamic criteria:
• Mean PAP ≥ 25 mmHg.
• A PVR ≥ 240 dyn/sec/cm5.
• A PCWP or left ventricular (LV) end-diastolic pressure of ≤ 15 mmHg.
• Subjects must be able to walk a distance of at least 150 m but no more than 450 m. In addition, the screening and baseline 6MWT test values must not vary by greater than 10% (calculated using (baseline - screening)/screening with the result to be between -0.1 and 0.1).
• Subjects must meet both of the following pulmonary function criteria. The tests should have been completed no more than 24 weeks prior to the Screening Visit, if not performed within the previous 24 weeks, the test must be completed at Day 0:
• Total lung capacity (TLC) ≥ 60% of predicted normal.
• Forced expiratory volume in one second (FEV1) ≥ 55% of predicted normal.
• Subjects receiving CCBs must be on stable therapy (i.e., the dose level does not need to change to maintain disease control) for at least 1 month prior to the Screening Visit.
• Subjects receiving 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (i.e., statins) must be on stable therapy (i.e., the dose level does not need to change to maintain disease control) for at least 12 weeks prior to the Screening Visit.

You may not qualify if:

• The subject has received PAH therapy (PDE-5 inhibitors, ERA, chronic prostanoid\*) within 4 weeks prior to the Screening Visit.
• \*Prostanoid use is classed as chronic when treatment continues for more than 7 days.
• The subject has received intravenous inotropes (e.g., dopamine, dobutamine) within 2 weeks prior to the Screening Visit.
• The subject has previously been discontinued from ERA treatment (e.g., bosentan) due to safety or tolerance issues other than those associated with liver function abnormalities.
• The subject has a serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value that is \>2 x the upper limit of normal (ULN) at the Screening Visit.
• The subject has serum bilirubin value that is \>1.5 x ULN at the Screening Visit.
• The subject has severe hepatic impairment (Child-Pugh class C with or without cirrhosis) at the Screening Visit.
• The subject has severe renal impairment (creatinine clearance \<30 mL/min) at the Screening Visit.
• The subject has clinically significant anaemia, defined as haemoglobin concentration \<10 g/dL or haematocrit \<30% at the Screening Visit.
• The subject has a laboratory result, physical examination finding, medical history incident or other finding, which is a contraindication for treatment with an ERA. Contraindications for treatment include, but are not limited to, evidence of elevated liver functions test or previously experiencing an event that would be defined as a serious AE (SAE) in a clinical trial (see Section 6.3.3.2), which was attributed to treatment with an ERA.
• The subject has severe hypotension (either diastolic blood pressure \<50 mmHg or systolic blood pressure \<90 mmHg).
• The 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 LV dysfunction (defined as LV ejection fraction \<45%), LV outflow obstruction, symptomatic coronary artery disease, autonomic hypotension or fluid depletion.
• The subject has a history of malignancies within the past 5 years, with the exception of basal cell carcinoma of the skin or in situ carcinoma of the cervix.
• The subject has cardiovascular, liver, renal, haematological, gastrointestinal, immunological, endocrine, metabolic or central nervous system disease that, in the opinion of the Investigator, may adversely affect the safety of the subject and/or efficacy of the study drug or severely limit the lifespan of the subject.
• A female subject who is pregnant or breastfeeding.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (12)

GSK Investigational Site

Harbin, Heilongjiang, 150001, China

Location

GSK Investigational Site

Wuhan, Hubei, 430022, China

Location

GSK Investigational Site

Hunan, Hunan, 410008, China

Location

GSK Investigational Site

Changchun, Jilin, 130021, China

Location

GSK Investigational Site

Xi'an, Shaanxi, 710032, China

Location

GSK Investigational Site

Jinan, Shandong, 250012, China

Location

GSK Investigational Site

Beijing, 100032, China

Location

GSK Investigational Site

Beijing, 100034, China

Location

GSK Investigational Site

Beijing, 100037, China

Location

GSK Investigational Site

Beijing, 100038, China

Location

GSK Investigational Site

Shanghai, 200001, China

Location

GSK Investigational Site

Shanghai, 200433, China

Location

Related Publications (3)

• Zhao QH, Peng FH, Yu ZX, Zhang GC, Ji QS, Wang Y, Liu JM, Huo Y, Zeng XF, Li JH, Zi L, Jing ZC. Effect of ambrisentan on echocardiographic and Doppler measures from patients in China with pulmonary arterial hypertension. Expert Rev Cardiovasc Ther. 2020 Sep;18(9):643-649. doi: 10.1080/14779072.2020.1807942. Epub 2020 Sep 29.

  PMID: 32799568 DERIVED

• Li M, Jing ZC, Li Y, Huo Y, Yu Z, Zhang G, Zhu P, Liu J, Ji Q, Wu B, Zhong J, Wang P, Zhu W, Zeng X. Efficacy and safety of ambrisentan in Chinese patients with connective tissue disease-pulmonary arterial hypertension: a post-hoc analysis. BMC Cardiovasc Disord. 2020 Jul 17;20(1):339. doi: 10.1186/s12872-020-01591-1.

  PMID: 32680480 DERIVED

• Huo Y, Jing ZC, Zeng XF, Liu JM, Yu ZX, Zhang GC, Li Y, Wang Y, Ji QS, Zhu P, Wu BX, Zheng Y, Wang PP, Li J. Evaluation of efficacy, safety and tolerability of Ambrisentan in Chinese adults with pulmonary arterial hypertension: a prospective open label cohort study. BMC Cardiovasc Disord. 2016 Oct 22;16(1):201. doi: 10.1186/s12872-016-0361-9.

  PMID: 27770771 DERIVED

MeSH Terms

Conditions

Vascular Diseases

Interventions

ambrisentan

Condition Hierarchy (Ancestors)

Cardiovascular Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2013
• First Posted: March 11, 2013
• Study Start: December 1, 2012
• Primary Completion: August 15, 2014
• Study Completion: August 15, 2014
• Last Updated: June 6, 2017
• Results First Posted: May 12, 2015

Record last verified: 2017-05

Locations

CN (12)