Evaluation of efficacy, safety and tolerability of Ambrisentan in Chinese adults with pulmonary arterial hypertension: a prospective open label cohort study

Abstract

BackgroundAlthough several new drugs have been approved in recent years, pulmonary arterial hypertension (PAH) remains a rapidly progressive disease with a poor prognosis. Ambrisentan, a selective endothelin type A antagonist, has been approved for treatment of PAH. This open label study assessed the efficacy and safety of ambrisentan in Chinese subjects with PAH.MethodsEligible patients with PAH (World Health Organisation [WHO] functional class [FC] II orIII) were enrolled and received Ambrisentan (5 mg) once daily for a 12-week preliminary evaluation period, and a 12-week dose-adjustment period (dose titration to 10 mgallowed). Endpoints included: change from baseline in 6-Minute Walk Distance (6-MWD), N-Terminal Pro B-Type Natriuretic Peptide (NT-pro-BNP), WHO FC, Borg Dyspnoea Index (BDI), clinical worsening of PAH and incidences of adverse events (AE).ResultsOne hundred thirty-three subjects (85 % women, mean age: 36 years) with PAH (WHOFC II or III) were enrolled and received ambrisentan (5 mg) once daily for a 12-week preliminary evaluation period, and a 12-week dose-adjustment period. Mean (SD) duration of drug exposure was 161.7 (27.13) days. Ambrisentan (average daily dose of 6.27 mg) significantly improved exercise capacity (6MWD) from baseline (mean: 377.1 m [m]) at week 12 (+53.6 m, p < 0.001) (primary endpoint). Improvement in exercise capacity was noted as early as week 4, and was sustained up to week 24 (+ 64.4 m, p < 0.001). NT-pro-BNP plasma levels decreased significantly (p < 0.001) at week 12 (−861.4 ng/L) and week 24 (−806 ng/L) from baseline (mean: 1600.7 ng/L). The WHO FC showed improvements for 44 subjects at week 12 and 51 subjects at week 24. BDI scores decreased significantly at week 12 (−0.3, p < 0.001) and week 24 (−0.2, p = 0.003) from baseline (mean: 2.5). Four patients died during the study (sudden cardiac death [n = 2], cerebral haemorrhage [n = 1], cardiac failure [n = 1]). Drug related adverse events occurred in 34.3 % of subjects; peripheral oedema (11.2 %) and flushing (8.2 %) occurred most frequently.ConclusionAmbrisentan (5 and 10 mg, orally) significantly improved the exercise capacity in Chinese PAH subjects with a safety profile similar to that observed in global studies.Trial registrationNCT No. (ClinicalTrials.gov): NCT01808313; Registration date (first time): February 28, 2013.Electronic supplementary materialThe online version of this article (doi:10.1186/s12872-016-0361-9) contains supplementary material, which is available to authorized users.

Efficacy and safety of ambrisentan in Chinese patients with connective tissue disease-pulmonary arterial hypertension: a post-hoc analysis

“…An open-label, phase IIIb, single-arm study was conducted in China in patients with PAH between 21 December 2012 and 15 August 2014 (NCT01808313). The detailed study design and results of the study have been reported elsewhere [17]. This post-hoc analysis was conducted using a subgroup of patients with CTD-PAH and IPAH/HPAH.…”

“…This post-hoc analysis was conducted using a subgroup of patients with CTD-PAH and IPAH/HPAH. Briefly, eligible patients received oral 5 mg ambrisentan once daily for 12 weeks in the primary evaluation period, followed by a 12-week dose adjustment period, during which the dose of ambrisentan was titrated to 10 mg depending on patients' dose tolerance [17].…”

“…CTD patients were in an inactive state after the treatment of steroid with or without immunosuppresants. The detailed inclusion and exclusion criteria of patients have been described previously [17].…”

“…Of the 134 patients with PAH enrolled in the primary study [17], all received at least one dose of ambrisentan and were included in the safety analyses. One subject did not have post-baseline assessments, and thus 133 patients were included in the ITT population.…”

“…In addition to the observed heterogeneity in treatment response, there is insufficient data in the existing literature for CTD-PAH subgroup that necessitate the understanding of specific therapeutic needs in managing individuals with different ethnicities. In the recent study conducted in Chinese patients with PAH, it was shown that ambrisentan improved exercise capacity, measured by 6-min walk test (6MWT) in the 24-week treatment period [17]. This study included about 53% patients with CTD at baseline, thus providing an opportunity to evaluate whether ambrisentan is efficacious in patients with CTD-PAH to the same extent as in the overall PAH population.…”