Randomized, double-blind, multinational, placebo-controlled, 12-week, phase 3 study
Primary endpoint1
Baseline characteristics1
6MWD = 6-minute walk distance; m = meters; mPAP = mean pulmonary arterial pressure; PAH = pulmonary arterial hypertension; PATENT-1 = Pulmonary Arterial Hypertension Soluble Guanylate Cyclase-Stimulator Trial; PVR = pulmonary vascular resistance; WHO FC = World Health Organization Functional Class.
Adempas can be used as monotherapy or in combination
ITT = intention-to-treat; WHO FC = World Health Organization Functional Class.
Right heart catheterization was performed at the beginning and end of the study period in 339 patients.
*Placebo-adjusted mean change from baseline.
NT-proBNP = n-terminal pro-brain natriuretic peptide.
*Time to clinical worsening was a combined endpoint defined as death (all-cause mortality), heart/lung transplantation, atrial septostomy, hospitalization due to persistent worsening of PH, start of new PAH-specific treatment, persistent decrease in 6MWD, and persistent worsening of WHO Functional Class.
†Patients may have had more than one event of clinical worsening.
Efficacy data are shown for the Adempas 2.5 mg and placebo arms.
Data from the PAH-CTD subgroup analysis are exploratory as PATENT-1 was not designed to show statistically significant differences in subgroup populations. The primary efficacy analysis was performed on data from the modified intent-to-treat population (all patients who were randomized and received one or more doses of the study drug). The data presented here are observed values and are analyzed descriptively; observed values were used due to the small sample size and the retrospective, exploratory nature of the analysis.
*Exploratory subgroup analysis.
6MWD = 6-minute walk distance; m = meters; mm Hg = millimeters mercury; mPAP = mean pulmonary arterial pressure; PATENT-1 = Pulmonary Arterial Hypertension Soluble Guanylate Cyclase-Stimulator Trial; PVR = pulmonary vascular resistance; WHO FC = World Health Organization Functional Class.
*Week 12/last observation until Week 12.
ERA = endothelin receptor antagonist; PCA = prostacyclin analogues.
The data in these analyses should be considered exploratory and not designed to detect statistically significant differences in subgroups. The analysis is limited due to the post hoc sub-classification of patients with PAH-CTD by patients’ medical histories using MedDRA terms. The low patient numbers in the PAH-SSc and PAH-other defined CTD subgroups should be taken into consideration when interpreting the data.3
*Week 12/last observation until Week 12.
ITT population.
*Week 12/last observation until Week 12. ITT population. Missing values, where the patient withdrew or dies, were imputed at Week 12 according to the last observed value.
*Time to clinical worsening was a combined endpoint defined as death (all-cause mortality), heart/lung transplantation, atrial septostomy, hospitalization due to persistent worsening of PH, start of new PAH-specific treatment, persistent decrease in 6MWD, and persistent worsening of WHO Functional Class.
†Patients may have had more than one event of clinical worsening.
An open-label extension study (PATENT-2) included 396 patients who had completed PATENT-1. At the cut-off date in the PATENT-2 study, the mean treatment duration for the total population was 1146 days (±479). The probabilities of survival at 1 and 2 years were 97% and 93%, respectively. Without a control group, these data must be interpreted cautiously.
– About 10%-18% of patients with SSc or SLE develop PAH over their lifetime8,9
ITT = intention to treat; NT-proBNP = n-terminal pro-brain natriuretic peptide; SLE = systemic lupus erythematosus; SSc = systemic scleroderma.
References:
References: