Figures
- Figure 1–
Change in pulmonary vascular resistance (PVR) from baseline to week 17. a) Per protocol set and b) all-treated set. Data are presented as means and error bars represent 95% confidence limits (CL). Baseline PVR values (mean±sd) for per protocol population for selexipag were 951.9±434.5 dyn·s·cm−5 and for placebo were 826.8±195.8 dyn·s·cm−5. Baseline PVR values (mean± sd) for the all-treated population for selexipag were 948.6±428.0 dyn·s·cm−5 and for placebo were 867.2±379.38 dyn·s·cm−5. TE: treatment effect.
- Figure 2–
Change in 6-min walk distance (6MWD) from baseline to week 17 (all-treated population). Baseline values (mean±sd) for selexipag were 394.7±72.0 m and for placebo were 350.3±123.5 m. Week 17 values (mean±sd) for selexipag were 419.3±106.3 m and for placebo were 350.7±139.6 m. TE: treatment effect; CL: confidence limits.
Tables
- Table 1– Demographics and aetiology of pulmonary arterial hypertension (PAH) (all-treated set)
Placebo Selexipag Subjects n 10 33 Demographics Male/female 2/8 (20.0/80.0) 6/27 (18.2/81.8) Age yrs 53.8±16.3 54.8±16.8 Weight kg 70.6±13.9 68.7±12.4 Caucasian/other 9/1 (90.0/10.0) 29/4 (88.0/12.0) Aetiology of PAH Idiopathic PAH 7 (70.0) 24 (72.7) Hereditary PAH 1 (10.0) 1 (3.0) Anorexigen-induced PAH 2 (6.1) PAH-CTD 2 (20.0) 4 (12.1) PAH associated with congenial heart disease 2 (6.1) Data are presented as n (%) or mean±sd, unless otherwise stated. CTD: connective tissue disease.
- Table 2– Disease characteristics and pulmonary arterial hypertension (PAH) background therapy (all-treated set)
Placebo Selexipag Subjects n 10 33 Time from diagnosis yrs 4.0±3.1 5.5±6.1 PVR dyn·s·cm−5 867.2±379.3 928.6±436.6 6-min walk distance m 350.3±123.5 396.2±71.4 WHO FC I II 2 (20.0) 15 (45.5) III 8 (80.0) 18 (54.5) IV Borg dyspnoea score 4.1±2.6 3.3±2.1+ NT-proBNP pg·mL−1# 2400.9±1269.8¶ 1601.4±2443.0§ Background PAH therapy ERA monotherapy 4 (40.0) 12 (36.4) Sildenafil monotherapy 3 (30.0) 9 (27.2) ERA plus sildenafil 3 (30.0) 12 (36.4) Data are presented as mean±sd or n (%), unless otherwise stated. PVR: pulmonary vascular resistance; WHO FC: World Health Organization functional class; NT-proBNP: N-terminal pro-brain natriuretic peptide; ERA: endothelin receptor antagonist. #: Upper reference values are 100 pg·mL−1 and 172 pg·mL−1 for males aged 45–59 and ≥60 yrs, respectively, and 164 pg·mL−1 and 225 pg·mL−1 for females aged 45–59 and ≥60 yrs, respectively [18]; ¶: n=8; +: n=32; §: n=27.
- Table 3– Baseline, week 17 and change from baseline to week 17 in secondary haemodynamic parameters (all-treated set)
RHC parameter Baseline Week 17 Change from baseline to week 17 Treatment effect (95% CL) Wilcoxon p-value Placebo Selexipag Placebo Selexipag Placebo Selexipag Subjects n 10 33 10 33 10 33 PVR dyn·s·cm−5 867.2±379.3 948.6±428.0# 1090.8±421.3 818.8±416.9# 223.6±355.4 -129.8±309.7# -33.0%ƒ (-47.0– -15.2) 0.0022 Cardiac index L·min·m−2 2.5±0.5 2.4±0.6# 2.3±0.4 2.7±0.6# -0.2±0.2 0.3±0.5# 0.5 (0.13–0.83) 0.01 Mean pulmonary arterial pressure mmHg 54.6±13.8 54.5±15.3# 60.3±20.2 52.8±19.1# 5.7±13.3 -1.7±11.0# -7.4 (-15.9–1.1) 0.1 Right atrial pressure mmHg 11.2±5.7 6.9±3.6¶ 8.3±4.9 7.2±3.6¶ -2.9±2.8 0.3±3.5¶ 3.2 (0.8–5.7) 0.02 Pulmonary capillary wedge pressure mmHg 10.3±2.5 8.5±3.1+ 8.7±1.7 9.1±2.7+ -1.6±2.7 0.6±3.4+ 2.2 (-0.2–4.6) 0.07 SVR dyn·s·cm−5 1399.2±475.1 1572.8±544.7¶ 1687.1±429.2 1452.8±433.6¶ 287.9±227.8 -119.9±498.8¶ -407.8 (-740.2– -75.5) 0.01 Mixed venous oxygen saturation % 60.6±8.4 61.0±12.3§ 58.4±9.3 62.9±10.0§ -2.1±4.1 1.9±10.6 4.1 (-3.8–11.9) 0.3 Data are shown as mean±sd, unless otherwise stated. RHC: right heart catheterisation; CL: confidence limits; PVR: pulmonary vascular resistance; SVR: systemic vascular resistance. #: n=32; ¶: n=30; +: n=31; §: n=26; ƒ: treatment effect calculated at week 17 as the change in the geometric mean expressed as a percentage of the baseline value. Although p-values were calculated for secondary end-points, they are only exploratory in nature as there was no formal statistical hypothesis for secondary end-points.
- Table 4– Baseline and end of study period values, and change from baseline to end of study period in vital sign parameters (safety set)
Vital signs parameter# Baseline End of study period Change from baseline to end of study period Placebo Selexipag Placebo Selexipag Placebo Selexipag Subjects n 10 33 10 33 10 33 Systolic blood pressure mmHg 116.2±11.7 117.3±18.5 112.7±17.3 114.0±15.8 −3.5±17.1 −3.6±17.3 Diastolic blood pressure mmHg 66.8±10.4 65.9±10.9 70.0±9.8 71.8±9.1 3.2±12.8 5.4±11.2 Heart rate beats·min−1 74.8±13.2 75.3±15.8 77.9±10.5 75.2±12.1 3.1±6.0 −0.1±7.7 Data are presented as mean±sd. #: Treatment effect was not calculated for these safety parameters.
- Table 5– Treatment-emergent adverse events during the study (safety set)
Adverse events Placebo Selexipag Subjects 10 33 Patients with ≥1 adverse event 10 31 Adverse events >10% on selexipag Headache 2 22 Jaw pain 12 Pain in an extremity 10 Nausea 9 Nasopharyngitis 2 8 Diarrhoea 1 6 Flushing 6 Dizziness 5 Cough 4 Myalgia 4 Data are presented as n.
Supplementary material
Please note: supplementary material is not edited by the Editorial Office, and is put online as it has been supplied by the author.
Files in this Data Supplement:
- Supplementary tables - Tables 1-3
- Supplemental figure 1 - Study flow chart
