Selexipag: an oral, selective prostacyclin receptor agonist for the treatment of pulmonary arterial hypertension

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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.
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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.

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)

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
RHC parameter	Placebo	Selexipag	Placebo	Selexipag	Placebo	Selexipag	Treatment effect (95% CL)
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
Vital signs parameter^#	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)