A DUE TRIAL

A DUE Is the First and Only
Phase 3 Clinical Trial of a
Single-Tablet Combination Therapy vs ERA or PDE5
Inhibitor Monotherapy for PAH WHO FC II-III¹

Study design: Multinational, multicenter, double-blind, randomized, and active-controlled phase 3 study of a once-daily, single-tablet dual combination of macitentan 10 mg and tadalafil 40 mg. The primary endpoint was change from baseline in pulmonary vascular resistance at Week 16.²

Change in PVR at Week 16
(OPSYNVI® [n=70] vs macitentan
[n=35])²

29^%

REDUCTION

P<0.0001; 95% CL, –39%, –18%

Primary Endpoint | Ratio of Geometric Means 0.71; P<0.0001 (95% CL; 0.61-0.82)

Change in PVR at Week 16
(OPSYNVI® [n=86] vs tadalafil
[n=44])²

28^%

REDUCTION

P<0.0001; 95% CL, –36%, –20%

Primary Endpoint | Ratio of Geometric Means 0.72; P<0.0001 (95% CL; 0.64-0.80)

Treatment with OPSYNVI® (macitentan/tadalafil) resulted in greater reductions in PVR compared with macitentan and tadalafil alone²

STUDY DESIGN

Patients were randomized into treatment arms depending on their treatment status at baseline¹

Select inclusion criteria¹:

mPAP ≥25 mmHg
PAWP or left ventricle end-diastolic pressure ≤15 mmHg
PVR ≥3 Woods units (ie, ≥240 dyn•s/cm⁵)

WHO FC II-III
PAH-specific treatment-naïve or on a stable dose of ERA or PDE5 inhibitor monotherapy for at least 3 months

^*One treatment-naïve patient did not receive any treatment and was not included in the full analysis set.

BASELINE CHARACTERISTICS

Patient demographics at baseline (N=187)^1,2

Treatment History

47^%

Previously
treated

53^%

Treatment
naïve

17^%ERA

30^%PDE5i

Etiology

35^%

PAH-CTD

51^%

Idiopathic
PAH

3^%PAH-CHD

6^%Other^†

5^%Heritable
PAH

Mean Age

years (range 18-80)

Gender

78^%

Female

22^%

Male

WHO Functional Class

51^%

FC II

49^%

FC III

^†Other etiologies include PAH associated with HIV infection, portal hypertension, corrected CHD, or drugs or toxins.¹

A DUE TITRATION

Titration used in A DUE trial¹

The double-blind treatment period began with a 2-week tadalafil titration phase followed by a maintenance phase:

WEEK1

Patients received macitentan 10 mg once daily, tadalafil 20 mg once daily, or both as separate tablets, plus respective placebos
Patients who were receiving a stable dose of a PDE5 inhibitor at baseline did not require titration, and tadalafil 40 mg was administered

WEEK2

Tadalafil was up-titrated to 40 mg once daily

Maintenance
Phase

Started on Day 15
Patients received either OPSYNVI®, macitentan 10 mg once daily, or tadalafil 40 mg once daily, along with respective placebos depending on treatment arm

Prespecified stable doses were¹:

40 mg

tadalafil

60 mg to
120 mg

sildenafil

10 mg

vardenafil

NOTE

Make sure patients are receiving a stable dose of PDE5i before transitioning directly to OPSYNVI® 10 mg/40 mg without titration.²

Review safety

and see how OPSYNVI® compares to monotherapy

A DUE Safety

A DUE Is the First and Only Phase 3 Clinical Trial of a Single-Tablet Combination Therapy vs ERA or PDE5 Inhibitor Monotherapy for PAH WHO FC II-III1

Patients were randomized into treatment arms depending on their treatment status at baseline1

Select inclusion criteria1:

Patient demographics at baseline (N=187)1,2

Treatment History

Etiology

Mean Age

Gender

WHO Functional Class

Titration used in A DUE trial1

What were the dosages for patients already receiving a PDE5i at baseline?

What were the dosages for patients already receiving a PDE5i at baseline?

40 mg

60 mg to 120 mg

10 mg

A DUE Is the First and Only
Phase 3 Clinical Trial of a
Single-Tablet Combination Therapy vs ERA or PDE5
Inhibitor Monotherapy for PAH WHO FC II-III¹

Patients were randomized into treatment arms depending on their treatment status at baseline¹

Select inclusion criteria¹:

Patient demographics at baseline (N=187)^1,2

Titration used in A DUE trial¹

60 mg to
120 mg