Clinical Study to Compare the Efficacy and Safety of Macitentan and Tadalafil Monotherapies With the Corresponding Fixed-dose Combination Therapy in Subjects With Pulmonary Arterial Hypertension (PAH)

Summary

Combination therapy in pulmonary arterial hypertension (PAH) has been the subject of active investigation for more than a decade, with the benefit of targeting different pathways known to be involved in the pathogenesis of the disease. Adherence to prescribed therapy has an impact on clinical outcomes. Reducing the pill/tablet count and frequency has a major impact on patients' adherence to therapies and therefore the observed clinical outcomes. One way to simplify treatment is to use fixed-dose combination (FDC) products that combine multiple treatments targeting different pathways into a single tablet. This study aims to demonstrate that the FDC of macitentan and tadalafil is more effective than therapy with 10 mg of macitentan alone or 40 mg of tadalafil alone. This phase 3 study will evaluate the efficacy and safety at 16 weeks of an FDC (macitentan 10 mg and tadalafil 40 mg) against these two PAH-approved therapies given as monotherapy to further confirm the added value of the FDC.

Timeline

Start

2019-07-29

Primary completion

2022-08-23

Completion

2024-09-27

Publications

• Ford HJ, Chin KM, Fan F, Friberg M, Grunig E, Hauser JA, Pannaux M, Rofael H, Jansa P. Long-Term Treatment with Single-Tablet Combination of Macitentan and Tadalafil in Pulmonary Arterial Hypertension: Results from A DUE and Its Open-Label Period. Adv Ther. 2026 May;43(5):2106-2124. doi: 10.1007/s12325-026-03525-3. Epub 2026 Mar 12.
• Fan F, Sun L, Yang Z, Wang L, Wang Q, Li J, Gu H, Xie W, Zhang N, Bin J, Rofael H, Friberg M, Hauser JA. Macitentan Plus Tadalafil Single-Tablet Combination Therapy in Chinese Patients With Pulmonary Arterial Hypertension: A Subgroup Analysis of the A DUE Study. Pulm Circ. 2025 Nov 16;15(4):e70194. doi: 10.1002/pul2.70194. eCollection 2025 Oct.
• Grunig E, Jansa P, Fan F, Hauser JA, Pannaux M, Morganti A, Rofael H, Chin KM. Randomized Trial of Macitentan/Tadalafil Single-Tablet Combination Therapy for Pulmonary Arterial Hypertension. J Am Coll Cardiol. 2024 Jan 30;83(4):473-484. doi: 10.1016/j.jacc.2023.10.045.

Drugs

Indications