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OPSYNVI® (macitentan and tadalafil)
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OPSYNVI - Treatment Discontinuation Due to Adverse Events in Phase 3 A DUE Study
Last Updated: 06/03/2025
SUMMARY
- A DUE was a prospective, multicenter, double-blind, randomized, active-controlled, triple-dummy, parallel group, group-sequential, adaptive phase 3 study (NCT03904693) that evaluated the efficacy and safety of OPSYNVI as a single-tablet combination therapy (STCT) vs macitentan 10 mg and tadalafil 40 mg monotherapies in patients with pulmonary arterial hypertension (PAH).1
- The incidence of treatment discontinuation due to adverse events (AEs) among patients receiving OPSYNVI in the double-blind phase of the study was 8.4%.
- In the 24-month open-label extension of the A DUE study, 19/185 (10.3%) patients prematurely discontinued study treatment due to 1 or more AEs.2
CLINICAL DATA
The A DUE Study
triple-dummy, parallel group, group-sequential, adaptive phase 3 study (NCT03904693) that evaluated the efficacy and safety of OPSYNVI as a STCT vs macitentan 10 mg and tadalafil 40 mg monotherapies in patients with PAH, including treatment-naïve patients and patients on prior endothelin receptor antagonist (ERA) or phosphodiesterase type-5 inhibitor (PDE-5i) monotherapy at baseline.1
Of the 294 patients screened between October 15, 2019, and August 23, 2022, 187 were randomized. Overall, 108 patients were assigned to receive OPSYNVI, 35 to macitentan
10 mg monotherapy, and 44 to tadalafil 40 mg monotherapy. Eleven patients prematurely discontinued the study treatment (OPSYNVI, n=9 [8.4%]; macitentan 10 mg, n=0; tadalafil 40 mg, n=2 [4.5%]; see Table: AEs Leading to Treatment Discontinuation in the A DUE Study).1
| Treatment-naïve and Prior ERA Strata: Macitentan 10 mg Monotherapy | Treatment-naïve and Prior PDE-5i Strata: Tadalafil 40 mg Monotherapy | Treatment-naïve and Prior ERA or PDE-5i Strata: OPSYNVI | |
|---|---|---|---|
| Patients randomized, n | 35 | 44 | 108a |
| Patients treated (SAS), n | 35 | 44 | 107a |
| Patients who prematurely discontinued the study treatment owing to ≥1 AE,b | 0 | 2 (4.5) | 9 (8.4) |
| Reasons for discontinuation, n (%) | |||
| Myalgia | - | - | 1 (0.9) |
| Pulmonary veno-occlusive disease | - | - | 1 (0.9) |
| Anemia | - | - | 1 (0.9) |
| Swelling of the face | - | - | 1 (0.9) |
| Angioedema | - | - | 1 (0.9) |
| Decreased hemoglobin | - | - | 1 (0.9) |
| Hypotension | - | - | 1 (0.9) |
| Edema of the lower extremities | - | - | 1 (0.9) |
| Liver transaminase elevation | - | 1 (2.3) | 1 (0.9) |
| Reason not recorded during the double-blind treatment | - | 1 (2.3) | - |
| Abbreviations: AE, adverse event; ERA, endothelin receptor antagonist; PDE-5i, phosphodiesterase type-5 inhibitor; SAS, safety analysis set.aOPSYNVI, n=108 (prior ERA, n=21; prior PDE-5i, n=37; treatment-naïve, n=50); 1 treatment-naïve patient did not receive any treatment and was not included in the full analysis set. Of the 49 treatment-naïve patients in the OPSYNVI arm, 40 completed the study and 6 discontinued the study treatment due to AEs.bTreatment-emergent period is defined as the first intake of the study treatment in the double-blind period up to and including minimum of end-of-treatment of the double-blind period plus 30 days or the start date of the open-label treatment. | |||
Ford et al (2025)2 reported results from the 24-month open-label extension of the phase 3 A DUE study that evaluated the long-term effect of OPSYNVI on survival, exercise capacity, reduction of N-terminal pro B-type natriuretic peptide (NT-proBNP), hospitalizations, and safety and tolerability in patients with PAH. Among the 185 patients evaluated, which included patients from both the double-blind and open-label treatment phases, 19 (10.3%) patients prematurely discontinued study treatment due to 1 or more AEs.
Literature Search
A literature search of MEDLINE®
References
| 1 | Grünig E, Jansa P, Fan F, et al. Randomized trial of macitentan/tadalafil single-tablet combination therapy for pulmonary arterial hypertension. J Am Coll Cardiol. 2024;83(4):473-484. |
| 2 | |
| 3 |