Ralinepag Phase II Open-Label Extension Study in Patients with Pulmonary Arterial Hypertension.
Adv Ther
; 41(3): 1062-1074, 2024 Mar.
Article
em En
| MEDLINE
| ID: mdl-38198043
ABSTRACT
INTRODUCTION:
Ralinepag is a potent, titratable, orally administered prostacyclin (IP) receptor agonist to treat pulmonary arterial hypertension. A phase II randomized, double-blind, parallel-group, placebo-controlled, 22-week study of immediate-release (IR) ralinepag safety and efficacy met its primary endpoint, significantly reducing pulmonary vascular resistance (PVR) compared with placebo. This phase II open-label extension (OLE) study assessed long-term safety and tolerability of ralinepag.METHODS:
Participants were eligible for the OLE if they completed the parent study or experienced a clinical worsening event while receiving placebo. Those previously receiving IR ralinepag remained on their current dose, and participants formerly administered placebo were titrated to the highest tolerated dose. Participants were transitioned to an extended-release ralinepag formulation toward the end of the OLE. The primary objective evaluated long-term safety and tolerability; secondary endpoints included changes in 6-min walk distance (6MWD), World Health Organization/New York Heart Association functional class, clinical worsening, and hemodynamic measures.RESULTS:
In total, 45/61 participants enrolled in the OLE study, 30 from the IR ralinepag group and 15 from the placebo group. The most common adverse events (AEs) were known prostacyclin-related effects (e.g., headache, 64.4%; diarrhea, 37.8%; jaw pain, 33.3%). There was a notable decline in AEs after reaching and maintaining a stable dose. At month 24 after entering the OLE, 6MWD significantly increased by a mean of 36.3 m (P = 0.004) from OLE baseline, and most participants remained stable in their functional class (84.8%). Post-baseline PVR in 1 or 2 years decreased by a median of 52.2 dyn.s/cm5 and mean pulmonary arterial pressure decreased by a median of 2.0 mmHg (P = 0.05).CONCLUSION:
Ralinepag produced sustained, durable improvements in 6MWD along with durable reductions in PVR and a manageable AE profile. Most participants continuing treatment with ralinepag maintained functional measures throughout the OLE and those switching from placebo to ralinepag often experienced functional improvements.
Pulmonary arterial hypertension is a rare disease caused by elevated pressure in the blood vessels connecting the heart to the lungs. A previous phase 2 study found that ralinepag significanlty reduced pulmonary vascular resistance (the force or resistance that blood encounters as it flows through the blood vessels in the lungs) compared with placebo. This clinical study of 45 patients investigated whether ralinepag was safe and effective for long-term use to treat people with pulmonary arterial hypertension. All participants received ralinepag twice daily until a new once daily pill was available later in the study. The primary endpoints were long-term safety and tolerability, and secondary endpoints included exercise capacity, impact on daily life (functional class), clinical worsening, and hemodynamic measures (metrics to measure how well the heart is working). The study found that ralinepag had a manageable side effect profile, with a decrease in side effects for patients who continued taking ralinepag over time. Moreover, the study showed that ralinepag improved the ability to exercise, maintained functional measures, and helped to reduce pressure in the blood vessels connecting the heart to the lungs over a 24-month period for participants with pulmonary arterial hypertension.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carbamatos
/
Hipertensão Arterial Pulmonar
/
Acetatos
Tipo de estudo:
Clinical_trials
Limite:
Humans
Idioma:
En
Revista:
Adv Ther
Assunto da revista:
TERAPEUTICA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Espanha