Conţinutul numărului revistei |
Articolul precedent |
Articolul urmator |
184 0 |
SM ISO690:2012 BAJWA, Ednan Khalid, CISLAK, Dawn, PALCZA, John S., FENG, Hwa-ping, MESSINA, Eric J., REYNDERS, Tom, DENEF, Jean-Francois, CORCEA, Vasile, LAI, Eseng, STOCH, Selwyn Aubrey. Effects of an inhaled soluble guanylate cyclase (sGC) stimulator MK-5475 in pulmonary arterial hypertension (PAH). In: Respiratory Medicine, 2023, nr. 206, p. 0. ISSN 0954-6111. DOI: https://doi.org/10.1016/j.rmed.2022.107065 |
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Respiratory Medicine | ||||||
Numărul 206 / 2023 / ISSN 0954-6111 /ISSNe 1532-3064 | ||||||
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DOI:https://doi.org/10.1016/j.rmed.2022.107065 | ||||||
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Background: Novel therapeutics for pulmonary arterial hypertension (PAH) with improved safety/tolerability profiles are needed to address continued high rates of morbidity/mortality. Methods: This Phase 1 study evaluated efficacy/safety of inhaled single-dose MK-5475, an investigational, small-molecule stimulator of soluble guanylate cyclase designed for inhaled delivery via a dry-powder inhaler device, in participants with PAH (Clinicaltrials.gov: NCT03744637). Eligible participants were 18–70 years of age; body mass index ≤35 kg/m2; diagnosis of PAH (Group 1 pulmonary hypertension). In Part 1, participants received double-blind MK-5475 or placebo for safety assessment (primary outcome). In Part 2, 4 panels participated in ≤3 open-label periods. Part 2/Period 1 assessed safety/tolerability. Part 2/Periods 2 and 3, respectively, involved functional respiratory imaging for measuring pulmonary blood volume (secondary outcome) and right heart catheterization for measuring pulmonary vascular resistance (primary outcome). Results: MK-5475 was generally well tolerated without systemic side effects on blood pressure or heart rate up to 24 h post dose. With respect to the primary pharmacodynamic outcome, mean reductions in pulmonary vascular resistance ranged from 21% to 30% across 120 μg and 360 μg doses. Conclusions: Treatment with inhaled single-dose MK-5475 showed rapid and sustained reductions in pulmonary vascular resistance and increases in pulmonary blood volume. MK-5475 was generally well tolerated versus placebo without vasodilatory systemic side effects. The promising pulmonary selectivity and favorable safety/tolerability profile of MK-5475 seen in this study of adult participants with PAH lays the foundation for further clinical development. |
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Cuvinte-cheie Dry-powder inhaler, Functional respiratory imaging, Pulmonary blood volume, Pulmonary selectivity, pulmonary vascular resistance |
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