Effect of difelikefalin, a selective kappa opioid receptor agonist, on respiratory depression: A randomized, double‐blind, placebo‐controlled trial
| Autor: | Catherine Munera, Eugene R. Viscusi, Beatrice Setnik, Joseph W. Stauffer, Sukirti N. Bagal, Marc C. Torjman |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Respiratory rate Adolescent Placebo-controlled study RM1-950 Placebo General Biochemistry Genetics and Molecular Biology Article Placebos chemistry.chemical_compound Young Adult Double-Blind Method Piperidines Respiratory Rate Medicine Humans General Pharmacology Toxicology and Pharmaceutics Respiratory system Adverse effect Cross-Over Studies business.industry General Neuroscience Research Incidence Pruritus Receptors Opioid kappa General Medicine Hypoesthesia Articles Carbon Dioxide Middle Aged Crossover study Healthy Volunteers chemistry Oxygen Saturation Anesthesia Female Therapeutics. Pharmacology Public aspects of medicine RA1-1270 medicine.symptom business Respiratory Insufficiency Difelikefalin |
| Zdroj: | Clinical and Translational Science Clinical and Translational Science, Vol 14, Iss 5, Pp 1886-1893 (2021) |
| ISSN: | 1752-8062 1752-8054 |
| Popis: | Difelikefalin, a selective kappa opioid receptor agonist designed to limit central nervous system (CNS) penetration, is under development for the treatment of pruritus. Its hydrophilic, small‐peptidic structure limits CNS entry, minimizing potential CNS‐mediated adverse events (AEs). This study assessed the effect of difelikefalin on key relevant measures of respiratory depression in healthy volunteers. This single‐center, randomized, double‐blind, placebo‐controlled, three‐way crossover study enrolled healthy, nonsmoking volunteers. Subjects were randomized to 1 of 3 treatment sequences of difelikefalin (1.0 or 5.0 mcg/kg i.v.) or placebo on sequential days with an intervening 24 (±2) h washout period. The primary end points included incidence of increased end‐tidal carbon dioxide (ETCO2) greater than or equal to 10 mm Hg versus baseline or a level greater than 50 mm Hg sustained greater than or equal to 30 seconds, and incidence of reduction in saturation of peripheral oxygen (SpO2) to less than 92% sustained greater than or equal to 30 seconds. Secondary end points included incidence of reduced respiratory rate and other safety assessments. Fifteen subjects were randomized and completed the study. No subject on placebo or difelikefalin met the increased ETCO2 or reduced SpO2 primary end point criteria for respiratory depression. All respiratory measures in each group remained near baseline values during 4‐h postdose observations. No subject met the reduced respiratory rate criterion or experienced clinically significant changes in ETCO2, SpO2, or respiratory rate. The most commonly reported treatment‐emergent AEs (TEAEs; ≥20% of subjects) were paresthesia, hypoesthesia, and somnolence in the difelikefalin arms. All TEAEs were mild and resolved without intervention. Difelikefalin 1.0 and 5.0 mcg/kg i.v. did not produce respiratory depression. |
| Databáze: | OpenAIRE |
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