{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T23:16:51Z","timestamp":1774567011566,"version":"3.50.1"},"reference-count":23,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2001,7,24]],"date-time":"2001-07-24T00:00:00Z","timestamp":995932800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Pulmonology"],"published-print":{"date-parts":[[2001,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cystic fibrosis (CF) is characterized by defective cystic fibrosis transmembrane regulator (CFTR) expression and function, associated with abnormal ion transport and mucociliary clearance, and clinical lung disease. Triphosphate nucleotides such as uridine\u20105\u2032\u2010triphosphate (UTP) and INS 365, may be useful for CF through actions, mediated via P2Y<jats:sub>2<\/jats:sub> extracellular receptors, on chloride and liquid secretion, and ciliary beat frequency. INS 365 may offer chemical stability advantages over UTP. In a randomized, double\u2010blind, multicenter phase I study, we studied the safety and maximally tolerated dose of escalating, single doses of aerosolized INS 365, in adult and pediatric patients with mild to moderate CF lung disease (FEV<jats:sub>1<\/jats:sub>\u2009\u2265\u200945% predicted). In four successive dose cohorts of adult patients (n\u2009=\u200912 per cohort, age\u2009\u2265\u200918 years) and four successive pediatric dose cohorts (n\u2009=\u200912 per cohort, age 5\u201312 years), patients were randomized 3:1 active\/placebo (0.9% saline) to evaluate doses of 20, 40, 80, and 100 mg INS 365 delivered by nebulizer (Pari Star\u2122). Sputum was collected pre\u2010 and post\u2010dosing to obtain preliminary results on clinical efficacy. After each dose cohort, a Data Safety Monitoring Committee (DSMC) reviewed the data.<\/jats:p><jats:p>Forty\u2010eight adult and 36 pediatric patients completed the protocol (up to 100 mg for adults, 80 mg for pediatric patients). The predominant adverse events were cough, wheezing, chest tightness, and a decrease in FEV<jats:sub>1<\/jats:sub> (occurring in 8\/48 adults, and 5\/36 pediatric patients), which occurred predominantly in the 80\u2010mg and 100\u2010mg dose cohorts. Though a few adult patients had a tendency to increase sputum production, there was little consistent effect noted on sputum production in this acute, single\u2010dose study.<\/jats:p><jats:p>The data suggest that aerosolized INS 365 is safe when delivered at single doses of up to 40 mg in adults and children with CF, but that higher doses are unlikely to be tolerated. Pediatr Pulmonol. 2001; 32:122\u2013128. \u00a9 2001 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ppul.1098","type":"journal-article","created":{"date-parts":[[2004,10,28]],"date-time":"2004-10-28T23:11:04Z","timestamp":1099005064000},"page":"122-128","source":"Crossref","is-referenced-by-count":29,"title":["Safety of aerosolized INS 365 in patients with mild to moderate cystic fibrosis: Results of a phase I multi\u2010center study"],"prefix":"10.1002","volume":"32","author":[{"given":"Peadar G.","family":"Noone","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Hamblett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Accurso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moira 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