Phase 2 randomized safety and efficacy trial of nebulized denufosol tetrasodium in cystic fibrosis.

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Deterding RR, Lavange LM, Engels JM, Mathews DW, Coquillette SJ, Brody AS, Millard SP, Ramsey BW

Phase 2 randomized safety and efficacy trial of nebulized denufosol tetrasodium in cystic fibrosis.

Am J Respir Crit Care Med. 2007 Aug 15;176(4):362-9. Epub 2007 Apr 19.

PubMed ID

17446337 [ View in PubMed

]

Abstract

RATIONALE: Denufosol tetrasodium is a selective P2Y(2) agonist that enhances mucosal hydration and mucus clearance by activating Cl(-) secretion and inhibiting epithelial Na(+) transport through a non-cystic fibrosis transmembrane conductance regulator mechanism in the lung. OBJECTIVES: To examine the safety and efficacy of 28 days of treatment with denufosol compared with placebo in patients with mild cystic fibrosis. METHODS: The study was a randomized, double-blind, multi-center, 28-day, phase 2 clinical trial of denufosol tetrasodium inhalation solution (20, 40, or 60 mg) versus placebo (normal saline). Patients with screening FEV(1) >or= 75% of predicted normal value and not treated with inhaled antibiotics for the past 30 days were randomized to receive one of three doses of denufosol or placebo administered three times daily. MEASUREMENTS AND MAIN RESULTS: Eighty-nine patients were randomized and received the study drug, 94% completed the study, and 98% were compliant with dosing. All treatments were generally well tolerated, with no dose-response trends observed with respect to safety parameters. The most common adverse event was cough (52% of placebo patients and 47% of denufosol patients). Five patients discontinued early due to adverse events, two on placebo and three on denufosol. Denufosol patients (pooling active doses) had significantly higher changes from baseline in FEV(1) (P = 0.006), FEF(25%-75%) (P = 0.008), FVC (P = 0.022), and FEV(1)/FVC (P = 0.047) than placebo patients at the end of the study. CONCLUSIONS: Denufosol administered three times daily for 28 days appeared to be safe and well tolerated in this population with mild cystic fibrosis and provided preliminary evidence of potential benefit in lung function.

DrugBank Data that Cites this Article

Drugs

Denufosol

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Denufosol	P2Y purinoceptor 2	Protein	Humans	Unknown	Not Available	Details