Denufosol: A review of studies with inhaled P2Y2 agonists that led to Phase 3

Pulmonary Pharmacology and Therapeutics

Volumn 21, Issue 4, 2008, Pages 600-607

  Kellerman, Donald ^a   Rossi Mospan, Andrea ^a   Engels, Jean ^a   Schaberg, Amy ^a   Gorden, JoAnn ^a   Smiley, Lynn ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Cystic fibrosis; Denufosol; P2Y2 receptor agonist

Indexed keywords

AZTREONAM; CHLORIDE CHANNEL; DENUFOSOL; DIQUAFOSOL; DORNASE ALFA; PLACEBO; PURINERGIC P2Y2 RECEPTOR; TOBRAMYCIN; TRANSMEMBRANE CONDUCTANCE REGULATOR;

AIRWAY; CLINICAL TRIAL; COUGHING; CYSTIC FIBROSIS; DRUG BIOAVAILABILITY; DRUG HALF LIFE; DRUG TOLERABILITY; FORCED EXPIRATORY VOLUME; HUMAN; HYDRATION; ISOTOPE LABELING; MUCOCILIARY CLEARANCE; NEBULIZER; PHARMACODYNAMICS; PHASE 3 CLINICAL TRIAL; PRIORITY JOURNAL; RESPIRATORY EPITHELIUM; REVIEW; SIDE EFFECT; SPUTUM;

ADMINISTRATION, INHALATION; CLINICAL TRIALS, PHASE I AS TOPIC; CLINICAL TRIALS, PHASE II AS TOPIC; CYSTIC FIBROSIS; DEOXYCYTOSINE NUCLEOTIDES; FEMALE; FORCED EXPIRATORY VOLUME; HUMANS; MALE; POLYPHOSPHATES; RECEPTORS, PURINERGIC P2; URACIL NUCLEOTIDES; URIDINE;

EID: 47049114203     PISSN: 10945539     EISSN: 15229629     Source Type: Journal    
DOI: 10.1016/j.pupt.2007.12.003     Document Type: Review

References (32)

1. Davis P.B., Drumm M., and Konstan M.W. Cystic fibrosis. Am J Respir Crit Care Med 154 (1996) 1229-1256
2. Boucher R.C. Human airway ion transport. Am J Respir Crit Care Med 150 (1994) 271-281
3. Mickle J.E., and Cutting G.R. Clinical implications of cystic fibrosis transmembrane conductance regulator mutations. Clinic Chest Med 19 3 (1998) 443-458
4. Cystic Fibrosis Foundation. Patient registry 2004 annual report, Bethesda, MD. ©2005 Cystic Fibrosis Foundation. 〈http://www.cff.org/aboutcf〉.
5. Ramsey B.W. Management of pulmonary disease in patients with cystic fibrosis. N Engl J Med 335 3 (1996) 179-188
6. Knowles M.R., Clarke L.L., and Boucher R.C. Activation by extracellular nucleotides of chloride secretion in the airway epithelia of patients with cystic fibrosis. New Engl J Med 325 (1991) 533-538
7. Mason S.J., Paradiso A.M., and Boucher R.C. Regulation of transepithelial ion transport and intracellular calcium by extracellular ATP in human normal and cystic fibrosis airway epithelium. Br J Pharmacol 103 (1991) 1649-1656
8. Jiang C., Finkbeiner W.E., Widdecombe J.A., et al. Altered fluid transport across airway epithelium in cystic fibrosis. Science 262 (1993) 424-427
9. Benali R., Pierrot D., Zahm J.M., et al. Effect of extracellular ATP and UTP on fluid transport by human nasal epithelial cells in culture. Am J Respir Cell Mol Biol 10 (1994) 363-368
10. Lethem M.I., Dowell M.L., Van Scott M., et al. Nucleotide regulation of goblet cells in human airway epithelial explants: normal exocytosis in cystic fibrosis. Am J Respir Cell Mol Biol 9 (1993) 315-322
11. Drutz D., Shaffer C., LaCroix K., et al. Uridine 5′-triphosphate (UTP) regulates mucociliary clearance via purinergic receptor activation. Drug Dev Res 37 (1996) 185
12. Olivier K.N., Bennett W.D., Hohneker K.W., et al. Acute safety and effects on mucociliary clearance of aerosolized uridine 5′-triphosphate±amiloride in normal human adults. Am J Respir Crit Care Med 154 (1996) 217-223
13. 2 receptor agonist for the treatment of cystic fibrosis. J Pharmacol Exp Ther 302 (2002) 871-880
14. ® delivery system. Am J Respir Crit Care Med 161 3 (2000) A815 (May 2000. Abstract)
15. 2 agonist INS365 on mucociliary clearance in smokers. J Allergy Clin Immunol Suppl. (2001) S164 (Abstract 541)
16. 2 receptor agonists as a treatment for patients with cystic fibrosis lung disease. Adv Drug Deliv Rev 54 (2002) 1463-1474
17. Kellerman DJ, Mills-Wilson M, Johnson C. Pharmacokinetics of INS37217 after inhaled and intravenous administration in healthy volunteers. Pediatr Pulmonol 2004;38 (Suppl. 27):249. North American cystic fibrosis conference, October 14-17, 2003 (Abstract #178).
18. Data on File. Inspire Pharmaceuticals, Inc., Durham, NC, USA.
19. Bhalla K., Birkhofer M., Grant S., et al. Phase I clinical and pharmacologic study of deoxycytidine. Leukemia 2 (1988) 709-710
20. Grant S., Baker M., and Bhalla K. Phase I study of a continuous infusion of high-dose ara-C in conjunction with a fixed dose of 2′-deoxycytidine (IND 28108) in patients with refractory leukemia: an interim report. Leukemia 7 (1993) 1933-1938
21. van Groeningen C.J., Leyva A., Kraal I., et al. Clinical and pharmacokinetic studies of prolonged administration of high-dose uridine intended for rescue from 5-FU toxicity. Cancer Treat Rep 70 6 (1986) 745-750
22. 2 receptor agonist: results of a phase 1/phase 2 multicenter study in mild to moderate cystic fibrosis. Pediatr Pulmonol 39 4 (2005) 339-348
23. 2 receptor agonist, in patients with mild to moderate cystic fibrosis: results of a phase 2 multi-center study. Pediatr Pulmonol 2004;(Suppl. 27) (Abstract # 177).
24. Mathews D, Schaberg A, Kellerman D, LaVange L, Engels J, Shaffer C. INS37217 (denufosol tetrasodium) inhalation solution: phase 1 & 2 clinical experience. J Cyst Fibros 2005;4 (Suppl. 1):S27 (Abstract #97).
25. LaVange L, Engels J, Knowles M, Deterding R, Mathews D, Shaffer C. Safety and efficacy of INS37217 inhalation solution in patient subgroups: results of a phase 2 multicentre trial. J Cyst Fibros 2005;4 (Suppl. 1):S27 (Abstract #98).
26. Smiley L, Rossi A, Mathews D, Engels J, Schaberg A, Kellerman D, et al. Denufosol tetrasodium inhalation solution: Results from two phase 2 trials in CF patients with mild to moderate lung disease. J Cyst Fibros 2006;5 (Suppl. 1):S11 (Abstract #47).
27. Elkins M.R., Robinson M., Rose B.R., Harbour C., Moriarity C.P., Marks G.B., et al. A controlled trial of long-term inhaled hypertonic saline in patients with cystic fibrosis. New Eng J Med 354 3 (2006) 229-240
28. Fuchs H.J., Borowitz D.S., Christiansen D.H., Morris E.M., Nash M.L., Ramsey B.W., et al. Effect of aerosolized recombinant human DNase on exacerbations of respiratory symptoms and on pulmonary function in patients with cystic fibrosis. N Engl J Med 331 (1994) 637-642
29. Gibson R.L., Burns J.L., and Ramsey B.W. Pathophysiology and management of pulmonary infections in cystic fibrosis. Am J Resp Crit Care Med 168 (2003) 918-951
30. Tauber J., Davitt W.F., Bokosky J.E., Nichols K.K., Yerxa B.R., Schaberg A.E., et al. Double-masked, placebo-controlled safety and efficacy trial of diquafosol tetrasodium (INS365) ophthalmic solution for the treatment of dry eye. Cornea 23 8 (2004) 784-792
31. Nichols KK, King-Smith PE, Nichols JJ, Kellerman D. Tear film thickness and thinning rate following a six-week trial of 2% diquafosol tetrasodium vs. placebo in dry eye patients. IOVS 2006 (Abstract B449).
32. Kellerman D.J., Morshige R.J., and Otulana B.A. Issues on regulatory approval of mucoactive drugs. In: Rubin B.K., and Van der Schans C.P. (Eds). Therapy for mucus-clearance disorders (2004), Dekker Press, New York 395-412