title: The Safety and Efficacy of PF-04958242 in Age-Related Sensorineural Hearing Loss: A Randomized Clinical Trial.
abstract: OBJECTIVE
  To our knowledge, this is the first study to assess the potential to pharmacologically improve auditory function in adults with age-related sensorineural hearing loss.
  
  
  OBJECTIVE
  To explore the potential for the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid potentiator mechanism to affect auditory function in individuals with mild to moderate age-related sensorineural hearing loss.
  
  
  METHODS
  A randomized, double-blind, placebo-controlled, single-dose, 3-way crossover study was conducted in 3 academic ear, nose, and throat clinics and 2 private clinical research centers between December 22, 2011, and February 26, 2013. Participants were 50- to 75-year-old men and women of nonchildbearing potential with mild to moderate sensorineural hearing loss.
  
  
  METHODS
  Three single doses of PF-04958242, an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate-positive allosteric modulator, and placebo.
  
  
  METHODS
  Pure-tone average, speech discrimination score, and speech in noise testing change from baseline at 1 and 5 hours after a single dose of PF-04958242.
  
  
  RESULTS
  The treatment was safe and well tolerated. The estimates for the primary end point change from baseline in pure-tone average compared with placebo at 1 hour were -0.77 (95% CI, -2.14 to 0.59) and 0.37 (95% CI, -0.97 to 1.72) for 0.27 and 0.35 mg, respectively. At 5 hours the estimates were -0.57 (95% CI, -2.43 to 1.29) and -0.56 (95% CI, -2.45 to 1.33) for 0.27 and 0.35 mg, respectively. No significant change from baseline was demonstrated compared with placebo in the primary or secondary study end points at 1 or 5 hours after receiving treatment.
  
  
  CONCLUSIONS
  To our knowledge, this clinical trial is the first study of a pharmacologic treatment for age-related sensorineural hearing loss and provides information with regard to study design, end points, variability, data characteristics, and operational feasibility to guide the design of future hearing loss trials.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01518920.
authors.affiliation: Neuroscience Research Unit, Pfizer Worldwide Research & Development, Cambridge, Massachusetts.
authors.forename: Martin M
authors.initials: MM
authors.lastname: Bednar
authors.affiliation: Neuroscience Research Unit, Pfizer Worldwide Research & Development, Cambridge, Massachusetts.
authors.forename: Nick
authors.initials: N
authors.lastname: DeMartinis
authors.affiliation: Biotherapeutics Clinical Research & Development, Pfizer Worldwide Research & Development, Cambridge, Massachusetts.
authors.forename: Anindita
authors.initials: A
authors.lastname: Banerjee
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Stephen
authors.initials: S
authors.lastname: Bowditch
authors.affiliation: Neuroscience Research Unit, Pfizer Worldwide Research & Development, Cambridge, Massachusetts.
authors.forename: Francois
authors.initials: F
authors.lastname: Gaudreault
authors.affiliation: Clinical Operations, Pfizer Worldwide Research & Development, New York, New York.
authors.forename: Laura
authors.initials: L
authors.lastname: Zumpano
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Frank R
authors.initials: FR
authors.lastname: Lin
mesh_terms: D000367:Age Factors; D000368:Aged; D001299:Audiometry; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013449:Sulfonamides / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013876:Thiophenes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: C000600968:PF-04958242; D013449:Sulfonamides; D013876:Thiophenes