The safety and efficacy of PF-04958242 in age-related sensorineural hearing loss a randomized clinical trial

Martin M. Bednar, Nick De Martinis, Anindita Banerjee, Stephen P Bowditch, Francois Gaudreault, Laura Zumpano, Frank Lin

Research output: Contribution to journalArticle

Abstract

IMPORTANCE 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 a-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. DESIGN, SETTING, AND PARTICIPANTS 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. INTERVENTIONS Three single doses of PF-04958242, an a-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid glutamate-positive allosteric modulator, and placebo. MAIN OUTCOMES AND MEASURES 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 0.35mg, 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 0.35mg, 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 AND RELEVANCE 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.

Original languageEnglish (US)
Pages (from-to)607-613
Number of pages7
JournalJAMA Otolaryngology - Head and Neck Surgery
Volume141
Issue number7
DOIs
StatePublished - Jul 1 2015

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Sensorineural Hearing Loss
Randomized Controlled Trials
Placebos
Safety
Speech Perception
Acids
Pharynx
Hearing Loss
Nose
Cross-Over Studies
Ear
Noise
Glutamic Acid
Therapeutics
Clinical Trials
PF-04958242
Research

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Surgery
  • Medicine(all)

Cite this

The safety and efficacy of PF-04958242 in age-related sensorineural hearing loss a randomized clinical trial. / Bednar, Martin M.; De Martinis, Nick; Banerjee, Anindita; Bowditch, Stephen P; Gaudreault, Francois; Zumpano, Laura; Lin, Frank.

In: JAMA Otolaryngology - Head and Neck Surgery, Vol. 141, No. 7, 01.07.2015, p. 607-613.

Research output: Contribution to journalArticle

Bednar, Martin M. ; De Martinis, Nick ; Banerjee, Anindita ; Bowditch, Stephen P ; Gaudreault, Francois ; Zumpano, Laura ; Lin, Frank. / The safety and efficacy of PF-04958242 in age-related sensorineural hearing loss a randomized clinical trial. In: JAMA Otolaryngology - Head and Neck Surgery. 2015 ; Vol. 141, No. 7. pp. 607-613.
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abstract = "IMPORTANCE 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 a-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. DESIGN, SETTING, AND PARTICIPANTS 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. INTERVENTIONS Three single doses of PF-04958242, an a-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid glutamate-positive allosteric modulator, and placebo. MAIN OUTCOMES AND MEASURES 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 0.35mg, 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 0.35mg, 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 AND RELEVANCE 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.",
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N2 - IMPORTANCE 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 a-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. DESIGN, SETTING, AND PARTICIPANTS 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. INTERVENTIONS Three single doses of PF-04958242, an a-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid glutamate-positive allosteric modulator, and placebo. MAIN OUTCOMES AND MEASURES 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 0.35mg, 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 0.35mg, 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 AND RELEVANCE 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.

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