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

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.