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 language | English (US) |
|---|---|
| Pages (from-to) | 607-613 |
| Number of pages | 7 |
| Journal | JAMA Otolaryngology - Head and Neck Surgery |
| Volume | 141 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 1 2015 |
Fingerprint
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 journal › Article
}
TY - JOUR
T1 - The safety and efficacy of PF-04958242 in age-related sensorineural hearing loss a randomized clinical trial
AU - Bednar, Martin M.
AU - De Martinis, Nick
AU - Banerjee, Anindita
AU - Bowditch, Stephen P
AU - Gaudreault, Francois
AU - Zumpano, Laura
AU - Lin, Frank
PY - 2015/7/1
Y1 - 2015/7/1
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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84937847249&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84937847249&partnerID=8YFLogxK
U2 - 10.1001/jamaoto.2015.0791
DO - 10.1001/jamaoto.2015.0791
M3 - Article
C2 - 25997115
AN - SCOPUS:84937847249
VL - 141
SP - 607
EP - 613
JO - Archives of Otolaryngology
JF - Archives of Otolaryngology
SN - 2168-6181
IS - 7
ER -