The primary purpose of this study was to evaluate the safety and tolerability of ASP0598 Otic Solution. This study also evaluated the efficacy of ASP0598 otic solution.
This study consisted of a dose escalation (single ascending dose - SAD and multiple ascending dose- MAD) and dose expansion (single dose expansion and/or multiple dose expansion). Dose escalation consisted of up to 4 cohorts for single ascending dose (SAD) and up to 2 cohorts for multiple ascending dose (MAD) with different dose levels. For SAD, after randomization on Day 1, participants received ASP0598 Otic Solution or placebo administration into the affected ear. Participants returned to the site on days 2, 3, 8, 15, 29, and 57 \[end of study (EOS)\]. Day 3 evaluations were only performed for cohorts 1, 2 and 3. For MAD, after randomization on Day 1, participants received ASP0598 Otic Solution or placebo administration into the affected ear and received additional treatments into the same ear on Days 15 and 29. Participants returned to the investigative site on Days 8, 15, 22, 29, 36, 57, and 85 (EOS). Dose expansion was based on the safety and efficacy results from an interim analysis. An interim analysis was conducted after completion of SAD and again after completion of MAD. The single and multiple dose expansion parts of the study were not opened following review of safety and efficacy results of SAD and MAD parts of the study by the DMC per the Interim Analysis Plan.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
36
Stanford Hospital
Palo Alto, California, United States
Breathe Clear Institute
Torrance, California, United States
ENT and Allergy Associates of Florida
Boca Raton, Florida, United States
Number of Participants With Treatment Emergent Adverse Events (TEAEs) in SAD
An adverse event (AE) is any untoward medical occurrence in a participant administered an investigational product (IP), and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of IP whether or not considered related to the IP. A TEAE is defined as an AE observed after starting administration of the study drug through end of study visit.
Time frame: From first dose up to day 57
Number of Participants With AE of Special Interest as Cholesteatoma or Ear Neoplasm in SAD
An AE is any untoward medical occurrence in a participant administered an IP, and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of IP whether or not considered related to the IP. Number of participants with cholesteatoma or ear neoplasm is reported.
Time frame: From first dose up to day 57
Number of Participants With AE of Special Interest as Ototoxic Symptoms (Tinnitus, Sensorineural Hearing Loss, Dizziness) in SAD
An AE is any untoward medical occurrence in a participant administered an IP, and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of IP whether or not considered related to the IP. Number of participants with any ototoxic symptoms (tinnitus, sensorineural hearing loss, dizziness) is reported.
Time frame: From first dose up to day 57
Number of Participants With AE of Special Interest as Otitis Media or Otitis Externa in SAD
An AE is any untoward medical occurrence in a participant administered an IP, and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of IP whether or not considered related to the IP. Number of participants with otitis media or otitis externa is reported.
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Advanced ENT
New Albany, Indiana, United States
Advanced ENT
Louisville, Kentucky, United States
University of Michigan
Ann Arbor, Michigan, United States
Charlotte ENT Associates
Matthews, North Carolina, United States
Piedmont ENT
Winston-Salem, North Carolina, United States
Carolina ENT Clinic
Orangeburg, South Carolina, United States
Richmond ENT
Richmond, Virginia, United States
Time frame: From first dose up to day 57
Change From Baseline in Bone Conduction Hearing at 1, 2, 4 kHz by Pure Tone Audiometry at Week 8/EOS in SAD
PTA was a behavioral and quantitative hearing test to assess hearing. Pure tone air conduction and bone conduction tests were used to determine whether there was any unilateral or bilateral hearing loss, what type of hearing loss was present, which frequencies were impacted, and the magnitude of the hearing loss.
Time frame: Baseline and week 8
Change From Baseline in TVAS at Week 8/EOS in SAD
TVAS was used by participants to rate their tinnitus at baseline and week 8. The scale was a numeric scale and ranged from 0 (not at all strong or loud) to 10 (extremely strong or loud). A lower value indicates less level of discomfort. For the change from baseline, a negative value indicates improvement (less level of discomfort).
Time frame: Baseline and week 8
Number of Participants With TEAEs in MAD
An AE is any untoward medical occurrence in a participant administered an IP, and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of IP whether or not considered related to the IP. A TEAE is defined as an AE observed after starting administration of the study drug through end of study visit.
Time frame: From first dose up to day 85
Number of Participants With AE Special Interest as Cholesteatoma or Ear Neoplasm in MAD
An AE is any untoward medical occurrence in a participant administered an IP, and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of IP whether or not considered related to the IP. Number of participants with cholesteatoma or ear neoplasm is reported.
Time frame: From first dose up to day 85
Number of Participants With AE of Special Interest as Ototoxic Symptoms (Tinnitus, Sensorineural Hearing Loss, Dizziness) in MAD
An AE is any untoward medical occurrence in a participant administered an IP, and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of IP whether or not considered related to the IP. Number of participants with any Ototoxic symptoms (tinnitus, sensorineural hearing loss, dizziness) is reported
Time frame: From first dose up to day 85
Number of Participants With AE of Special Interest as Otitis Media or Otitis Externa in MAD
An AE is any untoward medical occurrence in a participant administered an IP, and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of IP whether or not considered related to the IP. Number of participants with otitis media or otitis externa is reported.
Time frame: From first dose up to day 85
Change From Baseline in Bone Conduction Hearing at 1, 2, 4 kHz by Pure Tone Audiometry at Week 12/EOS in MAD
PTA was a behavioral and quantitative hearing test to assess hearing. Pure tone air conduction and bone conduction tests were used to determine whether there was any unilateral or bilateral hearing loss, what type of hearing loss was present, which frequencies were impacted, and the magnitude of the hearing loss.
Time frame: Baseline and week 12
Change From Baseline in TVAS at Week 12/EOS in MAD
TVAS was used by participants to rate their tinnitus at baseline and week 12. The scale was a numeric scale and ranged from 0 (not at all strong or loud) to 10 (extremely strong or loud). A lower value indicates less level of discomfort. For the change from baseline, a negative value indicates improvement (less level of discomfort).
Time frame: Baseline and week 12
Number of Participants With Complete Closure of Tympanic Membrane Perforation (TMP) at Week 8 for SAD
Tympanic membrane perforation is a hole in the thin membrane that separates the ear canal from the middle ear. TMP closure is defined as microscopic TMP closure without presence of pin hole.
Time frame: Week 8
Number of Participants With Complete Closure of TMP at Week 12 for Dose Expansion
Tympanic membrane perforation is a hole in the thin membrane that separates the ear canal from the middle ear. TMP closure is defined as microscopic TMP closure without presence of pin hole.
Time frame: Week 12
Change From Baseline in the Ratio of TMP Size Per Total Area of Tympanic Membrane at Week 8 for SAD
Ratio of TMP size per total area of tympanic membrane calculation was performed by central imaging vendor and measured in percentage.
Time frame: Baseline and week 8
Change From Baseline in the Ratio of TMP Size Per Total Area of Tympanic Membrane at Week 12 for Dose Expansion
Ratio of TMP size per total area of tympanic membrane calculation was performed by central imaging vendor and was measured by percentage.
Time frame: Baseline and week 12
Change From Baseline in TMP Size at Week 8 for SAD
TMP size calculation was be performed by central imaging vendor.
Time frame: Baseline and week 8
Change From Baseline in TMP Size at Week 12 for Dose Expansion
TMP size calculation was be performed by central imaging vendor.
Time frame: Baseline and week 12
Number of Participants With Complete Closure of TMP at Week 12 for MAD
Tympanic membrane perforation is a hole in the thin membrane that separates the ear canal from the middle ear. TMP closure is defined as microscopic TMP closure without presence of pin hole.
Time frame: Week 12
Number of Participants With Complete Closure of TMP at Week 16 for Dose Expansion
Tympanic membrane perforation is a hole in the thin membrane that separates the ear canal from the middle ear. TMP closure is defined as microscopic TMP closure without presence of pin hole.
Time frame: Week 16
Change From Baseline in the Ratio of TMP Size Per Total Area of Tympanic Membrane at Week 12 for MAD
Ratio of TMP size per total area of tympanic membrane calculation was performed by central imaging vendor and measured in percentage.
Time frame: Baseline and week 12
Change From Baseline in the Ratio of TMP Size Per Total Area of Tympanic Membrane at Week 16 for Dose Expansion
Ratio of TMP size per total area of tympanic membrane calculation was performed by central imaging vendor and measured in percentage.
Time frame: Baseline and week 16
Change From Baseline in TMP Size at Week 12 for MAD
TMP size calculation was be performed by central imaging vendor.
Time frame: Baseline and week 12
Change From Baseline in TMP Size at Week 16 for Dose Expansion
TMP size calculation was be performed by central imaging vendor.
Time frame: Baseline and week 16