Chronic Tympanic Membrane Perforation
Conditions
Keywords
ASP0598
Brief summary
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.
Detailed description
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.
Interventions
DRUGASP0598
ASP0598 Otic solution was administered onto the Tympanic Membrane (TM) through the external auditory canal via syringe.
OTHERPlacebo
Placebo matched to ASP0598 Otic solution was administered onto the TM through the external auditory canal via syringe.
Sponsors
Astellas Pharma Global Development, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Subject has chronic tympanic membrane perforation (CTMP) documented as persisting longer than 3 months. * A female subject is eligible to participate if she is not pregnant and at least one of the following conditions applies: * Not a woman of childbearing potential (WOCBP) OR * WOCBP who agrees to follow the contraceptive guidance starting at screening and for at least 28 days after investigational product (IP) application. * Female subject must agree not to breastfeed starting at drug application on Day 1 and for at least 28 days after IP application. * Female subject must not donate ova starting on Day 1 and for at least 28 days after investigational product (IP) application. * A male subject with female partner(s) of child-bearing potential must agree to use contraception starting on Day 1 and for at least 28 days after IP application. * A male subject must not donate sperm starting on Day 1 and for at least 28 days after IP application. * Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom from Day 1 and for at least 28 days after IP application. * Subject must be willing and able to comply with the study requirements including refraining from using prohibited concomitant medications. * Subject agrees not to participate in another interventional study during the study period.
Exclusion criteria
* Subject has one of following conditions that may affect the ipsilateral side of the ear with chronic tympanic membrane perforation (CTMP): * Perforation involving 3 or more quadrants. * Pin hole perforation (only for the expansion cohort). * Presence of tympanosclerosis adjacent to the perforation. * Perforation involves malleus erosion. * Absent malleus. * Marginal perforation (i.e., involving the annulus or exposing the handle of malleus). * Tympanic membrane perforation (TMP) caused by electric/slag/blast/burn injury. * Post radiated TMP. * History of tympanic membrane repair by any type of live tissue. * Active otorrhea or active treatment for otorrhea within the last 3 months prior to Screening. * Bellucci otorrhea grade 3 or above. * Active external ear canal inflammation (otitis externa, dermatitis) or within the last 3 months prior to Screening. * Active diagnosis of Eustachian Tube dysfunction or diagnosis within 6 months prior to Screening. * Craniofacial abnormalities, History of head and neck surgery within the last 3 months prior to Screening, history of radiation to head and neck. * Recent (within 2 weeks) diagnosis of upper respiratory tract infection. * Presence or history of cholesteatoma. * Presence of pars-flaccida or pars tensa retraction or adhesion. * Presence or history of tumors of the middle or external ear. * Contraindications to tympanic membrane closure. * An audiometric finding indicates a characteristic of Carhart's notch which is an increase in bone conduction threshold with a peak at 2,000 hertz (Hz). * Only hearing ear or better hearing ear and the contralateral ear ≥ 40 dB (decibels) by average four-frequency (500, 1000, 2000 and 4000 Hz). * Whole circumference of the tympanic membrane perforation is not visible by endoscope. * Presence/history of eosinophilic otitis media in either ear. * Subject has a presence of adhesive otitis media in the contralateral ear. * Subject has a presence of any wound healing systemic condition. * Subject has Obstructive Sleep Apnea where the subject is required to use Continuous Positive Airway Pressure (CPAP) during the study period. * Subject is exposed in their daily life to high volume of water into the ear canal (e.g., swimmer or surfer). * Subject has health conditions that would prevent him/her from fulfilling the study requirements on the basis of medical history and laboratory test (Serum Chemistries, complete blood count \[CBC\] with Differential, Urinalysis) results at the screening visit. * Subject is receiving any other investigational agents during study participation. * Subject has any form of substance abuse, or psychiatric illness/social situations that would limit compliance with study requirements, or a condition that could invalidate communication. * Subject has a known or suspected hypersensitivity to ASP0598, or any components of the formulation used. * Subject has had previous exposure with ASP0598. * Subject is unlikely to comply with the visits scheduled in the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in TVAS at Week 12/EOS in MAD | Baseline and week 12 | 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). |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) in SAD | From first dose up to day 57 | 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. |
| Number of Participants With AE of Special Interest as Cholesteatoma or Ear Neoplasm in SAD | From first dose up to day 57 | 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. |
| Number of Participants With AE of Special Interest as Ototoxic Symptoms (Tinnitus, Sensorineural Hearing Loss, Dizziness) in SAD | From first dose up to day 57 | 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. |
| Number of Participants With AE of Special Interest as Otitis Media or Otitis Externa in SAD | From first dose up to day 57 | 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. |
| Change From Baseline in Bone Conduction Hearing at 1, 2, 4 kHz by Pure Tone Audiometry at Week 8/EOS in SAD | Baseline and week 8 | 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. |
| Change From Baseline in TVAS at Week 8/EOS in SAD | Baseline and week 8 | 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). |
| Number of Participants With TEAEs in MAD | From first dose up to day 85 | 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. |
| Number of Participants With AE Special Interest as Cholesteatoma or Ear Neoplasm in MAD | From first dose up to day 85 | 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. |
| Number of Participants With AE of Special Interest as Ototoxic Symptoms (Tinnitus, Sensorineural Hearing Loss, Dizziness) in MAD | From first dose up to day 85 | 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 |
| Number of Participants With AE of Special Interest as Otitis Media or Otitis Externa in MAD | From first dose up to day 85 | 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. |
| Change From Baseline in Bone Conduction Hearing at 1, 2, 4 kHz by Pure Tone Audiometry at Week 12/EOS in MAD | Baseline and week 12 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Complete Closure of Tympanic Membrane Perforation (TMP) at Week 8 for SAD | Week 8 | 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. |
| Number of Participants With Complete Closure of TMP at Week 12 for Dose Expansion | Week 12 | 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. |
| Change From Baseline in the Ratio of TMP Size Per Total Area of Tympanic Membrane at Week 8 for SAD | Baseline and week 8 | Ratio of TMP size per total area of tympanic membrane calculation was performed by central imaging vendor and measured in percentage. |
| Change From Baseline in the Ratio of TMP Size Per Total Area of Tympanic Membrane at Week 12 for Dose Expansion | Baseline and week 12 | Ratio of TMP size per total area of tympanic membrane calculation was performed by central imaging vendor and was measured by percentage. |
| Change From Baseline in TMP Size at Week 8 for SAD | Baseline and week 8 | TMP size calculation was be performed by central imaging vendor. |
| Change From Baseline in TMP Size at Week 12 for Dose Expansion | Baseline and week 12 | TMP size calculation was be performed by central imaging vendor. |
| Number of Participants With Complete Closure of TMP at Week 12 for MAD | Week 12 | 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. |
| Number of Participants With Complete Closure of TMP at Week 16 for Dose Expansion | Week 16 | 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. |
| Change From Baseline in the Ratio of TMP Size Per Total Area of Tympanic Membrane at Week 12 for MAD | Baseline and week 12 | Ratio of TMP size per total area of tympanic membrane calculation was performed by central imaging vendor and measured in percentage. |
| Change From Baseline in the Ratio of TMP Size Per Total Area of Tympanic Membrane at Week 16 for Dose Expansion | Baseline and week 16 | Ratio of TMP size per total area of tympanic membrane calculation was performed by central imaging vendor and measured in percentage. |
| Change From Baseline in TMP Size at Week 12 for MAD | Baseline and week 12 | TMP size calculation was be performed by central imaging vendor. |
| Change From Baseline in TMP Size at Week 16 for Dose Expansion | Baseline and week 16 | TMP size calculation was be performed by central imaging vendor. |
Countries
United States
Participant flow
Recruitment details
Participants with Chronic Tympanic Membrane Perforation (CTMP) documented as persisting longer than 3 months were enrolled in this study.
Pre-assignment details
Single Ascending Dose (SAD) Multiple Ascending Dose (MAD)
Participants by arm
| Arm | Count |
|---|---|
| SAD: 0.03 mcg Participants received single dose of 0.03 mcg ASP0598 Otic Solution into the affected ear on day 1 and returned to the investigative site for assessments on days 2, 3, 8, 15, 29, and 57 (EOS). | 4 |
| SAD: ASP0598 0.15 mcg Participants received single dose of 0.15 mcg ASP0598 Otic Solution into the affected ear on Day 1 and returned to the investigative site for assessments on days 2, 3, 8, 15, 29, and 57 (EOS). | 4 |
| SAD: ASP0598 0.75 mcg Participants received single dose of 0.75 mcg ASP0598 Otic Solution into the affected ear on day 1 and returned to the investigative site for assessments on days 2, 3, 8, 15, 29, and 57 (EOS). | 4 |
| SAD: ASP0598 2.25 mcg Participants received single dose of 2.25 mcg ASP0598 Otic Solution into the affected ear on day 1 and returned to the investigative site for assessments on days 2, 3, 8, 15, 29, and 57 (EOS). | 4 |
| SAD: Placebo Participants received single dose of placebo matched to ASP0598 Otic Solution into the affected ear on day 1 and returned to the investigative site for assessments on days 2, 3, 8, 15, 29, and 57 (EOS). | 4 |
| MAD: 0.75 mcg Participants received multiple doses of 0.75 mcg ASP0598 Otic Solution into the affected ear on days 1, 15 and 29 and returned to the investigative site for assessments on days 8, 15, 22, 29, 36, 57, and 85 (EOS). | 6 |
| MAD: ASP0598 2.25 mcg Participants received multiple doses of 2.25 mcg ASP0598 Otic Solution into the affected ear on days 1, 15 and 29 and returned to the investigative site for assessments on days 8, 15, 22, 29, 36, 57, and 85 (EOS). | 6 |
| MAD: Placebo Participants received multiple doses of placebo matched to ASP0598 Otic Solution into the affected ear on days 1, 15 and 29 and returned to the investigative site for assessments on days 8, 15, 22, 29, 36, 57, and 85 (EOS). | 4 |
| Total | 36 |
Baseline characteristics
| Characteristic | Total | MAD: Placebo | MAD: ASP0598 2.25 mcg | MAD: 0.75 mcg | SAD: 0.03 mcg | SAD: Placebo | SAD: ASP0598 2.25 mcg | SAD: ASP0598 0.75 mcg | SAD: ASP0598 0.15 mcg |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 45.11 Years STANDARD_DEVIATION 13.9 | 47.5 Years STANDARD_DEVIATION 14 | 44.3 Years STANDARD_DEVIATION 20.1 | 36.5 Years STANDARD_DEVIATION 18.6 | 32.5 Years STANDARD_DEVIATION 7 | 51.5 Years STANDARD_DEVIATION 8.1 | 49.5 Years STANDARD_DEVIATION 16 | 50.8 Years STANDARD_DEVIATION 7.1 | 48.3 Years STANDARD_DEVIATION 20.4 |
| Bone Conduction Hearing at 1, 2,4 kilohertz (kHz) by Pure Tone Audiometry (PTA) 1 kHz | 9.8 decibles STANDARD_DEVIATION 9.9 | 3.8 decibles STANDARD_DEVIATION 4.8 | 14.2 decibles STANDARD_DEVIATION 15.3 | 1.7 decibles STANDARD_DEVIATION 4.1 | 6.3 decibles STANDARD_DEVIATION 7.5 | 12.5 decibles STANDARD_DEVIATION 9.6 | 11.3 decibles STANDARD_DEVIATION 11.1 | 22.5 decibles STANDARD_DEVIATION 20.2 | 6.3 decibles STANDARD_DEVIATION 6.3 |
| Bone Conduction Hearing at 1, 2,4 kilohertz (kHz) by Pure Tone Audiometry (PTA) 2 kHz | 17.6 decibles STANDARD_DEVIATION 12.5 | 10.0 decibles STANDARD_DEVIATION 5.8 | 20.8 decibles STANDARD_DEVIATION 14.6 | 10.0 decibles STANDARD_DEVIATION 13.4 | 11.3 decibles STANDARD_DEVIATION 10.3 | 30.0 decibles STANDARD_DEVIATION 21.2 | 22.5 decibles STANDARD_DEVIATION 13.2 | 25.0 decibles STANDARD_DEVIATION 14.7 | 11.3 decibles STANDARD_DEVIATION 7.5 |
| Bone Conduction Hearing at 1, 2,4 kilohertz (kHz) by Pure Tone Audiometry (PTA) 4 kHz | 19.5 decibles STANDARD_DEVIATION 14.2 | 17.5 decibles STANDARD_DEVIATION 9.6 | 21.7 decibles STANDARD_DEVIATION 15.4 | 9.2 decibles STANDARD_DEVIATION 17.7 | 6.3 decibles STANDARD_DEVIATION 6.3 | 27.5 decibles STANDARD_DEVIATION 25.3 | 28.8 decibles STANDARD_DEVIATION 11.1 | 30.0 decibles STANDARD_DEVIATION 24.2 | 15.0 decibles STANDARD_DEVIATION 4.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants | 4 Participants | 6 Participants | 6 Participants | 4 Participants | 3 Participants | 4 Participants | 3 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 29 Participants | 3 Participants | 5 Participants | 5 Participants | 4 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants |
| Ratio of TMP size per total area of tympanic membrane | 11.8 Percentage of total area of TM STANDARD_DEVIATION 7.8 | 8.7 Percentage of total area of TM STANDARD_DEVIATION 6.7 | 17.1 Percentage of total area of TM STANDARD_DEVIATION 9.6 | 18.8 Percentage of total area of TM STANDARD_DEVIATION 13.4 | 10.3 Percentage of total area of TM STANDARD_DEVIATION 5.1 | 7.3 Percentage of total area of TM STANDARD_DEVIATION 3.8 | 15.8 Percentage of total area of TM STANDARD_DEVIATION 11.7 | 4.7 Percentage of total area of TM STANDARD_DEVIATION 3.8 | 11.6 Percentage of total area of TM STANDARD_DEVIATION 8.1 |
| Sex: Female, Male Female | 18 Participants | 1 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 4 Participants | 3 Participants |
| Sex: Female, Male Male | 18 Participants | 3 Participants | 4 Participants | 4 Participants | 2 Participants | 2 Participants | 2 Participants | 0 Participants | 1 Participants |
| Tinnitus Visual Analog Scale (TVAS) | 2.2 Score on a scale STANDARD_DEVIATION 2.6 | 2.5 Score on a scale STANDARD_DEVIATION 2.1 | 3.3 Score on a scale STANDARD_DEVIATION 2.1 | 0.7 Score on a scale STANDARD_DEVIATION 1.6 | 1.0 Score on a scale STANDARD_DEVIATION 2 | 2.5 Score on a scale STANDARD_DEVIATION 2.9 | 3.0 Score on a scale STANDARD_DEVIATION 3.8 | 3.0 Score on a scale STANDARD_DEVIATION 3.6 | 1.5 Score on a scale STANDARD_DEVIATION 3 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 4 |
| other Total, other adverse events | 4 / 4 | 1 / 4 | 3 / 4 | 3 / 4 | 2 / 4 | 6 / 6 | 5 / 6 | 4 / 4 |
| serious Total, serious adverse events | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 4 |
Outcome results
Primary
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
Population: SAF population with available data was analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAD: 0.03 mcg | Change From Baseline in Bone Conduction Hearing at 1, 2, 4 kHz by Pure Tone Audiometry at Week 12/EOS in MAD | 2 kHz | 1.0 decibles | Standard Deviation 2.2 |
| SAD: 0.03 mcg | Change From Baseline in Bone Conduction Hearing at 1, 2, 4 kHz by Pure Tone Audiometry at Week 12/EOS in MAD | 1 kHz | 1.0 decibles | Standard Deviation 2.2 |
| SAD: 0.03 mcg | Change From Baseline in Bone Conduction Hearing at 1, 2, 4 kHz by Pure Tone Audiometry at Week 12/EOS in MAD | 4 kHz | 2.0 decibles | Standard Deviation 7.6 |
| SAD: 0.15 mcg | Change From Baseline in Bone Conduction Hearing at 1, 2, 4 kHz by Pure Tone Audiometry at Week 12/EOS in MAD | 2 kHz | -2.5 decibles | Standard Deviation 5.2 |
| SAD: 0.15 mcg | Change From Baseline in Bone Conduction Hearing at 1, 2, 4 kHz by Pure Tone Audiometry at Week 12/EOS in MAD | 1 kHz | -3.3 decibles | Standard Deviation 6.1 |
| SAD: 0.15 mcg | Change From Baseline in Bone Conduction Hearing at 1, 2, 4 kHz by Pure Tone Audiometry at Week 12/EOS in MAD | 4 kHz | -1.7 decibles | Standard Deviation 6.8 |
| SAD: 0.75 mcg | Change From Baseline in Bone Conduction Hearing at 1, 2, 4 kHz by Pure Tone Audiometry at Week 12/EOS in MAD | 1 kHz | -1.7 decibles | Standard Deviation 2.9 |
| SAD: 0.75 mcg | Change From Baseline in Bone Conduction Hearing at 1, 2, 4 kHz by Pure Tone Audiometry at Week 12/EOS in MAD | 4 kHz | -6.7 decibles | Standard Deviation 2.9 |
| SAD: 0.75 mcg | Change From Baseline in Bone Conduction Hearing at 1, 2, 4 kHz by Pure Tone Audiometry at Week 12/EOS in MAD | 2 kHz | 0.0 decibles | Standard Deviation 5 |
Primary
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
Population: SAF population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAD: 0.03 mcg | Change From Baseline in Bone Conduction Hearing at 1, 2, 4 kHz by Pure Tone Audiometry at Week 8/EOS in SAD | 1 kHz | -1.3 decibles | Standard Deviation 2.5 |
| SAD: 0.03 mcg | Change From Baseline in Bone Conduction Hearing at 1, 2, 4 kHz by Pure Tone Audiometry at Week 8/EOS in SAD | 4 kHz | 0.0 decibles | Standard Deviation 4.1 |
| SAD: 0.03 mcg | Change From Baseline in Bone Conduction Hearing at 1, 2, 4 kHz by Pure Tone Audiometry at Week 8/EOS in SAD | 2 kHz | 1.3 decibles | Standard Deviation 2.5 |
| SAD: 0.15 mcg | Change From Baseline in Bone Conduction Hearing at 1, 2, 4 kHz by Pure Tone Audiometry at Week 8/EOS in SAD | 2 kHz | -1.3 decibles | Standard Deviation 2.5 |
| SAD: 0.15 mcg | Change From Baseline in Bone Conduction Hearing at 1, 2, 4 kHz by Pure Tone Audiometry at Week 8/EOS in SAD | 1 kHz | 0.0 decibles | Standard Deviation 4.1 |
| SAD: 0.15 mcg | Change From Baseline in Bone Conduction Hearing at 1, 2, 4 kHz by Pure Tone Audiometry at Week 8/EOS in SAD | 4 kHz | -1.3 decibles | Standard Deviation 4.8 |
| SAD: 0.75 mcg | Change From Baseline in Bone Conduction Hearing at 1, 2, 4 kHz by Pure Tone Audiometry at Week 8/EOS in SAD | 2 kHz | 2.5 decibles | Standard Deviation 8.7 |
| SAD: 0.75 mcg | Change From Baseline in Bone Conduction Hearing at 1, 2, 4 kHz by Pure Tone Audiometry at Week 8/EOS in SAD | 1 kHz | 0.0 decibles | Standard Deviation 4.1 |
| SAD: 0.75 mcg | Change From Baseline in Bone Conduction Hearing at 1, 2, 4 kHz by Pure Tone Audiometry at Week 8/EOS in SAD | 4 kHz | 1.3 decibles | Standard Deviation 7.5 |
| SAD: 2.25 mcg | Change From Baseline in Bone Conduction Hearing at 1, 2, 4 kHz by Pure Tone Audiometry at Week 8/EOS in SAD | 1 kHz | -2.5 decibles | Standard Deviation 6.5 |
| SAD: 2.25 mcg | Change From Baseline in Bone Conduction Hearing at 1, 2, 4 kHz by Pure Tone Audiometry at Week 8/EOS in SAD | 4 kHz | -1.3 decibles | Standard Deviation 4.8 |
| SAD: 2.25 mcg | Change From Baseline in Bone Conduction Hearing at 1, 2, 4 kHz by Pure Tone Audiometry at Week 8/EOS in SAD | 2 kHz | -3.8 decibles | Standard Deviation 8.5 |
| SAD: Placebo | Change From Baseline in Bone Conduction Hearing at 1, 2, 4 kHz by Pure Tone Audiometry at Week 8/EOS in SAD | 2 kHz | -1.3 decibles | Standard Deviation 4.8 |
| SAD: Placebo | Change From Baseline in Bone Conduction Hearing at 1, 2, 4 kHz by Pure Tone Audiometry at Week 8/EOS in SAD | 1 kHz | 1.3 decibles | Standard Deviation 6.3 |
| SAD: Placebo | Change From Baseline in Bone Conduction Hearing at 1, 2, 4 kHz by Pure Tone Audiometry at Week 8/EOS in SAD | 4 kHz | 0.0 decibles | Standard Deviation 7.1 |
Primary
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
Population: SAF population with available data was analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SAD: 0.03 mcg | Change From Baseline in TVAS at Week 12/EOS in MAD | -0.6 Score on a scale | Standard Deviation 1.3 |
| SAD: 0.15 mcg | Change From Baseline in TVAS at Week 12/EOS in MAD | -0.7 Score on a scale | Standard Deviation 2 |
| SAD: 0.75 mcg | Change From Baseline in TVAS at Week 12/EOS in MAD | 0.0 Score on a scale | Standard Deviation 2 |
Primary
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
Population: SAF population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SAD: 0.03 mcg | Change From Baseline in TVAS at Week 8/EOS in SAD | -0.3 Score on a scale | Standard Deviation 0.5 |
| SAD: 0.15 mcg | Change From Baseline in TVAS at Week 8/EOS in SAD | 0.0 Score on a scale | Standard Deviation 0 |
| SAD: 0.75 mcg | Change From Baseline in TVAS at Week 8/EOS in SAD | -1.0 Score on a scale | Standard Deviation 2 |
| SAD: 2.25 mcg | Change From Baseline in TVAS at Week 8/EOS in SAD | 0.3 Score on a scale | Standard Deviation 2.9 |
| SAD: Placebo | Change From Baseline in TVAS at Week 8/EOS in SAD | -1.5 Score on a scale | Standard Deviation 2.4 |
Primary
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
Population: SAF population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SAD: 0.03 mcg | Number of Participants With AE of Special Interest as Cholesteatoma or Ear Neoplasm in SAD | 0 Participants |
| SAD: 0.15 mcg | Number of Participants With AE of Special Interest as Cholesteatoma or Ear Neoplasm in SAD | 0 Participants |
| SAD: 0.75 mcg | Number of Participants With AE of Special Interest as Cholesteatoma or Ear Neoplasm in SAD | 0 Participants |
| SAD: 2.25 mcg | Number of Participants With AE of Special Interest as Cholesteatoma or Ear Neoplasm in SAD | 0 Participants |
| SAD: Placebo | Number of Participants With AE of Special Interest as Cholesteatoma or Ear Neoplasm in SAD | 0 Participants |
Primary
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
Population: SAF population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SAD: 0.03 mcg | Number of Participants With AE of Special Interest as Otitis Media or Otitis Externa in MAD | 1 Participants |
| SAD: 0.15 mcg | Number of Participants With AE of Special Interest as Otitis Media or Otitis Externa in MAD | 0 Participants |
| SAD: 0.75 mcg | Number of Participants With AE of Special Interest as Otitis Media or Otitis Externa in MAD | 0 Participants |
Primary
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.
Time frame: From first dose up to day 57
Population: SAF population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SAD: 0.03 mcg | Number of Participants With AE of Special Interest as Otitis Media or Otitis Externa in SAD | 1 Participants |
| SAD: 0.15 mcg | Number of Participants With AE of Special Interest as Otitis Media or Otitis Externa in SAD | 0 Participants |
| SAD: 0.75 mcg | Number of Participants With AE of Special Interest as Otitis Media or Otitis Externa in SAD | 0 Participants |
| SAD: 2.25 mcg | Number of Participants With AE of Special Interest as Otitis Media or Otitis Externa in SAD | 1 Participants |
| SAD: Placebo | Number of Participants With AE of Special Interest as Otitis Media or Otitis Externa in SAD | 0 Participants |
Primary
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
Population: SAF population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SAD: 0.03 mcg | Number of Participants With AE of Special Interest as Ototoxic Symptoms (Tinnitus, Sensorineural Hearing Loss, Dizziness) in MAD | 2 Participants |
| SAD: 0.15 mcg | Number of Participants With AE of Special Interest as Ototoxic Symptoms (Tinnitus, Sensorineural Hearing Loss, Dizziness) in MAD | 1 Participants |
| SAD: 0.75 mcg | Number of Participants With AE of Special Interest as Ototoxic Symptoms (Tinnitus, Sensorineural Hearing Loss, Dizziness) in MAD | 0 Participants |
Primary
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
Population: SAF population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SAD: 0.03 mcg | Number of Participants With AE of Special Interest as Ototoxic Symptoms (Tinnitus, Sensorineural Hearing Loss, Dizziness) in SAD | 2 Participants |
| SAD: 0.15 mcg | Number of Participants With AE of Special Interest as Ototoxic Symptoms (Tinnitus, Sensorineural Hearing Loss, Dizziness) in SAD | 0 Participants |
| SAD: 0.75 mcg | Number of Participants With AE of Special Interest as Ototoxic Symptoms (Tinnitus, Sensorineural Hearing Loss, Dizziness) in SAD | 1 Participants |
| SAD: 2.25 mcg | Number of Participants With AE of Special Interest as Ototoxic Symptoms (Tinnitus, Sensorineural Hearing Loss, Dizziness) in SAD | 1 Participants |
| SAD: Placebo | Number of Participants With AE of Special Interest as Ototoxic Symptoms (Tinnitus, Sensorineural Hearing Loss, Dizziness) in SAD | 0 Participants |
Primary
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
Population: SAF population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SAD: 0.03 mcg | Number of Participants With AE Special Interest as Cholesteatoma or Ear Neoplasm in MAD | 0 Participants |
| SAD: 0.15 mcg | Number of Participants With AE Special Interest as Cholesteatoma or Ear Neoplasm in MAD | 0 Participants |
| SAD: 0.75 mcg | Number of Participants With AE Special Interest as Cholesteatoma or Ear Neoplasm in MAD | 0 Participants |
Primary
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
Population: SAF population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SAD: 0.03 mcg | Number of Participants With TEAEs in MAD | 6 Participants |
| SAD: 0.15 mcg | Number of Participants With TEAEs in MAD | 5 Participants |
| SAD: 0.75 mcg | Number of Participants With TEAEs in MAD | 4 Participants |
Primary
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
Population: SAF population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SAD: 0.03 mcg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in SAD | 4 Participants |
| SAD: 0.15 mcg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in SAD | 1 Participants |
| SAD: 0.75 mcg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in SAD | 3 Participants |
| SAD: 2.25 mcg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in SAD | 3 Participants |
| SAD: Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in SAD | 2 Participants |
Secondary
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
Population: The single and multiple dose expansion parts of the study were not opened following review of safety and efficacy results of the SAD part of the study by the DMC, therefore the data was not collected.
Secondary
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
Population: FAS population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SAD: 0.03 mcg | Change From Baseline in the Ratio of TMP Size Per Total Area of Tympanic Membrane at Week 12 for MAD | -0.2 Percentage of total area of TM | Standard Deviation 2.4 |
| SAD: 0.15 mcg | Change From Baseline in the Ratio of TMP Size Per Total Area of Tympanic Membrane at Week 12 for MAD | 2.5 Percentage of total area of TM | Standard Deviation 2.3 |
| SAD: 0.75 mcg | Change From Baseline in the Ratio of TMP Size Per Total Area of Tympanic Membrane at Week 12 for MAD | 0.3 Percentage of total area of TM | Standard Deviation 2.3 |
Secondary
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
Population: The single and multiple dose expansion parts of the study were not opened following review of safety and efficacy results of the MAD part of the study by the DMC, therefore the data was not collected.
Secondary
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
Population: FAS population with available data was analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SAD: 0.03 mcg | Change From Baseline in the Ratio of TMP Size Per Total Area of Tympanic Membrane at Week 8 for SAD | -0.4 Percentage of total area of TM | Standard Deviation 0.6 |
| SAD: 0.15 mcg | Change From Baseline in the Ratio of TMP Size Per Total Area of Tympanic Membrane at Week 8 for SAD | 4.2 Percentage of total area of TM | Standard Deviation 6.3 |
| SAD: 0.75 mcg | Change From Baseline in the Ratio of TMP Size Per Total Area of Tympanic Membrane at Week 8 for SAD | -1.8 Percentage of total area of TM | Standard Deviation 2.3 |
| SAD: 2.25 mcg | Change From Baseline in the Ratio of TMP Size Per Total Area of Tympanic Membrane at Week 8 for SAD | 1.0 Percentage of total area of TM | Standard Deviation 0.5 |
| SAD: Placebo | Change From Baseline in the Ratio of TMP Size Per Total Area of Tympanic Membrane at Week 8 for SAD | 0.3 Percentage of total area of TM | Standard Deviation 3 |
Secondary
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
Population: The single and multiple dose expansion parts of the study were not opened following review of safety and efficacy results of the SAD part of the study by the DMC, therefore the data was not collected.
Secondary
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
Population: FAS population with available data was analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SAD: 0.03 mcg | Change From Baseline in TMP Size at Week 12 for MAD | 1904.2 mm^2 | Standard Deviation 18056.6 |
| SAD: 0.15 mcg | Change From Baseline in TMP Size at Week 12 for MAD | 545.8 mm^2 | Standard Deviation 9706.9 |
| SAD: 0.75 mcg | Change From Baseline in TMP Size at Week 12 for MAD | -1237.3 mm^2 | Standard Deviation 672.5 |
Secondary
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
Population: The single and multiple dose expansion parts of the study were not opened following review of safety and efficacy results of the MAD part of the study by the DMC, therefore the data was not collected.
Secondary
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
Population: FAS population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SAD: 0.03 mcg | Change From Baseline in TMP Size at Week 8 for SAD | 13451.0 mm^2 | Standard Deviation 9700.9 |
| SAD: 0.15 mcg | Change From Baseline in TMP Size at Week 8 for SAD | 14271.5 mm^2 | Standard Deviation 11800.6 |
| SAD: 0.75 mcg | Change From Baseline in TMP Size at Week 8 for SAD | 9572.0 mm^2 | Standard Deviation 9462.7 |
| SAD: 2.25 mcg | Change From Baseline in TMP Size at Week 8 for SAD | 12784.3 mm^2 | Standard Deviation 5277.9 |
| SAD: Placebo | Change From Baseline in TMP Size at Week 8 for SAD | 27389.0 mm^2 | Standard Deviation 37917.3 |
Secondary
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
Population: The single and multiple dose expansion parts of the study were not opened following review of safety and efficacy results of the SAD part of the study by the DMC, therefore the data was not collected.
Secondary
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
Population: FAS population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SAD: 0.03 mcg | Number of Participants With Complete Closure of TMP at Week 12 for MAD | 0 Participants |
| SAD: 0.15 mcg | Number of Participants With Complete Closure of TMP at Week 12 for MAD | 0 Participants |
| SAD: 0.75 mcg | Number of Participants With Complete Closure of TMP at Week 12 for MAD | 1 Participants |
Secondary
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
Population: The single and multiple dose expansion parts of the study were not opened following review of safety and efficacy results of the MAD part of the study by the DMC, therefore the data was not collected.
Secondary
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
Population: The Full Analysis Set (FAS) consisted of all randomized participants who received a dose of study drug and had baseline value and at least 1 post baseline complete closure assessment during study period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SAD: 0.03 mcg | Number of Participants With Complete Closure of Tympanic Membrane Perforation (TMP) at Week 8 for SAD | 0 Participants |
| SAD: 0.15 mcg | Number of Participants With Complete Closure of Tympanic Membrane Perforation (TMP) at Week 8 for SAD | 0 Participants |
| SAD: 0.75 mcg | Number of Participants With Complete Closure of Tympanic Membrane Perforation (TMP) at Week 8 for SAD | 1 Participants |
| SAD: 2.25 mcg | Number of Participants With Complete Closure of Tympanic Membrane Perforation (TMP) at Week 8 for SAD | 0 Participants |
| SAD: Placebo | Number of Participants With Complete Closure of Tympanic Membrane Perforation (TMP) at Week 8 for SAD | 0 Participants |