A Study to Assess ASP0598 Otic Solution Following Topical... | NCT04305184

NCT04305184

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Single Ascending Dose (SAD): 0.03 mcg	Experimental	Participants received single dose of 0.03 microgram (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 [End of Study (EOS)].	Drug: ASP0598
SAD: 0.15 mcg	Experimental	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).	Drug: ASP0598
SAD: 0.75 mcg	Experimental	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).	Drug: ASP0598
SAD: 2.25 mcg	Experimental	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).	Drug: ASP0598
SAD: Placebo	Placebo Comparator	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).

Interventions

Name	Type	Description	Arm Group Labels	Other Names
ASP0598	Drug	ASP0598 Otic solution was administered onto the Tympanic Membrane (TM) through the external auditory canal via syringe.	MAD: 2.25 mcg Multiple Ascending Dose (MAD): 0.75 mcg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	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.	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.	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.

Secondary Outcomes

Measure	Description	Time Frame
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.	Week 8
Number of Participants With Complete Closure of TMP at Week 12 for Dose Expansion

Eligibility Module

Eligibility Criteria

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.

Contacts/Locations Module

Name	Affiliation	Role
Medical Director	Astellas Pharma Global Development, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Stanford Hospital		Palo Alto	California	94304	United States
Breathe Clear Institute

References Module

Label	URL
Link to results and other applicable study documents on the Astellas Clinical Trials website	View source
Link to plain language summary of the study on the Trial Results Summaries website	View source

ID	Title	Description
FG000	SAD: 0.03 mcg	Participants received single dose of 0.03 microgram (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 [End of Study (EOS)].
FG001	SAD: 0.15 mcg

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Aug 29, 2022	Jan 11, 2024

Categories

Title	Measurements
	BG00032.5± 7.0 BG00148.3± 20.4 BG00250.8± 7.1 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0002 BG0013 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0000 BG0010 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Bone Conduction Hearing at 1, 2,4 kilohertz (kHz) by Pure Tone Audiometry (PTA)

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.

Mean

Standard Deviation

decibles

Title

Denominators

Categories

1 kHz

Title	Measurements
	BG0006.3± 7.5 BG001

Tinnitus Visual Analog Scale (TVAS)

TVAS was used by participants to rate their tinnitus at baseline and during all subsequent follow-up visits. 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.

Mean

Standard Deviation

Score on a scale

Title

Denominators

Categories

Title	Measurements
	BG0001.0± 2.0 BG001

Ratio of TMP size per total area of tympanic membrane

Ratio of TMP size per total area of tympanic membrane calculation was performed by central imaging vendor and reported as percentage.

Mean

Standard Deviation

Percentage of total area of TM

Title

Denominators

Categories

Title	Measurements
	BG00010.3± 5.1 BG001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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.

SAF population

Posted

Number

Participants

From first dose up to day 57

ID	Title	Description
OG000	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).
OG001	SAD: 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).
OG002	SAD: 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).
OG003	SAD: 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).
OG004	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).

Units	Counts
Participants	OG0004 OG0014 OG0024 OG003

Title

Denominators

Categories

Title	Measurements
	OG0004 OG0011 OG0023 OG003

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.

SAF population

Posted

Number

Participants

From first dose up to day 57

ID	Title	Description
OG000	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).
OG001	SAD: 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).
OG002	SAD: 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).

Primary

Number of Participants With AE of Special Interest as Ototoxic Symptoms (Tinnitus, Sensorineural Hearing Loss, Dizziness) in SAD

SAF population

Posted

Number

Participants

From first dose up to day 57

ID	Title	Description
OG000	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).
OG001	SAD: 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).
OG002	SAD: 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).

Primary

Number of Participants With AE of Special Interest as Otitis Media or Otitis Externa in SAD

SAF population

Posted

Number

Participants

From first dose up to day 57

ID	Title	Description
OG000	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).
OG001	SAD: 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).
OG002	SAD: 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).

Primary

Change From Baseline in Bone Conduction Hearing at 1, 2, 4 kHz by Pure Tone Audiometry at Week 8/EOS in SAD

SAF population

Posted

Mean

Standard Deviation

decibles

Baseline and week 8

ID	Title	Description
OG000	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).
OG001	SAD: 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).
OG002	SAD: 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).

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).

SAF population

Posted

Mean

Standard Deviation

Score on a scale

Baseline and week 8

ID	Title	Description
OG000	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).
OG001	SAD: 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).
OG002	SAD: 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).

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.

SAF population

Posted

Number

Participants

From first dose up to day 85

ID	Title	Description
OG000	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).
OG001	MAD: 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).
OG002	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).

Primary

Number of Participants With AE Special Interest as Cholesteatoma or Ear Neoplasm in MAD

SAF population

Posted

Number

Participants

From first dose up to day 85

ID	Title	Description
OG000	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).
OG001	MAD: 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).
OG002	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).

Primary

Number of Participants With AE of Special Interest as Ototoxic Symptoms (Tinnitus, Sensorineural Hearing Loss, Dizziness) in MAD

SAF population

Posted

Number

Participants

From first dose up to day 85

ID	Title	Description
OG000	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).
OG001	MAD: 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).
OG002	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).

Primary

Number of Participants With AE of Special Interest as Otitis Media or Otitis Externa in MAD

SAF population

Posted

Number

Participants

From first dose up to day 85

ID	Title	Description
OG000	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).
OG001	MAD: 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).
OG002	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).

Primary

Change From Baseline in Bone Conduction Hearing at 1, 2, 4 kHz by Pure Tone Audiometry at Week 12/EOS in MAD

SAF population with available data was analyzed.

Posted

Mean

Standard Deviation

decibles

Baseline and week 12

ID	Title	Description
OG000	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).
OG001	MAD: 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).
OG002	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).

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).

SAF population with available data was analyzed.

Posted

Mean

Standard Deviation

Score on a scale

Baseline and week 12

ID	Title	Description
OG000	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).
OG001	MAD: 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).
OG002	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).

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.

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.

Posted

Number

Participants

Week 8

ID	Title	Description
OG000	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).
OG001	SAD: 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).
OG002	SAD: 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).

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.

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.

Posted

Week 12

ID	Title	Description
OG000	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).
OG001	SAD: 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).
OG002	SAD: 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).

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.

FAS population with available data was analyzed.

Posted

Mean

Standard Deviation

Percentage of total area of TM

Baseline and week 8

ID	Title	Description
OG000	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).
OG001	SAD: 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).
OG002	SAD: 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).
OG003	SAD: 2.25 mcg

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.

Posted

Baseline and week 12

ID	Title	Description
OG000	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).
OG001	SAD: 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).
OG002	SAD: 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).

Secondary

Change From Baseline in TMP Size at Week 8 for SAD

TMP size calculation was be performed by central imaging vendor.

FAS population

Posted

Mean

Standard Deviation

mm^2

Baseline and week 8

ID	Title	Description
OG000	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).
OG001	SAD: 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).
OG002	SAD: 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).
OG003	SAD: 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).

Secondary

Change From Baseline in TMP Size at Week 12 for Dose Expansion

TMP size calculation was be performed by central imaging vendor.

Posted

Baseline and week 12

ID	Title	Description
OG000	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).
OG001	SAD: 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).
OG002	SAD: 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).
OG003	SAD: 2.25 mcg

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.

FAS population

Posted

Number

Participants

Week 12

ID	Title	Description
OG000	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).
OG001	MAD: 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).
OG002	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).

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.

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.

Posted

Week 16

ID	Title	Description
OG000	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).
OG001	MAD: 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).
OG002	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).

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.

FAS population

Posted

Mean

Standard Deviation

Percentage of total area of TM

Baseline and week 12

ID	Title	Description
OG000	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).
OG001	MAD: 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).
OG002	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).

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.

Posted

Baseline and week 16

ID	Title	Description
OG000	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).
OG001	MAD: 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).
OG002	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).

Secondary

Change From Baseline in TMP Size at Week 12 for MAD

TMP size calculation was be performed by central imaging vendor.

FAS population with available data was analyzed.

Posted

Mean

Standard Deviation

mm^2

Baseline and week 12

ID	Title	Description
OG000	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).
OG001	MAD: 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).
OG002	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).

Secondary

Change From Baseline in TMP Size at Week 16 for Dose Expansion

TMP size calculation was be performed by central imaging vendor.

Posted

Baseline and week 16

ID	Title	Description
OG000	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).
OG001	MAD: 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).
OG002	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).

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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	4	4	4
EG001	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	4	1	4
EG002	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	4	3	4
EG003	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	4	3	4
EG004	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	4	2	4
EG005	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	6	6	6
EG006	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	6	5	6
EG007	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	4	4	4

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Ear canal erythema	Ear and labyrinth disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected4 at risk EG0010 events0 affected4 at risk EG0020 events0 affected4 at risk EG0030 events0 affected4 at risk EG0040 events0 affected4 at risk EG0052 events2 affected6 at risk EG0061 events1 affected6 at risk EG0072 events2 affected4 at risk
Ear discomfort	Ear and labyrinth disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected4 at risk EG0010 events0 affected4 at risk EG0020 events0 affected4 at risk EG003
Ear pain	Ear and labyrinth disorders	MedDRA v23.0	Systematic Assessment	EG0003 events3 affected4 at risk EG0011 events1 affected4 at risk EG0022 events2 affected4 at risk EG003
Ear pruritus	Ear and labyrinth disorders	MedDRA v23.0	Systematic Assessment	EG0003 events2 affected4 at risk EG0010 events0 affected4 at risk EG0021 events1 affected4 at risk EG003
Hypoacusis	Ear and labyrinth disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected4 at risk EG0020 events0 affected4 at risk EG003
Middle ear inflammation	Ear and labyrinth disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected4 at risk EG0020 events0 affected4 at risk EG003
Otorrhoea	Ear and labyrinth disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected4 at risk EG0010 events0 affected4 at risk EG0020 events0 affected4 at risk EG003
Tinnitus	Ear and labyrinth disorders	MedDRA v23.0	Systematic Assessment	EG0002 events2 affected4 at risk EG0010 events0 affected4 at risk EG0021 events1 affected4 at risk EG003
Administration site pain	General disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected4 at risk EG0020 events0 affected4 at risk EG003
Application site pruritus	General disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected4 at risk EG0020 events0 affected4 at risk EG003
COVID-19	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected4 at risk EG0020 events0 affected4 at risk EG003
Myringitis	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected4 at risk EG0010 events0 affected4 at risk EG0020 events0 affected4 at risk EG003
Sinusitis	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected4 at risk EG0020 events0 affected4 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected4 at risk EG0020 events0 affected4 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected4 at risk EG0020 events0 affected4 at risk EG003
Joint injury	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected4 at risk EG0020 events0 affected4 at risk EG003
Skin laceration	Injury, poisoning and procedural complications	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected4 at risk EG0020 events0 affected4 at risk EG003
Audiogram abnormal	Investigations	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected4 at risk EG0020 events0 affected4 at risk EG003
SARS-CoV-2 test positive	Investigations	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected4 at risk EG0020 events0 affected4 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected4 at risk EG0010 events0 affected4 at risk EG0020 events0 affected4 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected4 at risk EG0020 events0 affected4 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected4 at risk EG0020 events0 affected4 at risk EG003
Headache	Nervous system disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected4 at risk EG0020 events0 affected4 at risk EG003
Sleep disorder	Psychiatric disorders	MedDRA v23.0	Systematic Assessment	EG0001 events1 affected4 at risk EG0010 events0 affected4 at risk EG0020 events0 affected4 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected4 at risk EG0020 events0 affected4 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected4 at risk EG0020 events0 affected4 at risk EG003
Excessive granulation tissue	Skin and subcutaneous tissue disorders	MedDRA v23.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected4 at risk EG0020 events0 affected4 at risk EG003

Due to limitations of the TM imaging data as evaluated by the central reader, secondary endpoints related to change in TMP size could not be fully evaluated. Following SAD and MAD data review by DMC, the single dose of ASP0598 Otic Solution provided insufficient efficacy to open the single dose expansion study.

Certain Agreements

Units	Counts
Participants	OG0006 OG0016 OG0024

Units	Counts
Participants	OG0005 OG0016 OG0023

Units	Counts
Participants	OG0000 OG0010 OG0020

EG0041 events1 affected4 at risk

EG0053 events2 affected6 at risk

EG0065 events3 affected6 at risk

EG0070 events0 affected4 at risk

EG0041 events1 affected4 at risk

EG00511 events5 affected6 at risk

EG0063 events2 affected6 at risk

EG0073 events3 affected4 at risk

EG0040 events0 affected4 at risk

EG0050 events0 affected6 at risk

EG0062 events1 affected6 at risk

EG0070 events0 affected4 at risk

EG0040 events0 affected4 at risk

EG0052 events2 affected6 at risk

EG0060 events0 affected6 at risk

EG0070 events0 affected4 at risk

EG0040 events0 affected4 at risk

EG0051 events1 affected6 at risk

EG0060 events0 affected6 at risk

EG0070 events0 affected4 at risk

EG0040 events0 affected4 at risk

EG0052 events2 affected6 at risk

EG0060 events0 affected6 at risk

EG0070 events0 affected4 at risk

EG0040 events0 affected4 at risk

EG0053 events2 affected6 at risk

EG0061 events1 affected6 at risk

EG0070 events0 affected4 at risk

EG0040 events0 affected4 at risk

EG0050 events0 affected6 at risk

EG0060 events0 affected6 at risk

EG0070 events0 affected4 at risk

EG0041 events1 affected4 at risk

EG0050 events0 affected6 at risk

EG0060 events0 affected6 at risk

EG0070 events0 affected4 at risk

EG0041 events1 affected4 at risk

EG0050 events0 affected6 at risk

EG0060 events0 affected6 at risk

EG0070 events0 affected4 at risk

EG0040 events0 affected4 at risk

EG0051 events1 affected6 at risk

EG0060 events0 affected6 at risk

EG0070 events0 affected4 at risk

EG0040 events0 affected4 at risk

EG0050 events0 affected6 at risk

EG0061 events1 affected6 at risk

EG0070 events0 affected4 at risk

EG0040 events0 affected4 at risk

EG0051 events1 affected6 at risk

EG0060 events0 affected6 at risk

EG0070 events0 affected4 at risk

EG0040 events0 affected4 at risk

EG0050 events0 affected6 at risk

EG0060 events0 affected6 at risk

EG0071 events1 affected4 at risk

EG0040 events0 affected4 at risk

EG0050 events0 affected6 at risk

EG0060 events0 affected6 at risk

EG0071 events1 affected4 at risk

EG0040 events0 affected4 at risk

EG0050 events0 affected6 at risk

EG0060 events0 affected6 at risk

EG0070 events0 affected4 at risk

EG0040 events0 affected4 at risk

EG0050 events0 affected6 at risk

EG0061 events1 affected6 at risk

EG0070 events0 affected4 at risk

EG0040 events0 affected4 at risk

EG0051 events1 affected6 at risk

EG0060 events0 affected6 at risk

EG0071 events1 affected4 at risk

EG0040 events0 affected4 at risk

EG0050 events0 affected6 at risk

EG0060 events0 affected6 at risk

EG0070 events0 affected4 at risk

EG0040 events0 affected4 at risk

EG0050 events0 affected6 at risk

EG0061 events1 affected6 at risk

EG0070 events0 affected4 at risk

EG0040 events0 affected4 at risk

EG0051 events1 affected6 at risk

EG0061 events1 affected6 at risk

EG0070 events0 affected4 at risk

EG0041 events1 affected4 at risk

EG0052 events2 affected6 at risk

EG0060 events0 affected6 at risk

EG0071 events1 affected4 at risk

EG0040 events0 affected4 at risk

EG0050 events0 affected6 at risk

EG0060 events0 affected6 at risk

EG0070 events0 affected4 at risk

EG0040 events0 affected4 at risk

EG0050 events0 affected6 at risk

EG0061 events1 affected6 at risk

EG0070 events0 affected4 at risk

EG0040 events0 affected4 at risk

EG0050 events0 affected6 at risk

EG0060 events0 affected6 at risk

EG0070 events0 affected4 at risk

EG0040 events0 affected4 at risk

EG0050 events0 affected6 at risk

EG0061 events1 affected6 at risk

EG0070 events0 affected4 at risk

ID	Title	Description
BG000	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).
BG001	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).
BG002	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).
BG003	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).
BG004	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).
BG005	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).
BG006	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).
BG007	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).
BG008	Total	Total of all reporting groups