A Clinical Trial of YH1177 in Patients With Otitis Media and Otorrhea

Study Overview
=================
Brief Summary
-----------------
In patients with otitis media presenting with otoscopy-confirmed otorrhea who had tympanostomy tube insertion or tympanic perforation, to evaluate the safety, tolerability, and the proportion of patients with cessation of otorrhea after ear-drop administration of YH1177 or YH1177-D for 14 days and therefore to determine the optimal clinical dose.

Detailed Description
-----------------
Patients with otitis media presenting with otoscopy-confirmed otorrhea who had tympanostomy tube insertion or tympanic perforation. Screening should be completed within 7 days prior to randomization. patients with otitis media presenting with otoscopy-confirmed otorrhea who had tympanostomy tube insertion or tympanic perforation at randomization visit will be randomized in one of the defined groups.

Official Title
-----------------
A Randomized, Double-blind, Multicenter, Phase2 Trial to Evaluate the Safety and Efficacy of YH1177 or YH1177-D Otic Soultion in Patients With Otitis Media and Otorrhea

Conditions
-----------------
Otitis Media, Otorrhea

Intervention / Treatment
-----------------
* Drug: piperacillin 4% + tazobactam 0.5% + dexamethasone 0.1%
* Drug: piperacillin 8% + tazobactam 1.0% + dexamethasone 0.1%
* Drug: piperacillin 2% + tazobactam 0.25%
* Drug: piperacillin 4% + tazobactam 0.5%
* Drug: piperacillin 8% + tazobactam 1.0%


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed Written Informed Consent A detailed explanation about the study, including the study purpose and procedures and drug properties, had been provided, and the patient gave voluntary written informed consent. Target Population Patients with otitis media presenting with otorrhea, as evidenced by otoscopy, who had tympanostomy tube insertion or tympanic perforation Sex and age Male or female patients 19 years of age or older at screening Women of childbearing potential (WOCBP) must have 'negative' pregnancy test at screening, and use an acceptable method of contraception throughout the study. Exclusion Criteria: Excluded Disease Patients diagnosed with otitis media with cholesteatoma, otitis media with effusion or otitis externa at screening Patients who had a otologic surgery within 1 year prior to screening (except for tympanostomy tube insertion) Subjects who previously had cholesteatoma or mastoid surgery Medical History and Concurrent Disease Patients with complication of labyrinthine fistula at screening Patients with clinically significant medical or mental illness. Patients with infectious disease requiring the use of systemic antimicrobial therapy Physical and Laboratory Test Results a)Clinically significant finding based on the principal investigator/investigator's opinion. Allergies and Adverse Drug Reactions Known drug allergy (e.g., a history of anaphylaxis or hepatotoxicity) History of hypersensitivity to penicillins or -lactamase inhibitors. History of serious skin reaction such as Stevens-Johnson syndrome or toxic epidermal necrosis Prohibited Therapies and/or Medication Patients undergoing a ventilation tube insertion on the day of screening Patients with ventilation tube containing silver oxide or silver salt (e.g., T-type tube) Reproductive status, Women only a)Woman of childbearing potential (WOCBP) who is unable, or unwilling to use an acceptable method of contraception during the study Other Exclusion Criteria History of alcohol or drug abuse/addiction within the last 1 year prior to the study entry Patient who, in the investigator's opinion, is not suitable for the study for any reason (e.g., ECG or hepatitis test results at screening)

Ages Eligible for Study
-----------------
Minimum Age: 19 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: YH1177 (4/0.5%+0.1%)<br>piperacillin 4% + tazobactam 0.5% + dexamethasone 0.1% | Drug: piperacillin 4% + tazobactam 0.5% + dexamethasone 0.1%<br> <br> * Other names: YH1177 (4/0.5%+0.1%);|
| Experimental: YH1177 (8/1.0%+0.1%)<br>piperacillin 8% + tazobactam 1.0% + dexamethasone 0.1% | Drug: piperacillin 8% + tazobactam 1.0% + dexamethasone 0.1%<br> <br> * Other names: YH1177 (8/1.0%+0.1%);|
| Experimental: YH1177-D (2/0.25%)<br>piperacillin 2% + tazobactam 0.25% | Drug: piperacillin 2% + tazobactam 0.25%<br> <br> * Other names: YH1177-D (2/0.25%);|
| Experimental: YH1177-D (4/0.5%)<br>piperacillin 4% + tazobactam 0.5% | Drug: piperacillin 4% + tazobactam 0.5%<br> <br> * Other names: YH1177-D (4/0.5%);|
| Experimental: YH1177-D (8/1.0%)<br>piperacillin 8% + tazobactam 1.0% | Drug: piperacillin 8% + tazobactam 1.0%<br> <br> * Other names: YH1177-D (8/1.0 %);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients achieving cessation of otorrhea on Day 15. | The proportion of patients achieving cessation of otorrhea (grade 0) on Day 15, as evidenced by otoscopy | Day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients with cessation of otorrhea on Day 8. | The proportion of patients with cessation of otorrhea on Day 8 as evidenced by otoscopy. | Day 8 | 
| The proportion of patients with cessation of otorrhea on Day 22. | The proportion of patients with cessation of otorrhea on Day 22 as evidenced by otoscopy. | Day 22 | 
| Proportion of patients with improved otorrhea at each visit, as evidenced by otoscopy | 'improved otorrhea' is defined as at least one level decrease from baseline in the otorrhea severity grading scale | Day 8 | 
| Proportion of patients with improved otorrhea at each visit, as evidenced by otoscopy | 'improved otorrhea' is defined as at least one level decrease from baseline in the otorrhea severity grading scale | Day 15 | 
| Proportion of patients with improved otorrhea at each visit, as evidenced by otoscopy | 'improved otorrhea' is defined as at least one level decrease from baseline in the otorrhea severity grading scale | Day 22 | 
| Microbiological eradication | Proportion of patients with microbiological eradicationat each visit | Day 8, 15, 22 |