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

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

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.

Study Overview

• Status: Terminated
• 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%

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.

• Study Type: Interventional
• Enrollment (Actual): 135
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Chonnam
    • Gwangju, Chonnam, Korea, Republic of, 501-757
      • Chonnam National Universitiy Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

  1. Patients diagnosed with otitis media with cholesteatoma, otitis media with effusion or otitis externa at screening
  2. Patients who had a otologic surgery within 1 year prior to screening (except for tympanostomy tube insertion)
  3. Subjects who previously had cholesteatoma or mastoid surgery

• Medical History and Concurrent Disease

  1. Patients with complication of labyrinthine fistula at screening
  2. Patients with clinically significant medical or mental illness.
  3. 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

  1. Known drug allergy (e.g., a history of anaphylaxis or hepatotoxicity)
  2. History of hypersensitivity to penicillins or -lactamase inhibitors.
  3. History of serious skin reaction such as Stevens-Johnson syndrome or toxic epidermal necrosis

• Prohibited Therapies and/or Medication

  1. Patients undergoing a ventilation tube insertion on the day of screening
  2. 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

  1. History of alcohol or drug abuse/addiction within the last 1 year prior to the study entry
  2. 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Maximum plasma concentration	pre-dose, and at 0.25, 0.5, 1, 2, 4 and 6 hours
AUClast	The area under the plasma concentration-time curve from time zero until the last measurable concentration	pre-dose, and at 0.25, 0.5, 1, 2, 4 and 6 hours
AUCinf	The area under the plasma concentration - time curve from time zero to infinite time	pre-dose, and at 0.25, 0.5, 1, 2, 4 and 6 hours
Tmax	Time to reach Cmax	pre-dose, and at 0.25, 0.5, 1, 2, 4 and 6 hours
t1/2	Terminal elimination half-life	pre-dose, and at 0.25, 0.5, 1, 2, 4 and 6 hours
CL/F	Apparent plasma clearance	pre-dose, and at 0.25, 0.5, 1, 2, 4 and 6 hours
Vd/F	Apparent volume of distribution	pre-dose, and at 0.25, 0.5, 1, 2, 4 and 6 hours

Collaborators and Investigators

• Sponsor: Yuhan Corporation
• Investigators: Study Chair: chulho jang, M.D Ph.D, Chonnam National Universitiy Hospital

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (Actual): April 13, 2017
• Study Completion (Actual): April 13, 2017

Study Registration Dates

• First Submitted: June 13, 2016
• First Submitted That Met QC Criteria: June 26, 2016
• First Posted (Estimate): June 29, 2016

Study Record Updates

• Last Update Posted (Actual): January 13, 2022
• Last Update Submitted That Met QC Criteria: December 26, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Otorhinolaryngologic Diseases; Ear Diseases; Otitis; Otitis Media; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Dexamethasone; Dexamethasone acetate; BB 1101; Piperacillin; Tazobactam
• Other Study ID Numbers: YH1177-201