Back to resultsA Phase III Study of Ciprofloxacin Plus Fluocinolone in Acute Otitis Externa (AOE)
Primary Purpose
Acute Otitis Externa
Status
Unknown status
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Ciprofloxacin-Fluocinolone Acetonide, 0.3%-0.025% Otic Solution
Ciprofloxacin 0.3% solution
Sponsored by
About this trial
This is an interventional treatment trial for Acute Otitis Externa focused on measuring ciprofloxacin, fluocinolone acetonide 0.025%, AOE
Eligibility Criteria
Inclusion Criteria:
- Male or female subjects with age of ≥3 years.
- Subjects with clinical diagnosis of unilateral Acute Otitis Externa (AOE) within 21 days (3 weeks) prior to screening.
- Subjects with graded II or III of AOE must experience each of symptoms or signs: as at least 2 for swelling (0-3 scale) and 1 for otorrhea (0-3 scale) and 2 for tenderness (0-3 scale).
- Willingness to prevent water getting into the ear canal through end of the study (e.g. refrain from swimming, wear shower caps to cover the ears during showers).
- For adult subjects, ability to fully understand the clinical trial and provide written informed consent. For subjects under the legal age (≥8 years and <18 of age) and capable of giving informed consent, informed consent form sign by both the subject and the parent/legal guardian. For subjects under 8 years of age, signed consent form from the parent/legal guardian.
- For females of childbearing potential (including partners of male subjects), not planning a pregnancy during the study and agree to use adequate birth control methods (from screening until 28 days after the final dose).
Exclusion Criteria:
- Subjects with bilateral AOE
- Subjects who can't accept otoscopy (≤6 years of age) or oto-endoscope (>6 years of age).
- Previous episode of AOE within 4 weeks prior to enrollment, or 2 or more episodes of AOE within 6 months prior to enrollment.
- Tympanic membrane perforation (including tympanostomy tubes).
- Known or suspected of fungal or viral ear infections, cholesteatoma, otitis media, malignant otitis externa, mastoiditis, seborrheic dermatitis, neurodermatitis in the external ear canal, ear trauma or other non-infectious suppurative ear diseases.
- Known or suspected of hearing loss.
- History of malignant tumors in the external ear canal, or currently receiving chemotherapy or radiotherapy.
- Current diagnosis of diabetes mellitus, psoriasis, immunodeficiency or history of drug abuse.
- Current diagnosis of cardiovascular, respiratory, urinary, gastrointestinal and neurological diseases which require intervention after at least 4 weeks of drug therapy.
- Use of any systemic antibacterial or topical antibiotic, corticosteroids, analgesic and anti-inflammatory drugs and other drug that affect the study results within 1 week prior to screening.
- Known or suspected hypersensitivity to quinolones, corticosteroid or any component of the study medication.
- Participation in another clinical trial within the previous 3 months.
- Pregnant women or nursing mothers.
- Any condition that, in the judgment of the principal investigator, render the subject not suitable for the study.
Sites / Locations
- Eye & Ent Hospital of Fudan University
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
ciprofloxacin 0.3% plus fluocinolone acetonide 0.025%
ciprofloxacin 0.3%
Arm Description
Warm the otic solution by holding the vial in the hands for 1 to 2 minutes. Twist off the vial cap. Tilt the subjects' head to one side to keep the affected ear up. Instill the content of 1 vial in the ear (0.25mL). Gently pull the outer ear lobe upward and outward to allow the solution to flow into the ear canal. Keep the subjects' head tilted sideways for approximately 5 minutes to allow the drug time to penetrate the ear. Use twice daily (every 12±1h , morning and evening) for 7 consecutive days.
Warm the otic solution by holding the vial in the hands for 1 to 2 minutes. Twist off the vial cap. Tilt the subjects' head to one side to keep the affected ear up. Instill the content of 1 vial in the ear (0.25mL). Gently pull the outer ear lobe upward and outward to allow the solution to flow into the ear canal. Keep the subjects' head tilted sideways for approximately 5 minutes to allow the drug time to penetrate the ear. Use twice daily (every 12±1h, morning and evening) for 7 consecutive days
Outcomes
Primary Outcome Measures
Clinical cure
The proportion of patients who have all symptoms scored as 0. Treatment failure is defined as any symptoms scored > 0.
Swelling:
None(0), Mild(1), Moderate(2), Severe(3).
Otorrhea:
None(0), Mild(1), Moderate(2), Severe(3).
Tenderness:
None(0), Mild(1), Moderate(2), Severe(3).
Secondary Outcome Measures
Microbiological cure
Microbiological response will be classified as Eradicated, Presumed Eradicated, Persistence, Presumed Persistence, Partial Eradication, Superinfection and Reinfection. Microbiological cure rate is defined as the percentage of patients who achieve the eradication and presume eradication.
Overall therapeutic cure
Overall therapeutic cure will only be assessed among subjects whose microbiological culture are positive at baseline. Overall therapeutic cure is defined as the percentage of patients who achieve both clinical cure and microbiological cure.
Clinical cure
same as primary outcome measure
Change in clinical improvement
The percentage of patients whose any symptoms (swelling, otorrhea, tenderness) is improved ≥1 grade, compared to the first day
change in each of Signs and Symptoms
The percentage of patients whose each of signs and symptoms (swelling, otorrhea or tenderness) is improved ≥1 grade, compared to the first day
Change in Granulation Tissue
Granulation tissue will be scored as either 1=present or 0=absent. Improve rate of granulation tissue is defined as the percentage of patients whose granulation tissue in external ear canal at baseline is absent on 8 and 15 days after first dose
Change in ear pain
Pain improvement is defined as ear pain improved ≥1 grade on 8 and 15 days after first dose, compared to the first day.
Time to end of ear pain
Time to end of ear pain is the interval (in days) between the first dose of the study medication and the day of the cessation of the ear pain in the evaluable ear and will not recur until the end of the study. Time to end of ear pain in the whole group.
Full Information
NCT ID
NCT04636957
First Posted
October 28, 2020
Last Updated
November 13, 2020
Sponsor
Lee's Pharmaceutical Limited
1. Study Identification
Unique Protocol Identification Number
NCT04636957
Brief Title
A Phase III Study of Ciprofloxacin Plus Fluocinolone in Acute Otitis Externa (AOE)
Official Title
A Phase III, Multicenter, Randomized, Evaluator-blinded, Parallel-Group, Active-controlled Clinical Trial to Evaluate the Efficacy and Safety of Ciprofloxacin 0.3% Plus Fluocinolone Acetonide 0.025% Otic Solution in the Treatment of Acute Otitis Externa (AOE)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2020
Overall Recruitment Status
Unknown status
Study Start Date
November 2020 (Anticipated)
Primary Completion Date
December 2021 (Anticipated)
Study Completion Date
July 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Lee's Pharmaceutical Limited
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a phase Ⅲ, multicenter, randomized, evaluator-blinded, parallel-group, active-controlled study to assess the efficacy and safety of ciprofloxacin 0.3% plus fluocinolone acetonide 0.025% otic solution vs ciprofloxacin 0.3% otic solution in the treatment of AOE, and to assess the pharmacokinetic properties in 12 selected adult subjects. Eligible subjects will be randomized at 1:1 ration to either the treatment arm or control arm. All subject will receive 7 consecutive days of either ciprofloxacin 0.3% plus fluocinolone acetonide 0.025% otic solution or ciprofloxacin 0.3% otic solution alone. The main objectives are to assess the efficacy and safety of ciprofloxacin 0.3% plus fluocinolone acetonide 0.025% otic solution in the treatment of AOE, and to assess the plasma concentration of ciprofloxacin and fluocinolone acetonide after multiple doses of test drug in 12 adult subjects, and evaluate the PK parameters.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Otitis Externa
Keywords
ciprofloxacin, fluocinolone acetonide 0.025%, AOE
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
600 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
ciprofloxacin 0.3% plus fluocinolone acetonide 0.025%
Arm Type
Experimental
Arm Description
Warm the otic solution by holding the vial in the hands for 1 to 2 minutes. Twist off the vial cap. Tilt the subjects' head to one side to keep the affected ear up. Instill the content of 1 vial in the ear (0.25mL). Gently pull the outer ear lobe upward and outward to allow the solution to flow into the ear canal. Keep the subjects' head tilted sideways for approximately 5 minutes to allow the drug time to penetrate the ear. Use twice daily (every 12±1h , morning and evening) for 7 consecutive days.
Arm Title
ciprofloxacin 0.3%
Arm Type
Active Comparator
Arm Description
Warm the otic solution by holding the vial in the hands for 1 to 2 minutes. Twist off the vial cap. Tilt the subjects' head to one side to keep the affected ear up. Instill the content of 1 vial in the ear (0.25mL). Gently pull the outer ear lobe upward and outward to allow the solution to flow into the ear canal. Keep the subjects' head tilted sideways for approximately 5 minutes to allow the drug time to penetrate the ear. Use twice daily (every 12±1h, morning and evening) for 7 consecutive days
Intervention Type
Drug
Intervention Name(s)
Ciprofloxacin-Fluocinolone Acetonide, 0.3%-0.025% Otic Solution
Intervention Description
0.25mL/vial, each vial contains 0.75mg of ciprofloxacin and 0.0625mg of fluocinolone acetonide.
Intervention Type
Drug
Intervention Name(s)
Ciprofloxacin 0.3% solution
Other Intervention Name(s)
CETRAXAL OTICO®
Intervention Description
0.4mL/vial, each vial contains 1.2mg ciprofloxacin
Primary Outcome Measure Information:
Title
Clinical cure
Description
The proportion of patients who have all symptoms scored as 0. Treatment failure is defined as any symptoms scored > 0.
Swelling:
None(0), Mild(1), Moderate(2), Severe(3).
Otorrhea:
None(0), Mild(1), Moderate(2), Severe(3).
Tenderness:
None(0), Mild(1), Moderate(2), Severe(3).
Time Frame
15 days after first dose
Secondary Outcome Measure Information:
Title
Microbiological cure
Description
Microbiological response will be classified as Eradicated, Presumed Eradicated, Persistence, Presumed Persistence, Partial Eradication, Superinfection and Reinfection. Microbiological cure rate is defined as the percentage of patients who achieve the eradication and presume eradication.
Time Frame
8 and 15 days after first dose
Title
Overall therapeutic cure
Description
Overall therapeutic cure will only be assessed among subjects whose microbiological culture are positive at baseline. Overall therapeutic cure is defined as the percentage of patients who achieve both clinical cure and microbiological cure.
Time Frame
8 and 15 days after first dose
Title
Clinical cure
Description
same as primary outcome measure
Time Frame
8 days after first dose
Title
Change in clinical improvement
Description
The percentage of patients whose any symptoms (swelling, otorrhea, tenderness) is improved ≥1 grade, compared to the first day
Time Frame
8 and 15 days after first dose
Title
change in each of Signs and Symptoms
Description
The percentage of patients whose each of signs and symptoms (swelling, otorrhea or tenderness) is improved ≥1 grade, compared to the first day
Time Frame
8 and 15 days after first dose
Title
Change in Granulation Tissue
Description
Granulation tissue will be scored as either 1=present or 0=absent. Improve rate of granulation tissue is defined as the percentage of patients whose granulation tissue in external ear canal at baseline is absent on 8 and 15 days after first dose
Time Frame
8 and 15 days after first dose
Title
Change in ear pain
Description
Pain improvement is defined as ear pain improved ≥1 grade on 8 and 15 days after first dose, compared to the first day.
Time Frame
8 and 15 days after first dose
Title
Time to end of ear pain
Description
Time to end of ear pain is the interval (in days) between the first dose of the study medication and the day of the cessation of the ear pain in the evaluable ear and will not recur until the end of the study. Time to end of ear pain in the whole group.
Time Frame
8 and 15 days after first dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
3 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female subjects with age of ≥3 years.
Subjects with clinical diagnosis of unilateral Acute Otitis Externa (AOE) within 21 days (3 weeks) prior to screening.
Subjects with graded II or III of AOE must experience each of symptoms or signs: as at least 2 for swelling (0-3 scale) and 1 for otorrhea (0-3 scale) and 2 for tenderness (0-3 scale).
Willingness to prevent water getting into the ear canal through end of the study (e.g. refrain from swimming, wear shower caps to cover the ears during showers).
For adult subjects, ability to fully understand the clinical trial and provide written informed consent. For subjects under the legal age (≥8 years and <18 of age) and capable of giving informed consent, informed consent form sign by both the subject and the parent/legal guardian. For subjects under 8 years of age, signed consent form from the parent/legal guardian.
For females of childbearing potential (including partners of male subjects), not planning a pregnancy during the study and agree to use adequate birth control methods (from screening until 28 days after the final dose).
Exclusion Criteria:
Subjects with bilateral AOE
Subjects who can't accept otoscopy (≤6 years of age) or oto-endoscope (>6 years of age).
Previous episode of AOE within 4 weeks prior to enrollment, or 2 or more episodes of AOE within 6 months prior to enrollment.
Tympanic membrane perforation (including tympanostomy tubes).
Known or suspected of fungal or viral ear infections, cholesteatoma, otitis media, malignant otitis externa, mastoiditis, seborrheic dermatitis, neurodermatitis in the external ear canal, ear trauma or other non-infectious suppurative ear diseases.
Known or suspected of hearing loss.
History of malignant tumors in the external ear canal, or currently receiving chemotherapy or radiotherapy.
Current diagnosis of diabetes mellitus, psoriasis, immunodeficiency or history of drug abuse.
Current diagnosis of cardiovascular, respiratory, urinary, gastrointestinal and neurological diseases which require intervention after at least 4 weeks of drug therapy.
Use of any systemic antibacterial or topical antibiotic, corticosteroids, analgesic and anti-inflammatory drugs and other drug that affect the study results within 1 week prior to screening.
Known or suspected hypersensitivity to quinolones, corticosteroid or any component of the study medication.
Participation in another clinical trial within the previous 3 months.
Pregnant women or nursing mothers.
Any condition that, in the judgment of the principal investigator, render the subject not suitable for the study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yasheng Yuan, M.D
Phone
13585586213
Email
yuanyasheng@163.com
Facility Information:
Facility Name
Eye & Ent Hospital of Fudan University
City
Shanghai
ZIP/Postal Code
200031
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yasheng Yuan, M.D
Phone
13585586213
Email
yuanyasheng@163.com
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Phase III Study of Ciprofloxacin Plus Fluocinolone in Acute Otitis Externa (AOE)
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