Acute Otitis ExternaPhase 3NCT04636957
Efficacy and Safety of Ciprofloxacin Plus Fluocinolone Acetonide Otic Solution in the Treatment of Acute Otitis Externa
A Phase 3 study testing Ciprofloxacin-Fluocinolone Acetonide, 0.3%-0.025% Otic Solution and Ciprofloxacin 0.3% solution in people with Acute Otitis Externa, run by Lee's Pharmaceutical Limited at 1 site in China.
Trial 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 acute otitis externa (AOE), and to assess the… Read more about this study
- Who is it for?
- Ages 3 years and older
- Conditions the study is for
- Acute Otitis Externa
- What is being tested?
- Ciprofloxacin-Fluocinolone Acetonide, 0.3%-0.025% Otic Solution and Ciprofloxacin 0.3% solution
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 600 participants
- Where
- 1 siteChina
- Study dates
- 4 Jan 2021to 17 Oct 2021
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male or female subjects with age of ≥3 years.
- Diagnosis of unilateral or bilateral diffuse acute otitis externa (AOE) within 21 days (3 weeks) before screening.
- Grade II or III AOE, with at least Grade 2 edema (ear canal swelling), at least Grade 2 ear tenderness (pain on palpation), and at least Grade 1 otorrhea present concurrently.
- 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).
Who cannot join
- Subjects unable to undergo otoscopy or otoendoscopy.
- An episode of AOE 21 to 28 days before screening, or 2 or more episodes of AOE 21 to 180 days before screening.
- 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.
- Children aged 6 years or younger with an abnormal result on audiological assessment using behavioral audiometry, multi-frequency auditory steady-state response (ASSR), auditory brainstem response (ABR), distortion product otoacoustic emissions (DPOAE), play audiometry, or another non-pure-tone audiometric method.
- History of malignant tumors in the external ear canal, or currently receiving chemotherapy or radiotherapy.
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- Current diagnosis of diabetes mellitus, psoriasis, immunodeficiency or history of drug abuse.
- A severe cardiovascular, respiratory, urinary, digestive, or nervous system disease that remains unstable after at least 4 weeks of pharmacotherapy and requires additional intervention.
- Use within 1 week before screening of any systemic or topical antimicrobial agent, corticosteroid, anti-inflammatory or analgesic medication, or any other medication that could affect evaluation of the study results, when the interval between the last dose and screening was less than 6 half-lives of the medication.
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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)
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 acute otitis externa (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 pharmacokinetic parameters.
- Conditions
- Acute Otitis Externa
- Being tested
- Ciprofloxacin-Fluocinolone Acetonide, 0.3%-0.025% Otic Solution, Ciprofloxacin 0.3% solution
- Keywords
- ciprofloxacin, fluocinolone acetonide 0.025%, AOE
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ciprofloxacin-Fluocinolone Acetonide, 0.3%-0.025% Otic SolutionDrug
0.25mL/vial, each vial contains 0.75mg of ciprofloxacin and 0.0625mg of fluocinolone acetonide.
Ciprofloxacin 0.3% solutionDrug
Also called CETRAXAL OTICO®
0.4mL/vial, each vial contains 1.2mg ciprofloxacin
| Study group | Role | What they receive |
|---|---|---|
| ciprofloxacin 0.3% plus fluocinolone acetonide 0.025% | Experimental | 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. Receives: Drug: Ciprofloxacin-Fluocinolone Acetonide, 0.3%-0.025% Otic Solution |
| ciprofloxacin 0.3% | Active comparator | 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 5 drops (0.25 mL) into the study ear. 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. Receives: Drug: Ciprofloxacin 0.3% solution |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Cure
Clinical cure was reported as the number and percentage of participants with a score of 0 (absent) for each of 3 signs or symptoms: edema, otorrhea and ear tenderness. Each item was assessed using the investigator-rated 4-Point Scale for Clinical Efficacy Assessment, ranging from 0 to 3: 0 = absent, 1 = mild, 2 = moderate, and 3 = severe. Higher scores indicated greater severity and a worse outcome. A score greater than 0 for any item was classified as clinical failure. For participants who achieved clinical cure at Visit 3 and completed the study early, the Visit 3 cure assessment was carried forward to End of Study.
Measured: End of Study (Visit 4, Day 15+2)
Secondary outcomes (7)
Microbiological Cure
Microbiological response will be classified as Eradicated, Presumed Eradicated, Persistence, Presumed Persistence, Partial Eradication, Superinfection and Recurrence. Microbiological cure rate is defined as the percentage of patients who achieve the eradication and presumed eradication.
Measured: Visit 3 (Day 8+2) and Visit 4 (Day 15+2)
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.
Measured: Visit 3 (Day 8+2) and Visit 4 (Day 15+2)
Clinical Improvement
Clinical improvement was defined as an improvement of at least 1 grade from baseline (Visit 1) in any 1 of the 3 investigator-assessed clinical signs or symptoms (edema, otorrhea, or ear tenderness), without worsening in either of the other 2 assessments. The outcome was reported as the number and percentage of participants with clinical improvement at Visit 3 and Visit 4.
Measured: Visit 3 (Day 8+2) and Visit 4 (Day 15+2)
Improvement in Each of Signs and Symptoms
Each sign or symptom (edema, otorrhea, and ear tenderness) was analyzed separately. For each assessment, improvement was defined as a decrease of at least 1 grade from baseline (Visit 1) and was reported as the number and percentage of participants with improvement at Visit 3 and Visit 4.
Measured: Visit 3 (Day 8+2) and Visit 4 (Day 15+2)
Improvement in Granulation Tissue
Granulation tissue formation in the external auditory canal was assessed by the investigator using an otoscope or an ear, nose, and throat (ENT) video-endoscopy system and classified as absent (0) or present (1). Among participants with granulation tissue present at baseline (Visit 1), resolution was defined as granulation tissue absent at Visit 3 (Day 8+2) or Visit 4 (Day 15+2).
Measured: Visit 3 (Day 8+2) and Visit 4 (Day 15+2)
Improvement of 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.
Measured: Visit 3 (Day 8+2) and Visit 4 (Day 15+2)
Time to End of Ear Pain
Time to end of ear pain was calculated in days from the first dose to the last recorded resolution of ear pain (resolution date minus first-dose date plus 1). This endpoint was analyzed only among participants with ear pain at baseline. Participants whose ear pain had not resolved by the end of the study were censored according to the prespecified statistical analysis plan. If the last recorded resolution occurred after rescue medication, the participant was treated as not having pain resolution and was censored at the date of first rescue medication.
Measured: From the first dose to the end of the study (Visit 4, Day 15+2)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2020
- Study start4 Jan 2021
- Primary completion17 Oct 2021
- Study completion17 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute Otitis ExternaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 600 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lee's Pharmaceutical Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04636957
- Sponsor's protocol ID
- ZK- CIPRO+FLUO-201911
- Status last verified
- Oct 2026
- First submitted
- 28 Oct 2020
- Last updated
- 13 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04636957
- Acronym / sponsor ID
- ZK- CIPRO+FLUO-201911
- Conditions
- Acute Otitis Externa
- Keywords
- ciprofloxacin, fluocinolone acetonide 0.025%, AOE
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 600 participants (actual)
- Lead sponsor
- Lee's Pharmaceutical LimitedIndustry (pharma, biotech, devices)
- Study start
- 4 Jan 2021 (actual)
- Primary completion
- 17 Oct 2021 (actual)
- Study completion
- 17 Oct 2021 (actual)
- First posted
- 19 Nov 2020 (actual)
- Results
- Posted 13 Oct 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 acute otitis externa (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 pharmacokinetic parameters.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ciprofloxacin 0.3% plus fluocinolone acetonide 0.025% | Experimental | Drug: Ciprofloxacin-Fluocinolone Acetonide, 0.3%-0.025% Otic SolutionWarm 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. |
| ciprofloxacin 0.3% | Active comparator | Drug: Ciprofloxacin 0.3% solutionWarm 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 5 drops (0.25 mL) into the study ear. 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. |
Who may qualify
- Ages
- 3 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Male or female subjects with age of ≥3 years.
- Diagnosis of unilateral or bilateral diffuse acute otitis externa (AOE) within 21 days (3 weeks) before screening.
- Grade II or III AOE, with at least Grade 2 edema (ear canal swelling), at least Grade 2 ear tenderness (pain on palpation), and at least Grade 1 otorrhea present concurrently.
- 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.
Key exclusion criteria (13 listed)
- Subjects unable to undergo otoscopy or otoendoscopy.
- An episode of AOE 21 to 28 days before screening, or 2 or more episodes of AOE 21 to 180 days before screening.
- 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.
- Children aged 6 years or younger with an abnormal result on audiological assessment using behavioral audiometry, multi-frequency auditory steady-state response (ASSR), auditory brainstem response (ABR), distortion product otoacoustic emissions (DPOAE), play audiometry, or another non-pure-tone audiometric method.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ciprofloxacin-Fluocinolone Acetonide, 0.3%-0.025% Otic Solution0.25mL/vial, each vial contains 0.75mg of ciprofloxacin and 0.0625mg of fluocinolone acetonide. | Drug | ciprofloxacin 0.3% plus fluocinolone acetonide 0.025% |
| Ciprofloxacin 0.3% solutionAlso: CETRAXAL OTICO®0.4mL/vial, each vial contains 1.2mg ciprofloxacin | Drug | ciprofloxacin 0.3% |
Primary outcome
Clinical Cure
Time frame: End of Study (Visit 4, Day 15+2)
Clinical cure was reported as the number and percentage of participants with a score of 0 (absent) for each of 3 signs or symptoms: edema, otorrhea and ear tenderness. Each item was assessed using the investigator-rated 4-Point Scale for Clinical Efficacy Assessment, ranging from 0 to 3: 0 = absent, 1 = mild, 2 = moderate, and 3 = severe. Higher scores indicated greater severity and a worse outcome. A score greater than 0 for any item was classified as clinical failure. For participants who achieved clinical cure at Visit 3 and completed the study early, the Visit 3 cure assessment was carried forward to End of Study.
7 secondary outcomes
Microbiological Cure
Time frame: Visit 3 (Day 8+2) and Visit 4 (Day 15+2)
Overall Therapeutic Cure
Time frame: Visit 3 (Day 8+2) and Visit 4 (Day 15+2)
Clinical Improvement
Time frame: Visit 3 (Day 8+2) and Visit 4 (Day 15+2)
Improvement in Each of Signs and Symptoms
Time frame: Visit 3 (Day 8+2) and Visit 4 (Day 15+2)
Improvement in Granulation Tissue
Time frame: Visit 3 (Day 8+2) and Visit 4 (Day 15+2)
Improvement of Ear Pain
Time frame: Visit 3 (Day 8+2) and Visit 4 (Day 15+2)
Time to End of Ear Pain
Time frame: From the first dose to the end of the study (Visit 4, Day 15+2)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ciprofloxacin-Fluocinolone Acetonide, 0.3%-0.025% Otic Solution and Ciprofloxacin 0.3% solution in people with Acute Otitis Externa, run by Lee's Pharmaceutical Limited at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Oct 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical Cure (time frame: End of Study (Visit 4, Day 15+2)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Oct 2026.