Study to Evaluate the Safety and Clinical Efficacy of Augmentin® Extra Strength-600 in Children With Acute Otitis Media in India

Study Overview
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Brief Summary
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Augmentin (ES)-600 is a high-dose amoxicillin/clavulanic acid 14:1 formulation that allows administration at 90/6.4 milligrams (mg)/kilograms (kg)/day in two divided doses. Most physicians in India use the standard Augmentin (amoxicillin:clavulanic acid 7:1) (45/6.4 mg/kg/day) formulation and double the dose to achieve higher dose of amoxicillin/clavulanic acid at 90 mg/kg/day in pediatric acute otitis media (AOM) due to non-availability of Augmentin (ES)-600. Using the 7:1 formulation causes unnecessary exposure to higher proportionate dose of clavulanic acid (12.8 mg/kg/day) as a unit dose of 6.4 mg/kg/day of clavulanic acid is only required for efficacy against beta-lactamase producing AOM pathogens. Hence, there is an unmet need for availability of Augmentin (ES)-600 in India. This is an open label, single arm, multicenter, non-comparative study in participants aged 6 months to 12 years with AOM. It aims to assess the safety and clinical efficacy of Augmentin (ES)-600 administered in two divided doses, every 12 hours in pediatric population in India. AUGMENTIN is a registered trademark of the GlaxoSmithKline group of companies.

Official Title
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A Multicenter, Open-label, Non-comparative Phase IV Clinical Study to Evaluate the Safety and Clinical Efficacy of Augmentin Extra Strength (ES)-600 in Children With Acute Otitis Media (AOM) in India

Conditions
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Otitis Media, Infections, Respiratory Tract, Respiratory Tract Infections

Intervention / Treatment
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* Drug: Augmentin (ES)-600


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants aged: 6 months to 12 years; no gender restriction. Diagnosis of AOM on basis of otoscopic findings as defined below: Purulent otorrhea of less than 24 hours duration or Middle ear effusion Middle ear effusion is evidenced by at least two of the following: Decreased or absent tympanic mobility measured by pneumatic otoscopy, Yellow or white discoloration of the tympanic membrane, or Opacification of the tympanic membrane plus At least one of the following indicators of acute inflammation: Ear pain within 24 hours, including unaccustomed tugging or rubbing of ear, Marked redness of the tympanic membrane, or Distinct fullness or bulging of the tympanic membrane. The participant and parent(s)/legal guardian(s) are willing and able to comply with the study protocol. In accordance with regional/local laws and regulations, the parent(s)/legal guardian(s) has given signed informed, dated consent; and the participant has given written assent, if applicable, to participate in the study. Exclusion Criteria: Weight more than 40 kg. Spontaneous perforation of the tympanic membrane and drainage for longer than 24 hours. Tympanoplastic tube(s) in place, or has anatomic abnormalities associated with recurrent AOM, prolonged middle ear effusion, including cleft palate or repair, high-arched palate or Down's syndrome. A serious underlying disease as per clinician's judgment. Concomitant infection which would preclude evaluation of the response of his/her acute otitis media to the study intervention. Pre-existing renal insufficiency (plasma creatinine greater than [>]1.5 times upper limit of normal range for age). Pre-existing liver disease(s) and/or hepatic dysfunction. Evidence of leukopenia and/or thrombocytopenia. History of previous hypersensitivity reaction to penicillins, cephalosporins or other beta-lactam antibiotics. History of Augmentin-associated cholestatic jaundice/hepatic dysfunction. History of phenylketonuria or a known hypersensitivity to aspartame. Received, within 48 hours of study entry, or is scheduled to receive during the study period, any medication which may alter bowel function. Currently receiving or has received more than one dose of systemic antibiotic therapy within one week prior to the initiation of the study. AOM treatment failures with Amoxicillin, erythromycin, sulfamethoxazole or Trimethoprim-Sulfamethoxazole are not subject to this criterion. Receipt of an investigational compound (non-Food and Drug Administration [FDA] and non- Drugs Controller General Of India [DCGI] approved) or device within the previous 30 days or five half-lives, whichever is longer, preceding the first dose of study intervention or during the study. Participants with symptoms suggestive of active Coronavirus Disease 2019 (COVID-19) infection (fever, cough, et cetera). Participants with known COVID-19 positive contacts within the past 14 days.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This is a single arm, multicenter, non-comparative study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Participants receiving Augmentin (ES)-600<br>Eligible participants will receive Augmentin (ES)-600 at 90/6.4 mg/kg/day administered in two divided doses, every 12 hours with food for 10 days. | Drug: Augmentin (ES)-600<br>* Augmentin ES will be administered as reconstituted oral suspension containing Amoxicillin and Potassium Clavulanate 600 mg/42.9 mg per 5 milliliters.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment emergent adverse events (TEAE) and serious adverse events (SAEs) | TEAEs and SAEs will be collected. | From start of treatment (Day 1) to follow-up visit at Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants achieving Primary Clinical Response | Primary clinical response will be assessed at the end of therapy (EOT) visit (Day 12 to 14) in terms of success or failure to study intervention. A treatment success at EOT will be defined as either clinical cure or improvement. A treatment failure will be defined as a participant whose clinical outcome will be clinical failure (due to worsening or non-improvement in symptoms) or unable to determine. | From start of treatment (Day 1) to end of therapy visit at Day 12-14 | 
| Number of participants achieving Secondary Clinical response | Secondary clinical response will be assessed at follow-up (Day 22 to 28) in terms of success or failure to study intervention. A treatment success at follow-up will be defined as persistent clinical cure and treatment failure will be clinical recurrence or unable to determine. | From end of treatment visit (Day 12-14) to follow up visit at Day 22-28 | 
| Number of participants with protocol defined diarrhea (PDD) (due to study medication) | Protocol-defined diarrhea is 3 or more watery stools in one day or 4 or more loose/watery stools in one day or 2 watery stools per day for two consecutive days or 3 loose/watery stools per day for two consecutive days. | From start of treatment (Day 1) to end of therapy visit at Day 12-14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pediatric, Acute otitis media, Augmentin Extra Strength, Amoxicillin-clavulanic acid, Beta-lactamase