A Pharmacokinetics and Safety Study of Augmentin ES-600 in Children With CAP and ABRS

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the pharmacokinetics, safety or tolerability through treatment emergent adverse event (TEAE) and to explore primary and secondary clinical response of treatment with Augmentin ES in pediatric population presenting with CAP and ABRS in Brazil.

Official Title
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An Open Label, Single Arm Study, to Evaluate the Pharmacokinetics and Safety of Augmentin Extra Strength (ES)-600 Suspension in Children Presenting With Community Acquired Pneumonia (CAP) and Acute Bacterial Rhinosinusitis (ABRS) in Brazil

Conditions
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Infections, Bacterial

Intervention / Treatment
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* Drug: Augmentin ES


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The participant and/or parent(s)/legal guardian(s) are willing and able to comply with the study protocol. In accordance with regional/local laws and regulations, a. the parent(s)/legal guardian(s) has given signed informed, dated consent; and the participant has b.given written assent, if applicable, to participate in the study (for participants between 7 to 12 years) Age: Participant must be aged greater than or equal to (>=) 3 months to 12 years, of either gender. Participants who are otherwise healthy and presenting with suspected CAP. For participants clinically suspected of CAP, at least 3 of the following 4 criteria are applicable: a) History of productive cough and/or shortness of breath. b)Fever greater than (>)38.5 degree Celsius (○C) (Axillary temperature) c) Tachypnea as defined by Respiratory rate (RR) >= 50 breaths/minute in children up to 11 months RR >= 40 breaths/minute in children from 12 months onwards d) Chest X-Ray with shadow or lobar condensation, unilateral or bilateral. For participants of ABRS: The participant and/or parent(s)/legal guardian(s) are willing and able to comply with the study protocol. In accordance with regional/local laws and regulations, a..The parent(s)/legal guardian(s) has given signed informed, dated consent; and the participant has b. given written assent, if applicable, to participate in the study (for participants between 7 to 12 years). Age: Participant must be between >=3 months to 12 years of either gender. Participants who are otherwise healthy and presenting with suspected ABRS. For participants of clinically suspected ABRS, the participants would be eligible if any of the following 2 of the 3 criteria stated below are met: a.Children with purulent nasal discharge or daytime productive cough (which may worsen at night) or both persisting for 10 days or more without evidence of improvement. b. Fever > 38.3○C (Axillary temperature) c. Double sickness defined as initial improvement of symptoms and further worsening/ deterioration after 5 days. Exclusion Criteria: Severe ABRS/CAP requiring hospitalization. Currently receiving or has received more than one dose of systemic antibiotic therapy within one week prior to the initiation of the study. A serious underlying disease as per clinician's judgment. Human immunodeficiency virus (HIV) infection/or any other immunosuppressive condition Pre-existing renal insufficiency (for example [e.g.], plasma creatinine > 1.5 times upper limit of normal range for age). Pre-existing liver disease(s) and/or hepatic dysfunction. Any pre-existing malignancy/any participants undergoing any kind of chemotherapy. Evidence of leukopenia and/or thrombocytopenia. History of previous hypersensitivity reaction to penicillins, cephalosporins or other Beta-lactam antibiotics. History of amoxicillin-clavulanate 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. Received, within 48 hours of study entry, or is scheduled to receive during the study period, any medication which may alter renal function like probenecid. Participants who have chronic sinusitis (signs and symptoms lasting greater than 28 days prior to screening visit. Significant abnormalities of the sinuses and any complications of ABRS. Have concurrent streptococcal pharyngitis or acute otitis media (as the standard doses for both of these conditions is 10 days). Any other infection or condition, which necessitates use of a concomitant systemic antimicrobial. History of infectious mononucleosis. History of pseudomembranous colitis. Participants that are on warfarin therapy. Receipt of an investigational compound (non-food and drug administration [FDA] and non-Brazil National Health Surveillance Agency [ANVISA] 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 (that is (i.e.), fever, cough, etc.) Participants with known COVID-19 positive contacts within the past 14 days. Female participants who have attained menarche

Ages Eligible for Study
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Minimum Age: 3 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 study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Participants with CAP and ABRS<br> | Drug: Augmentin ES<br>* Amoxicillin and clavulanic acid in fixed dose combination will be administered<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absorption rate constant (Ka) of amoxicillin and clavulanic acid combination |  | Up to 10 days | 
| Area under the serum concentration-time curve (AUC) of amoxicillin and clavulanic acid combination |  | Up to 10 days | 
| Maximum serum concentration (Cmax) of amoxicillin and clavulanic acid combination |  | Up to 10 days | 
| Clearance (CL) of amoxicillin and clavulanic acid combination |  | Up to 10 days | 
| Volume of distribution (Vd) of amoxicillin and clavulanic acid combination |  | Up to 10 days | 
| Terminal half-life (t1/2) of amoxicillin and clavulanic acid combination |  | Up to 10 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment emergent adverse events (TEAE) |  | Up to Day 14 | 
| Number of participants achieving Primary Clinical Response |  | Day 11 to Day 14 | 
| Number of participants achieving Secondary Clinical response |  | Day 22 to Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Amoxicillin, Clavulanic acid, Community Acquired Pneumonia, Acute Bacterial Rhinosinusitis, Pharmacokinetics, Safety, Clinical response, Augmentin ES