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

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

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.

Study Overview

• Status: Completed
• Conditions: Respiratory Tract Infections; Otitis Media; Infections, Respiratory Tract
• Intervention / Treatment: Drug: Augmentin (ES)-600

• Study Type: Interventional
• Enrollment (Actual): 310
• Phase: Phase 4

Contacts and Locations

Study Locations

• India
  • Belgaun, India, 590010
    • GSK Investigational Site
  • Hyderabad, India, 500018
    • GSK Investigational Site
  • Kanpur, India, 208002
    • GSK Investigational Site
  • Kolkata, India, 700017
    • GSK Investigational Site
  • Ludhiana, India, 141008
    • GSK Investigational Site
  • Madurai, India, 625107
    • GSK Investigational Site
  • Nagpur, India, 440009
    • GSK Investigational Site
  • New Delhi, India, 110002
    • GSK Investigational Site
  • Pune, India, 411043
    • GSK Investigational Site
  • Purne, India, 411030
    • GSK Investigational Site
  • Chhattisgarh
    • Raipur, Chhattisgarh, India, 492099
      • GSK Investigational Site
  • Rajasthan
    • Jaipur, Rajasthan, India, 302016
      • GSK Investigational Site
  • Uttar Pradesh
    • Varanasi, Uttar Pradesh, India, 221001
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 12 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants aged: 6 months to 12 years; no gender restriction.

• Diagnosis of AOM on basis of otoscopic findings as defined below:

  1. Purulent otorrhea of less than 24 hours duration or
  2. Middle ear effusion

• Middle ear effusion is evidenced by at least two of the following:

  1. Decreased or absent tympanic mobility measured by pneumatic otoscopy,
  2. Yellow or white discoloration of the tympanic membrane, or
  3. Opacification of the tympanic membrane plus

At least one of the following indicators of acute inflammation:

1. Ear pain within 24 hours, including unaccustomed tugging or rubbing of ear,
2. Marked redness of the tympanic membrane, or

3. 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, etc).
• Participants with known COVID-19 positive contacts within the past 14 days.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Participants receiving Augmentin (ES)-600; 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; Augmentin ES will be administered as reconstituted oral suspension containing Amoxicillin and Potassium Clavulanate 600 mg/42.9 mg per 5 milliliters.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. A treatment emergent AE event has its onset date on or after treatment start date and on or before treatment stop date + 1 day	Up to 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Early Clinical Response at On-therapy (OT) Visit	Early clinical response was categorized as treatment 'success' or treatment 'failure' at OT Visit (Day 3 to 5). Success was defined as 'clinical cure' that included sufficient resolution or improvement of the signs and symptoms such that no additional antibiotic therapy was indicated or 'improvement' that included improvement in at least 1 presenting signs/symptoms such that no additional antibiotic indicated. Failure is defined as 'Clinical Failure' that included as non-improvement or deterioration in any sign/symptoms after 2 or more days of therapy and additional antibiotic therapy is indicated or 'Unable to Determine' included a valid assessment of clinical outcome could not be made (eg, participant did not attend or consent to clinical examination or lost to follow-up). Participants who were not taking minimum 4 doses in two days were categorized as non evaluable.	On-therapy (OT) visit (Day 3 to 5)
Number of Participants With Primary Clinical Response at End of Therapy (EOT)	Primary clinical response at the end-of-therapy visit was categorized as treatment 'success' or treatment 'failure'. Success was defined as 'Clinical Cure' that included sufficient resolution or improvement of the signs and symptoms that no additional antibiotic therapy was indicated or 'Improvement' that included improvement, but incomplete resolution of presenting signs/symptoms and no additional antibiotic indicated. Failure is defined as 'Clinical Failure' that included non-improvement or deterioration in any sign/symptoms after 2 or more days of therapy and additional antibiotic therapy indicated, or 'Unable to determine' defined as a valid assessment of clinical outcome could not be made (e.g., participant did not attend or consent to clinical examination or lost to follow-up). Non-Evaluable is defined as participants who had less than (<) 80% compliance	End of therapy visit (Day 12 to 14)
Number of Participants With Secondary Clinical Response at Follow-up (FU)	Secondary clinical response at follow-up was categorized as treatment 'success' or treatment 'failure'. Success was defined as 'Persistent clinical cure' that included sufficient resolution of signs/symptoms for those participants who were clinically cured or improved at the end of therapy and no additional antibiotic indicated. Failure was defined as 'Clinical recurrence' that included reappearance of signs/symptoms for those participants who were clinically cured or improved at the end of therapy and additional antibiotic therapy was indicated, or 'Unable to determine' that included valid assessment of clinical outcome could not be made (e.g., participant did not attend end of therapy visit, or extenuating circumstances or lost to follow-up). Participant with missing responses were categorized as 'Missing'.	Follow up visit (Day 22 to 28)
Number of Participants With Protocol-defined Diarrhea (PDD) (Due to Study Medication)	Protocol-defined diarrhea was defined as a) 3 or more watery stools in one day or b) 4 or more loose/watery stools in one day or c) 2 watery stools per day for two consecutive days or d) 3 loose/watery stools per day for two consecutive days.	From OT visit (Day 3 to 5) to FU visit (Day 22-28)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Collaborators: IQVIA Pty Ltd
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): May 7, 2022
• Primary Completion (Actual): November 12, 2022
• Study Completion (Actual): November 12, 2022

Study Registration Dates

• First Submitted: October 19, 2020
• First Submitted That Met QC Criteria: October 19, 2020
• First Posted (Actual): October 23, 2020

Study Record Updates

• Last Update Posted (Actual): June 10, 2024
• Last Update Submitted That Met QC Criteria: May 24, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Pediatric; Acute otitis media; Augmentin Extra Strength; Amoxicillin-clavulanic acid; Beta-lactamase
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease Attributes; Otorhinolaryngologic Diseases; Ear Diseases; Infections; Communicable Diseases; Otitis; Otitis Media; Respiratory Tract Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Amoxicillin-Potassium Clavulanate Combination
• Other Study ID Numbers: 213514

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No