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

NCT04600752 | Completed Phase 4 Results

• 1 other identifier: 213514
• Study Type: interventional
• Target: 310
• Locations: 1 country
• Sites: 13

Brief Summary

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.

Conditions

Otitis Media; Infections, Respiratory Tract; Respiratory Tract Infections

Keywords

Acute otitis media; Augmentin Extra Strength; Amoxicillin-clavulanic acid; Pediatric; Beta-lactamase

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Number of Participants With Early Clinical Response at On-therapy (OT) Visit

  On-therapy (OT) visit (Day 3 to 5)

• Number of Participants With Primary Clinical Response at End of Therapy (EOT)

  End of therapy visit (Day 12 to 14)

• Number of Participants With Secondary Clinical Response at Follow-up (FU)

  Follow up visit (Day 22 to 28)

• Number of Participants With Protocol-defined Diarrhea (PDD) (Due to Study Medication)

  From OT visit (Day 3 to 5) to FU visit (Day 22-28)

Study Arms (1)

Participants receiving Augmentin (ES)-600

EXPERIMENTAL

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

Interventions

Augmentin (ES)-600 DRUG

Augmentin ES will be administered as reconstituted oral suspension containing Amoxicillin and Potassium Clavulanate 600 mg/42.9 mg per 5 milliliters.

Participants receiving Augmentin (ES)-600

Eligibility Criteria

• Age: 6 Months - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• GlaxoSmithKline: lead
• Iqvia Pty Ltd: collaborator

Study Sites (13)

GSK Investigational Site

Raipur, Chhattisgarh, 492099, India

Location

GSK Investigational Site

Jaipur, Rajasthan, 302016, India

Location

GSK Investigational Site

Varanasi, Uttar Pradesh, 221001, India

Location

GSK Investigational Site

Belgaun, 590010, India

Location

GSK Investigational Site

Hyderabad, 500018, India

Location

GSK Investigational Site

Kanpur, 208002, India

Location

GSK Investigational Site

Kolkata, 700017, India

Location

GSK Investigational Site

Ludhiana, 141008, India

Location

GSK Investigational Site

Madurai, 625107, India

Location

GSK Investigational Site

Nagpur, 440009, India

Location

GSK Investigational Site

New Delhi, 110002, India

Location

GSK Investigational Site

Pune, 411043, India

Location

GSK Investigational Site

Purne, 411030, India

Location

MeSH Terms

Conditions

Otitis Media; Respiratory Tract Infections

Interventions

Amoxicillin-Potassium Clavulanate Combination

Condition Hierarchy (Ancestors)

Otitis; Ear Diseases; Otorhinolaryngologic Diseases; Infections; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Clavulanic Acid; Clavulanic Acids; beta-Lactams; Lactams; Amides; Organic Chemicals; Amoxicillin; Ampicillin; Penicillin G; Penicillins; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Masking Details: This is an open-label study.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a single arm, multicenter, non-comparative study.

Study Record Dates

• First Submitted: October 19, 2020
• First Posted: October 23, 2020
• Study Start: May 7, 2022
• Primary Completion: November 12, 2022
• Study Completion: November 12, 2022
• Last Updated: June 10, 2024
• Results First Posted: April 25, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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.

Locations

IN (13)