Reduced Clavulanate Formulation of Amoxicillin-Clavulanate in Children 6-23 Months With Acute Otitis Media

Nader Shaikh

Status and phase: Completed; Phase 3

Conditions: Acute Otitis Media

Treatments: Drug: Amoxicillin-Clavulanate potassium

Study type: Interventional

Funder types: Other

Identifiers

NCT02630992

PRO15080192

Details and patient eligibility

About

To evaluate the safety profile of amoxicillin-clavulanate potassium containing a reduced concentration of clavulanate potassium, 600 mg/21.5 mg/5 mL (a ratio of 28:1), administered at 90/3.2 mg/kg/day (formulation 1) or at 80/2.85 mg/kg/day (formulation 2) in two divided doses for 10 days. Investigators will focus on the proportion of subjects who develop protocol-defined diarrhea and proportion who develop diaper dermatitis that occasions the prescription of antifungal medication.

Full description

Amoxicillin-clavulanate potassium has been shown to be efficacious in eradicating causative pathogens in acute otitis media (AOM) with resulting high clinical cure rates at end-of-treatment (85%). However, relatively high rates (~25%) of clinically significant diarrhea have been reported, the occurrence of which has been directly related to the clavulanate potassium component of the drug combination. A reduced concentration of clavulanate potassium in the drug formulation would be expected to have an improved safety profile regarding the occurrence of diarrhea. This study will examine whether the concentration of the clavulanate potassium component of amoxicillin-clavulanate potassium could be reduced in the treatment of children 6 months through 23 months of age diagnosed with AOM using stringent criteria. A total of 75 participants (n=75) with AOM will receive amoxicillin-clavulanate potassium (600 mg/21.5 mg/5 mL; 28:1) administered at 90/3.2 mg/kg/day (formulation 1) or at 80/2.85 mg/kg/day (formulation 2) in two divided doses for 10 days.

The primary outcome measure will be rates of clinically significant diarrhea and diaper dermatitis. These rates will be compared with the rate observed in our previous studies of AOM in children who received amoxicillin-clavulanate potassium (600 mg/42.9 mg/5 mL; 14:1) administered at 90/6.4 mg/kg/day in two divided doses for 10 days.

A subset of this group will have pharmacokinetic studies performed. Each participant that agrees will have a single blood draw (n=50). Investigators will analyze amoxicillin and clavulanate potassium in the blood samples using validated methods.

Enrollment: 112 patients

Sex: All

Ages: 6 to 23 months old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age range: 6 to 23 months
• Evidence of AOM
• Recent (within 48 hours) onset of signs and symptoms.
• Middle ear effusion evidenced by the presence of at least 2 of the following: decreased or absent mobility of the tympanic membrane (TM), yellow of white discoloration of the TM, and/or opacification of the TM
• Acute inflammation evidenced by one of the following: 1+ bulging of the TM with either intense erythema or otalgia or 2+ or 3+ bulging of the TM

Exclusion criteria

• Toxic appearance (capillary refill >3 seconds, systolic blood pressure <60 mm Hg)
• Inpatient hospitalization
• Clinical or anatomical characteristics that might obscure response to treatment (e.g., tympanostomy tubes in place, cleft palate, Down syndrome)
• Sensorineural hearing loss (unilateral or bilateral)
• Allergy to amoxicillin or amoxicillin clavulanate
• Recent treatment of AOM within the last 14 days

Trial design

Primary purpose: Other

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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112 participants in 1 patient group

amoxicillin-clavulanate potassium

Experimental group

Description:

amoxicillin-clavulanate potassium (600 mg/221.5 mg/5 mL; 28:1) administered prior to February 25, 2016 at 90/3.2 mg/kg/day in two divided doses for 10 days; oral, liquid (formulation 1) or administered as of February 25, 2016 at 80/2.85 mg/kg/day in two divided doses for 10 days; oral, liquid (formulation 2)

Treatment:

Drug: Amoxicillin-Clavulanate potassium