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

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.

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