Acute Otitis Media
Conditions
Keywords
ear infections, antibiotics, antibiotic resistance, pediatrics, infants, children, amoxicillin-clavulanate
Brief summary
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.
Detailed 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.
Interventions
Sponsors
Nader Shaikh
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Months to 23 Months
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Distribution of Participants Receiving Formulation 1 for Whom Protocol-Defined Diarrhea (PDD) Was Reported and Associated With Study Product | Day 1 of administration of amoxicillin-clavulanate until day 12. | Participants receiving formulation 1 were administered 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 in two divided doses for 10 days. Protocol-defined diarrhea is defined as the occurrence of three or more watery stools in 1 day or two watery stools daily for 2 consecutive days and is limited to events associated with study product. |
| The Distribution of Participants Receiving Formulation 2 for Whom Protocol-Defined Diarrhea (PDD) Was Reported and Associated With Study Product | Day 1 of administration of amoxicillin-clavulanate until day 12. | Participants receiving formulation 2 were administered amoxicillin-clavulanate potassium containing a reduced concentration of clavulanate potassium, 600 mg/21.5 mg/5 mL (a ratio of 28:1), administered at 80/2.85 mg/kg/day in two divided doses for 10 days. Protocol-defined diarrhea is defined as the occurrence of three or more watery stools in 1 day or two watery stools daily for 2 consecutive days and is limited to events associated with study product. |
| The Distribution of Participants Receiving Formulation 1 for Whom Diaper Dermatitis Was Reported and Associated With Study Product | Day 1 of administration of amoxicillin-clavulanate until day 12. | Participants receiving formulation 1 were administered 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 in two divided doses for 10 days. Diaper dermatitis is defined as dermatitis in the diaper area calling for prescription of a topical antifungal agent and is limited to events associated with study product. |
| The Distribution of Participants Receiving Formulation 2 for Whom Diaper Dermatitis Was Reported and Associated With Study Product | Day 1 of administration of amoxicillin-clavulanate until day 12. | Participants receiving formulation 2 were administered amoxicillin-clavulanate potassium containing a reduced concentration of clavulanate potassium, 600 mg/21.5 mg/5 mL (a ratio of 28:1), administered at 80/2.85 mg/kg/day in two divided doses for 10 days. Diaper dermatitis is defined as dermatitis in the diaper area calling for prescription of a topical antifungal agent and is limited to events associated with study product.. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Mean Score Representing the Parent or Guardian's Level of Satisfaction With Therapy for Participants Receiving Formulation 1 | The end-of-treatment visit. The mean day for this visit was 14.9. | Participants receiving formulation 1 were administered 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 in two divided doses for 10 days. The parent or guardian will answer a questionnaire regarding their satisfaction with the therapy their child received. The responses 'very dissatisfied', 'somewhat dissatisfied', 'neither satisfied nor dissatisfied', 'somewhat satisfied' and 'very satisfied' correspond to scores of 1, 2, 3, 4, and 5, respectively. |
| The Mean Score Representing the Parent or Guardian's Level of Satisfaction With Therapy for Participants Receiving Formulation 2 | The end-of-treatment visit. The mean day for this visit was 13.9. | Participants receiving formulation 2 were administered amoxicillin-clavulanate potassium containing a reduced concentration of clavulanate potassium, 600 mg/21.5 mg/5 mL (a ratio of 28:1), administered at 80/2.85 mg/kg/day in two divided doses for 10 days. The parent or guardian will answer a questionnaire regarding their satisfaction with the therapy their child received. The responses 'very dissatisfied', 'somewhat dissatisfied', 'neither satisfied nor dissatisfied', 'somewhat satisfied' and 'very satisfied' correspond to scores of 1, 2, 3, 4, and 5, respectively. |
| Distribution of Population Plasma Concentration of Amoxicillin According to Time For Participants Receiving Formulation 1 | From administration of a single dose of amoxicillin-clavulanate until approximately 4 hours after. | Participants receiving formulation 1 were administered 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 in two divided doses for 10 days. Plasma concentration of amoxicillin 45 mg/kg/dose was measured. Data points up to 4 hours with a standard deviation of 0 indicate that the assessment was available for only one child. |
| The Distribution of Participants Receiving Formulation 1 Categorized as Treatment Failure (TF) at or Before the End-of-Treatment Visit | From 72 hours after the initial AOM until the end-of-treatment visit. The mean day for this visit was 14.9. | Participants receiving formulation 1 were administered 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 in two divided doses for 10 days. Treatment failure is defined as substantial persistence or worsening of symptoms specifically attributable to AOM or of otoscopic signs of acute inflammation (bulging of the TM or intense erythema) after 72 hours from the initial AOM, such that additional antimicrobial therapy is deemed advisable. Clinical success is defined as complete or substantial resolution of symptoms specifically attributable to AOM for 48 hours and of otoscopic signs of acute inflammation (bulging of the TM or intense erythema), with or without persistence of middle-ear effusion, such that no additional antibiotic therapy is deemed advisable. |
| Distribution of Population Plasma Concentration of Clavulanate According to Time For Participants Receiving Formulation 1 | From administration of a single dose of amoxicillin-clavulanate until approximately 4 hours after. | Participants receiving formulation 1 were administered 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 in two divided doses for 10 days. Plasma concentration of clavulanate 1.6 mg/kg/dose was measured. Data points up to 4 hours with a standard deviation of 0 indicate that the assessment was available for only one child. |
| Distribution of Population Plasma Concentration of Clavulanate According to Time For Participants Receiving Formulation 2 | From administration of a single dose of amoxicillin-clavulanate until approximately 4 hours after. | Participants receiving formulation 2 were administered amoxicillin-clavulanate potassium containing a reduced concentration of clavulanate potassium, 600 mg/21.5 mg/5 mL (a ratio of 28:1), administered at 80/2.85 mg/kg/day in two divided doses for 10 days. Plasma concentration of clavulanate 1.425 mg/kg/dose was measured. Data points up to 4 hours with a standard deviation of 0 indicate that the assessment was available for only one child. |
| Distribution of Population Plasma Concentration of Amoxicillin According to Time For Participants Receiving Formulation 2 | From administration of a single dose of amoxicillin-clavulanate until approximately 4 hours after. | Participants treated with formulation 2 were administered amoxicillin-clavulanate potassium containing a reduced concentration of clavulanate potassium, 600 mg/21.5 mg/5 mL (a ratio of 28:1), administered at 80/2.85 mg/kg/day in two divided doses for 10 days. Plasma concentration of amoxicillin 40 mg/kg/dose was measured. Data points up to 4 hours with a standard deviation of 0 indicate that the assessment was available for only one child. |
| The Distribution of Participants Receiving Formulation 2 Categorized as Treatment Failure (TF) at or Before the End-of-Treatment Visit | From 72 hours after the initial AOM until the end-of-treatment visit. The mean day for this visit was 13.9. | Participants receiving formulation 2 were administered amoxicillin-clavulanate potassium containing a reduced concentration of clavulanate potassium, 600 mg/21.5 mg/5 mL (a ratio of 28:1), administered at 80/2.85 mg/kg/day in two divided doses for 10 days. Treatment failure is defined as substantial persistence or worsening of symptoms specifically attributable to AOM or of otoscopic signs of acute inflammation (bulging of the TM or intense erythema) after 72 hours from the initial AOM, such that additional antimicrobial therapy is deemed advisable. Clinical success is defined as complete or substantial resolution of symptoms specifically attributable to AOM for 48 hours and of otoscopic signs of acute inflammation (bulging of the TM or intense erythema), with or without persistence of middle-ear effusion, such that no additional antibiotic therapy is deemed advisable. |
| The Distribution of Participants Receiving Formulation 1 Demonstrating Resolution of Acute Otitis Media (AOM) and Substantial Improvement of Symptoms That Would Allow Discontinuing Therapy at the Day 7 Visit | Day 1 of administration of amoxicillin-clavulanate until the day 7 visit. The mean day for this visit was 7.5. | Participants receiving formulation 1 were administered 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 in two divided doses for 10 days. An assessment of participants was conducted at the day 7 visit using the AOM-SOS scale. The AOM-SOS scale measures five discrete items: tugging of ears, crying, irritability, difficulty sleeping, and fever. Parents are asked to rate these symptoms in comparison with the child's usual state, as none, a little, or a lot, with corresponding scores of 0, 1, and 2. Thus, total scores range from 0 to 10, with higher scores indicating greater severity of symptoms. |
| The Distribution of Participants Receiving Formulation 2 Demonstrating Resolution of Acute Otitis Media (AOM) and Substantial Improvement of Symptoms That Would Allow Discontinuing Therapy at the Day 7 Visit | Day 1 of administration of amoxicillin-clavulanate until the day 7 visit. The mean day for this visit was 7.6. | Participants receiving formulation 2 were administered amoxicillin-clavulanate potassium containing a reduced concentration of clavulanate potassium, 600 mg/21.5 mg/5 mL (a ratio of 28:1), administered at 80/2.85 mg/kg/day in two divided doses for 10 days. An assessment of participants was conducted at the day 7 visit using the AOM-SOS scale. The AOM-SOS scale measures five discrete items: tugging of ears, crying, irritability, difficulty sleeping, and fever. Parents are asked to rate these symptoms in comparison with the child's usual state, as none, a little, or a lot, with corresponding scores of 0, 1, and 2. Thus, total scores range from 0 to 10, with higher scores indicating greater severity of symptoms. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Amoxicillin-clavulanate Potassium 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) | 112 |
| Total | 112 |
Baseline characteristics
| Characteristic | Amoxicillin-clavulanate Potassium |
|---|---|
| Acute Otitis Media Severity of Symptoms (AOM-SOS) Score 3-5 | 40 Participants |
| Acute Otitis Media Severity of Symptoms (AOM-SOS) Score 6-8 | 50 Participants |
| Acute Otitis Media Severity of Symptoms (AOM-SOS) Score 9-10 | 22 Participants |
| Age, Customized 12-23 months | 53 Participants |
| Age, Customized 6-11 months | 59 Participants |
| Degree of Tympanic Membrane (TM) Bulging Moderate or marked | 103 Participants |
| Degree of Tympanic Membrane (TM) Bulging Slight | 9 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 99 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Exposure to Other Children No | 47 Participants |
| Exposure to Other Children Yes | 65 Participants |
| Laterality of Acute Otitis Media (AOM) Bilateral | 47 Participants |
| Laterality of Acute Otitis Media (AOM) Unilateral | 65 Participants |
| Maternal Education Below high school graduate | 7 Participants |
| Maternal Education College graduate | 24 Participants |
| Maternal Education High school graduate or equivalent | 80 Participants |
| Maternal Education Unknown | 1 Participants |
| Mean AOM-SOS Score | 6.4 AOM-SOS score STANDARD_DEVIATION 2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants |
| Race (NIH/OMB) Black or African American | 74 Participants |
| Race (NIH/OMB) More than one race | 13 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 17 Participants |
| Sex: Female, Male Female | 45 Participants |
| Sex: Female, Male Male | 67 Participants |
| Type of Health Insurance Private | 34 Participants |
| Type of Health Insurance Public | 78 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 112 |
| other Total, other adverse events | 38 / 112 |
| serious Total, serious adverse events | 0 / 112 |
Outcome results
Primary
The Distribution of Participants Receiving Formulation 1 for Whom Diaper Dermatitis Was Reported and Associated With Study Product
Participants receiving formulation 1 were administered 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 in two divided doses for 10 days. Diaper dermatitis is defined as dermatitis in the diaper area calling for prescription of a topical antifungal agent and is limited to events associated with study product.
Time frame: Day 1 of administration of amoxicillin-clavulanate until day 12.
Population: The number of participants is equal to the number of children receiving formulation 1.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Amoxicillin-clavulanate Potassium | The Distribution of Participants Receiving Formulation 1 for Whom Diaper Dermatitis Was Reported and Associated With Study Product | Diaper dermatitis reported | 10 Participants |
| Amoxicillin-clavulanate Potassium | The Distribution of Participants Receiving Formulation 1 for Whom Diaper Dermatitis Was Reported and Associated With Study Product | Diaper dermatitis not reported | 30 Participants |
Primary
The Distribution of Participants Receiving Formulation 1 for Whom Protocol-Defined Diarrhea (PDD) Was Reported and Associated With Study Product
Participants receiving formulation 1 were administered 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 in two divided doses for 10 days. Protocol-defined diarrhea is defined as the occurrence of three or more watery stools in 1 day or two watery stools daily for 2 consecutive days and is limited to events associated with study product.
Time frame: Day 1 of administration of amoxicillin-clavulanate until day 12.
Population: The number of participants is equal to the number of children receiving formulation 1.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Amoxicillin-clavulanate Potassium | The Distribution of Participants Receiving Formulation 1 for Whom Protocol-Defined Diarrhea (PDD) Was Reported and Associated With Study Product | PDD reported | 10 Participants |
| Amoxicillin-clavulanate Potassium | The Distribution of Participants Receiving Formulation 1 for Whom Protocol-Defined Diarrhea (PDD) Was Reported and Associated With Study Product | PDD not reported | 30 Participants |
Primary
The Distribution of Participants Receiving Formulation 2 for Whom Diaper Dermatitis Was Reported and Associated With Study Product
Participants receiving formulation 2 were administered amoxicillin-clavulanate potassium containing a reduced concentration of clavulanate potassium, 600 mg/21.5 mg/5 mL (a ratio of 28:1), administered at 80/2.85 mg/kg/day in two divided doses for 10 days. Diaper dermatitis is defined as dermatitis in the diaper area calling for prescription of a topical antifungal agent and is limited to events associated with study product..
Time frame: Day 1 of administration of amoxicillin-clavulanate until day 12.
Population: The number of participants is equal to the number of children receiving formulation 2.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Amoxicillin-clavulanate Potassium | The Distribution of Participants Receiving Formulation 2 for Whom Diaper Dermatitis Was Reported and Associated With Study Product | Diaper dermatitis reported | 15 Participants |
| Amoxicillin-clavulanate Potassium | The Distribution of Participants Receiving Formulation 2 for Whom Diaper Dermatitis Was Reported and Associated With Study Product | Diaper dermatitis not reported | 57 Participants |
Primary
The Distribution of Participants Receiving Formulation 2 for Whom Protocol-Defined Diarrhea (PDD) Was Reported and Associated With Study Product
Participants receiving formulation 2 were administered amoxicillin-clavulanate potassium containing a reduced concentration of clavulanate potassium, 600 mg/21.5 mg/5 mL (a ratio of 28:1), administered at 80/2.85 mg/kg/day in two divided doses for 10 days. Protocol-defined diarrhea is defined as the occurrence of three or more watery stools in 1 day or two watery stools daily for 2 consecutive days and is limited to events associated with study product.
Time frame: Day 1 of administration of amoxicillin-clavulanate until day 12.
Population: The number of participants is equal to the number of children receiving formulation 2.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Amoxicillin-clavulanate Potassium | The Distribution of Participants Receiving Formulation 2 for Whom Protocol-Defined Diarrhea (PDD) Was Reported and Associated With Study Product | PDD reported | 12 Participants |
| Amoxicillin-clavulanate Potassium | The Distribution of Participants Receiving Formulation 2 for Whom Protocol-Defined Diarrhea (PDD) Was Reported and Associated With Study Product | PDD not reported | 60 Participants |
Secondary
Distribution of Population Plasma Concentration of Amoxicillin According to Time For Participants Receiving Formulation 1
Participants receiving formulation 1 were administered 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 in two divided doses for 10 days. Plasma concentration of amoxicillin 45 mg/kg/dose was measured. Data points up to 4 hours with a standard deviation of 0 indicate that the assessment was available for only one child.
Time frame: From administration of a single dose of amoxicillin-clavulanate until approximately 4 hours after.
Population: The participants are the children receiving formulation 1 whose parent or guardian agreed to a single blood draw after administration of a single dose of amoxicillin-clavulanate and who had an ensuing measure of plasma concentration.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Amoxicillin-clavulanate Potassium | Distribution of Population Plasma Concentration of Amoxicillin According to Time For Participants Receiving Formulation 1 | 0.5 hours (approximate) | 14.36 micrograms per milliliter (mcg/ml) | Standard Deviation 10.07 |
| Amoxicillin-clavulanate Potassium | Distribution of Population Plasma Concentration of Amoxicillin According to Time For Participants Receiving Formulation 1 | 1.5 hours (approximate) | 15.3 micrograms per milliliter (mcg/ml) | Standard Deviation 0 |
| Amoxicillin-clavulanate Potassium | Distribution of Population Plasma Concentration of Amoxicillin According to Time For Participants Receiving Formulation 1 | 2.0 hours (approximate) | 11.42 micrograms per milliliter (mcg/ml) | Standard Deviation 5 |
| Amoxicillin-clavulanate Potassium | Distribution of Population Plasma Concentration of Amoxicillin According to Time For Participants Receiving Formulation 1 | 3.0 hours (approximate) | 8.07 micrograms per milliliter (mcg/ml) | Standard Deviation 0 |
| Amoxicillin-clavulanate Potassium | Distribution of Population Plasma Concentration of Amoxicillin According to Time For Participants Receiving Formulation 1 | 3.5 hours (approximate) | 9.78 micrograms per milliliter (mcg/ml) | Standard Deviation 0 |
| Amoxicillin-clavulanate Potassium | Distribution of Population Plasma Concentration of Amoxicillin According to Time For Participants Receiving Formulation 1 | 4.0 hours (approximate) | 7.39 micrograms per milliliter (mcg/ml) | Standard Deviation 8.33 |
Secondary
Distribution of Population Plasma Concentration of Amoxicillin According to Time For Participants Receiving Formulation 2
Participants treated with formulation 2 were administered amoxicillin-clavulanate potassium containing a reduced concentration of clavulanate potassium, 600 mg/21.5 mg/5 mL (a ratio of 28:1), administered at 80/2.85 mg/kg/day in two divided doses for 10 days. Plasma concentration of amoxicillin 40 mg/kg/dose was measured. Data points up to 4 hours with a standard deviation of 0 indicate that the assessment was available for only one child.
Time frame: From administration of a single dose of amoxicillin-clavulanate until approximately 4 hours after.
Population: The participants are the children receiving formulation 2 whose parent or guardian agreed to a single blood draw after administration of a single dose of amoxicillin-clavulanate and who had an ensuing measure of plasma concentration.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Amoxicillin-clavulanate Potassium | Distribution of Population Plasma Concentration of Amoxicillin According to Time For Participants Receiving Formulation 2 | 0.5 hours (approximate) | 8.63 micrograms per milliliter (mcg/ml) | Standard Deviation 3.89 |
| Amoxicillin-clavulanate Potassium | Distribution of Population Plasma Concentration of Amoxicillin According to Time For Participants Receiving Formulation 2 | 1.5 hours (approximate) | 7.49 micrograms per milliliter (mcg/ml) | Standard Deviation 1.59 |
| Amoxicillin-clavulanate Potassium | Distribution of Population Plasma Concentration of Amoxicillin According to Time For Participants Receiving Formulation 2 | 2.0 hours (approximate) | 7.76 micrograms per milliliter (mcg/ml) | Standard Deviation 6.56 |
| Amoxicillin-clavulanate Potassium | Distribution of Population Plasma Concentration of Amoxicillin According to Time For Participants Receiving Formulation 2 | 2.5 hours (approximate) | 10.22 micrograms per milliliter (mcg/ml) | Standard Deviation 7.18 |
| Amoxicillin-clavulanate Potassium | Distribution of Population Plasma Concentration of Amoxicillin According to Time For Participants Receiving Formulation 2 | 3.0 hours (approximate) | 13.00 micrograms per milliliter (mcg/ml) | Standard Deviation 0.5 |
| Amoxicillin-clavulanate Potassium | Distribution of Population Plasma Concentration of Amoxicillin According to Time For Participants Receiving Formulation 2 | 3.5 hours (approximate) | 10.36 micrograms per milliliter (mcg/ml) | Standard Deviation 1.94 |
| Amoxicillin-clavulanate Potassium | Distribution of Population Plasma Concentration of Amoxicillin According to Time For Participants Receiving Formulation 2 | 4.0 hours (approximate) | 8.52 micrograms per milliliter (mcg/ml) | Standard Deviation 4.54 |
Secondary
Distribution of Population Plasma Concentration of Clavulanate According to Time For Participants Receiving Formulation 1
Participants receiving formulation 1 were administered 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 in two divided doses for 10 days. Plasma concentration of clavulanate 1.6 mg/kg/dose was measured. Data points up to 4 hours with a standard deviation of 0 indicate that the assessment was available for only one child.
Time frame: From administration of a single dose of amoxicillin-clavulanate until approximately 4 hours after.
Population: The participants are the children receiving formulation 1 whose parent or guardian agreed to a single blood draw after administration of a single dose of amoxicillin-clavulanate and who had an ensuing measure of plasma concentration.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Amoxicillin-clavulanate Potassium | Distribution of Population Plasma Concentration of Clavulanate According to Time For Participants Receiving Formulation 1 | 0.5 hours (approximate) | 1047.67 nanograms per milliliter (ng/ml) | Standard Deviation 419.9 |
| Amoxicillin-clavulanate Potassium | Distribution of Population Plasma Concentration of Clavulanate According to Time For Participants Receiving Formulation 1 | 1.5 hours (approximate) | 2050 nanograms per milliliter (ng/ml) | Standard Deviation 0 |
| Amoxicillin-clavulanate Potassium | Distribution of Population Plasma Concentration of Clavulanate According to Time For Participants Receiving Formulation 1 | 2.0 hours (approximate) | 730.50 nanograms per milliliter (ng/ml) | Standard Deviation 442.93 |
| Amoxicillin-clavulanate Potassium | Distribution of Population Plasma Concentration of Clavulanate According to Time For Participants Receiving Formulation 1 | 3.0 hours (approximate) | 338 nanograms per milliliter (ng/ml) | Standard Deviation 0 |
| Amoxicillin-clavulanate Potassium | Distribution of Population Plasma Concentration of Clavulanate According to Time For Participants Receiving Formulation 1 | 3.5 hours (approximate) | 842 nanograms per milliliter (ng/ml) | Standard Deviation 0 |
| Amoxicillin-clavulanate Potassium | Distribution of Population Plasma Concentration of Clavulanate According to Time For Participants Receiving Formulation 1 | 4.0 hours (approximate) | 313.80 nanograms per milliliter (ng/ml) | Standard Deviation 146.91 |
Secondary
Distribution of Population Plasma Concentration of Clavulanate According to Time For Participants Receiving Formulation 2
Participants receiving formulation 2 were administered amoxicillin-clavulanate potassium containing a reduced concentration of clavulanate potassium, 600 mg/21.5 mg/5 mL (a ratio of 28:1), administered at 80/2.85 mg/kg/day in two divided doses for 10 days. Plasma concentration of clavulanate 1.425 mg/kg/dose was measured. Data points up to 4 hours with a standard deviation of 0 indicate that the assessment was available for only one child.
Time frame: From administration of a single dose of amoxicillin-clavulanate until approximately 4 hours after.
Population: The participants are the children receiving formulation 2 whose parent or guardian agreed to a single blood draw after administration of a single dose of amoxicillin-clavulanate and who had an ensuing measure of plasma concentration.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Amoxicillin-clavulanate Potassium | Distribution of Population Plasma Concentration of Clavulanate According to Time For Participants Receiving Formulation 2 | 0.5 hours (approximate) | 407 nanograms per milliliter (ng/ml) | Standard Deviation 335.47 |
| Amoxicillin-clavulanate Potassium | Distribution of Population Plasma Concentration of Clavulanate According to Time For Participants Receiving Formulation 2 | 1.5 hours (approximate) | 655.50 nanograms per milliliter (ng/ml) | Standard Deviation 20.5 |
| Amoxicillin-clavulanate Potassium | Distribution of Population Plasma Concentration of Clavulanate According to Time For Participants Receiving Formulation 2 | 2.0 hours (approximate) | 1125.33 nanograms per milliliter (ng/ml) | Standard Deviation 418.49 |
| Amoxicillin-clavulanate Potassium | Distribution of Population Plasma Concentration of Clavulanate According to Time For Participants Receiving Formulation 2 | 2.5 hours (approximate) | 660.16 nanograms per milliliter (ng/ml) | Standard Deviation 389.69 |
| Amoxicillin-clavulanate Potassium | Distribution of Population Plasma Concentration of Clavulanate According to Time For Participants Receiving Formulation 2 | 3.0 hours (approximate) | 986.95 nanograms per milliliter (ng/ml) | Standard Deviation 963.05 |
| Amoxicillin-clavulanate Potassium | Distribution of Population Plasma Concentration of Clavulanate According to Time For Participants Receiving Formulation 2 | 3.5 hours (approximate) | 866.00 nanograms per milliliter (ng/ml) | Standard Deviation 534 |
| Amoxicillin-clavulanate Potassium | Distribution of Population Plasma Concentration of Clavulanate According to Time For Participants Receiving Formulation 2 | 4.0 hours (approximate) | 555.50 nanograms per milliliter (ng/ml) | Standard Deviation 494.53 |
Secondary
The Distribution of Participants Receiving Formulation 1 Categorized as Treatment Failure (TF) at or Before the End-of-Treatment Visit
Participants receiving formulation 1 were administered 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 in two divided doses for 10 days. Treatment failure is defined as substantial persistence or worsening of symptoms specifically attributable to AOM or of otoscopic signs of acute inflammation (bulging of the TM or intense erythema) after 72 hours from the initial AOM, such that additional antimicrobial therapy is deemed advisable. Clinical success is defined as complete or substantial resolution of symptoms specifically attributable to AOM for 48 hours and of otoscopic signs of acute inflammation (bulging of the TM or intense erythema), with or without persistence of middle-ear effusion, such that no additional antibiotic therapy is deemed advisable.
Time frame: From 72 hours after the initial AOM until the end-of-treatment visit. The mean day for this visit was 14.9.
Population: The number of participants is equal to the number of children receiving formulation 1 who had an end-of-treatment assessment at or before the day 12 visit.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Amoxicillin-clavulanate Potassium | The Distribution of Participants Receiving Formulation 1 Categorized as Treatment Failure (TF) at or Before the End-of-Treatment Visit | Treatment failure | 4 Participants |
| Amoxicillin-clavulanate Potassium | The Distribution of Participants Receiving Formulation 1 Categorized as Treatment Failure (TF) at or Before the End-of-Treatment Visit | Clinical success | 31 Participants |
Secondary
The Distribution of Participants Receiving Formulation 1 Demonstrating Resolution of Acute Otitis Media (AOM) and Substantial Improvement of Symptoms That Would Allow Discontinuing Therapy at the Day 7 Visit
Participants receiving formulation 1 were administered 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 in two divided doses for 10 days. An assessment of participants was conducted at the day 7 visit using the AOM-SOS scale. The AOM-SOS scale measures five discrete items: tugging of ears, crying, irritability, difficulty sleeping, and fever. Parents are asked to rate these symptoms in comparison with the child's usual state, as none, a little, or a lot, with corresponding scores of 0, 1, and 2. Thus, total scores range from 0 to 10, with higher scores indicating greater severity of symptoms.
Time frame: Day 1 of administration of amoxicillin-clavulanate until the day 7 visit. The mean day for this visit was 7.5.
Population: The number of participants is equal to the number of children receiving formulation 1 who had a day 7 assessment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Amoxicillin-clavulanate Potassium | The Distribution of Participants Receiving Formulation 1 Demonstrating Resolution of Acute Otitis Media (AOM) and Substantial Improvement of Symptoms That Would Allow Discontinuing Therapy at the Day 7 Visit | Resolution of AOM and improvement of symptoms | 23 Participants |
| Amoxicillin-clavulanate Potassium | The Distribution of Participants Receiving Formulation 1 Demonstrating Resolution of Acute Otitis Media (AOM) and Substantial Improvement of Symptoms That Would Allow Discontinuing Therapy at the Day 7 Visit | No resolution of AOM or no improvement of symptoms | 11 Participants |
Secondary
The Distribution of Participants Receiving Formulation 2 Categorized as Treatment Failure (TF) at or Before the End-of-Treatment Visit
Participants receiving formulation 2 were administered amoxicillin-clavulanate potassium containing a reduced concentration of clavulanate potassium, 600 mg/21.5 mg/5 mL (a ratio of 28:1), administered at 80/2.85 mg/kg/day in two divided doses for 10 days. Treatment failure is defined as substantial persistence or worsening of symptoms specifically attributable to AOM or of otoscopic signs of acute inflammation (bulging of the TM or intense erythema) after 72 hours from the initial AOM, such that additional antimicrobial therapy is deemed advisable. Clinical success is defined as complete or substantial resolution of symptoms specifically attributable to AOM for 48 hours and of otoscopic signs of acute inflammation (bulging of the TM or intense erythema), with or without persistence of middle-ear effusion, such that no additional antibiotic therapy is deemed advisable.
Time frame: From 72 hours after the initial AOM until the end-of-treatment visit. The mean day for this visit was 13.9.
Population: The number of participants is equal to the number of children receiving formulation 2 who had an end-of-treatment assessment at or before the day 12 visit.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Amoxicillin-clavulanate Potassium | The Distribution of Participants Receiving Formulation 2 Categorized as Treatment Failure (TF) at or Before the End-of-Treatment Visit | Treatment failure | 8 Participants |
| Amoxicillin-clavulanate Potassium | The Distribution of Participants Receiving Formulation 2 Categorized as Treatment Failure (TF) at or Before the End-of-Treatment Visit | Clinical success | 56 Participants |
Secondary
The Distribution of Participants Receiving Formulation 2 Demonstrating Resolution of Acute Otitis Media (AOM) and Substantial Improvement of Symptoms That Would Allow Discontinuing Therapy at the Day 7 Visit
Participants receiving formulation 2 were administered amoxicillin-clavulanate potassium containing a reduced concentration of clavulanate potassium, 600 mg/21.5 mg/5 mL (a ratio of 28:1), administered at 80/2.85 mg/kg/day in two divided doses for 10 days. An assessment of participants was conducted at the day 7 visit using the AOM-SOS scale. The AOM-SOS scale measures five discrete items: tugging of ears, crying, irritability, difficulty sleeping, and fever. Parents are asked to rate these symptoms in comparison with the child's usual state, as none, a little, or a lot, with corresponding scores of 0, 1, and 2. Thus, total scores range from 0 to 10, with higher scores indicating greater severity of symptoms.
Time frame: Day 1 of administration of amoxicillin-clavulanate until the day 7 visit. The mean day for this visit was 7.6.
Population: The number of participants is equal to the number of children receiving formulation 2 who had a day 7 assessment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Amoxicillin-clavulanate Potassium | The Distribution of Participants Receiving Formulation 2 Demonstrating Resolution of Acute Otitis Media (AOM) and Substantial Improvement of Symptoms That Would Allow Discontinuing Therapy at the Day 7 Visit | Resolution of AOM and improvement of symptoms | 31 Participants |
| Amoxicillin-clavulanate Potassium | The Distribution of Participants Receiving Formulation 2 Demonstrating Resolution of Acute Otitis Media (AOM) and Substantial Improvement of Symptoms That Would Allow Discontinuing Therapy at the Day 7 Visit | No resolution of AOM or no improvement of symptoms | 31 Participants |
Secondary
The Mean Score Representing the Parent or Guardian's Level of Satisfaction With Therapy for Participants Receiving Formulation 1
Participants receiving formulation 1 were administered 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 in two divided doses for 10 days. The parent or guardian will answer a questionnaire regarding their satisfaction with the therapy their child received. The responses 'very dissatisfied', 'somewhat dissatisfied', 'neither satisfied nor dissatisfied', 'somewhat satisfied' and 'very satisfied' correspond to scores of 1, 2, 3, 4, and 5, respectively.
Time frame: The end-of-treatment visit. The mean day for this visit was 14.9.
Population: The number of participants is equal to the number of children receiving formulation 1 whose parent or guardian completed a level of satisfaction questionnaire at the end-of-treatment visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amoxicillin-clavulanate Potassium | The Mean Score Representing the Parent or Guardian's Level of Satisfaction With Therapy for Participants Receiving Formulation 1 | 4.69 units on a scale | Standard Deviation 0.72 |
Secondary
The Mean Score Representing the Parent or Guardian's Level of Satisfaction With Therapy for Participants Receiving Formulation 2
Participants receiving formulation 2 were administered amoxicillin-clavulanate potassium containing a reduced concentration of clavulanate potassium, 600 mg/21.5 mg/5 mL (a ratio of 28:1), administered at 80/2.85 mg/kg/day in two divided doses for 10 days. The parent or guardian will answer a questionnaire regarding their satisfaction with the therapy their child received. The responses 'very dissatisfied', 'somewhat dissatisfied', 'neither satisfied nor dissatisfied', 'somewhat satisfied' and 'very satisfied' correspond to scores of 1, 2, 3, 4, and 5, respectively.
Time frame: The end-of-treatment visit. The mean day for this visit was 13.9.
Population: The number of participants is equal to the number of children receiving formulation 2 whose parent or guardian completed a level of satisfaction questionnaire at the end-of-treatment visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amoxicillin-clavulanate Potassium | The Mean Score Representing the Parent or Guardian's Level of Satisfaction With Therapy for Participants Receiving Formulation 2 | 4.75 units on a scale | Standard Deviation 0.76 |