Acute Otitis Media
Conditions
Keywords
azithromycin, pharmacokinetics, pediatrics
Brief summary
The purpose of this study was to determine the pharmacokinetics (PK), safety and clinical response following a single dose of either 30 mg/kg IR (Immediate Release) or 60 mg/kg ER (Extended Release) formulation in pediatric subjects 6 months to 6 years of age inclusive.
Interventions
DRUG60 mg/kg azithromycin ER
subjects taken 60 mg/kg azithromycin ER
DRUG30 mg/kg azithromycin IR
subjects taken 30 mg/kg azithromycin IR (Immediate Release)
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Months to 11 Years
Healthy volunteers
No
Inclusion criteria
* Subjects age 6 months to \< 12 years. * Have clinical signs/symptoms of acute otitis media in at least one ear. * Parent(s)/legal guardian(s) provide written informed consent.
Exclusion criteria
* Clinical significant other disease. * Recent use of investigational drugs, prescription or nonprescription drugs.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve From Time Zero to 72 Hours (AUC72Hours) | Predose/0 to 72 Hours | AUC72 = Area under the plasma concentration versus time curve from time zero (pre-dose) to 72 hours. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Azithromycin | Predose/0, 1, 2, 3, 4, 8, 24, 48, 72 hours post-dose | — |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) and Plasma Decay Half Life (t1/2) of Azithromycin | Predose/0, 1, 2, 3, 4, 8, 24, 48, 72 hours post-dose | Plasma decay half-life is the time measured for the plasma concentration to decrease by one-half. |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC Inf) | Predose/0, 1, 2, 3, 4, 8, 24, 48, 72 hours post-dose | AUCinf = AUClast + (Clast\* divided by kel), where AUClast is calculated by Linear-Log trapezoidal method, Clast\* is the predicted serum concentration at the last quantifiable time point estimated from the log-linear regression analysis and kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. |
| Number of Participants With a Clinical Response | Days 7,8,9 or 10 | Clinical response was assesed between Days 7 and 10, or when subjects discontinued the study prematurely (if applicable). Response was assessed by the investigator as cure or failure. Cure = Clinical signs and symptoms related to the acute illness have resolved, or clinical improvement is such that no additional therapy is necessary. Failure = One or more of the following: * Signs and symptoms related to the acute illness have persisted or worsened and additional therapy is necessary; * New clinical signs and symptoms of acute illness have developed and additional therapy is necessary |
| Adverse Events (AEs) and Serious AEs (SAEs) | Baseline up to 28 days | All observed or volunteered AEs and SAEs regardless of treatment group or suspected causal relationship to the investigational product(s) was reported. |
| Serum Concentrations of Azithromycin ER (Test) and Azithromycin IR (Reference) | 1,2,3,4,8,24,48,72 hours postdose | — |
Countries
Costa Rica
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 60 mg/kg Azithromycin ER Subjects received 60 mg/kg Azithromycin ER single oral dose on Day 1. | 19 |
| 30 mg/kg Azithromycin IR Subjects received 30 mg/kg Azithromycin IR single oral dose on Day 1. | 19 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | 60 mg/kg Azithromycin ER | 30 mg/kg Azithromycin IR | Total |
|---|---|---|---|
| Age, Customized 1 month to <2 years | 13 participants | 6 participants | 19 participants |
| Age, Customized 2 years to <12 years | 6 participants | 13 participants | 19 participants |
| Sex: Female, Male Female | 8 Participants | 7 Participants | 15 Participants |
| Sex: Female, Male Male | 11 Participants | 12 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 19 | 5 / 19 |
| serious Total, serious adverse events | 0 / 19 | 0 / 19 |
Outcome results
Primary
Area Under the Curve From Time Zero to 72 Hours (AUC72Hours)
AUC72 = Area under the plasma concentration versus time curve from time zero (pre-dose) to 72 hours.
Time frame: Predose/0 to 72 Hours
Population: All subjects randomized and treated who had at least 1 of the pharmacokinetic parameters of primary interest.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 60 mg/kg Azithromycin ER | Area Under the Curve From Time Zero to 72 Hours (AUC72Hours) | 12173.023 ng*hr/ml | Standard Deviation 6305.0325 |
| 30 mg/kg Azithromycin IR | Area Under the Curve From Time Zero to 72 Hours (AUC72Hours) | 7950.949 ng*hr/ml | Standard Deviation 4759.301 |
Comparison: Test (60 mg/kg Azithromycin ER)/ Reference (30 mg/kg Azithromycin IR)90% CI: [98.87, 252.44]ANOVA
Secondary
Adverse Events (AEs) and Serious AEs (SAEs)
All observed or volunteered AEs and SAEs regardless of treatment group or suspected causal relationship to the investigational product(s) was reported.
Time frame: Baseline up to 28 days
Population: All subjects who received at least 1 dose of study medication were included in the safety analyses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 60 mg/kg Azithromycin ER | Adverse Events (AEs) and Serious AEs (SAEs) | AEs | 4 participants |
| 60 mg/kg Azithromycin ER | Adverse Events (AEs) and Serious AEs (SAEs) | SAEs | 0 participants |
| 30 mg/kg Azithromycin IR | Adverse Events (AEs) and Serious AEs (SAEs) | AEs | 5 participants |
| 30 mg/kg Azithromycin IR | Adverse Events (AEs) and Serious AEs (SAEs) | SAEs | 0 participants |
Secondary
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC Inf)
AUCinf = AUClast + (Clast\* divided by kel), where AUClast is calculated by Linear-Log trapezoidal method, Clast\* is the predicted serum concentration at the last quantifiable time point estimated from the log-linear regression analysis and kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Time frame: Predose/0, 1, 2, 3, 4, 8, 24, 48, 72 hours post-dose
Population: All subjects randomized and treated who had at least 1 of the pharmacokinetic parameters of primary interest.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 60 mg/kg Azithromycin ER | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC Inf) | 15536.196 ng*hr/ml | Standard Deviation 9310.3993 |
| 30 mg/kg Azithromycin IR | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC Inf) | 9645.630 ng*hr/ml | Standard Deviation 6062.6789 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Azithromycin
Time frame: Predose/0, 1, 2, 3, 4, 8, 24, 48, 72 hours post-dose
Population: All subjects randomized and treated who had at least 1 of the pharmacokinetic parameters of primary interest.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 60 mg/kg Azithromycin ER | Maximum Observed Plasma Concentration (Cmax) of Azithromycin | 774.750 ng/ml | Standard Deviation 477.9896 |
| 30 mg/kg Azithromycin IR | Maximum Observed Plasma Concentration (Cmax) of Azithromycin | 901.644 ng/ml | Standard Deviation 600.6826 |
90% CI: [56.21, 149.38]ANOVA
Secondary
Number of Participants With a Clinical Response
Clinical response was assesed between Days 7 and 10, or when subjects discontinued the study prematurely (if applicable). Response was assessed by the investigator as cure or failure. Cure = Clinical signs and symptoms related to the acute illness have resolved, or clinical improvement is such that no additional therapy is necessary. Failure = One or more of the following: * Signs and symptoms related to the acute illness have persisted or worsened and additional therapy is necessary; * New clinical signs and symptoms of acute illness have developed and additional therapy is necessary
Time frame: Days 7,8,9 or 10
Population: Any worsening of existing signs and symptoms, or new signs and symptoms, were documented as adverse events.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 60 mg/kg Azithromycin ER | Number of Participants With a Clinical Response | Cure | 18 participants |
| 60 mg/kg Azithromycin ER | Number of Participants With a Clinical Response | Failure | 0 participants |
| 30 mg/kg Azithromycin IR | Number of Participants With a Clinical Response | Cure | 16 participants |
| 30 mg/kg Azithromycin IR | Number of Participants With a Clinical Response | Failure | 2 participants |
Secondary
Serum Concentrations of Azithromycin ER (Test) and Azithromycin IR (Reference)
Time frame: 1,2,3,4,8,24,48,72 hours postdose
Population: All subjects randomized and treated who had at least 1 of the pharmacokinetic parameters of primary interest.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 60 mg/kg Azithromycin ER | Serum Concentrations of Azithromycin ER (Test) and Azithromycin IR (Reference) | Serum Concentration 1 hour postdose | 99.96 ng/ml |
| 60 mg/kg Azithromycin ER | Serum Concentrations of Azithromycin ER (Test) and Azithromycin IR (Reference) | Serum Concentration 2 hour postdose | 293.14 ng/ml |
| 60 mg/kg Azithromycin ER | Serum Concentrations of Azithromycin ER (Test) and Azithromycin IR (Reference) | Serum Concentration 3 hour postdose | 381.96 ng/ml |
| 60 mg/kg Azithromycin ER | Serum Concentrations of Azithromycin ER (Test) and Azithromycin IR (Reference) | Serum Concentration 4 hour postdose | 441.79 ng/ml |
| 60 mg/kg Azithromycin ER | Serum Concentrations of Azithromycin ER (Test) and Azithromycin IR (Reference) | Serum Concentration 8 hour postdose | 244.75 ng/ml |
| 60 mg/kg Azithromycin ER | Serum Concentrations of Azithromycin ER (Test) and Azithromycin IR (Reference) | Serum Concentration 24 hour postdose | 142.41 ng/ml |
| 60 mg/kg Azithromycin ER | Serum Concentrations of Azithromycin ER (Test) and Azithromycin IR (Reference) | Serum Concentration 48 hour postdose | 94.79 ng/ml |
| 60 mg/kg Azithromycin ER | Serum Concentrations of Azithromycin ER (Test) and Azithromycin IR (Reference) | Serum Concentration 72 hour postdose | 56.03 ng/ml |
| 30 mg/kg Azithromycin IR | Serum Concentrations of Azithromycin ER (Test) and Azithromycin IR (Reference) | Serum Concentration 72 hour postdose | 30.6 ng/ml |
| 30 mg/kg Azithromycin IR | Serum Concentrations of Azithromycin ER (Test) and Azithromycin IR (Reference) | Serum Concentration 1 hour postdose | 152.75 ng/ml |
| 30 mg/kg Azithromycin IR | Serum Concentrations of Azithromycin ER (Test) and Azithromycin IR (Reference) | Serum Concentration 8 hour postdose | 140.33 ng/ml |
| 30 mg/kg Azithromycin IR | Serum Concentrations of Azithromycin ER (Test) and Azithromycin IR (Reference) | Serum Concentration 2 hour postdose | 579.72 ng/ml |
| 30 mg/kg Azithromycin IR | Serum Concentrations of Azithromycin ER (Test) and Azithromycin IR (Reference) | Serum Concentration 48 hour postdose | 50.06 ng/ml |
| 30 mg/kg Azithromycin IR | Serum Concentrations of Azithromycin ER (Test) and Azithromycin IR (Reference) | Serum Concentration 3 hour postdose | 381.69 ng/ml |
| 30 mg/kg Azithromycin IR | Serum Concentrations of Azithromycin ER (Test) and Azithromycin IR (Reference) | Serum Concentration 24 hour postdose | 82.31 ng/ml |
| 30 mg/kg Azithromycin IR | Serum Concentrations of Azithromycin ER (Test) and Azithromycin IR (Reference) | Serum Concentration 4 hour postdose | 267.86 ng/ml |
Comparison: Serum Concentration 1 hour postdose90% CI: [23.56, 181.77]ANOVA
Comparison: Serum Concentration 2 hours postdose90% CI: [25.24, 101.3]ANOVA
Comparison: Serum Concentration 3 hours postdose90% CI: [57.91, 172.92]ANOVA
Comparison: Serum Concentration 4 hours postdose90% CI: [103.78, 262.12]ANOVA
Comparison: Serum Concentration 8 hours postdose90% CI: [110.07, 276.36]ANOVA
Comparison: Serum Concentration 24 hours postdose90% CI: [111.45, 268.55]ANOVA
Comparison: Serum Concentration 48 hours postdose90% CI: [129.76, 276.3]ANOVA
Comparison: Serum Concentration 72 hours postdose90% CI: [124.61, 269.14]ANOVA
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) and Plasma Decay Half Life (t1/2) of Azithromycin
Plasma decay half-life is the time measured for the plasma concentration to decrease by one-half.
Time frame: Predose/0, 1, 2, 3, 4, 8, 24, 48, 72 hours post-dose
Population: All subjects randomized and treated who had at least 1 of the pharmacokinetic parameters of primary interest.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 60 mg/kg Azithromycin ER | Time to Reach Maximum Observed Plasma Concentration (Tmax) and Plasma Decay Half Life (t1/2) of Azithromycin | Tmax | 3.0 hr |
| 60 mg/kg Azithromycin ER | Time to Reach Maximum Observed Plasma Concentration (Tmax) and Plasma Decay Half Life (t1/2) of Azithromycin | t1/2 | 30.303 hr |
| 30 mg/kg Azithromycin IR | Time to Reach Maximum Observed Plasma Concentration (Tmax) and Plasma Decay Half Life (t1/2) of Azithromycin | Tmax | 2.0 hr |
| 30 mg/kg Azithromycin IR | Time to Reach Maximum Observed Plasma Concentration (Tmax) and Plasma Decay Half Life (t1/2) of Azithromycin | t1/2 | 28.959 hr |