Clinical Trial Results:
An open label study to determine the pharmacokinetic profiles of amoxicillin and clavulanate in adolescent patients weighing at least 40 kg and no more than 16 years of age receiving AUGMENTIN™XR (amoxicillin 2000 mg/clavulanate 125 mg) orally twice daily for 10 days.
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Summary
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EudraCT number |
2015-004874-13 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
02 Apr 2007
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Results information
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Results version number |
v1(current) |
This version publication date |
30 Nov 2016
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First version publication date |
30 Nov 2016
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
AUG102821
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
GlaxoSmithKline
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Sponsor organisation address |
980 Great West Road, Brentford, Middlesex, United Kingdom,
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Public contact |
GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
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Scientific contact |
GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
13 Jul 2007
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
02 Apr 2007
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To obtain pharmacokinetic data on amoxicillin/clavulanate and time above MIC
(T>MIC) for amoxicillin when AUGMENTIN XR (amoxicillin 2000 mg/clavulanate
125 mg) is given orally twice daily to adolescents weighing at least 40 kg.
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Protection of trial subjects |
Not Applicable
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
19 Jan 2006
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 44
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Worldwide total number of subjects |
44
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
15
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Adolescents (12-17 years) |
29
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Eligible participants received amoxicillin 2000 milligrams (mg)/clavulanate 125 mg tablets twice daily for 10 days. The study consisted of a follow-up visit (within 3 days of the final dose). | ||||||||||||
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Pre-assignment
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Screening details |
Adolescent participants with acute bacterial sinusitis, who weigh at least 40 kilograms (kg) and are no more than 16 years old were enrolled into the study. A total of 52 participants who met eligibility criteria were screened, and 44 participants were randomized. | ||||||||||||
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Period 1
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Period 1 title |
Overall study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||
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Arms
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Arm title
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Amoxicillin 2000 mg/Clavulanate 125 mg BD | ||||||||||||
Arm description |
Participants received 2 tablets of combination product prolonged release amoxicillin 1000 mg/clavulanate 62.5 mg twice daily (BD) orally with food for 10 days. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Amoxicillin 1000 mg/clavulanate 62.5 mg
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Two tablets (approximately every 12 hours apart) twice daily with food were administered for 10-days.
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Baseline characteristics reporting groups
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Reporting group title |
Overall study
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Reporting group description |
Overall study | |||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Amoxicillin 2000 mg/Clavulanate 125 mg BD
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Reporting group description |
Participants received 2 tablets of combination product prolonged release amoxicillin 1000 mg/clavulanate 62.5 mg twice daily (BD) orally with food for 10 days. | ||
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End point title |
Time (percentage) above the minimum inhibitory concentration (T>MIC) for amoxicillin MIC of 2 microgram/milliliter (μg/mL) and 4 μg/mL/ over the 12 hour dosing interval [1] | ||||||||||||
End point description |
MIC is defined as the lowest concentration of antimicrobial that prevents visible growth of an organism. T>MIC was calculated for an amoxicillin MIC of 2 μg/mL [T>MIC2]) and 4 μg/mL (T>MIC4). Blood samples for pharmacokinetic (PK) analyses of amoxicillin were collected during one dosing interval (i.e., 12-hour period) after administration of medication on any of the 10 days in the dosing period. PK Parameter Population is defined as all participants in the PK Concentration Population (all participants for whom PK data had been collected for any dosing day and analyzed) who had provided PK parameters.
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End point type |
Primary
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End point timeframe |
Predose, and 0.5, 1, 1.5, 2, 4, 5, 6, 7, 8, 10 and 12 hours post-dose, during one of the dosing interval in any of the 10-day treatment period
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
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| Notes [2] - PK Parameter Population |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Time (hours) above the minimum inhibitory concentration (T>MIC) for amoxicillin MIC of 2 microgram/milliliter (μg/mL) and 4 μg/mL/ over the 12 hour dosing interval [3] | ||||||||||||
End point description |
MIC is defined as the lowest concentration of antimicrobial that prevents visible growth of an organism. Blood samples PK analyses of amoxicillin were collected during one dosing interval (i.e., 12-hour period) after administration of medication on any of the 10 days in the dosing period. The mean time above MIC (T>MIC) for amoxicillin MIC of 2 μg/mL and 4 μg/mL was calculated.
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End point type |
Primary
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End point timeframe |
Predose, and 0.5, 1, 1.5, 2, 4, 5, 6, 7, 8, 10 and 12 hours post-dose, during one of the dosing interval in any of the 10-day treatment period
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
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| Notes [4] - PK Parameter Population |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Maximum plasma drug concentration (Cmax) for amoxicillin and clavulanate [5] | ||||||||||||
End point description |
Maximum plasma drug concentration (Cmax) for amoxicillin and clavulanate was analyzed. Blood samples for PK analyses of amoxicillin and clavulanate were collected during one dosing interval (i.e 12-hour period) after administration of medication on any of the 10 days in the dosing period. Only those participants available at the indicated time points were assessed (represented by n=X in the category titles).
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End point type |
Primary
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End point timeframe |
Predose, and 0.5, 1, 1.5, 2, 4, 5, 6, 7, 8, 10 and 12 hours post-dose, during one of the dosing interval in any of the 10-day treatment period
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| Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
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| Notes [6] - PK Concentration Population |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Apparent terminal phase half-life (T1/2) for amoxicillin and clavulanate [7] | ||||||||||||
End point description |
Apparent terminal phase half life (T1/2) for amoxicillin and clavulanate was analyzed. Blood samples for PK analyses of amoxicillin and clavulanate were collected during one dosing interval (i.e 12-hour period) after administration of medication on any of the 10 days in the dosing period. Only those participants available at the indicated time points were assessed (represented by n=X in the category titles).
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End point type |
Primary
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End point timeframe |
Predose, and 0.5, 1, 1.5, 2, 4, 5, 6, 7, 8, 10 and 12 hours post-dose, during one of the dosing interval in any of the 10-day treatment period
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| Notes [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
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| Notes [8] - PK Concentration Population |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Time to reach maximum observed concentration (Tmax) for amoxicillin and clavulanate [9] | ||||||||||||
End point description |
Time to reach maximum observed concentration (Tmax) for amoxicillin and clavulanate was analyzed. Blood samples for PK analyses of amoxicillin and clavulanate were collected during one dosing interval (i.e 12-hour period) after administration of medication on any of the 10 days in the dosing period. Only those participants available at the indicated time points were assessed (represented by n=X in the category titles).
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End point type |
Primary
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End point timeframe |
Predose, and 0.5, 1, 1.5, 2, 4, 5, 6, 7, 8, 10 and 12 hours post-dose, during one of the dosing interval in any of the 10-day treatment period
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| Notes [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
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| Notes [10] - PK Concentration Population |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Area under the plasma concentration-time curve over the dosing interval on multiple dosing AUC(0-tau) of amoxicllin and clavulanate. [11] | ||||||||||||
End point description |
Area under the plasma concentration – time curve from time zero to the time of last detectable concentration AUC (0-tau) for amoxicillin and clavulanate was analyzed. Blood samples for PK analyses of amoxicillin and clavulanate were collected during one dosing interval (i.e 12-hour period) after administration of medication on any of the 10 days in the dosing period. Only those participants available at the indicated time points were assessed (represented by n=X in the category titles).
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End point type |
Primary
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End point timeframe |
Predose, and 0.5, 1, 1.5, 2, 4, 5, 6, 7, 8, 10 and 12 hours post-dose, during one of the dosing interval in any of the 10-day treatment period
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| Notes [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There are no statistical data to report. |
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| Notes [12] - PK Concentration Population |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of participants with any adverse events (AEs) and any serious averse events (SAE) during the treatment period | ||||||||||
End point description |
An adverse event (AE) is any untoward medical occurrence in a participant temporally of a medicinal product, whether or not considered related to the medicinal. A serious adverse event is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity and is a congenital anomaly/birth defect. Safety Population is defined as all participants who received at least one dose of study medication.
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End point type |
Secondary
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End point timeframe |
Up to Day 13
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| Notes [13] - Safety Population |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Alanine amino transferase and aspartate amino transferase values at the indicated time points | ||||||||||||||||
End point description |
Clinical chemistry included analysis of alanine amino transferase and aspartate amino transferase at screening and follow-up (within 3 days of receipt of the last dose) period. Only those participants available at the indicated time points were assessed (represented by n=X in the category titles).
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End point type |
Secondary
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End point timeframe |
Screening and Follow-up (up to Day 13)
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| Notes [14] - Safety Population |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Basophils, eosinophils, lymphocytes, mopnocytes, total neutrophils, platelet count and white blood cell count values at the indicated time points | ||||||||||||||||||||||||||||||||||||
End point description |
Hematology included analysis of basophils, eosinophils, lymphocytes, monocytes, potal neutrophils, platelet count and white blood cell count during screening and follow-up (within 3 days of receipt of the last dose) period Only those participants available at the indicated time points were assessed (represented by n=X in the category titles).
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End point type |
Secondary
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End point timeframe |
Screening and Follow-up (up to Day 13)
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| Notes [15] - Safety Population |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||
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End point title |
Hemoglobin values at the indicated time points | ||||||||||||
End point description |
Hematology included analysis of hemoglobin during screening and follow-up (within 3 days of receipt of the last dose) period. Only those participants available at the indicated time points were assessed (represented by n=X in the category titles).
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End point type |
Secondary
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End point timeframe |
Screening and Follow-up (up to Day 13)
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| Notes [16] - Safety Population |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Total bilirubin and creatinine values at the indicated time points | ||||||||||||||||
End point description |
Clinical chemistry included analysis of total bilirubin and creatinine during screening and follow-up (within 3 days of receipt of the last dose) period. Only those participants available at the indicated time points were assessed (represented by n=X in the category titles).
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End point type |
Secondary
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End point timeframe |
Screening and Follow-up (up to Day 13)
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| Notes [17] - Safety Population |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Carbon Dioxide content or bicarbonate, sodium, potassium and urea values at the indicated time points | ||||||||||||||||||||||||
End point description |
Clinical chemistry included carbon dioxide content/bicarbonate, potassium, sodium and urea during screening and follow-up (within 3 days of receipt of the last dose) period. Only those participants available at the indicated time points were assessed (represented by n=X in the category titles).
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End point type |
Secondary
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End point timeframe |
Screening and Follow-up (up to Day 13)
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| Notes [18] - Safety Population |
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Red blood cell count values at the indicated time points | ||||||||||||
End point description |
Hematology included analysis of red blood cell count during screening and follow-up (within 3 days of receipt of the last dose) period. Only those participants available at the indicated time points were assessed (represented by n=X in the category titles).
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End point type |
Secondary
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End point timeframe |
Screening and Follow-up (up to Day 13)
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| Notes [19] - Safety Population |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Heart rate values at the indicated time points | ||||||||||||||
End point description |
Heart rate was recorded during screening, telephone clinic visit and follow-up (within 3 days of receipt of the last dose) period. Only those participants available at the indicated time points were assessed (represented by n=X in the category titles).
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End point type |
Secondary
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End point timeframe |
Screening and Follow-up (up to Day 13)
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| Notes [20] - Safety Population |
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Temperature values at the indicated time points | ||||||||||||||
End point description |
Temperature was recorded during screening, telephone clinic visit and follow-up (within 3 days of receipt of the last dose) period. Only those participants available at the indicated time points were assessed (represented by n=X in the category titles).
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End point type |
Secondary
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End point timeframe |
Screening and Follow-up (up to Day 13)
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| Notes [21] - Safety Population |
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| No statistical analyses for this end point | |||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Serious Adverse events (SAEs) and AEs will be analyzed up to Day 13.
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Adverse event reporting additional description |
Adverse events were monitored throughout the study by spontaneous patient/parent-guardian reporting, direct questioning ,observation, clinical responses, and clinical laboratory tests.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
10.0
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Reporting groups
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Reporting group title |
Amoxicillin 2000 mg/Clavulanate 125 mg BD
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Reporting group description |
Participants received 2 tablets of combination product prolonged release amoxicillin 1000 mg/clavulanate 62.5 mg twice daily (BD) orally with food for 10 days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
