Trial Outcomes & Findings for Bioavailability of Amoxicillin Dissolved in Human Milk (NCT NCT01435824)
NCT ID: NCT01435824
Last Updated: 2020-01-21
Results Overview
Amoxicillin plasma concentrations were determined by HPLC-MS/MS and AUC∞ (to time infinity) was estimated using a model-independent approach. Specifically, the log-trapezoidal method was used to calculate AUC last (AUC from time 0 to 8 h), and AUC∞ was further estimated with the elimination rate constant (Kel) of the terminal log-linear phase (β phase) of the concentration time profile extrapolating to time infinity as follows: AUC∞ = AUC last + \[C\]8h/Kel; where \[C\]8h is the plasma concentration at time 8 h postdose.
COMPLETED
PHASE2
16 participants
Baseline, 0.25, 0.5, 1, 1.5, 3, 4 and 8 hours after dosing
2020-01-21
Participant Flow
Healthy young adults were enrolled. 16 individuals were assessed and randomly assigned to either "water-based first, then milk-based amoxicillin administration" or "milk-based first and then water-based administration" arms. The washout period was 1-2 weeks. The study was conducted at Hospital for Sick Children in Toronto, Canada.
Participants were interviewed and underwent basic vital sign checking, and filled health status questionnaire to declare lack of any significant medical conditions. Urine pregnancy tests, with consents, were performed before dosing for female participants.Wash-out period between water and human milk phases was 1-2 weeks.
Participant milestones
| Measure |
Water-based First, Then Milk-based Administration
First, participants were orally given 10 mL of water-dissolved amoxicillin (50mg/mL) in a fasting state. A PK sampling was performed. The washout period was for 1-2 weeks and then participants underwent the milk-based administration of amoxicillin, followed by PK sampling.
|
Milk-based First, and Then Water-based Drug Administration
First, participants were orally given 10 mL of human milk-dissolved amoxicillin (50mg/mL) in fasting state, followed by PK sampling. The washout period was for 1-2 weeks and then participants underwent a water-based administration if amoxicillin followed by PK sampling. .
|
|---|---|---|
|
First Intervention
STARTED
|
8
|
8
|
|
First Intervention
COMPLETED
|
8
|
8
|
|
First Intervention
NOT COMPLETED
|
0
|
0
|
|
Washout of 1-2 Weeks
STARTED
|
8
|
8
|
|
Washout of 1-2 Weeks
COMPLETED
|
8
|
8
|
|
Washout of 1-2 Weeks
NOT COMPLETED
|
0
|
0
|
|
Second Intervention
STARTED
|
8
|
8
|
|
Second Intervention
COMPLETED
|
8
|
8
|
|
Second Intervention
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Entire Study Population
n=16 Participants
This study was designed as a randomized 2x2 crossover single-dose study where participants either given water-dissolved amoxicillin first or human milk-dissolved amoxicillin first switched over during period 2.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=16 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
16 Participants
n=16 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=16 Participants
|
|
Age, Continuous
|
36.3 years
STANDARD_DEVIATION 9.0 • n=16 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=16 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=16 Participants
|
|
Region of Enrollment
Canada
|
16 participants
n=16 Participants
|
|
Height
|
167.6 cm
STANDARD_DEVIATION 12.3 • n=16 Participants
|
|
Weight
|
67.1 kg
STANDARD_DEVIATION 14.3 • n=16 Participants
|
PRIMARY outcome
Timeframe: Baseline, 0.25, 0.5, 1, 1.5, 3, 4 and 8 hours after dosingAmoxicillin plasma concentrations were determined by HPLC-MS/MS and AUC∞ (to time infinity) was estimated using a model-independent approach. Specifically, the log-trapezoidal method was used to calculate AUC last (AUC from time 0 to 8 h), and AUC∞ was further estimated with the elimination rate constant (Kel) of the terminal log-linear phase (β phase) of the concentration time profile extrapolating to time infinity as follows: AUC∞ = AUC last + \[C\]8h/Kel; where \[C\]8h is the plasma concentration at time 8 h postdose.
Outcome measures
| Measure |
Water as a Vehicle of Amoxicillin
n=16 Participants
Amoxicillin 500 mg was dissolved in 10 ml water and orally administered in a fasting state.
Water-dissolved amoxicillin: An amoxicillin suspension bottle containing 5 grams of amoxicillin (powder) will be resuspended in 60 ml of water to have 100mL of a 50mg/mL suspension.
|
Human Milk as a Vehicle of Amoxicillin
n=16 Participants
Amoxicillin 500 mg was dissolved in 10 ml human milk and orally administered in a fasting state.
Human milk-dissolved amoxicillin: An amoxicillin suspension bottle containing 5 grams of amoxicillin (powder) will be resuspended in 60 ml of breast milk to have 100mL of a 50mg/mL suspension.
|
|---|---|---|
|
Area Under the Curve to Time Infinity (AUC to Time Infinity)
|
1394.1 mcg*min/mL
Standard Deviation 256.1
|
1477.2 mcg*min/mL
Standard Deviation 260.7
|
PRIMARY outcome
Timeframe: Baseline, 0.25, 0.5, 1, 1.5, 3, 4 and 8 hours after dosingAmoxicillin plasma concentrations were determined by HPLC-MS/MS and PK parameters were estimated using a model-independent approach. Specifically, the log-trapezoidal method was used to calculate AUC last (AUC from time 0 to 8 h).
Outcome measures
| Measure |
Water as a Vehicle of Amoxicillin
n=16 Participants
Amoxicillin 500 mg was dissolved in 10 ml water and orally administered in a fasting state.
Water-dissolved amoxicillin: An amoxicillin suspension bottle containing 5 grams of amoxicillin (powder) will be resuspended in 60 ml of water to have 100mL of a 50mg/mL suspension.
|
Human Milk as a Vehicle of Amoxicillin
n=16 Participants
Amoxicillin 500 mg was dissolved in 10 ml human milk and orally administered in a fasting state.
Human milk-dissolved amoxicillin: An amoxicillin suspension bottle containing 5 grams of amoxicillin (powder) will be resuspended in 60 ml of breast milk to have 100mL of a 50mg/mL suspension.
|
|---|---|---|
|
Area Under the Curve to 8h (AUC Last)
|
1355.8 mcg*min/mL
Standard Deviation 254.2
|
1435.0 mcg*min/mL
Standard Deviation 241.7
|
PRIMARY outcome
Timeframe: 0, 0.25, 0.5, 1, 1.5, 3, 4 and 8 hours after dosingA maximum plasma concentration of amoxicillin within the time frame of a dosing
Outcome measures
| Measure |
Water as a Vehicle of Amoxicillin
n=16 Participants
Amoxicillin 500 mg was dissolved in 10 ml water and orally administered in a fasting state.
Water-dissolved amoxicillin: An amoxicillin suspension bottle containing 5 grams of amoxicillin (powder) will be resuspended in 60 ml of water to have 100mL of a 50mg/mL suspension.
|
Human Milk as a Vehicle of Amoxicillin
n=16 Participants
Amoxicillin 500 mg was dissolved in 10 ml human milk and orally administered in a fasting state.
Human milk-dissolved amoxicillin: An amoxicillin suspension bottle containing 5 grams of amoxicillin (powder) will be resuspended in 60 ml of breast milk to have 100mL of a 50mg/mL suspension.
|
|---|---|---|
|
Cmax
|
8653.8 ng/ml
Standard Deviation 2217.6
|
8690.6 ng/ml
Standard Deviation 1972.4
|
PRIMARY outcome
Timeframe: Data points were taken at 0, 0.25, 0.5, 1, 1.5, 3, 4 and 8 hours after dosing.Time to reach Cmax after administration
Outcome measures
| Measure |
Water as a Vehicle of Amoxicillin
n=16 Participants
Amoxicillin 500 mg was dissolved in 10 ml water and orally administered in a fasting state.
Water-dissolved amoxicillin: An amoxicillin suspension bottle containing 5 grams of amoxicillin (powder) will be resuspended in 60 ml of water to have 100mL of a 50mg/mL suspension.
|
Human Milk as a Vehicle of Amoxicillin
n=16 Participants
Amoxicillin 500 mg was dissolved in 10 ml human milk and orally administered in a fasting state.
Human milk-dissolved amoxicillin: An amoxicillin suspension bottle containing 5 grams of amoxicillin (powder) will be resuspended in 60 ml of breast milk to have 100mL of a 50mg/mL suspension.
|
|---|---|---|
|
Tmax
|
101.3 min
Standard Deviation 52.4
|
106.9 min
Standard Deviation 49.0
|
SECONDARY outcome
Timeframe: Data points were taken at 0, 0.25, 0.5, 1, 1.5, 3, 4 and 8 hours after dosing.Elimination rate constant (Kel) was estimated from the terminal log-linear phase of the concentration-time profiles. Then, elimination half-life was calculated as follows: ln2/Kel.
Outcome measures
| Measure |
Water as a Vehicle of Amoxicillin
n=16 Participants
Amoxicillin 500 mg was dissolved in 10 ml water and orally administered in a fasting state.
Water-dissolved amoxicillin: An amoxicillin suspension bottle containing 5 grams of amoxicillin (powder) will be resuspended in 60 ml of water to have 100mL of a 50mg/mL suspension.
|
Human Milk as a Vehicle of Amoxicillin
n=16 Participants
Amoxicillin 500 mg was dissolved in 10 ml human milk and orally administered in a fasting state.
Human milk-dissolved amoxicillin: An amoxicillin suspension bottle containing 5 grams of amoxicillin (powder) will be resuspended in 60 ml of breast milk to have 100mL of a 50mg/mL suspension.
|
|---|---|---|
|
Elimination Half-life
|
77.7 min
Standard Deviation 17
|
76.1 min
Standard Deviation 11.7
|
SECONDARY outcome
Timeframe: Data points were taken at 0, 0.25, 0.5, 1, 1.5, 3, 4 and 8 hours after dosing.The log-trapezoidal method was used to calculate AUC last (AUC from time 0 to 8 h), and AUC∞ was estimated using an elimination rate constant (Kel) of the terminal log-linear phase (β phase) of the concentration time profile extrapolating to time infinity. Then, CL/F was derived from Dose/AUC∞. F is bioavailability, which cannot be determined in this study, and therefore, we estimate CL/F, but not CL itself.
Outcome measures
| Measure |
Water as a Vehicle of Amoxicillin
n=16 Participants
Amoxicillin 500 mg was dissolved in 10 ml water and orally administered in a fasting state.
Water-dissolved amoxicillin: An amoxicillin suspension bottle containing 5 grams of amoxicillin (powder) will be resuspended in 60 ml of water to have 100mL of a 50mg/mL suspension.
|
Human Milk as a Vehicle of Amoxicillin
n=16 Participants
Amoxicillin 500 mg was dissolved in 10 ml human milk and orally administered in a fasting state.
Human milk-dissolved amoxicillin: An amoxicillin suspension bottle containing 5 grams of amoxicillin (powder) will be resuspended in 60 ml of breast milk to have 100mL of a 50mg/mL suspension.
|
|---|---|---|
|
Clearance/F
|
5.63 ml/kg/min
Standard Deviation 1.05
|
5.34 ml/kg/min
Standard Deviation 1.22
|
SECONDARY outcome
Timeframe: Data points were taken at 0, 0.25, 0.5, 1, 1.5, 3, 4 and 8 hours after dosing.It was estimated from (Clearance/F)/Kel. Elimination rate constant (Kel) was estimated from the terminal log-linear phase of the concentration-time profiles. Then, elimination half-life was calculated as follows: ln2/Kel.
Outcome measures
| Measure |
Water as a Vehicle of Amoxicillin
n=16 Participants
Amoxicillin 500 mg was dissolved in 10 ml water and orally administered in a fasting state.
Water-dissolved amoxicillin: An amoxicillin suspension bottle containing 5 grams of amoxicillin (powder) will be resuspended in 60 ml of water to have 100mL of a 50mg/mL suspension.
|
Human Milk as a Vehicle of Amoxicillin
n=16 Participants
Amoxicillin 500 mg was dissolved in 10 ml human milk and orally administered in a fasting state.
Human milk-dissolved amoxicillin: An amoxicillin suspension bottle containing 5 grams of amoxicillin (powder) will be resuspended in 60 ml of breast milk to have 100mL of a 50mg/mL suspension.
|
|---|---|---|
|
Volume of Distribution/F
|
0.63 l/kg
Standard Deviation 0.18
|
0.59 l/kg
Standard Deviation 0.16
|
Adverse Events
Water-based Amoxicillin Administration
Human Milk-based Amoxicillin Administration
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place