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| ID | Type | Description | Link |
|---|---|---|---|
| IISP ID#37935 | Other Grant/Funding Number | Merck |
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| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
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The purpose of this study is to characterize and compare the concentration-time profiles and multiple dose pharmacokinetics of a 5 minute intravenous (IV) bolus of ertapenem 1 gram daily versus the standard 30 minute infusion in healthy volunteers. Safety and tolerability and pharmacodynamic target attainment using Monte Carlo simulation will also be assessed and compared.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ertapenem 1 gram intravenous (IV) 5 minute bolus | Experimental | Participants received ertapenem 1 gram every 24 hours for 3 doses with each dose infused as a 5 minute IV bolus. |
|
| Ertapenem 1 gram IV 30 minute infusion | Active Comparator | Participants received ertapenem 1 gram every 24 hours for 3 doses with each dose infused as a 30 minute infusion (i.e., the standard dose). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ertapenem | Drug | 1 gram IV bolus every 24 hours (q24h) for 3 days |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) at Steady-State (After 3rd Dose) | Cmax is measured at 5 minutes after the beginning of the infusion for the 5 minute IV bolus dosage regimen and at 30 minutes after the beginning of the infusion for the 30 minute infusion dosage regimen. | 5 or 30 minutes post start of infusion on Day 3 |
| Area Under the Curve From 48 to 72 Hours [AUC(48-72)] | AUC(48-72) is the 24 hour area under the concentration versus time curve after the 3rd dose of ertapenem, which is selected to measure approximate AUC at steady-state. | 0-24 hours after 3rd ertapenem dose |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events as a Measure of Safety and Tolerability | The following laboratory assessments will be make before and after participation in the study to determine if objective changes occurred: blood pressure, pulse rate, temperature, complete blood count with differential, platelet count, blood urea nitrogen, serum creatinine, liver function panel [aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase], total bilirubin, and urinalysis with microscopy. Monitoring of other pathologic or unintended changes in structure (signs),or function (symptoms) of the body associated with participation in the study will occur. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Josepth L Kuti, PharmD | Hartford Hospital | Principal Investigator |
| Dora E Wiskirchen, PharmD | Hartford Hospital | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hartford Hospital | Hartford | Connecticut | 06102 | United States |
The target enrollment of 12 volunteers was met. All 12 participants completed at least one phase of the study, while 11 completed the entire study.
Healthy adult volunteers were recruited in August/September 2010.
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| ID | Title | Description |
|---|---|---|
| FG000 | Ertapenem IV 5 Minute Bolus First, Then 30 Minute Infusion | Participants received ertapenem 1 gram as a 5 minute IV bolus every 24 hours for 3 doses. After a 4 day washout, participants were crossed over to receive ertapenem 1 gram as a 30 minute IV infusion every 24 hours for 3 doses. |
| FG001 | Ertapenem IV 30 Minute Infusion First, Then 5 Minute Bolus | Participants received ertapenem 1 gram as a 30 minute infusion every 24 hours for 3 doses. After a 4 day washout, participants crossed over to receive ertapenem 1 gram as a 5 minute IV bolus every 24 hours for 3 doses. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention |
| |||||||||||||
| Washout Period |
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| Second Intervention |
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| ID | Title | Description |
|---|---|---|
| BG000 | Ertapenem IV 5 Minute Bolus First, Then 30 Minute Infusion | Participants received ertapenem 1 gram as a 5 minute IV bolus every 24 hours for 3 doses. After a 4 day washout, participants were crossed over to receive ertapenem 1 gram as a 30 minute IV infusion every 24 hours for 3 doses. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Maximum Observed Plasma Concentration (Cmax) at Steady-State (After 3rd Dose) | Cmax is measured at 5 minutes after the beginning of the infusion for the 5 minute IV bolus dosage regimen and at 30 minutes after the beginning of the infusion for the 30 minute infusion dosage regimen. | Each participant received ertapenem as a 5 minute infusion and as a 30 minute infusion, only in different order due to cross-over design. Data for all participants receiving each dosage regimen are included in each arm for results. | Posted | Mean | Standard Deviation | mcg/mL | 5 or 30 minutes post start of infusion on Day 3 |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Ertapenem IV 5 Minute Bolus First, Then 30 Minute Infusion | Participants received ertapenem 1 gram as a 5 minute IV bolus every 24 hours for 3 doses. After a 4 day washout, participants were crossed over to receive ertapenem 1 gram as a 30 minute IV infusion every 24 hours for 3 doses. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Joseph L. Kuti, Pharm.D. / Associate Director, Clinical and Economic Studies | Center for Anti-Infective Research and Development, Hartford Hospital | 860-545-3612 | jkuti@harthosp.org |
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| ID | Term |
|---|---|
| D000077727 | Ertapenem |
| ID | Term |
|---|---|
| D015780 | Carbapenems |
| D047090 | beta-Lactams |
| D007769 | Lactams |
| D000577 | Amides |
| D009930 |
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| ertapenem | Drug | 1 gram 30 minute infusion q24h for 3 days |
|
| 3 days |
| Probability of Target Attainment (PTA) | After simulating 5000 patients receiving each dosing regimen, the probability of achieving free drug concentrations above an MIC of 0.25 mcg/mL and 0.5mcg/mL for at least 40% of the dosing interval (40% fT>MIC) is calculated at each MIC dilution. | Simulated Steady-State Exposure |
| NOT COMPLETED |
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| NOT COMPLETED |
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| Ertapenem IV 30 Minute Infusion First, Then 5 Minute Bolus |
Participants received ertapenem 1 gram as a 30 minute infusion every 24 hours for 3 doses. After a 4 day washout, participants crossed over to receive ertapenem 1 gram as a 5 minute IV bolus every 24 hours for 3 doses. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Ertapenem 1 Gram IV 30 Minute Infusion |
Participants received ertapenem 1 gram as a 30 minute infusion every 24 hours for 3 doses. |
|
|
| Secondary | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | The following laboratory assessments will be make before and after participation in the study to determine if objective changes occurred: blood pressure, pulse rate, temperature, complete blood count with differential, platelet count, blood urea nitrogen, serum creatinine, liver function panel [aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase], total bilirubin, and urinalysis with microscopy. Monitoring of other pathologic or unintended changes in structure (signs),or function (symptoms) of the body associated with participation in the study will occur. | Posted | Number | participants | 3 days |
|
|
|
| Secondary | Probability of Target Attainment (PTA) | After simulating 5000 patients receiving each dosing regimen, the probability of achieving free drug concentrations above an MIC of 0.25 mcg/mL and 0.5mcg/mL for at least 40% of the dosing interval (40% fT>MIC) is calculated at each MIC dilution. | The probability of achieving 40% T>MIC is reported at a MIC of 0.25mcg/mL and 0.5mcg/mL respectively. | Posted | Number | % of 5000 simulated patients | Simulated Steady-State Exposure | Simulated Patients | Participants |
|
|
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| Primary | Area Under the Curve From 48 to 72 Hours [AUC(48-72)] | AUC(48-72) is the 24 hour area under the concentration versus time curve after the 3rd dose of ertapenem, which is selected to measure approximate AUC at steady-state. | Posted | Mean | Standard Deviation | mcg*hr/mL | 0-24 hours after 3rd ertapenem dose |
|
|
|
| 0 |
| 11 |
| 10 |
| 11 |
| EG001 | Ertapenem IV 30 Minute Infusion First, Then 5 Minute Bolus | Participants received ertapenem 1 gram as a 30 minute infusion every 24 hours for 3 doses. After a 4 day washout, participants crossed over to receive ertapenem 1 gram as a 5 minute IV bolus every 24 hours for 3 doses. | 0 | 12 | 9 | 12 |
| Headache | General disorders |
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| Diarrhea | Gastrointestinal disorders |
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| Anemia | Blood and lymphatic system disorders | Reduction in Hemoglobin below normal. |
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| Liver Function Test out of range | Hepatobiliary disorders | Increases in ALT |
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| Organic Chemicals |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |