Trial Outcomes & Findings for Pharmacokinetics (PK) of Ertapenem Intravenous (IV) Bolus Versus Standard Infusion (NCT NCT01148771)

NCT ID: NCT01148771

Last Updated: 2012-05-11

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 12 participants
• Primary outcome timeframe: 5 or 30 minutes post start of infusion on Day 3
• Results posted on: 2012-05-11

Participant Flow

Healthy adult volunteers were recruited in August/September 2010.

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.

Participant milestones

Measure	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.	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.
First Intervention STARTED	6	6
First Intervention COMPLETED	6	6
First Intervention NOT COMPLETED	0	0
Washout Period STARTED	6	6
Washout Period COMPLETED	6	5
Washout Period NOT COMPLETED	0	1
Second Intervention STARTED	6	5
Second Intervention COMPLETED	6	5
Second Intervention NOT COMPLETED	0	0

Reasons for withdrawal

Measure	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.	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.
Washout Period Withdrawal by Subject	0	1

Baseline Characteristics

Pharmacokinetics (PK) of Ertapenem Intravenous (IV) Bolus Versus Standard Infusion

Baseline characteristics by cohort

Measure	Ertapenem IV 5 Minute Bolus First, Then 30 Minute Infusion n=11 Participants 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.	Ertapenem IV 30 Minute Infusion First, Then 5 Minute Bolus n=12 Participants 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.	Total n=23 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	11 Participants n=5 Participants	12 Participants n=7 Participants	23 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age Continuous	32.4 years STANDARD_DEVIATION 13.9 • n=5 Participants	32.4 years STANDARD_DEVIATION 13.9 • n=7 Participants	32.4 years STANDARD_DEVIATION 13.9 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	8 Participants n=7 Participants	16 Participants n=5 Participants
Region of Enrollment United States	11 participants n=5 Participants	12 participants n=7 Participants	23 participants n=5 Participants

PRIMARY outcome

Timeframe: 5 or 30 minutes post start of infusion on Day 3

Population: 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.

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.

Outcome measures

Measure	Ertapenem 1 Gram IV 5 Minute Bolus n=11 Participants Participants received ertapenem 1 gram as a 5 minute IV bolus every 24 hours for 3 doses.	Ertapenem 1 Gram IV 30 Minute Infusion n=12 Participants Participants received ertapenem 1 gram as a 30 minute infusion every 24 hours for 3 doses.
Maximum Observed Plasma Concentration (Cmax) at Steady-State (After 3rd Dose)	193.33 mcg/mL Standard Deviation 43.27	165.70 mcg/mL Standard Deviation 20.38

PRIMARY outcome

Timeframe: 0-24 hours after 3rd ertapenem dose

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.

Outcome measures

Measure	Ertapenem 1 Gram IV 5 Minute Bolus n=11 Participants Participants received ertapenem 1 gram as a 5 minute IV bolus every 24 hours for 3 doses.	Ertapenem 1 Gram IV 30 Minute Infusion n=12 Participants Participants received ertapenem 1 gram as a 30 minute infusion every 24 hours for 3 doses.
Area Under the Curve From 48 to 72 Hours [AUC(48-72)]	561.17 mcg*hr/mL Standard Deviation 77.01	531.32 mcg*hr/mL Standard Deviation 56.86

SECONDARY outcome

Timeframe: 3 days

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.

Outcome measures

Measure	Ertapenem 1 Gram IV 5 Minute Bolus n=11 Participants Participants received ertapenem 1 gram as a 5 minute IV bolus every 24 hours for 3 doses.	Ertapenem 1 Gram IV 30 Minute Infusion n=12 Participants Participants received ertapenem 1 gram as a 30 minute infusion every 24 hours for 3 doses.
Number of Participants With Adverse Events as a Measure of Safety and Tolerability	10 participants	9 participants

SECONDARY outcome

Timeframe: Simulated Steady-State Exposure

Population: The probability of achieving 40% T\>MIC is reported at a MIC of 0.25mcg/mL and 0.5mcg/mL respectively.

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.

Outcome measures

Measure	Ertapenem 1 Gram IV 5 Minute Bolus n=5000 Simulated Patients Participants received ertapenem 1 gram as a 5 minute IV bolus every 24 hours for 3 doses.	Ertapenem 1 Gram IV 30 Minute Infusion n=5000 Simulated Patients Participants received ertapenem 1 gram as a 30 minute infusion every 24 hours for 3 doses.
Probability of Target Attainment (PTA) PTA at 0.25	97.0 % of 5000 simulated patients	97.9 % of 5000 simulated patients
Probability of Target Attainment (PTA) PTA at 0.5	1.7 % of 5000 simulated patients	2.8 % of 5000 simulated patients

Adverse Events

Ertapenem IV 5 Minute Bolus First, Then 30 Minute Infusion

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Ertapenem IV 30 Minute Infusion First, Then 5 Minute Bolus

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Ertapenem IV 5 Minute Bolus First, Then 30 Minute Infusion n=11 participants at risk 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.	Ertapenem IV 30 Minute Infusion First, Then 5 Minute Bolus n=12 participants at risk 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.
Gastrointestinal disorders Nausea	27.3% 3/11 • Number of events 3	8.3% 1/12 • Number of events 1
General disorders Headache	27.3% 3/11 • Number of events 5	25.0% 3/12 • Number of events 7
Gastrointestinal disorders Diarrhea	54.5% 6/11 • Number of events 9	25.0% 3/12 • Number of events 8
Blood and lymphatic system disorders Anemia	18.2% 2/11 • Number of events 2	8.3% 1/12 • Number of events 1
Hepatobiliary disorders Liver Function Test out of range	9.1% 1/11 • Number of events 1	16.7% 2/12 • Number of events 2

Additional Information

Joseph L. Kuti, Pharm.D. / Associate Director, Clinical and Economic Studies

Center for Anti-Infective Research and Development, Hartford Hospital

Phone: 860-545-3612

Email: jkuti@harthosp.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60