Pharmacokinetics and Optimal Dose of Ertapenem in Hemodialysis Patients

• Sponsor: William Beaumont Hospitals (Other)
• Overall Status: Completed
• CT.gov ID: NCT02159859
• Collaborator: Wayne State University (Other)
• Enrollment: 7
• Location: 1
• Arm: 1
• Duration (Months): 16
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the amount of ertapenem in the blood over time between hemodialysis session.

Condition or Disease	Intervention/Treatment	Phase
End Stage Renal Disease	Drug: Ertapenem	Phase 2

Detailed Description

After a hemodialysis session, subject will be administered ertapenem and the amount of ertapenem in the blood will be measured at seven time periods before the initiation of the next hemodialysis session.

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Pharmacokinetics and Investigation of Optimal Dose of Invanz (Ertapenem) in Hemodialysis Patients
• Study Start Date: Dec 1, 2014
• Actual Primary Completion Date: Apr 1, 2016
• Actual Study Completion Date: Apr 1, 2016

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Ertapenem Subjects with end stage renal disease (ESRD) who undergo hemodialysis three times a week and without infection will be administered one gram of ertapenem once over five minutes through infusion access after a hemodialysis session, and will have blood drawn at time 0, 0.5, 1, 2, 6, and 12 hours after the ertapenem administration and once prior to the next hemodialysis session

Drug: Ertapenem; Subjects are hemodialysis patients who are admitted to Oakwood Hospital - Dearborn; Other Names: Invanz

Outcome Measures

Primary Outcome Measures

1. Mean Maximum Concentration (Cmax) of Ertapenem in Hemodialysis Patients [once after hemodialysis session prior to ertapenem administration and at 0.5, 1, 2, 6, 12 hours after the administration of one gram ertapenem over five minutes, and once before the next hemodialysis session]

   Mean Cmax will be calculated from a series of ertapenem concentration from the blood samples, i.e.once after hemodialysis session prior to ertapenem administration, and at 0.5, 1, 2, 6, 12 hours after the administration of one gram ertapenem over five minutes, and once before the next hemodialysis session

2. Mean Minimum Concentration (Cmin) of Ertapenem in Hemodialysis Patients [once after hemodialysis session prior to ertapenem administration, and at 0.5, 1, 2, 6, 12 hours after the administration of one gram ertapenem over five minutes, and once before the next hemodialysis session]

   Mean Cmin will be calculated from a series of ertapenem concentration from the blood samples, i.e.once after hemodialysis session prior to ertapenem administration, and at 0.5, 1, 2, 6, 12 hours after the administration of one gram ertapenem over five minutes, and once before the next hemodialysis session

3. Mean Area Under the Curve (AUC) of Ertapenem in Hemodialysis Patients [once after hemodialysis session prior to ertapenem administration, and at 0.5, 1, 2, 6, 12 hours after the administration of one gram ertapenem over five minutes, and once before the next hemodialysis session]

   Mean AUC will be calculated from a series of ertapenem concentration from the blood samples, i.e.once after hemodialysis session prior to ertapenem administration, and at 0.5, 1, 2, 6, 12 hours after the administration of one gram ertapenem over five minutes, and once before the next hemodialysis session

4. Mean Terminal Half Life (t1/2) of Ertpenem in Hemodialysis Patients [once after hemodialysis session prior to ertapenem administration, and at 0.5, 1, 2, 6, 12 hours after the administration of one gram ertapenem over five minutes, and once before the next hemodialysis session]

   Mean t1/2 will be calculated from a series of ertapenem concentration from the blood samples, i.e.once after hemodialysis session prior to ertapenem administration, and at 0.5, 1, 2, 6, 12 hours after the administration of one gram ertapenem over five minutes, and once before the next hemodialysis session

5. Mean Time to Cmax of Ertapenem in Hemodialysis Patients [once after hemodialysis session prior to ertapenem administration, and at 0.5, 1, 2, 6, 12 hours after the administration of one gram ertapenem over five minutes, and once before the next hemodialysis session]

   Mean time to Cmax will be calculated from a series of ertapenem concentration from the blood samples, i.e.once after hemodialysis session prior to ertapenem administration, and at 0.5, 1, 2, 6, 12 hours after the administration of one gram ertapenem over five minutes, and once before the next hemodialysis session

Secondary Outcome Measures

1. Number of Participants With Diarrhea [Up to seven days after the administration of ertapenem]

   Evaluation of diarrhea will be performed by the study physician at screening, predose, 24 hours, and 5 to 7 days after the ertapenem dose or the last day of patient's stay in the hospital

2. Number of Participants With Nausea and Vomiting [Up to seven days after the administration of ertapenem]

   Evaluation of nausea and vomiting will be performed by the study physician at screening, predose, 24 hours, and 5 to 7 days after the ertapenem dose or the last day of patient's stay in the hospital

3. Number of Participants With Headache [Up to seven days after the administration of ertapenem]

   Evaluation of headache will be performed by the study physician at screening, predose, 24 hours, and 5 to 7 days after the ertapenem dose or the last day of patient's stay in the hospital

4. Number of Participants With Injection Site Reaction [Up to seven days after the administration of ertapenem]

   Evaluation of injection site reaction will be performed by the study physician at screening, predose, 24 hours, and 5 to 7 days after the ertapenem dose or the last day of patient's stay in the hospital

Other Outcome Measures

1. Number of Participants With Any Adverse Events [Up to seven days after the administration of ertapenem]

   Evaluation of any adverse events will be performed by the study physician at screening, predose, 24 hours, and 5 to 7 days after the ertapenem dose or the last day of patient's stay in the hospital

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 88 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Men or women age between 18 and 88 at the time of admission to Oakwood Hospital and Medical Center during January 1, 2014 or date of Institutional Review Board (IRB) approval to December 1, 2015

• Diagnosed with end stage renal disease and requires hemodialysis three times a week

• No allergy to β lactam medications

• Existing IV access for parenteral ertapenem infusion

• Willing for blood draws, at predose, 0.5, 1, 2, 6, 12 hours post-hemodialysis and pre-hemodialysis for the following hemodialysis and immediately post hemodialysis session and 1 hour post.

• No evidence of hepatic disease

• No history of alcoholism or drug abuse within pervious 2 years

• Not pregnant

Exclusion Criteria:

• History of any form of epilepsy, seizure or convulsion

• Currently taking any forms of valproic acid or divalproex sodium for treatment of any disease states

• Currently taking probenecid

• Current Clostridium difficile (C. diff.) infection, defined as 30 days prior to day-1 of receiving ertapenem for this study

• Currently receiving any antimicrobial agents for prophylaxis or treatment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Oakwood Hospital - Dearborn	Dearborn	Michigan	United States	48124

Sponsors and Collaborators

• William Beaumont Hospitals
• Wayne State University

Investigators

• Principal Investigator: Lama Hsaiky, Pharm.D., Oakwood Hospital - Dearborn
• Study Chair: Lama Hsaiky, Pharm.D., Oakwood Hospital - Dearborn

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: William Beaumont Hospitals
• ClinicalTrials.gov Identifier: NCT02159859
• Other Study ID Numbers: OH-D-Ertapenem-HD
• First Posted: Jun 10, 2014
• Last Update Posted: Oct 17, 2018
• Last Verified: Sep 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by William Beaumont Hospitals: ertapenem; pharmacokinetic; pharmacodynamics; hemodialysis; requires hemodialysis three times a week
• Additional relevant MeSH terms: Kidney Failure, Chronic; Ertapenem

Study Results

Participant Flow

Arm/Group Title	Ertapenem
Arm/Group Description	Subjects with end stage renal disease (ESRD) who undergo hemodialysis three times a week and without infection will be administered one gram of ertapenem once over five minutes through infusion access after a hemodialysis session, and will have blood drawn at time 0, 0.5, 1, 2, 6, and 12 hours after the ertapenem administration and once prior to the next hemodialysis session Ertapenem: Subjects are hemodialysis patients who are admitted to Oakwood Hospital - Dearborn
Period Title: Overall Study
STARTED	7
COMPLETED	7
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Ertapenem
Arm/Group Description	Pharmacokinetics and Optimal Dose of Ertapenem in Hemodialysis Patients
Overall Participants	7
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60 (11.4)
Sex: Female, Male (Count of Participants)
Female	2 28.6%
Male	5 71.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	5 71.4%
White	2 28.6%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	7 100%
weight (kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms]	77.7 (18.3)

Outcome Measures

1. Primary Outcome

Title	Mean Maximum Concentration (Cmax) of Ertapenem in Hemodialysis Patients
Description	Mean Cmax will be calculated from a series of ertapenem concentration from the blood samples, i.e.once after hemodialysis session prior to ertapenem administration, and at 0.5, 1, 2, 6, 12 hours after the administration of one gram ertapenem over five minutes, and once before the next hemodialysis session
Time Frame	once after hemodialysis session prior to ertapenem administration and at 0.5, 1, 2, 6, 12 hours after the administration of one gram ertapenem over five minutes, and once before the next hemodialysis session

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ertapenem
Arm/Group Description	Pharmacokinetics and Optimal Dose of Ertapenem in Hemodialysis Patients
Measure Participants	7
Mean (Standard Deviation) [mcg/ml]	663.1 (904.9)

2. Primary Outcome

Title	Mean Minimum Concentration (Cmin) of Ertapenem in Hemodialysis Patients
Description	Mean Cmin will be calculated from a series of ertapenem concentration from the blood samples, i.e.once after hemodialysis session prior to ertapenem administration, and at 0.5, 1, 2, 6, 12 hours after the administration of one gram ertapenem over five minutes, and once before the next hemodialysis session
Time Frame	once after hemodialysis session prior to ertapenem administration, and at 0.5, 1, 2, 6, 12 hours after the administration of one gram ertapenem over five minutes, and once before the next hemodialysis session

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ertapenem
Arm/Group Description	Pharmacokinetics and Optimal Dose of Ertapenem in Hemodialysis Patients
Measure Participants	7
Mean (Standard Deviation) [mcg/ml]	44.3 (14.5)

3. Primary Outcome

Title	Mean Area Under the Curve (AUC) of Ertapenem in Hemodialysis Patients
Description	Mean AUC will be calculated from a series of ertapenem concentration from the blood samples, i.e.once after hemodialysis session prior to ertapenem administration, and at 0.5, 1, 2, 6, 12 hours after the administration of one gram ertapenem over five minutes, and once before the next hemodialysis session
Time Frame	once after hemodialysis session prior to ertapenem administration, and at 0.5, 1, 2, 6, 12 hours after the administration of one gram ertapenem over five minutes, and once before the next hemodialysis session

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ertapenem
Arm/Group Description	Pharmacokinetics and Optimal Dose of Ertapenem in Hemodialysis Patients
Measure Participants	7
Mean (Standard Deviation) [h*ug/mL]	6225 (1259)

4. Primary Outcome

Title	Mean Terminal Half Life (t1/2) of Ertpenem in Hemodialysis Patients
Description	Mean t1/2 will be calculated from a series of ertapenem concentration from the blood samples, i.e.once after hemodialysis session prior to ertapenem administration, and at 0.5, 1, 2, 6, 12 hours after the administration of one gram ertapenem over five minutes, and once before the next hemodialysis session
Time Frame	once after hemodialysis session prior to ertapenem administration, and at 0.5, 1, 2, 6, 12 hours after the administration of one gram ertapenem over five minutes, and once before the next hemodialysis session

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ertapenem
Arm/Group Description	Pharmacokinetics and Optimal Dose of Ertapenem in Hemodialysis Patients
Measure Participants	7
Mean (Standard Deviation) [hours]	19.3 (6.6)

5. Primary Outcome

Title	Mean Time to Cmax of Ertapenem in Hemodialysis Patients
Description	Mean time to Cmax will be calculated from a series of ertapenem concentration from the blood samples, i.e.once after hemodialysis session prior to ertapenem administration, and at 0.5, 1, 2, 6, 12 hours after the administration of one gram ertapenem over five minutes, and once before the next hemodialysis session
Time Frame	once after hemodialysis session prior to ertapenem administration, and at 0.5, 1, 2, 6, 12 hours after the administration of one gram ertapenem over five minutes, and once before the next hemodialysis session

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ertapenem
Arm/Group Description	Pharmacokinetics and Optimal Dose of Ertapenem in Hemodialysis Patients
Measure Participants	7
Mean (Standard Deviation) [hours]	0.5 (0)

6. Secondary Outcome

Title	Number of Participants With Diarrhea
Description	Evaluation of diarrhea will be performed by the study physician at screening, predose, 24 hours, and 5 to 7 days after the ertapenem dose or the last day of patient's stay in the hospital
Time Frame	Up to seven days after the administration of ertapenem

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ertapenem
Arm/Group Description	Pharmacokinetics and Optimal Dose of Ertapenem in Hemodialysis Patients
Measure Participants	7
Count of Participants [Participants]	1 14.3%

7. Secondary Outcome

Title	Number of Participants With Nausea and Vomiting
Description	Evaluation of nausea and vomiting will be performed by the study physician at screening, predose, 24 hours, and 5 to 7 days after the ertapenem dose or the last day of patient's stay in the hospital
Time Frame	Up to seven days after the administration of ertapenem

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ertapenem
Arm/Group Description	Pharmacokinetics and Optimal Dose of Ertapenem in Hemodialysis Patients
Measure Participants	7
Count of Participants [Participants]	1 14.3%

8. Secondary Outcome

Title	Number of Participants With Headache
Description	Evaluation of headache will be performed by the study physician at screening, predose, 24 hours, and 5 to 7 days after the ertapenem dose or the last day of patient's stay in the hospital
Time Frame	Up to seven days after the administration of ertapenem

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ertapenem
Arm/Group Description	Pharmacokinetics and Optimal Dose of Ertapenem in Hemodialysis Patients
Measure Participants	7
Count of Participants [Participants]	0 0%

9. Secondary Outcome

Title	Number of Participants With Injection Site Reaction
Description	Evaluation of injection site reaction will be performed by the study physician at screening, predose, 24 hours, and 5 to 7 days after the ertapenem dose or the last day of patient's stay in the hospital
Time Frame	Up to seven days after the administration of ertapenem

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ertapenem
Arm/Group Description	Pharmacokinetics and Optimal Dose of Ertapenem in Hemodialysis Patients
Measure Participants	7
Count of Participants [Participants]	0 0%

10. Other Pre-specified Outcome

Title	Number of Participants With Any Adverse Events
Description	Evaluation of any adverse events will be performed by the study physician at screening, predose, 24 hours, and 5 to 7 days after the ertapenem dose or the last day of patient's stay in the hospital
Time Frame	Up to seven days after the administration of ertapenem

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ertapenem
Arm/Group Description	Pharmacokinetics and Optimal Dose of Ertapenem in Hemodialysis Patients
Measure Participants	7
Count of Participants [Participants]	6 85.7%

Adverse Events

Time Frame	within 7days post enrollment
Arm/Group Title	Ertapenem
Arm/Group Description	Pharmacokinetics and Optimal Dose of Ertapenem in Hemodialysis Patients
All Cause Mortality
	Ertapenem
	Affected / at Risk (%)	# Events
Total	0/7 (0%)
Serious Adverse Events
	Ertapenem
	Affected / at Risk (%)	# Events
Total	0/7 (0%)
Other (Not Including Serious) Adverse Events
	Ertapenem
	Affected / at Risk (%)	# Events
Total	6/7 (85.7%)
Endocrine disorders
hypoglycemia	3/7 (42.9%)	3
Gastrointestinal disorders
nausea	1/7 (14.3%)	1
diarrhea	1/7 (14.3%)	1
Musculoskeletal and connective tissue disorders
Muscle jerking	1/7 (14.3%)	1
Renal and urinary disorders
Rusty urine	1/7 (14.3%)	1
Respiratory, thoracic and mediastinal disorders
shortness of breath	1/7 (14.3%)	1
Vascular disorders
hypertension	2/7 (28.6%)	2

Limitations/Caveats

some participants had missing lab values at the pre-determined times

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.