PK/PD of Ertapenem In Patients With TB

Sponsor

University Medical Center Groningen (Other)

Overall Status

Completed

CT.gov ID

NCT01730664

Collaborator

(none)

Enrollment

Location

Arm

5.5

Actual Duration (Months)

2.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Rationale:

Treatment of multidrug or extensively drug resistant tuberculosis (MDR/XDR-TB) is a real challenge as failure in response to treatment and serious side-effects are frequently encountered. New, more effective drugs with less side effects are therefore urgently needed to solve this problem. Although several new drugs against TB are in the pipeline, physicians currently have limited treatment options for treatment of complicated MDR/XDR-TB cases. Therefore, drugs developed and labeled for other infectious diseases are evaluated for TB.

Objective:

The main objective of this prospective clinical trial is to evaluate pharmacokinetics of a standard dose (2000mg) of ertapenem in TB patients. This clinical trial will provide important information on PK of ertapenem in TB patients for future studies. Data can be used for limited sampling strategies for ertapenem based on a pharmacokinetic population model constructed from the full PK curves of the patients.

Study design:

A prospective pharmacokinetic study.

Study population: 12 TB patients.

Intervention: Single dose of 2000mg in a 30 minutes intravenous infusion.

Main study parameters/endpoints:

The pharmacokinetic parameters (Vd, Cl, AUC, etc) of ertapenem are the primary endpoints of the study. The T>MIC and AUC0-24h/Minimal inhibitory concentration (MIC) ratio are most likely the best predictive parameters for efficacy of ertapenem treatment and will be calculated for a range of M tuberculosis isolates.

Condition or Disease	Intervention/Treatment	Phase
PK of Ertapenem in TB Patients	Drug: ertapenem	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

12 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

Pharmacokinetics and Pharmacodynamics of Ertapenem in Patients With Tuberculosis

Actual Study Start Date :

Jan 26, 2017

Actual Primary Completion Date :

Jul 13, 2017

Actual Study Completion Date :

Jul 13, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ertapenem single dose ertapenem	Drug: ertapenem single dose of 2000mg ertapenem IV

Arm

Intervention/Treatment

Experimental: ertapenem

single dose ertapenem

Drug: ertapenem

single dose of 2000mg ertapenem IV

Outcome Measures

Primary Outcome Measures

AUC [first day]
main objective of this prospective clinical trial is to evaluate AUC of a standard dose (1000mg) of ertapenem in TB patients

Secondary Outcome Measures

Safety: number of patients with organ dysfunction [day 1 and day 3]
renal function(eGFR) and liver enzymes(ALAT; ASAT)

Other Outcome Measures

limited sampling strategies [day 1]
limited sampling strategies for ertapenem based on a pharmacokinetic population model constructed from the full PK curves of the patients.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 64 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with TB, with Mycobacterium tuberculosis (or M. africanum) by culture and / or molecular test
Adults: from 18 years until 64 years of age

Exclusion Criteria:

-Contra-indications for ertapenem:

There are few adverse effects of ertapenem. The only absolute contra- indication is a previous anaphylactic reaction to ertapenem or other β-lactam antibiotic.
Renal Insufficiency, defined by a eGFR of 30ml/min
Pregnancy
HIV
Body weight < 40 kg