Back to results

Evaluation of Innovative Tools in Development of Antibiotics

Primary Purpose

Pneumonia

Status

Completed

Phase

Phase 1

Locations

Austria

Study Type

Interventional

Intervention

Ciprofloxacin

Imipenem

About this trial

This is an interventional other trial for Pneumonia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Healthy male subjects aged 18 to 55 years
Good state of health (mentally and physically)
Body mass index within a range of 18 to 28kg/m2 inclusive.
Non-Smoker
A signed and dated written informed consent form.
The subject is able to understand and willing to comply with protocol requirements and timetables, instructions and protocol-stated restrictions.
Negative serology (human immunodeficiency virus, hepatitis B-AG and C-AB) at screening.
Vital signs should be within the following ranges:
Oral or tympanic temperature between 35 and 37.5°C.
Systolic blood pressure, 90-140 mmHg.
Diastolic blood pressure, 50-90 mmHg.
Pulse rate, 50-90 bpm.

Exclusion Criteria:

Any acute or chronic illness or clinically relevant (Investigator's judgement) abnormality identified on the screening medical assessment, laboratory tests or ECG, unless in the opinion of the Investigator it will not interfere with the study procedures, affect the outcome of the study or compromise the safety of the subject.
All subjects with known seizure disorder, with the exception of a febrile seizure in childhood
Use of prescription or non-prescription drugs within 7 days or 10 times the elimination half-life (whichever is longer) prior to the first dose of study medication.
Any intake of grapefruit juice within 1 week prior to the first dose.
Allergies (except for mild forms of hay fever), a history of hypersensitivity reactions including psychological or neurological symptoms or signs, or anaphylactic shock following administration of any medicine.
Allergy to or any contraindication against the active or inactive ingredients in the study medication (ciprofloxacin, imipenem, cilastatin, propofol, midazolam, remifentanil, xylocain, and sevoflurane) and radioactive labelling with 14C.
Smoker
Alcohol or drug abuse
Participation in a trial with any drug within 30 days or five half-lives (whichever is longer) before the start of the study.
Donation of blood within a period of 4 weeks prior to dosing.
Creatinine clearance ≤70mL/min/1.73m3
Any other reason that the Investigator considers to make the subject unsuitable to participate.

Sites / Locations

Medical University of Vienna

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Ciprofloxacin

Imipenem

Arm Description

Half of patients and healthy volunteers are receiving ciprofloxacin, the other half imipenem.

Outcomes

Primary Outcome Measures

Cmax (peak concentration in plasma and epithelial lining fluid) of imipenem and ciprofloxacin

Comparison of Cmax of ciprofloxacin and imipenem in plasma and epithelial lining fluid, alveolar macrophages and saliva (only healthy subjects) in healthy subjects and patients with bacterial pneumonia.

AUC (area under the concentration curve in plasma and epithelial lining fluid) of imipenem and ciprofloxacin.

Comparison of AUC of ciprofloxacin and imipenem in plasma and epithelial lining fluid, alveolar macrophages and saliva (only healthy subjects) in healthy subjects and patients with bacterial pneumonia.

Tmax (time of peak concentration in plasma and epithelial lining fluid) of imipenem and ciprofloxacin.

Cmax (peak concentration in plasma, epithelial lining fluid and microdialysate) of C14 ciprofloxacin (microdose)

Comparison of pharmacokinetics of microdoses and macrodoses in lung, subcutaneous tissue (microdialysis) and plasma in healthy volunteers.

AUC (area under the curve in plasma, epithelial lining fluid and microdialysate) of C14 ciprofloxacin (carbon-14 radiolabelled compound, microdose)

Comparison of pharmacokinetics of microdoses and macrodoses in lung, subcutaneous tissue (microdialysis) and plasma in healthy volunteers.

Tmax (time of peak concentration in plasma, epithelial lining fluid and microdialysate) of C14 ciprofloxacin (microdose)

Comparison of pharmacokinetics of microdoses and macrodoses in lung, subcutaneous tissue (microdialysis) and plasma in healthy volunteers.

Cmax (peak concentration in microdialysate) of ciprofloxacin (macrodose)

In healthy volunteers only for comparison of Cmax of C14 ciprofloxacin and Cmax of ciprofloxacin as macrodose.

AUC (area under the concentration curve in microdialysate) of ciprofloxacin (macrodose)

In healthy volunteers only for comparison of Cmax of C14 ciprofloxacin and Cmax of ciprofloxacin as macrodose.

Tmax (time of peak concentration in microdialysate) of ciprofloxacin (macrodose)

In healthy volunteers only for comparison of Cmax of C14 ciprofloxacin and Cmax of ciprofloxacin as macrodose.

Secondary Outcome Measures

Incidence of Treatment Emergent Adverse Events

Incidence of Treatment Emergent Adverse Events (Study drugs: ciprofloxacin, 14C labelled ciprofloxacin and imipenem)

Full Information

NCT ID

NCT03177720

First Posted

May 30, 2017

Last Updated

August 31, 2021

Sponsor

Medical University of Vienna

1. Study Identification

Unique Protocol Identification Number

NCT03177720

Brief Title

Evaluation of Innovative Tools in Development of Antibiotics

Official Title

Determination of Single-dose Intrapulmonary Pharmacokinetics of Ciprofloxacin and Imipenem in Healthy Subjects and Intubated Patients Suffering From Pneumonia Using Bronchoalveolar Lavage

Study Type

Interventional

2. Study Status

Record Verification Date

August 2021

Overall Recruitment Status

Completed

Study Start Date

May 29, 2016 (Actual)

Primary Completion Date

July 31, 2021 (Actual)

Study Completion Date

July 31, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Medical University of Vienna

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

The investigators will determine the difference of pharmacokinetics of ciprofloxacin and imipenem between healthy volunteers and intensive care patients suffering from pneumonia in plasma and at the target site - lung - using bronchoalveolar lavage. As additional aspect the feasibility of combining microdosing of C14 ciprofloxacin with microdialysis, saliva sampling and bronchoalveolar lavage is studied by comparing pharmacokinetics of microdose and macrodose.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pneumonia

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Model Description

24 patients and 18 healthy volunteers are included. 12 patients and 9 volunteers are receiving imipenem as study drug, the other 12 patients and 9 volunteers receive ciprofloxacin.

Masking

None (Open Label)

Allocation

Randomized

Enrollment

10 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ciprofloxacin

Arm Type

Active Comparator

Arm Description

Half of patients and healthy volunteers are receiving ciprofloxacin, the other half imipenem.

Arm Title

Imipenem

Arm Type

Active Comparator

Arm Description

Half of patients and healthy volunteers are receiving ciprofloxacin, the other half imipenem.

Intervention Type

Drug

Intervention Name(s)

Ciprofloxacin

Intervention Description

Ciprofloxacin 400mg will be administered as single dose infusion over 60 minutes, imipenem/cilastatin 1000mg as single intravenous dose applicated over 60 minutes.

Intervention Type

Drug

Intervention Name(s)

Imipenem

Intervention Description

Ciprofloxacin 400mg will be administered as single dose infusion over 60 minutes, imipenem/cilastatin 1000mg as single intravenous dose applicated over 60 minutes.

Primary Outcome Measure Information:

Title

Cmax (peak concentration in plasma and epithelial lining fluid) of imipenem and ciprofloxacin

Description

Time Frame

Plasma over 10 hours and BAL (bronchoalveolar lavage) Sampling at different time points in these 10 hours.

Title

AUC (area under the concentration curve in plasma and epithelial lining fluid) of imipenem and ciprofloxacin.

Description

Time Frame

Plasma over 10 hours and BAL Sampling at different time points in these 10 hours.

Title

Tmax (time of peak concentration in plasma and epithelial lining fluid) of imipenem and ciprofloxacin.

Description

Time Frame

Plasma over 10 hours and BAL Sampling at different time points in these 10 hours.

Title

Cmax (peak concentration in plasma, epithelial lining fluid and microdialysate) of C14 ciprofloxacin (microdose)

Description

Comparison of pharmacokinetics of microdoses and macrodoses in lung, subcutaneous tissue (microdialysis) and plasma in healthy volunteers.

Time Frame

Plasma sampling over 10 hours and microdialysate sampling.

Title

AUC (area under the curve in plasma, epithelial lining fluid and microdialysate) of C14 ciprofloxacin (carbon-14 radiolabelled compound, microdose)

Description

Comparison of pharmacokinetics of microdoses and macrodoses in lung, subcutaneous tissue (microdialysis) and plasma in healthy volunteers.

Time Frame

Plasma sampling over 10 hours and microdialysate sampling.

Title

Tmax (time of peak concentration in plasma, epithelial lining fluid and microdialysate) of C14 ciprofloxacin (microdose)

Description

Comparison of pharmacokinetics of microdoses and macrodoses in lung, subcutaneous tissue (microdialysis) and plasma in healthy volunteers.

Time Frame

Plasma sampling over 10 hours and microdialysate sampling.

Title

Cmax (peak concentration in microdialysate) of ciprofloxacin (macrodose)

Description

In healthy volunteers only for comparison of Cmax of C14 ciprofloxacin and Cmax of ciprofloxacin as macrodose.

Time Frame

Microdialysate sampling (Baseline sampling before study drug administration - sampling over 3 hours - retrodialysis)

Title

AUC (area under the concentration curve in microdialysate) of ciprofloxacin (macrodose)

Description

In healthy volunteers only for comparison of Cmax of C14 ciprofloxacin and Cmax of ciprofloxacin as macrodose.

Time Frame

Microdialysate sampling (Baseline sampling before study drug administration - sampling over 3 hours - retrodialysis)

Title

Tmax (time of peak concentration in microdialysate) of ciprofloxacin (macrodose)

Description

In healthy volunteers only for comparison of Cmax of C14 ciprofloxacin and Cmax of ciprofloxacin as macrodose.

Time Frame

Microdialysate sampling (Baseline sampling before study drug administration - sampling over 3 hours - retrodialysis)

Secondary Outcome Measure Information:

Title

Incidence of Treatment Emergent Adverse Events

Description

Incidence of Treatment Emergent Adverse Events (Study drugs: ciprofloxacin, 14C labelled ciprofloxacin and imipenem)

Time Frame

Screening visit and final examination are performed up to 7 days before/after the actual study day and safety and tolerability assessed.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Healthy male subjects aged 18 to 55 years Good state of health (mentally and physically) Body mass index within a range of 18 to 28kg/m2 inclusive. Non-Smoker A signed and dated written informed consent form. The subject is able to understand and willing to comply with protocol requirements and timetables, instructions and protocol-stated restrictions. Negative serology (human immunodeficiency virus, hepatitis B-AG and C-AB) at screening. Vital signs should be within the following ranges: Oral or tympanic temperature between 35 and 37.5°C. Systolic blood pressure, 90-140 mmHg. Diastolic blood pressure, 50-90 mmHg. Pulse rate, 50-90 bpm. Exclusion Criteria: Any acute or chronic illness or clinically relevant (Investigator's judgement) abnormality identified on the screening medical assessment, laboratory tests or ECG, unless in the opinion of the Investigator it will not interfere with the study procedures, affect the outcome of the study or compromise the safety of the subject. All subjects with known seizure disorder, with the exception of a febrile seizure in childhood Use of prescription or non-prescription drugs within 7 days or 10 times the elimination half-life (whichever is longer) prior to the first dose of study medication. Any intake of grapefruit juice within 1 week prior to the first dose. Allergies (except for mild forms of hay fever), a history of hypersensitivity reactions including psychological or neurological symptoms or signs, or anaphylactic shock following administration of any medicine. Allergy to or any contraindication against the active or inactive ingredients in the study medication (ciprofloxacin, imipenem, cilastatin, propofol, midazolam, remifentanil, xylocain, and sevoflurane) and radioactive labelling with 14C. Smoker Alcohol or drug abuse Participation in a trial with any drug within 30 days or five half-lives (whichever is longer) before the start of the study. Donation of blood within a period of 4 weeks prior to dosing. Creatinine clearance ≤70mL/min/1.73m3 Any other reason that the Investigator considers to make the subject unsuitable to participate.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Markus Zeitlinger, MD

Organizational Affiliation

Medical University of Vienna

Official's Role

Principal Investigator

Facility Information:

Facility Name

Medical University of Vienna

City

Vienna

ZIP/Postal Code

1090

Country

Austria

12. IPD Sharing Statement

Citations:

PubMed Identifier

34997559

Citation

Oesterreicher Z, Eberl S, Wulkersdorfer B, Matzneller P, Eder C, van Duijn E, Vaes WHJ, Reiter B, Stimpfl T, Jager W, Nussbaumer-Proell A, Marhofer D, Marhofer P, Langer O, Zeitlinger M. Microdosing as a Potential Tool to Enhance Clinical Development of Novel Antibiotics: A Tissue and Plasma PK Feasibility Study with Ciprofloxacin. Clin Pharmacokinet. 2022 May;61(5):697-707. doi: 10.1007/s40262-021-01091-1. Epub 2022 Jan 7.

Results Reference

derived

Learn more about this trial

Evaluation of Innovative Tools in Development of Antibiotics

We'll reach out to this number within 24 hrs