Pharmacodynamic of Ceftaroline and Levofloxacin Against Pathogens Associated With Community Acquired Bacterial Pneumonia

• Sponsor: Gary E. Stein, Pharm.D. (Other)
• Overall Status: Completed
• CT.gov ID: NCT01524302
• Collaborator: Forest Laboratories (Industry)
• Enrollment: 12
• Location: 1
• Arms: 2
• Duration (Months): 37.9
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This study will further analyze the use of ceftaroline for CABP and compare its potential to eradicate bacterial pathogens to standard fluoroquinolone therapy. The enhanced spectrum of ceftaroline compared to levofloxacin may be further highlighted from this investigation.

Condition or Disease	Intervention/Treatment	Phase
Pneumonia, Bacterial; Community-acquired	Drug: Ceftaroline; Drug: Levofloxacin	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pharmacodynamic of Ceftaroline and Levofloxacin Against Pathogens Associated With Community Acquired Bacterial Pneumonia (CABP)
• Study Start Date: Feb 1, 2012
• Actual Primary Completion Date: May 1, 2014
• Actual Study Completion Date: Apr 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Levofloxacin Pharmacodynamics	Drug: Levofloxacin; 750 mg QD; Other Names: Levaquin
Active Comparator: Ceftaroline Pharmacodynamics	Drug: Ceftaroline; 600 mg Q12h; Other Names: Teflaro

Outcome Measures

Primary Outcome Measures

1. Serum Cidal Activity as Tested Against Staphylococcus Aureus Isolates and Reported as Ex-vivo Effect (Log Inhibition of Growth) [2 hour (levofloxacin) and 12 hour (ceftaroline) after receiving the drug]

   Serum cidal activity of serum collected at 2 hour (levofloxacin) and 12 hour (ceftaroline) time points from the patients was tested against methyicillin-sensitive staphylococcus aureus isolates and the ex-vivo effect reported as log inhibition (logrithmic measurement of the decrease in microbiological growth). These staphylococcus aureus isolates had a range of minimum inhibitory concentrations (MIC) to Levofloxacin, 0.5, 1.0, 2.0, and 4.0 and the MIC's to Ceftaroline were 0.125, 0.19, 0.094, 0.094, respectively.

Secondary Outcome Measures

1. Mean (SD) Ceftaroline and Levofloxacin Pharmacokinetic Volume of Distribution Parameter in Community-Acquired Bacterial Pneumonia Patients [2, 6 and 12 hours after at least 2 days of treatment and a 1-hr antibiotic infusion]

   To determine the serum pharmacokinetic volume of distribution of ceftaroline and levofloxacin in community-acquired bacterial pneumonia patients. We obtained blood at 2, 6 and 12 hours after at least 2 days of treatment and a 1-hr antibiotic infusion and measured these levels (mg/L)by LC/MS/MS assay.

2. Mean (SD) Doripenem Pharmacokinetic (PK) Clearance of Drug Parameter in Community-Acquired Bacterial Pneumonia Patients [2, 6 and 12 hours after at least 2 days of treatment and a 1-hr antibiotic infusion]

   To determine the serum pharmacokinetic clearance of drug parameter of ceftaroline and levofloxacin in community-acquired bacterial pneumonia patients. We obtained blood at 2, 6 and 12 hours after at least 2 days of treatment and a 1-hr antibiotic infusion and measured these levels (mg/L)by LC/MS/MS assay.

3. Mean (SD) Ceftaroline and Levofloxacin Pharmacokinetic (PK) Half Life Parameter in Community-Acquired Bacterial Pneumonia Patients [2, 6 and 12 hours after at least 2 days of treatment and a 1-hr antibiotic infusion]

   To determine the serum pharmacokinetic half life parameter of ceftaroline and levofloxacin in community-acquired bacterial pneumonia patients. We obtained blood at 2, 6 and 12 hours after at least 2 days of treatment and a 1-hr antibiotic infusion and measured these levels (mg/L)by LC/MS/MS assay.

4. Mean (SD) Doripenem Pharmacokinetic (PK) Area Under Serum Curve (mg*h/L) Parameter in Community-Acquired Bacterial Pneumonia Patients. [2, 6 and 12 hours after at least 2 days of treatment and a 1-hr antibiotic infusion]

   To determine the serum pharmacokinetic Area Under Serum Curve parameter of ceftaroline and levofloxacin in community-acquired bacterial pneumonia patients. We obtained blood at 2, 6 and 12 hours after at least 2 days of treatment and a 1-hr antibiotic infusion and measured these levels (mg/L)by LC/MS/MS assay.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• non-pregnant adults (≥ 18 years old) with suspected CABP admitted to the hospital for parenteral antibiotic therapy.

• All patients will have a creatinine clearance (CrCl) >50 ml/min.

Exclusion Criteria:

• pregnant or nursing patients,

• allergy to penicillin/cephalosporin antibiotics,

• allergy to fluoroquinolones,

• renal or hepatic failure, or have received an antimicrobial in past 96h.

• Patients who require antibiotics other than the study drugs will also be excluded.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sparrow Hospital	Lansing	Michigan	United States

Sponsors and Collaborators

• Gary E. Stein, Pharm.D.
• Forest Laboratories

Investigators

• Principal Investigator: Gary E Stein, Pharm.D., Michigan State University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gary E. Stein, Pharm.D., Professor of Medicine and Pharmacology, Michigan State University
• ClinicalTrials.gov Identifier: NCT01524302
• Other Study ID Numbers: TEF-MD-02
• First Posted: Feb 1, 2012
• Last Update Posted: Apr 12, 2016
• Last Verified: Mar 1, 2016

• Keywords provided by Gary E. Stein, Pharm.D., Professor of Medicine and Pharmacology, Michigan State University: pneumonia; ceftaroline; community-aquired
• Additional relevant MeSH terms: Pneumonia; Pneumonia, Bacterial; Levofloxacin; Ofloxacin; Ceftaroline fosamil

Study Results

Participant Flow

Arm/Group Title	Levofloxacin	Ceftaroline
Arm/Group Description	Pharmacodynamics Levofloxacin: 750 mg QD	Pharmacodynamics Ceftaroline: 600 mg Q12h
Period Title: Overall Study
STARTED	6	6
COMPLETED	6	6
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Levofloxacin	Ceftaroline	Total
Arm/Group Description	Pharmacodynamics Levofloxacin: 750 mg QD	Pharmacodynamics Ceftaroline: 600 mg Q12h	Total of all reporting groups
Overall Participants	6	6	12
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	3 50%	6 100%	9 75%
>=65 years	3 50%	0 0%	3 25%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	56	52	54
Sex: Female, Male (Count of Participants)
Female	4 66.7%	5 83.3%	9 75%
Male	2 33.3%	1 16.7%	3 25%
Region of Enrollment (participants) [Number]
United States	6 100%	6 100%	12 100%

Outcome Measures

1. Secondary Outcome

Title	Mean (SD) Ceftaroline and Levofloxacin Pharmacokinetic Volume of Distribution Parameter in Community-Acquired Bacterial Pneumonia Patients
Description	To determine the serum pharmacokinetic volume of distribution of ceftaroline and levofloxacin in community-acquired bacterial pneumonia patients. We obtained blood at 2, 6 and 12 hours after at least 2 days of treatment and a 1-hr antibiotic infusion and measured these levels (mg/L)by LC/MS/MS assay.
Time Frame	2, 6 and 12 hours after at least 2 days of treatment and a 1-hr antibiotic infusion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levofloxacin	Ceftaroline
Arm/Group Description	Pharmacodynamics Levofloxacin: 750 mg QD	Pharmacodynamics Ceftaroline: 600 mg Q12h
Measure Participants	6	6
Mean (Standard Deviation) [Liters]	92 (15)	20.6 (5.2)

2. Secondary Outcome

Title	Mean (SD) Doripenem Pharmacokinetic (PK) Clearance of Drug Parameter in Community-Acquired Bacterial Pneumonia Patients
Description	To determine the serum pharmacokinetic clearance of drug parameter of ceftaroline and levofloxacin in community-acquired bacterial pneumonia patients. We obtained blood at 2, 6 and 12 hours after at least 2 days of treatment and a 1-hr antibiotic infusion and measured these levels (mg/L)by LC/MS/MS assay.
Time Frame	2, 6 and 12 hours after at least 2 days of treatment and a 1-hr antibiotic infusion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levofloxacin	Ceftaroline
Arm/Group Description	Pharmacodynamics Levofloxacin: 750 mg QD	Pharmacodynamics Ceftaroline: 600 mg Q12h
Measure Participants	6	6
Mean (Standard Deviation) [liters per hour]	9.4 (3.1)	7.3 (1.5)

3. Secondary Outcome

Title	Mean (SD) Ceftaroline and Levofloxacin Pharmacokinetic (PK) Half Life Parameter in Community-Acquired Bacterial Pneumonia Patients
Description	To determine the serum pharmacokinetic half life parameter of ceftaroline and levofloxacin in community-acquired bacterial pneumonia patients. We obtained blood at 2, 6 and 12 hours after at least 2 days of treatment and a 1-hr antibiotic infusion and measured these levels (mg/L)by LC/MS/MS assay.
Time Frame	2, 6 and 12 hours after at least 2 days of treatment and a 1-hr antibiotic infusion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levofloxacin	Ceftaroline
Arm/Group Description	Pharmacodynamics Levofloxacin: 750 mg QD	Pharmacodynamics Ceftaroline: 600 mg Q12h
Measure Participants	6	6
Mean (Standard Deviation) [hours]	7.2 (1.4)	1.9 (0.2)

4. Secondary Outcome

Title	Mean (SD) Doripenem Pharmacokinetic (PK) Area Under Serum Curve (mg*h/L) Parameter in Community-Acquired Bacterial Pneumonia Patients.
Description	To determine the serum pharmacokinetic Area Under Serum Curve parameter of ceftaroline and levofloxacin in community-acquired bacterial pneumonia patients. We obtained blood at 2, 6 and 12 hours after at least 2 days of treatment and a 1-hr antibiotic infusion and measured these levels (mg/L)by LC/MS/MS assay.
Time Frame	2, 6 and 12 hours after at least 2 days of treatment and a 1-hr antibiotic infusion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Levofloxacin	Ceftaroline
Arm/Group Description	Pharmacodynamics Levofloxacin: 750 mg QD	Pharmacodynamics Ceftaroline: 600 mg Q12h
Measure Participants	6	6
Mean (Standard Deviation) [mg*hr/L]	87 (23)	90 (15)

5. Primary Outcome

Title	Serum Cidal Activity as Tested Against Staphylococcus Aureus Isolates and Reported as Ex-vivo Effect (Log Inhibition of Growth)
Description	Serum cidal activity of serum collected at 2 hour (levofloxacin) and 12 hour (ceftaroline) time points from the patients was tested against methyicillin-sensitive staphylococcus aureus isolates and the ex-vivo effect reported as log inhibition (logrithmic measurement of the decrease in microbiological growth). These staphylococcus aureus isolates had a range of minimum inhibitory concentrations (MIC) to Levofloxacin, 0.5, 1.0, 2.0, and 4.0 and the MIC's to Ceftaroline were 0.125, 0.19, 0.094, 0.094, respectively.
Time Frame	2 hour (levofloxacin) and 12 hour (ceftaroline) after receiving the drug

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Log Inhibition of 0.5mg/L MIC Levofloxacin	Log Inhibition of 1.0mg/L MIC Levofloxacin	Log Inhibition of 2.0mg/L MIC Levofloxacin	Log Inhibition of 4.0mg/L MIC Levofloxacin
Arm/Group Description	Measurement of the decrease in organism (Staphylococcus aureus) colony counts following exposure of serum containing Levofloxacin or Ceftaroline	Measurement of the decrease in organism (Staphylococcus aureus) colony counts following exposure of serum containing Levofloxacin or Ceftaroline	Measurement of the decrease in organism (Staphylococcus aureus) colony counts following exposure of serum containing Levofloxacin or Ceftaroline	Measurement of the decrease in organism (Staphylococcus aureus) colony counts following exposure of serum containing Levofloxacin or Ceftaroline
Measure Participants	12	12	12	12
Levofloxacin	2	4	1	1
Ceftaroline	3	5	3	3

Adverse Events

Arm/Group Title	Levofloxacin		Ceftaroline
Arm/Group Description	Pharmacodynamics Levofloxacin: 750 mg QD		Pharmacodynamics Ceftaroline: 600 mg Q12h
All Cause Mortality
	Levofloxacin		Ceftaroline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Levofloxacin		Ceftaroline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Levofloxacin		Ceftaroline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.