Trial Outcomes & Findings for Pharmacodynamic of Ceftaroline and Levofloxacin Against Pathogens Associated With Community Acquired Bacterial Pneumonia (NCT NCT01524302)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

12 participants

Primary outcome timeframe

2 hour (levofloxacin) and 12 hour (ceftaroline) after receiving the drug

Results posted on

2016-04-12

Participant Flow

Participant milestones

Participant milestones
Measure	Levofloxacin Pharmacodynamics Levofloxacin: 750 mg QD	Ceftaroline Pharmacodynamics Ceftaroline: 600 mg Q12h
Overall Study STARTED	6	6
Overall Study COMPLETED	6	6
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Levofloxacin n=6 Participants Pharmacodynamics Levofloxacin: 750 mg QD	Ceftaroline n=6 Participants Pharmacodynamics Ceftaroline: 600 mg Q12h	Total n=12 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	3 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Age, Continuous	56 years n=5 Participants	52 years n=7 Participants	54 years n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment United States	6 participants n=5 Participants	6 participants n=7 Participants	12 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Levofloxacin n=12 Participants Pharmacodynamics Levofloxacin: 750 mg QD	Ceftaroline n=12 Participants Pharmacodynamics Ceftaroline: 600 mg Q12h	Log Inhibition of 2.0mg/L MIC Levofloxacin n=12 Participants Measurement of the decrease in organism (Staphylococcus aureus) colony counts following exposure of serum containing Levofloxacin or Ceftaroline	Log Inhibition of 4.0mg/L MIC Levofloxacin n=12 Participants Measurement of the decrease in organism (Staphylococcus aureus) colony counts following exposure of serum containing Levofloxacin or Ceftaroline
Serum Cidal Activity as Tested Against Staphylococcus Aureus Isolates and Reported as Ex-vivo Effect (Log Inhibition of Growth) Levofloxacin	2 Log inhibition	4 Log inhibition	1 Log inhibition	1 Log inhibition
Serum Cidal Activity as Tested Against Staphylococcus Aureus Isolates and Reported as Ex-vivo Effect (Log Inhibition of Growth) Ceftaroline	3 Log inhibition	5 Log inhibition	3 Log inhibition	3 Log inhibition

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Levofloxacin n=6 Participants Pharmacodynamics Levofloxacin: 750 mg QD	Ceftaroline n=6 Participants Pharmacodynamics Ceftaroline: 600 mg Q12h	Log Inhibition of 2.0mg/L MIC Levofloxacin Measurement of the decrease in organism (Staphylococcus aureus) colony counts following exposure of serum containing Levofloxacin or Ceftaroline	Log Inhibition of 4.0mg/L MIC Levofloxacin Measurement of the decrease in organism (Staphylococcus aureus) colony counts following exposure of serum containing Levofloxacin or Ceftaroline
Mean (SD) Ceftaroline and Levofloxacin Pharmacokinetic Volume of Distribution Parameter in Community-Acquired Bacterial Pneumonia Patients	92 Liters Standard Deviation 15	20.6 Liters Standard Deviation 5.2	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Levofloxacin n=6 Participants Pharmacodynamics Levofloxacin: 750 mg QD	Ceftaroline n=6 Participants Pharmacodynamics Ceftaroline: 600 mg Q12h	Log Inhibition of 2.0mg/L MIC Levofloxacin Measurement of the decrease in organism (Staphylococcus aureus) colony counts following exposure of serum containing Levofloxacin or Ceftaroline	Log Inhibition of 4.0mg/L MIC Levofloxacin Measurement of the decrease in organism (Staphylococcus aureus) colony counts following exposure of serum containing Levofloxacin or Ceftaroline
Mean (SD) Doripenem Pharmacokinetic (PK) Clearance of Drug Parameter in Community-Acquired Bacterial Pneumonia Patients	9.4 liters per hour Standard Deviation 3.1	7.3 liters per hour Standard Deviation 1.5	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Levofloxacin n=6 Participants Pharmacodynamics Levofloxacin: 750 mg QD	Ceftaroline n=6 Participants Pharmacodynamics Ceftaroline: 600 mg Q12h	Log Inhibition of 2.0mg/L MIC Levofloxacin Measurement of the decrease in organism (Staphylococcus aureus) colony counts following exposure of serum containing Levofloxacin or Ceftaroline	Log Inhibition of 4.0mg/L MIC Levofloxacin Measurement of the decrease in organism (Staphylococcus aureus) colony counts following exposure of serum containing Levofloxacin or Ceftaroline
Mean (SD) Ceftaroline and Levofloxacin Pharmacokinetic (PK) Half Life Parameter in Community-Acquired Bacterial Pneumonia Patients	7.2 hours Standard Deviation 1.4	1.9 hours Standard Deviation 0.2	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Levofloxacin n=6 Participants Pharmacodynamics Levofloxacin: 750 mg QD	Ceftaroline n=6 Participants Pharmacodynamics Ceftaroline: 600 mg Q12h	Log Inhibition of 2.0mg/L MIC Levofloxacin Measurement of the decrease in organism (Staphylococcus aureus) colony counts following exposure of serum containing Levofloxacin or Ceftaroline	Log Inhibition of 4.0mg/L MIC Levofloxacin Measurement of the decrease in organism (Staphylococcus aureus) colony counts following exposure of serum containing Levofloxacin or Ceftaroline
Mean (SD) Doripenem Pharmacokinetic (PK) Area Under Serum Curve (mg*h/L) Parameter in Community-Acquired Bacterial Pneumonia Patients.	87 mg*hr/L Standard Deviation 23	90 mg*hr/L Standard Deviation 15	—	—

Adverse Events

Levofloxacin

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Ceftaroline

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Gary E. Stein

Michigan State University

Phone: 517-353-5126

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place