Trial Outcomes & Findings for Population Pharmacokinetics and Safety of Intravenous Ceftolozane/Tazobactam in Adult Cystic Fibrosis Patients (NCT NCT02421120)

NCT ID: NCT02421120

Last Updated: 2020-08-04

Results Overview

This outcome determines the clearance of ceftolozane over the 8 hour dosing interval.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 21 participants
• Primary outcome timeframe: 0, 1-1.08, 1.25-1.5, 2-3, 4-5, and 7-8 hours after start of final dose
• Results posted on: 2020-08-04

Participant Flow

Participant milestones

Measure	Ceftolozane/Tazobactam Ceftolozane/Tazobactam 3 grams every 8 hours intravenously for 4-6 doses Ceftolozane/Tazobactam: 1 hour intravenous infusion
Overall Study STARTED	21
Overall Study COMPLETED	20
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure	Ceftolozane/Tazobactam Ceftolozane/Tazobactam 3 grams every 8 hours intravenously for 4-6 doses Ceftolozane/Tazobactam: 1 hour intravenous infusion
Overall Study Adverse Event	1

Baseline Characteristics

Population Pharmacokinetics and Safety of Intravenous Ceftolozane/Tazobactam in Adult Cystic Fibrosis Patients

Baseline characteristics by cohort

Measure	Ceftolozane/Tazobactam n=20 Participants Ceftolozane/Tazobactam 3 grams every 8 hours intravenously for 4-6 doses Ceftolozane/Tazobactam: 1 hour intravenous infusion
Age, Continuous	25.4 years n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	20 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	20 participants n=5 Participants
Weight	53.2 kilograms STANDARD_DEVIATION 8.2 • n=5 Participants
Height	161.8 centimeters STANDARD_DEVIATION 8.29 • n=5 Participants
Creatinine Clearance	117.7 milliliters per minute n=5 Participants

PRIMARY outcome

Timeframe: 0, 1-1.08, 1.25-1.5, 2-3, 4-5, and 7-8 hours after start of final dose

This outcome determines the clearance of ceftolozane over the 8 hour dosing interval.

Outcome measures

Measure	Ceftolozane/Tazobactam n=20 Participants Ceftolozane/Tazobactam 3 grams every 8 hours intravenously for 4-6 doses Ceftolozane/Tazobactam: 1 hour intravenous infusion
Ceftolozane Clearance	4.76 Liters per hour Standard Deviation 1.13

PRIMARY outcome

Timeframe: 0, 1-1.08, 1.25-1.5, 2-3, 4-5, and 7-8 hours after start of final dose

This outcome determines the volume of distribution of ceftolozane over the 8 hour dosing interval.

Outcome measures

Measure	Ceftolozane/Tazobactam n=20 Participants Ceftolozane/Tazobactam 3 grams every 8 hours intravenously for 4-6 doses Ceftolozane/Tazobactam: 1 hour intravenous infusion
Ceftolozane Volume of Distribution (Central Compartment)	7.51 Liters Standard Deviation 2.05

PRIMARY outcome

Timeframe: 0, 1-1.08, 1.25-1.5, 2-3, 4-5, and 7-8 hours after start of final dose

This outcome determines the clearance of tazobactam over the 8 hour dosing interval.

Outcome measures

Measure	Ceftolozane/Tazobactam n=20 Participants Ceftolozane/Tazobactam 3 grams every 8 hours intravenously for 4-6 doses Ceftolozane/Tazobactam: 1 hour intravenous infusion
Tazobactam Clearance	20.51 Liters per hour Standard Deviation 4.41

PRIMARY outcome

Timeframe: 0, 1-1.08, 1.25-1.5, 2-3, 4-5, and 7-8 hours after start of final dose

This outcome determines the volume of distribution of tazobactam over the 8 hour dosing interval.

Outcome measures

Measure	Ceftolozane/Tazobactam n=20 Participants Ceftolozane/Tazobactam 3 grams every 8 hours intravenously for 4-6 doses Ceftolozane/Tazobactam: 1 hour intravenous infusion
Tazobactam Volume of Distribution (Central Compartment)	7.85 Liters Standard Deviation 2.66

SECONDARY outcome

Timeframe: 24 hours

Population: The results of this analysis are based on 5000 simulated patients with the same pharmacokinetics to the 20 enrolled participants.

This simulated outcome indicates the likelihood that ceftolozane will retain drug concentrations above the MIC for >/= 60% of the dosing interval at an MIC of 8 mcg/ml when administered as a 3g (2g ceftolozane/1g tazobactam) every 8 hour dose infused over 1 hour. This analysis is conducted via a Monte Carlo simulation using the population pharmacokinetic parameter estimates and dispersion from the 20 participants who contributed pharmacokinetic data to the study.

Outcome measures

Measure	Ceftolozane/Tazobactam n=20 Participants Ceftolozane/Tazobactam 3 grams every 8 hours intravenously for 4-6 doses Ceftolozane/Tazobactam: 1 hour intravenous infusion
Ceftolozane Probability of Target Attainment at 8 mcg/ml	97.1 percent of simulated population

Adverse Events

Ceftolozane/Tazobactam

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Ceftolozane/Tazobactam n=21 participants at risk Ceftolozane/Tazobactam 3 grams every 8 hours intravenously for 4-6 doses Ceftolozane/Tazobactam: 1 hour intravenous infusion
Respiratory, thoracic and mediastinal disorders Type I Hypersensitivity Reaction	4.8% 1/21 • Number of events 1 • Adverse events were collected over the course of the 3 day study. Laboratory (chemistry, complete blood count, liver function tests, urinalysis) were completed systematically prior to first dose and within 24 hours after completion of the final pharmacokinetic blood sample. All other adverse events collected when reported by the participant or during daily physical examination.
Skin and subcutaneous tissue disorders Erythema	4.8% 1/21 • Number of events 1 • Adverse events were collected over the course of the 3 day study. Laboratory (chemistry, complete blood count, liver function tests, urinalysis) were completed systematically prior to first dose and within 24 hours after completion of the final pharmacokinetic blood sample. All other adverse events collected when reported by the participant or during daily physical examination.
General disorders Hypokalemia	9.5% 2/21 • Number of events 2 • Adverse events were collected over the course of the 3 day study. Laboratory (chemistry, complete blood count, liver function tests, urinalysis) were completed systematically prior to first dose and within 24 hours after completion of the final pharmacokinetic blood sample. All other adverse events collected when reported by the participant or during daily physical examination.
Hepatobiliary disorders Liver Function Test Elevation	4.8% 1/21 • Number of events 1 • Adverse events were collected over the course of the 3 day study. Laboratory (chemistry, complete blood count, liver function tests, urinalysis) were completed systematically prior to first dose and within 24 hours after completion of the final pharmacokinetic blood sample. All other adverse events collected when reported by the participant or during daily physical examination.
Reproductive system and breast disorders Vaginal Itching	4.8% 1/21 • Number of events 1 • Adverse events were collected over the course of the 3 day study. Laboratory (chemistry, complete blood count, liver function tests, urinalysis) were completed systematically prior to first dose and within 24 hours after completion of the final pharmacokinetic blood sample. All other adverse events collected when reported by the participant or during daily physical examination.

Additional Information

Dr. Joseph L. Kuti, PharmD

Hartford Hospital

Phone: 860-972-3612

Email: joseph.kuti@hhchealth.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place