A Single-centre, Randomised, Double-blind, Placebo-controlled, Four Way Crossover Phase I Study to Investigate the Effect on QT/QTc Interval of Ceftazidime NXL104 or Ceftaroline Fosamil NXL104, Compared With Placebo, Using Moxifloxacin (Avelox®) as a Positive Control, in Healthy Male Volunteers

August 31, 2017 updated by: Pfizer

A Single-centre, Randomised, Double-blind, Placebo-controlled, Four Way Crossover Phase I Study to Investigate the Effect on QT/QTc Interval of a Single Dose of Intravenous Ceftazidime NXL104 (3000/2000 mg) or Ceftaroline Fosamil NXL104 (1500/2000 mg), Compared With Placebo, Using Open-label Moxifloxacin (Avelox®) as a Positive Control, in Healthy Male Volunteers

This is a single dose study in healthy male volunteers to investigate the effect of high doses of ceftazidime NXL104 (CAZ104) or ceftaroline fosamil NXL104 (CXL104) on the QT interval

Study Overview

Study Type

Interventional

Enrollment (Actual)

54

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Kansas
      • Overland Park, Kansas, United States
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Provision of signed informed consent prior to any study specific procedures
  • Healthy male volunteers aged 18 to 45 years (inclusive) with suitable veins for cannulation or repeated venepuncture
  • Have a body mass index (BMI) between 19 and 30 kg/m2 and a body weight between 60 and 100 kg
  • Be a non-smoker or ex-smoker who has stopped smoking (or using other nicotine products) for more than 3 months prior to the start of the study

Exclusion Criteria:

  • History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer's ability to participate in the study
  • Any clinically significant abnormalities in physical examination, clinical chemistry, haematology or urinalysis results as judged by the Investigator
  • Abnormal vital signs, after 10 minutes supine rest, defined as any of the following: Systolic blood pressure (SBP) greater than 140 mmHg, Diastolic blood pressure (DBP) greater than 90 mmHg, Heart rate less than 40 or greater than 85 beats per minute - at Visit 1
  • Prolonged QTcF >450 ms or shortened QTcF <340 ms
  • Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG that may interfere with the interpretation of QTc interval changes. This includes volunteers with any of the following: Clinically significant PR (PQ) interval prolongation, Intermittent second or third degree AV block (Mobitz II type 1, Wenchebach during sleep is not disqualifying), Incomplete, full or intermittent bundle branch block (QRS less than 110 ms with normal QRS and T wave morphology is acceptable if there is no evidence of left ventricular hypertrophy), Abnormal T wave morphology, particularly in the protocol defined primary lead

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CXL104
2000 mg NXL104 + 1500 mg Ceftaroline (IV)
IV Solution
IV Solution
Experimental: CAZ104
Placebo Infusion (saline) + 2000 mg NXL104 + 3000 mg Ceftazidime (IV)
IV Solution
IV Saline
IV Solution
Active Comparator: Moxifloxacin
Moxifloxacin 400mg (1 tablet)
Tablet (1)
Placebo Comparator: Placebo
Placebo Infusion (saline)
IV Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To investigate the effect of supratherapeutic doses of ceftazidime NXL104 (CAZ104) or ceftaroline fosamil NXL104 (CXL104) on the QT interval (QTcF).
Time Frame: 12-lead dECG will be performed pre-dose
12-lead dECG will be performed pre-dose
To investigate the effect of supratherapeutic doses of ceftazidime NXL104 (CAZ104) or ceftaroline fosamil NXL104 (CXL104) on the QT interval (QTcF).
Time Frame: 12-lead dECG at 30 min after starting dosing.
12-lead dECG at 30 min after starting dosing.
To investigate the effect of supratherapeutic doses of ceftazidime NXL104 (CAZ104) or ceftaroline fosamil NXL104 (CXL104) on the QT interval (QTcF).
Time Frame: 12-lead dECG at 60 min after starting dosing.
12-lead dECG at 60 min after starting dosing.
To investigate the effect of supratherapeutic doses of ceftazidime NXL104 (CAZ104) or ceftaroline fosamil NXL104 (CXL104) on the QT interval (QTcF).
Time Frame: 12-lead dECG at 90 min after starting dosing.
12-lead dECG at 90 min after starting dosing.
To investigate the effect of supratherapeutic doses of ceftazidime NXL104 (CAZ104) or ceftaroline fosamil NXL104 (CXL104) on the QT interval (QTcF).
Time Frame: 12-lead dECG at 2 hour after starting dosing.
12-lead dECG at 2 hour after starting dosing.
To investigate the effect of supratherapeutic doses of ceftazidime NXL104 (CAZ104) or ceftaroline fosamil NXL104 (CXL104) on the QT interval (QTcF).
Time Frame: 12-lead dECG at 3 hour after starting dosing.
12-lead dECG at 3 hour after starting dosing.
To investigate the effect of supratherapeutic doses of ceftazidime NXL104 (CAZ104) or ceftaroline fosamil NXL104 (CXL104) on the QT interval (QTcF).
Time Frame: 12-lead dECG at 4 hour after starting dosing.
12-lead dECG at 4 hour after starting dosing.
To investigate the effect of supratherapeutic doses of ceftazidime NXL104 (CAZ104) or ceftaroline fosamil NXL104 (CXL104) on the QT interval (QTcF).
Time Frame: 12-lead dECG at 6 hour after starting dosing.
12-lead dECG at 6 hour after starting dosing.
To investigate the effect of supratherapeutic doses of ceftazidime NXL104 (CAZ104) or ceftaroline fosamil NXL104 (CXL104) on the QT interval (QTcF).
Time Frame: 12-lead dECG at 8 hour after starting dosing.
12-lead dECG at 8 hour after starting dosing.
To investigate the effect of supratherapeutic doses of ceftazidime NXL104 (CAZ104) or ceftaroline fosamil NXL104 (CXL104) on the QT interval (QTcF).
Time Frame: 12-lead dECG at 12 hour after starting dosing.
12-lead dECG at 12 hour after starting dosing.
To investigate the effect of supratherapeutic doses of ceftazidime NXL104 (CAZ104) or ceftaroline fosamil NXL104 (CXL104) on the QT interval (QTcF).
Time Frame: 12-lead dECG at 24 hour after starting dosing.
12-lead dECG at 24 hour after starting dosing.

Secondary Outcome Measures

Outcome Measure
Time Frame
To investigate the effect of CAZ104 and CXL104, on additional ECG variables (heart rate, RR, PR, QRS, QT, and QTcB).
Time Frame: 12-lead dECG will be performed pre-dose
12-lead dECG will be performed pre-dose
To investigate the effect of CAZ104 and CXL104, on additional ECG variables (heart rate, RR, PR, QRS, QT, and QTcB).
Time Frame: 12-lead dECG at 30 min after starting dosing.
12-lead dECG at 30 min after starting dosing.
To investigate the effect of CAZ104 and CXL104, on additional ECG variables (heart rate, RR, PR, QRS, QT, and QTcB).
Time Frame: 12-lead dECG at 60 min after starting dosing.
12-lead dECG at 60 min after starting dosing.
To investigate the effect of CAZ104 and CXL104, on additional ECG variables (heart rate, RR, PR, QRS, QT, and QTcB).
Time Frame: 12-lead dECG at 90 min after starting dosing.
12-lead dECG at 90 min after starting dosing.
To investigate the effect of CAZ104 and CXL104, on additional ECG variables (heart rate, RR, PR, QRS, QT, and QTcB).
Time Frame: 12-lead dECG at 2 hour after starting dosing.
12-lead dECG at 2 hour after starting dosing.
To investigate the effect of CAZ104 and CXL104, on additional ECG variables (heart rate, RR, PR, QRS, QT, and QTcB).
Time Frame: 12-lead dECG at 3 hour after starting dosing.
12-lead dECG at 3 hour after starting dosing.
To investigate the effect of CAZ104 and CXL104, on additional ECG variables (heart rate, RR, PR, QRS, QT, and QTcB).
Time Frame: 12-lead dECG at 4 hour after starting dosing.
12-lead dECG at 4 hour after starting dosing.
To investigate the effect of CAZ104 and CXL104, on additional ECG variables (heart rate, RR, PR, QRS, QT, and QTcB).
Time Frame: 12-lead dECG at 6 hour after starting dosing.
12-lead dECG at 6 hour after starting dosing.
To investigate the effect of CAZ104 and CXL104, on additional ECG variables (heart rate, RR, PR, QRS, QT, and QTcB).
Time Frame: 12-lead dECG at 8 hour after starting dosing.
12-lead dECG at 8 hour after starting dosing.
To investigate the effect of CAZ104 and CXL104, on additional ECG variables (heart rate, RR, PR, QRS, QT, and QTcB).
Time Frame: 12-lead dECG at 12 hour after starting dosing.
12-lead dECG at 12 hour after starting dosing.
To investigate the effect of CAZ104 and CXL104, on additional ECG variables (heart rate, RR, PR, QRS, QT, and QTcB).
Time Frame: 12-lead dECG at 24 hour after starting dosing.
12-lead dECG at 24 hour after starting dosing.
To assess the PK of NXL104, ceftaroline, ceftazidime and moxifloxacin by determination where applicable of Cmax, tmax, AUC(0-t), AUC, t½, CL, CL/F, Vss, and Vz/F.
Time Frame: Blood samples will be taken pre-dose
Blood samples will be taken pre-dose
To assess the PK of NXL104, ceftaroline, ceftazidime and moxifloxacin by determination where applicable of Cmax, tmax, AUC(0-t), AUC, t½, CL, CL/F, Vss, and Vz/F.
Time Frame: Blood samples will be taken at 30 min after starting dosing
Blood samples will be taken at 30 min after starting dosing
To assess the PK of NXL104, ceftaroline, ceftazidime and moxifloxacin by determination where applicable of Cmax, tmax, AUC(0-t), AUC, t½, CL, CL/F, Vss, and Vz/F.
Time Frame: Blood samples will be taken at 60 min after starting dosing
Blood samples will be taken at 60 min after starting dosing
To assess the PK of NXL104, ceftaroline, ceftazidime and moxifloxacin by determination where applicable of Cmax, tmax, AUC(0-t), AUC, t½, CL, CL/F, Vss, and Vz/F.
Time Frame: Blood samples will be taken at 75 min after starting dosing
Blood samples will be taken at 75 min after starting dosing
To assess the PK of NXL104, ceftaroline, ceftazidime and moxifloxacin by determination where applicable of Cmax, tmax, AUC(0-t), AUC, t½, CL, CL/F, Vss, and Vz/F.
Time Frame: Blood samples will be taken at 90 min after starting dosing
Blood samples will be taken at 90 min after starting dosing
To assess the PK of NXL104, ceftaroline, ceftazidime and moxifloxacin by determination where applicable of Cmax, tmax, AUC(0-t), AUC, t½, CL, CL/F, Vss, and Vz/F.
Time Frame: Blood samples will be taken at 2 hour after starting dosing
Blood samples will be taken at 2 hour after starting dosing
To assess the PK of NXL104, ceftaroline, ceftazidime and moxifloxacin by determination where applicable of Cmax, tmax, AUC(0-t), AUC, t½, CL, CL/F, Vss, and Vz/F.
Time Frame: Blood samples will be taken at 3 hour after starting dosing
Blood samples will be taken at 3 hour after starting dosing
To assess the PK of NXL104, ceftaroline, ceftazidime and moxifloxacin by determination where applicable of Cmax, tmax, AUC(0-t), AUC, t½, CL, CL/F, Vss, and Vz/F.
Time Frame: Blood samples will be taken at 4 hour after starting dosing
Blood samples will be taken at 4 hour after starting dosing
To assess the PK of NXL104, ceftaroline, ceftazidime and moxifloxacin by determination where applicable of Cmax, tmax, AUC(0-t), AUC, t½, CL, CL/F, Vss, and Vz/F.
Time Frame: Blood samples will be taken at 6 hour after starting dosing
Blood samples will be taken at 6 hour after starting dosing
To assess the PK of NXL104, ceftaroline, ceftazidime and moxifloxacin by determination where applicable of Cmax, tmax, AUC(0-t), AUC, t½, CL, CL/F, Vss, and Vz/F.
Time Frame: Blood samples will be taken at 8 hour after starting dosing
Blood samples will be taken at 8 hour after starting dosing
To assess the PK of NXL104, ceftaroline, ceftazidime and moxifloxacin by determination where applicable of Cmax, tmax, AUC(0-t), AUC, t½, CL, CL/F, Vss, and Vz/F.
Time Frame: Blood samples will be taken at 12 hour after starting dosing
Blood samples will be taken at 12 hour after starting dosing
To assess the PK of NXL104, ceftaroline, ceftazidime and moxifloxacin by determination where applicable of Cmax, tmax, AUC(0-t), AUC, t½, CL, CL/F, Vss, and Vz/F.
Time Frame: Blood samples will be taken at 18 hour after starting dosing
Blood samples will be taken at 18 hour after starting dosing
To assess the PK of NXL104, ceftaroline, ceftazidime and moxifloxacin by determination where applicable of Cmax, tmax, AUC(0-t), AUC, t½, CL, CL/F, Vss, and Vz/F.
Time Frame: Blood samples will be taken at 24 hour after starting dosing.
Blood samples will be taken at 24 hour after starting dosing.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Principal Investigator: David Mathews, MD, Quintiles, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2011

Primary Completion (Actual)

May 1, 2011

Study Completion (Actual)

May 1, 2011

Study Registration Dates

First Submitted

February 4, 2011

First Submitted That Met QC Criteria

February 4, 2011

First Posted (Estimate)

February 7, 2011

Study Record Updates

Last Update Posted (Actual)

September 1, 2017

Last Update Submitted That Met QC Criteria

August 31, 2017

Last Verified

August 1, 2017

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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