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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

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ClinicalTrials.gov Identifier: NCT01290900
Recruitment Status : Completed
First Posted : February 7, 2011
Last Update Posted : September 1, 2017
Sponsor:
Information provided by:
Pfizer

Tracking Information
First Submitted Date  ICMJE February 4, 2011
First Posted Date  ICMJE February 7, 2011
Last Update Posted Date September 1, 2017
Study Start Date  ICMJE February 2011
Actual Primary Completion Date May 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 4, 2011)
  • 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 ]
  • 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. ]
  • 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. ]
  • 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. ]
  • 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. ]
  • 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. ]
  • 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. ]
  • 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. ]
  • 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. ]
  • 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. ]
  • 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. ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01290900 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 4, 2011)
  • 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 ]
  • 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. ]
  • 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. ]
  • 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. ]
  • 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. ]
  • 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. ]
  • 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. ]
  • 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. ]
  • 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. ]
  • 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. ]
  • 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. ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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. ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
Brief Summary 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
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Condition  ICMJE Healthy Male Volunteers
Intervention  ICMJE
  • Drug: NXL104
    IV Solution
  • Drug: Ceftaroline
    IV Solution
  • Drug: Placebo Infusion
    IV Saline
  • Drug: Ceftazidime
    IV Solution
  • Drug: Moxifloxacin
    Tablet (1)
Study Arms  ICMJE
  • Experimental: CXL104
    2000 mg NXL104 + 1500 mg Ceftaroline (IV)
    Interventions:
    • Drug: NXL104
    • Drug: Ceftaroline
  • Experimental: CAZ104
    Placebo Infusion (saline) + 2000 mg NXL104 + 3000 mg Ceftazidime (IV)
    Interventions:
    • Drug: NXL104
    • Drug: Placebo Infusion
    • Drug: Ceftazidime
  • Active Comparator: Moxifloxacin
    Moxifloxacin 400mg (1 tablet)
    Intervention: Drug: Moxifloxacin
  • Placebo Comparator: Placebo
    Placebo Infusion (saline)
    Intervention: Drug: Placebo Infusion
Publications * Das S, Armstrong J, Mathews D, Li J, Edeki T. Randomized, placebo-controlled study to assess the impact on QT/QTc interval of supratherapeutic doses of ceftazidime-avibactam or ceftaroline fosamil-avibactam. J Clin Pharmacol. 2014 Mar;54(3):331-40. doi: 10.1002/jcph.199. Epub 2013 Oct 22.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 14, 2011)
54
Original Estimated Enrollment  ICMJE
 (submitted: February 4, 2011)
45
Actual Study Completion Date  ICMJE May 2011
Actual Primary Completion Date May 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01290900
Other Study ID Numbers  ICMJE D4280C00007
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Paul Newell / Medical Science Director, AstraZeneca
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Paul Newell, MD AstraZeneca
Principal Investigator: David Mathews, MD Quintiles, Inc.
PRS Account Pfizer
Verification Date August 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP