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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

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

Condition or disease Intervention/treatment Phase
Healthy Male Volunteers Drug: NXL104 Drug: Ceftaroline Drug: Placebo Infusion Drug: Ceftazidime Drug: Moxifloxacin Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 54 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: 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
Study Start Date : February 2011
Actual Primary Completion Date : May 2011
Actual Study Completion Date : May 2011


Arm Intervention/treatment
Experimental: CXL104
2000 mg NXL104 + 1500 mg Ceftaroline (IV)
Drug: NXL104
IV Solution

Drug: Ceftaroline
IV Solution

Experimental: CAZ104
Placebo Infusion (saline) + 2000 mg NXL104 + 3000 mg Ceftazidime (IV)
Drug: NXL104
IV Solution

Drug: Placebo Infusion
IV Saline

Drug: Ceftazidime
IV Solution

Active Comparator: Moxifloxacin
Moxifloxacin 400mg (1 tablet)
Drug: Moxifloxacin
Tablet (1)

Placebo Comparator: Placebo
Placebo Infusion (saline)
Drug: Placebo Infusion
IV Saline




Primary Outcome Measures :
  1. 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 ]
  2. 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. ]
  3. 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. ]
  4. 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. ]
  5. 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. ]
  6. 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. ]
  7. 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. ]
  8. 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. ]
  9. 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. ]
  10. 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. ]
  11. 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. ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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. ]
  3. 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. ]
  4. 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. ]
  5. 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. ]
  6. 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. ]
  7. 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. ]
  8. 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. ]
  9. 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. ]
  10. 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. ]
  11. 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. 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 ]
  13. 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 ]
  14. 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 ]
  15. 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 ]
  16. 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 ]
  17. 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 ]
  18. 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 ]
  19. 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 ]
  20. 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 ]
  21. 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 ]
  22. 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 ]
  23. 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 ]
  24. 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. ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01290900


Locations
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United States, Kansas
Research Site
Overland Park, Kansas, United States
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Paul Newell, MD AstraZeneca
Principal Investigator: David Mathews, MD Quintiles, Inc.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Paul Newell / Medical Science Director, AstraZeneca
ClinicalTrials.gov Identifier: NCT01290900    
Other Study ID Numbers: D4280C00007
First Posted: February 7, 2011    Key Record Dates
Last Update Posted: September 1, 2017
Last Verified: August 2017
Keywords provided by Pfizer:
NXL104
CAZ104
Ceftazidime
CXL104
Ceftaroline
Healthy Male Volunteers
Phase 1
OT
Single Dose Study
Additional relevant MeSH terms:
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Moxifloxacin
Ceftazidime
Ceftaroline fosamil
Avibactam
Anti-Bacterial Agents
Anti-Infective Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
beta-Lactamase Inhibitors