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

Pfizer

Status and phase: Completed; Phase 1

Conditions: Healthy Male Volunteers

Treatments: Drug: Ceftazidime; Drug: NXL104; Drug: Moxifloxacin; Drug: Placebo Infusion; Drug: Ceftaroline

Study type: Interventional

Funder types: Industry

Identifiers

NCT01290900

D4280C00007

Details and patient eligibility

About

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

Enrollment: 54 patients

Sex: Male

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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54 participants in 4 patient groups, including a placebo group

CXL104

Experimental group

Description:

2000 mg NXL104 + 1500 mg Ceftaroline (IV)

Treatment:

Drug: Ceftaroline

Drug: NXL104

CAZ104

Experimental group

Description:

Placebo Infusion (saline) + 2000 mg NXL104 + 3000 mg Ceftazidime (IV)

Treatment:

Drug: Placebo Infusion

Drug: NXL104

Drug: Ceftazidime

Moxifloxacin

Active Comparator group

Description:

Moxifloxacin 400mg (1 tablet)

Treatment:

Drug: Moxifloxacin

Placebo

Placebo Comparator group

Description:

Placebo Infusion (saline)

Treatment:

Drug: Placebo Infusion