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

NCT01290900 | Completed Phase 1

• 1 other identifier: D4280C00007
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

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

Conditions

Healthy Male Volunteers

Keywords

NXL104; CAZ104; Ceftazidime; CXL104; Ceftaroline; Healthy Male Volunteers; Phase 1; OT; Single Dose Study

Outcome Measures

Primary Outcomes (11)

• To investigate the effect of supratherapeutic doses of ceftazidime NXL104 (CAZ104) or ceftaroline fosamil NXL104 (CXL104) on the QT interval (QTcF).

  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).

  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).

  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).

  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).

  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).

  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).

  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).

  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).

  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).

  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).

  12-lead dECG at 24 hour after starting dosing.

Secondary Outcomes (24)

• To investigate the effect of CAZ104 and CXL104, on additional ECG variables (heart rate, RR, PR, QRS, QT, and QTcB).

  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).

  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).

  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).

  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).

  12-lead dECG at 2 hour after starting dosing.

Study Arms (4)

CXL104

EXPERIMENTAL

2000 mg NXL104 + 1500 mg Ceftaroline (IV)

Drug: NXL104; Drug: Ceftaroline

CAZ104

EXPERIMENTAL

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

Drug: NXL104; Drug: Placebo Infusion; Drug: Ceftazidime

Moxifloxacin

ACTIVE COMPARATOR

Moxifloxacin 400mg (1 tablet)

Drug: Moxifloxacin

Placebo

PLACEBO COMPARATOR

Placebo Infusion (saline)

Drug: Placebo Infusion

Interventions

NXL104 DRUG

IV Solution

CAZ104; CXL104

Ceftaroline DRUG

IV Solution

CXL104

Placebo Infusion DRUG

IV Saline

CAZ104; Placebo

Ceftazidime DRUG

IV Solution

CAZ104

Moxifloxacin DRUG

Tablet (1)

Moxifloxacin

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Research Site

Overland Park, Kansas, United States

Location

Related Publications (1)

• 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.

  PMID: 24150927 DERIVED

MeSH Terms

Interventions

avibactam; Ceftaroline; Ceftazidime; Moxifloxacin

Intervention Hierarchy (Ancestors)

Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cephaloridine; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines

Study Officials

• Paul Newell, MD

  AstraZeneca

  STUDY DIRECTOR

• David Mathews, MD

  Quintiles, Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: February 4, 2011
• First Posted: February 7, 2011
• Study Start: February 1, 2011
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: September 1, 2017

Record last verified: 2017-08

Locations

US (1)