Evaluation of Ceftaroline Fosamil vs Vancomycin Plus Aztreonam in the Treatment of Patients With Skin Infections.

Study identifier:D3720C00001sub

ClinicalTrials.gov identifier:NCT02202135

EudraCT identifier:N/A

CTIS identifier:N/A

Terminated/Withdrawn

Official Title

A Phase III, Multicentre, Randomised, Double-Blind Comparative Study to Evaluate the Efficacy and Safety of Ceftaroline Fosamil (600 mg every 8 hours) vs Vancomycin Plus Aztreonam in the Treatment of Patients with Complicated Bacterial Skin and Soft Tissue Infections With Evidence of Systemic Inflammatory Response or Underlying Comorbidities.

Medical condition

Complicated skin and soft tissue infection

Phase

Phase 3

Healthy volunteers

Study drug

Ceftaroline fosamil, Vancomycin, Aztreonam

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 99 Years

Date

Study Start Date: 01 Jun 2014

Primary Completion Date: 01 Jan 2015

Study Completion Date: 01 Jan 2015

Study design

Allocation: Randomized
Endpoint Classification: Safety
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Mar 2016 by AstraZeneca

Collaborators

Cerexa, Inc.

Inclusion and exclusion criteria

Location

Research site

Cordoba, Argentina

Location

Research site

Salvador, Bahia, Brazil

Location

Research site

Sao Jose do Rio Preto, Brazil

Location

Research site

Passo Fundo, Rio Grande Do Sul, Brazil

Location

Research site

Pleven, Bulgaria

Location

Research site

Temuco, Chile

Location

Research site

Zagreb, Croatia

Location

Research site

Athens, Greece

Arms	Assigned Interventions
Experimental: Ceftaroline fosamil Patients will receive 600 mg of ceftaroline fosamil administered as a 120-minute intravenous infusion very 8 hours. Each dose will be infused in a volume of 250 mL over 120-minutes followed by aztreonam placebo in a volume of 100 mL infused over 30 minutes every 8 hours. In addition vancomycin placebo will be given in a volume of 250 mL infused over 120 minutes every 12 hours. Doses will be adjusted according to the patient's renal function.	Drug: Ceftaroline fosamil IV ceftaroline 600mg every 8 hours
Active Comparator: Vancomycin plus aztreonam Patients will receive combination of vancomycin plus aztreonam. Dose of vancomycin will be based on the patient's actual weight and will receive intravenous vancomycin every 12 hours with each dose infused over 120-minutes. Aztreonam dose will be 1 gram intravenously in a volume of 100 mL infused over 30 minutes every 8 hours. In addition, ceftaroline fosamil placebo will be given in a volume of 250 mL infused over 120 minutes every 8 hours. Doses adjusted according to patients renal function	Drug: Vancomycin IV vancomycin 15mg/kg every 12 hours Drug: Aztreonam IV aztreonam 1 g every 8 hours

Arms

Assigned Interventions

Experimental: Ceftaroline fosamil
Patients will receive 600 mg of ceftaroline fosamil administered as a 120-minute intravenous infusion very 8 hours. Each dose will be infused in a volume of 250 mL over 120-minutes followed by aztreonam placebo in a volume of 100 mL infused over 30 minutes every 8 hours. In addition vancomycin placebo will be given in a volume of 250 mL infused over 120 minutes every 12 hours. Doses will be adjusted according to the patient's renal function.

Drug: Ceftaroline fosamil
IV ceftaroline 600mg every 8 hours

Active Comparator: Vancomycin plus aztreonam
Patients will receive combination of vancomycin plus aztreonam. Dose of vancomycin will be based on the patient's actual weight and will receive intravenous vancomycin every 12 hours with each dose infused over 120-minutes. Aztreonam dose will be 1 gram intravenously in a volume of 100 mL infused over 30 minutes every 8 hours. In addition, ceftaroline fosamil placebo will be given in a volume of 250 mL infused over 120 minutes every 8 hours. Doses adjusted according to patients renal function

Drug: Vancomycin
IV vancomycin 15mg/kg every 12 hours

Drug: Aztreonam
IV aztreonam 1 g every 8 hours

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Overall, 4 patients were enrolled from 2 centres in 1 regions in this study. The first patient was enrolled on 15 September 2014 and the last patient last visit was on 02 January 2015.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
None

Reporting Groups

	Description
Ceftaroline	Ceftaroline fosamil 600 mg 120 min

Participant Flow: Overall Study

	Ceftaroline
STARTED	4
COMPLETED	4
NOT COMPLETED	0

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Randomized patients

Reporting Groups

	Description
Ceftaroline	Ceftaroline fosamil 600 mg 120 min

Baseline Measures

	Ceftaroline
Number of Participants [units: Participants]	4
Age Continuous [units: years] Mean ± Standard Deviation	80.25 ± 4.875
Gender, Male/Female [units: Participant]
Female	4
Male	0
Race (NIH/OMB) [units: Participant]
American Indian or Alaska Native	0
Asian	0
Native Hawaiian or Other Pacific Islander	0
Black or African American	0
White	4
More than one race	0
Unknown or Not Reported	0

Outcome Measures

1. Primary Outcome Measure: Clinical response at TOC [ Time Frame: 7 to 20 days after last dose of study drug ]

Measure Type	Primary
Measure Name	Clinical response at TOC
Measure Description	Clinical cure is defined as resolution or improvement of signs and symptoms compared to baseline and no further antimicrobial therapy is necessary. Clinical failure is defined as any of the following: persistence or worsening in signs or symptoms, or requirement for concomitant antibiotic therapy, or requirement of an unplanned surgical intervention >48 hours after the first dose, or death caused by skin infection, or an AE leading to study drug discontinuation with alternative antimicrobial therapy required, or diagnosis of osteomyelitis >=8 days after the first dose.
Time Frame	7 to 20 days after last dose of study drug
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Randomized

Reporting Groups

	Description
Ceftaroline	Ceftaroline fosamil 600 mg 120 min

Measured Values

	Ceftaroline
Number of Participants Analyzed [units:participants]	4
Clinical response at TOC [units: Participant]
Clinical cure	3
Clinical failure	0
Indeterminate	1

No statistical analysis provided for Clinical response at TOC

Serious Adverse Events

Time Frame	Adverse events were collected from time of the first dose of study drug up to TOC visit (8 to 15 days after the last dose). Serious AEs were collected from time of signature of informed consent up to the LFU visit (21 to 35 days after the last dose).
Additional Description	No text entered.

Reporting Groups

	Description
Ceftaroline	Ceftaroline fosamil 600 mg 120 min

Serious Adverse Events

Ceftaroline

Total, serious adverse events

# participants affected / at risk

1/4 (25.00%)

Infections and infestations

Pneumonia¹,^†
SAE started at 12:00 pm on and resolved at 13:00 pm on 2014-08-08. It was reported as important medical event which was assessed as moderate and unrelated to study drug.

# participants affected / at risk

1/4 (25.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 17.0

Other Adverse Events

Time Frame	Adverse events were collected from time of the first dose of study drug up to TOC visit (8 to 15 days after the last dose). Serious AEs were collected from time of signature of informed consent up to the LFU visit (21 to 35 days after the last dose).
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Ceftaroline	Ceftaroline fosamil 600 mg 120 min

Other Adverse Events

Ceftaroline

Total, other (not including serious) adverse events

# participants affected / at risk

3/4 (75.00%)

Skin and subcutaneous tissue disorders

Rash generalised¹,^†

# participants affected / at risk

1/4 (25.00%)

# events

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

1/4 (25.00%)

# events

Infections and infestations

Urinary tract¹,^†

# participants affected / at risk

1/4 (25.00%)

# events

Cardiac disorders

Cardiac failure¹,^†

# participants affected / at risk

1/4 (25.00%)

# events

Infections and infestations

Fungal skin infection¹,^†

# participants affected / at risk

1/4 (25.00%)

# events

Skin and subcutaneous tissue disorders

Dermatitis contact¹,^†

# participants affected / at risk

1/4 (25.00%)

# events

Skin and subcutaneous tissue disorders

Dermatitis allergic¹,^†

# participants affected / at risk

1/4 (25.00%)

# events

Psychiatric disorders

Anxiety¹,^†

# participants affected / at risk

1/4 (25.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 17.0

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: The investigator agrees not to use such Confidential study information and not to disclose them to any other third parties, except that the undersigned shall not be prevented from using or disclosing information: (a) which by written records was previously known; (b) which is now public knowledge, (c) which is lawfully obtained by the undersigned from sources who have a lawful right to disclose such information.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Early termination leading to small number of subjects analyzed.

Results Point of Contact

Name/Title:	Yunxia Lu
Organization:	AstraZeneca-PPD
Phone	910-558-4197
E-mail:	[email protected]

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information

800-236-9933

ClinicalTrialTransparency@astrazeneca.com

Contact Backup

Kenneth Gray

+44 (0)1223 771180

Kenneth.Gray@ppdi.com

Investigators

Principal Investigator

David Melnick

AstraZeneca LP

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research site

Research site

Research site

Research site

Research site

Research site

Research site

Research site

Trial Results Summaries