A Study of Ceftobiprole in Patients With Fever and Neutropenia.

• Sponsor: Basilea Pharmaceutica (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00529282
• Collaborator: (none)
• Enrollment: 2
• Arms: 2
• Duration (Months): 3

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the safety and efficacy of ceftobiprole versus a comparator in patients with fever and neutropenia

Condition or Disease	Intervention/Treatment	Phase
Fever; Neutropenia; Gram-positive Bacterial Infections; Pseudomonas Infection	Drug: Ceftobiprole Medocaril; Drug: Cefepime with or without vancomycin	Phase 3

Detailed Description

This study is being discontinued due to issues regarding the comparator, cefepime. In Nov 2007 FDA issued a MedWatch regarding cefepime and the trial was suspended. As of May 14, 2008 the FDA was still evaluating the data on cefepime and final follow up is pending. There were no safety issues with ceftobiprole in this study based on the enrollment of 2 subjects in September of 2007. The study is being discontinued for administrative reasons. Ceftobiprole medocaril is a cephalosporin antibiotic with anti-MRSA (Methicillin-Resistant Staphylococcus Aureus) activity. Ceftobiprole is not yet approved, but undergoing regulatory review for treatment of skin infections. This is a randomized (patients are assigned to receive the different treatments under study based on chance), double-blind (neither the patient nor the physician knows whether the drug being investigated or the comparator agent is being taken), multicenter study of treatment with ceftobiprole medocaril versus treatment with a comparator in patients 18 years of age or older, who have fever and neutropenia after chemotherapy for cancer that requires intravenous therapy. Patients will be randomly assigned to receive either ceftobiprole medocaril or comparator. In addition, patients in the comparator group who are at risk of serious infections due to gram-positive pathogens (disease-causing bacteria) may also receive an antibiotic with MRSA activity. The study will consist of the following 3 phases: a prerandomization phase (includes screening and baseline assessments); a treatment phase, and a follow-up phase consisting of a primary efficacy visit and a late follow-up visit. The primary endpoint is the clinical cure rate. The total duration of of the study is determined by the time to resolution of fever and neutropenia and the conditions associated with the episode of fever and neutropenia. This is followed by the primary efficacy visit (7 to 10 days after the end of therapy) and the late follow-up visit (28 to 35 days after the end of treatment). Cultures (samples of blood or other suspected sites of infection) will be collected during the study as well as blood samples for hematology and chemistry (safety assessments). All adverse events will also be reported throughout the study and for about 4 to 5 weeks after the last dose of study drug. Patients will be randomized to either ceftobiprole or comparator for approximately 7 to 14 days.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Multicenter, Randomized, Double-Blind Study of Ceftobiprole Versus Comparators in the Treatment of Patients With Fever and Neutropenia
• Study Start Date: Oct 1, 2007
• Actual Primary Completion Date: Jan 1, 2008
• Actual Study Completion Date: Jan 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 001 Ceftobiprole Medocaril 500 mg every 8 hours 120-minute infusion [250 mL]	Drug: Ceftobiprole Medocaril; 500 mg every 8 hours
Active Comparator: 002 Cefepime with or without vancomycin 2 g every 8 hrs-30 min infusion vancomycin 1 000mg every 12 hrs-60 min infusion	Drug: Cefepime with or without vancomycin; 120-minute infusion [250 mL]

Outcome Measures

Primary Outcome Measures

1. Clinical Cure Rate of Ceftobiprole vs Comparator in Patients With Fever and Neutropenia. [7 to 10 days after end of therapy or before 24 hours of the initiation of the next course of chemotherapy, whichever is shorter.]

   Clinical cure rate (the ratio of the number of clinically cured patients to the total number of patients in the population) at 7 to 10 days after end of therapy or before 24 hours of the initiation of the next course of chemotherapy, whichever is shorter. Cure without modification: A subject will be considered to be cured at the primary efficacy visit if: The subject's fever and clinical signs and symptoms are resolved to the extent that no further anti-infective therapy is necessary as determined by the investigator Any infecting organisms that were identified at baseline were eradicated

Secondary Outcome Measures

1. Clinical Cure Regardless of Modification of Therapy [7 to 10 days after end of therapy or before 24 hours of the initiation of the next course of chemotherapy, whichever is shorter.]

   To demonstrate the noninferiority of ceftobiprole compared with cefepime with or without vancomycin with regard to clinical cure at the primary efficacy visit after completing the initial course of therapy, regardless of modification of therapy defined as addition of an anti-fungal agent and/or an aminoglycoside. Cure with modification: The subject requires antifungals, which will be considered a failure for the primary endpoint. The subject needs modification of study therapy by adding one or more agents (other than protocol-defined chemoprophylaxis antibiotics).

2. Clinical Success at 72 Hours [72 hours after starting study drug]

   To compare the clinical success rate (absence or improvement of signs and symptoms of infection) at 72 hours after starting ceftobiprole with that of cefepime with or without vancomycin

3. Clinical Cure Without Prophylactic Antibiotics After the End-of-treatment (EOT) Visit up to 28 Days of Study Drug [7 to 10 days after end of therapy or before 24 hours of the initiation of the next course of chemotherapy, whichever is shorter.]

   To demonstrate the noninferiority of ceftobiprole compared with cefepime with or without vancomycin with regard to clinical cure at the primary efficacy visit after completing the unmodified initial course of therapy, and receiving no prophylactic antibiotics after the EOT visit.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with neutropenia and fever associated with administration of chemotherapy for cancer that requires intravenous therapy with antibiotics.

Exclusion Criteria:

• Patients who have received antibacterial (oral or intravenous ) treatment for more than 24 hours for fever and neutropenia or have received systemic antibacterial therapy in the previous 72 hours for a defined infectious disease

• Patients with known or suspected hypersensitivity to any related anti-infective

• patients with hepatic impairment

• Patients with severe renal impairment

• Patients who are pregnant or lactating

• Patients who are likely to require major surgical intervention for infection.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Basilea Pharmaceutica

Investigators

• Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial, Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Basilea Pharmaceutica
• ClinicalTrials.gov Identifier: NCT00529282
• Other Study ID Numbers: CR014206; CEFTOFBN3004
• First Posted: Sep 14, 2007
• Last Update Posted: Aug 1, 2012
• Last Verified: Jul 1, 2012

• Keywords provided by Basilea Pharmaceutica: Low numbers of neutrophils in the blood; increased body temperature; cancer chemotherapy; ceftobiprole; pseudomonas infections
• Additional relevant MeSH terms: Infections; Communicable Diseases; Bacterial Infections; Pseudomonas Infections; Gram-Positive Bacterial Infections; Neutropenia; Fever; Vancomycin; Cefepime; Ceftobiprole; Ceftobiprole medocaril

Study Results

Participant Flow

Arm/Group Title	Ceftobiprole Medocaril	Cefepime With or Without Vancomycin
Arm/Group Description	500 mg every 8 hours - 120-minute infusion [250 mL]	2 g every 8 hrs-30 min infusion vancomycin 1,000mg every 12 hrs-60 min infusion
Period Title: Overall Study
STARTED	0	2
COMPLETED	0	2
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Ceftobiprole Medocaril	Cefepime With or Without Vancomycin	Total
Arm/Group Description	500 mg every 8 hours - 120-minute infusion [250 mL]	2 g every 8 hrs-30 min infusion vancomycin 1,000mg every 12 hrs-60 min infusion	Total of all reporting groups
Overall Participants	0	2	2
Age (participants) [Number]
<=18 years	0 NaN	0 0%
Between 18 and 65 years	2 Infinity	2 100%
>=65 years	0 NaN	0 0%
Gender (participants) [Number]
Female	1 Infinity	1 50%
Male	1 Infinity	1 50%
Region of Enrollment (participants) [Number]
United States	2 Infinity	2 100%

Outcome Measures

1. Primary Outcome

Title	Clinical Cure Rate of Ceftobiprole vs Comparator in Patients With Fever and Neutropenia.
Description	Clinical cure rate (the ratio of the number of clinically cured patients to the total number of patients in the population) at 7 to 10 days after end of therapy or before 24 hours of the initiation of the next course of chemotherapy, whichever is shorter. Cure without modification: A subject will be considered to be cured at the primary efficacy visit if: The subject's fever and clinical signs and symptoms are resolved to the extent that no further anti-infective therapy is necessary as determined by the investigator Any infecting organisms that were identified at baseline were eradicated
Time Frame	7 to 10 days after end of therapy or before 24 hours of the initiation of the next course of chemotherapy, whichever is shorter.

Outcome Measure Data

Analysis Population Description

No outcome measures were analyzed due to early termination of the study.

Arm/Group Title	Ceftobiprole Medocaril	Cefepime With or Without Vancomycin
Arm/Group Description	500 mg every 8 hours - 120-minute infusion [250 mL]	2 g every 8 hrs-30 min infusion vancomycin 1,000mg every 12 hrs-60 min infusion
Measure Participants	0	0

2. Secondary Outcome

Title	Clinical Cure Regardless of Modification of Therapy
Description	To demonstrate the noninferiority of ceftobiprole compared with cefepime with or without vancomycin with regard to clinical cure at the primary efficacy visit after completing the initial course of therapy, regardless of modification of therapy defined as addition of an anti-fungal agent and/or an aminoglycoside. Cure with modification: The subject requires antifungals, which will be considered a failure for the primary endpoint. The subject needs modification of study therapy by adding one or more agents (other than protocol-defined chemoprophylaxis antibiotics).
Time Frame	7 to 10 days after end of therapy or before 24 hours of the initiation of the next course of chemotherapy, whichever is shorter.

Outcome Measure Data

Analysis Population Description

No outcome measures were analyzed due to early termination of the study.

Arm/Group Title	Ceftobiprole Medocaril	Cefepime With or Without Vancomycin
Arm/Group Description	500 mg every 8 hours - 120-minute infusion [250 mL]	2 g every 8 hrs-30 min infusion vancomycin 1,000mg every 12 hrs-60 min infusion
Measure Participants	0	0

3. Secondary Outcome

Title	Clinical Success at 72 Hours
Description	To compare the clinical success rate (absence or improvement of signs and symptoms of infection) at 72 hours after starting ceftobiprole with that of cefepime with or without vancomycin
Time Frame	72 hours after starting study drug

Outcome Measure Data

Analysis Population Description

No outcome measures were analyzed due to early termination of the study.

Arm/Group Title	Ceftobiprole Medocaril	Cefepime With or Without Vancomycin
Arm/Group Description	500 mg every 8 hours - 120-minute infusion [250 mL]	2 g every 8 hrs-30 min infusion vancomycin 1,000mg every 12 hrs-60 min infusion
Measure Participants	0	0

4. Secondary Outcome

Title	Clinical Cure Without Prophylactic Antibiotics After the End-of-treatment (EOT) Visit up to 28 Days of Study Drug
Description	To demonstrate the noninferiority of ceftobiprole compared with cefepime with or without vancomycin with regard to clinical cure at the primary efficacy visit after completing the unmodified initial course of therapy, and receiving no prophylactic antibiotics after the EOT visit.
Time Frame	7 to 10 days after end of therapy or before 24 hours of the initiation of the next course of chemotherapy, whichever is shorter.

Outcome Measure Data

Analysis Population Description

No outcome measures were analyzed due to early termination of the study.

Arm/Group Title	Ceftobiprole Medocaril	Cefepime With or Without Vancomycin
Arm/Group Description	500 mg every 8 hours - 120-minute infusion [250 mL]	2 g every 8 hrs-30 min infusion vancomycin 1,000mg every 12 hrs-60 min infusion
Measure Participants	0	0

Adverse Events

Time Frame	The first subject completed on day 41 and the second subject completed on day 56.
Arm/Group Title	Ceftobiprole Medocaril		Cefepime With or Without Vancomycin
Arm/Group Description	500 mg every 8 hours - 120-minute infusion [250 mL]		2 g every 8 hrs-30 min infusion vancomycin 1,000mg every 12 hrs-60 min infusion
All Cause Mortality
	Ceftobiprole Medocaril		Cefepime With or Without Vancomycin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ceftobiprole Medocaril		Cefepime With or Without Vancomycin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		2/2 (100%)
Infections and infestations
Bacteraemia	0/0 (NaN)		1/2 (50%)
Sepsis	0/0 (NaN)		1/2 (50%)
Other (Not Including Serious) Adverse Events
	Ceftobiprole Medocaril		Cefepime With or Without Vancomycin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		2/2 (100%)
Blood and lymphatic system disorders
Thrombocytopenia	0/0 (NaN)		1/2 (50%)
Anemia	0/0 (NaN)		1/2 (50%)
Febrile Neutropenia	0/0 (NaN)		1/2 (50%)
Ear and labyrinth disorders
Ear pain	0/0 (NaN)		1/2 (50%)
Gastrointestinal disorders
Anorectal disorder	0/0 (NaN)		1/2 (50%)
Diarrhoea	0/0 (NaN)		1/2 (50%)
Dyspepsia	0/0 (NaN)		1/2 (50%)
Constipation	0/0 (NaN)		2/2 (100%)
Stomatitis	0/0 (NaN)		1/2 (50%)
Vomiting	0/0 (NaN)		1/2 (50%)
General disorders
Catheter- related complication	0/0 (NaN)		1/2 (50%)
Infections and infestations
escherichia bacteremia	0/0 (NaN)		1/2 (50%)
Injury, poisoning and procedural complications
Procedural Pain	0/0 (NaN)		2/2 (100%)
Metabolism and nutrition disorders
Dehydration	0/0 (NaN)		1/2 (50%)
Hypokalemia	0/0 (NaN)		1/2 (50%)
Hypomagnesemia	0/0 (NaN)		1/2 (50%)
Psychiatric disorders
Depression	0/0 (NaN)		1/2 (50%)
Insomnia	0/0 (NaN)		1/2 (50%)
Respiratory, thoracic and mediastinal disorders
Pulmonary Mass	0/0 (NaN)		1/2 (50%)
Epistaxis	0/0 (NaN)		1/2 (50%)
Nasal Congestion	0/0 (NaN)		1/2 (50%)
Skin and subcutaneous tissue disorders
Rash	0/0 (NaN)		1/2 (50%)
Skin hemorrhage	0/0 (NaN)		1/2 (50%)

Limitations/Caveats

No analysis was performed due to early termination of the study.

More Information

Certain Agreements

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

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.