Safety, Potential Efficacy, and Pharmacokinetics of PZ-601 in the Treatment of Complicated Skin and Skin Structure Infection

Sponsor

Protez Pharmaceuticals, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT00671580

Collaborator

(none)

Enrollment

Locations

Arms

9.1

Duration (Months)

6.6

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the potential effect and safety of two different doses of PZ-601 and to compare this with another antibiotic that is approved by the US Food and Drug Administration (also known as FDA) to treat adults with skin and skin structure infections.

Condition or Disease	Intervention/Treatment	Phase
Skin Infections	Drug: PZ-601 Drug: PZ-601 Drug: Standard of Care	Phase 2

Detailed Description

PZ-601 is a novel investigational carbapenem antibiotic with an antimicrobial spectrum of activity that includes pathogens responsible for community-acquired bacterial infections as well as multidrug-resistant Gram-positive pathogens - MRSA and vancomycin-resistant enterococci. PZ-601 also has activity against Gram-negative organisms including cephalosporin and quinolone resistant Enterobacteriaceae as well as Bacteriodes fragilis and peptostreptococci. Based on the antimicrobial profile, PZ-601 is a potentially promising agent for the treatment of complicated skin and skin structure infections.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

99 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Phase II Randomized, Observer-Blind, Multi-Center Study to Evaluate the Safety, Potential Efficacy, and Pharmacokinetics of Two Dosing Regimens of Intravenous PZ-601 and Standard of Care in the Treatment of Complicated Skin and Skin Structure Infections

Study Start Date :

May 1, 2008

Actual Primary Completion Date :

Feb 1, 2009

Actual Study Completion Date :

Feb 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A PZ-601	Drug: PZ-601 750 mg
Experimental: B PZ-601	Drug: PZ-601 1000 mg
Active Comparator: C Standard of Care	Drug: Standard of Care as directed

Arm

Intervention/Treatment

Experimental: A

PZ-601

Drug: PZ-601

750 mg

Experimental: B

PZ-601

Drug: PZ-601

1000 mg

Active Comparator: C

Standard of Care

Drug: Standard of Care

as directed

Outcome Measures

Primary Outcome Measures

The primary efficacy parameter is the proportion of patients experiencing clinical response based on improvement or resolution of clinical signs and symptoms of infection in the Clinically Evaluable population at the Test of Cure visit. [up to 6 weeks]

Secondary Outcome Measures

Clinical Response in the Clinically Evaluable (CE) population at the End of Treatment (EOT) visit [Up to 4 weeks]
Clinical Response in the Intent-to-Treat (ITT), Microbiological ITT (mITT), and Microbiologically Evaluable (ME) populations at the Test of Cure (TOC) visit [Up to 4 weeks]
Clinical Response in the Intent-to-Treat (ITT), Microbiological ITT (mITT), and Microbiologically Evaluable (ME) populations at the End of Treatment (EOT) visit [Up to 4 weeks]
By-pathogen and by-patient Microbiological Response in the Microbiological ITT (mITT) and Microbiologically Evaluable (ME) populations at the Test of Cure (TOC) visit [Up to 4 weeks]
By-pathogen and by-patient Microbiological Response in the Microbiological ITT (mITT) and Microbiologically Evaluable (ME) populations at the End of Treatment (EOT) visit [Up to 4 weeks]
Overall combined Clinical and Microbiological Response in the Microbiological ITT (mITT) and Microbiologically Evaluable (ME) populations at the Test of Cure (TOC) visit [Up to 4 weeks]
Overall combined Clinical and Microbiological Response in the Microbiological ITT (mITT) and Microbiologically Evaluable (ME) populations at the End of Therapy (EOT) visit [Up to 4 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Written informed consent provided by the patient
Males and females ≥ 18 years of age
Diagnosis of complicated skin and skin structure infection defined as infection which meets the following criteria:

Suspected to be caused by bacterial pathogens, including multi-drug resistant organisms such as MRSA, and
Involves deeper soft tissue and/or require significant surgical intervention such as:
major abscesses
infected burn (less than or equal to 20% body surface area)
traumatic wound infection
deep/extensive cellulitis
surgical wound infection
infected ulcer (with the exception of multiple infected ulcers at distant sites.) Please Note: Patients with multiple sites of skin infection may be enrolled in the study. The most severely affected site or the one most likely to yield a positive culture should be chosen to follow throughout the course of evaluations.

Presents with at least TWO of the following local symptoms:

Purulent or seropurulent drainage/discharge
Erythema
Fluctuance
Heat/Localized Warmth
Pain/tenderness to palpation
Swelling/induration

At least ONE of the following systemic signs of infection

Increased Temperature (≥100.4ºF/≥38.0ºC) measured orally or its equivalent (note: other methods of obtaining temperature are acceptable)
WBC (>10,000 cells/mm3)
Immature neutrophils (>10% band forms regardless of the total peripheral white count)

Require initial hospitalization with at least 7 days of parenteral therapy for treatment of suspected cSSSI infection
Ability to obtain a culture and Gram stain of the cSSSI site within 48 hours prior to the initiation of study medication;

Exclusion Criteria:

Female patients who are pregnant, lactating (breast milk feeding), or planning a pregnancy during the course of the study, or who are of child bearing potential and not using an acceptable method of birth control (ie, surgically sterile, intrauterine device, oral contraceptive plus barrier contraceptive, hormone delivery system plus barrier contraceptive or condom in combination with contraceptive cream, jelly or foam)
Received more than 24 hours of systemic antibiotic therapy within 96 hours of initiation of study medication for the current episode of cSSSI, unless:

there is evidence of clinical failure following at least 48 hours of prior, non-study systemic therapy OR
there is microbiological evidence of failure (ie, Gram stain reveals WBC and at least one potential pathogen or isolation of an organism resistant to the prior therapy)

Concomitant conditions requiring antimicrobial therapy that would interfere with the evaluability of the condition under study
Anticipated need for prolonged antibiotic therapy (ie, >14 days)
Topical use of antimicrobials (excluding vaginally or topically administered antifungal agents)
cSSSI known or suspected to be caused by fungal, parasitic or viral infections
cSSSI of the following categories:

infected diabetic foot ulcers or decubitus ulcer
multiple infected ulcers at distant sites
involve an ischemic ulcer due to peripheral vascular disease
presence of gangrene of any etiology

Necrotizing fasciitis or gas gangrene
Infections resulting from human or animal bites (excluding infections secondary to arthropod bites)
Known or suspected osteomyelitis or septic arthritis
Superinfected eczema or other chronic medical conditions (eg, atopic dermatitis, hidradentitis suppurativa) characterized by prominent signs of inflammation for an extended period even after successful bacterial eradication
Patients who have undergone more than two surgical interventions (defined as surgery that cannot be performed at the bedside) for treatment of cSSSI at the time of enrollment
Patients who are expected to require more than two surgical interventions (defined as surgery that cannot be performed at the bedside) for treatment of cSSSI during the first 48 hours following study enrollment
Infections complicated by the presence of prosthetic materials that will not be removed such as permanent intracardiac devices or joint replacement prosthesis
Moderately or severely impaired renal function with known creatinine clearance <50 mL/min (based on the Cockcroft-Gault formula using ideal body weight)
ALT or AST >3x upper limit of normal or bilirubin >1.5x upper limit of normal (ULN)
Neutropenia defined as an absolute neutrophil count <500/mm3
Thrombocytopenia defined as a platelet count <50,000 cells/mm3
Infection with human immunodeficiency virus and a CD4 count known at the time of enrollment to be <200 cells/mm3 or another Acquired Immune Deficiency Syndrome (AIDS)-defining illness
Requiring concomitant administration of systemic corticosteroids greater than 40 mg/day of prednisolone (or equivalent)
Treatment with cancer chemotherapy, radiotherapy, or potent, non-corticosteroid immunosuppressant drugs (eg, cyclosporine, azathioprine, tacrolimus, immune-modulating monoclonal antibody therapy, etc.) within the 3 months prior to study enrollment
Concomitant therapy with medications known to lower seizure threshold or those patients with a history of seizure disorder
Concomitant therapy with medications known to be associated with QTc prolongation potential (eg, Class IA and Class III anti-arrhythmic agents)
History or significant cardiac disease defined by the following:

New York Heart Association (NYHA) Class III or IV heart failure
History or risk of ventricular arrhythmia (excluding isolated premature ventricular contractions [PVC's] or consecutive PVC's <10 beats), Torsades de Pointes, 2nd or 3rd degree AV block, or QTc interval >470 mm/sec

History of any hypersensitivity or allergic reaction to beta-lactam drugs such as carbapenems, penicillins, or cephalosporins
History of any hypersensitivity or allergic reaction to vancomycin or history of Red Man Syndrome
Any planned medical intervention or personal event that might interfere with the ability to comply with the study requirements
Any condition that, in the opinion of the principal investigator, would compromise the safety of the patient or the quality of the data
Life expectancy of less than 3 months from the time of enrollment
Use of an investigational drug or device (ie, a drug or device without an FDA approved indication) within the previous 30 days
Prior participation in this protocol
Unable or unwilling to adhere to the study-specified procedures and restrictions

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	eStudySite - Sharp Chula Vista	Chula Vista	California	United States	91911
2	Novellus Research Site	Fountain Valley	California	United States	92708
3	Novellus Research Site	Long Beach	California	United States	90806
4	eStudySite - Tri-City Medical Center	Oceanside	California	United States	92056
5	eStudySite - Good Samaritan Hospital	San Jose	California	United States	95124
6	Infectious Disease of Indiana, PSC	Indianapolis	Indiana	United States	46280
7	Gulf Coast Research, LLC	Baton Rouge	Louisiana	United States	70808
8	Henry Ford Hospital	Detroit	Michigan	United States	48202
9	University of Missouri Health Care	Columbia	Missouri	United States	65212
10	Truman Medical Center - Hospital Hill	Kansas City	Missouri	United States	64108
11	Mercury Street Medical Group	Butte	Montana	United States	59701
12	Holy Name Hospital Institute for Clinical Research	Teaneck	New Jersey	United States	07666
13	Summa Health System	Akron	Ohio	United States	44304
14	Remington-Davis, Inc.	Columbus	Ohio	United States	43215
15	NewBridge Medical Research	Warren	Pennsylvania	United States	16365