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

Primary Purpose

Skin Infections

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
PZ-601
PZ-601
Standard of Care
Sponsored by
Protez Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Skin Infections focused on measuring Skin Infections, Complicated Skin and Skin Structure Infections

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Written informed consent provided by the patient
  2. Males and females ≥ 18 years of age
  3. 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.
  4. 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
  5. 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)
  6. Require initial hospitalization with at least 7 days of parenteral therapy for treatment of suspected cSSSI infection
  7. Ability to obtain a culture and Gram stain of the cSSSI site within 48 hours prior to the initiation of study medication;

Exclusion Criteria:

  1. 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)
  2. 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)
  3. Concomitant conditions requiring antimicrobial therapy that would interfere with the evaluability of the condition under study
  4. Anticipated need for prolonged antibiotic therapy (ie, >14 days)
  5. Topical use of antimicrobials (excluding vaginally or topically administered antifungal agents)
  6. cSSSI known or suspected to be caused by fungal, parasitic or viral infections
  7. 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
  8. Necrotizing fasciitis or gas gangrene
  9. Infections resulting from human or animal bites (excluding infections secondary to arthropod bites)
  10. Known or suspected osteomyelitis or septic arthritis
  11. 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
  12. 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
  13. 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
  14. Infections complicated by the presence of prosthetic materials that will not be removed such as permanent intracardiac devices or joint replacement prosthesis
  15. Moderately or severely impaired renal function with known creatinine clearance <50 mL/min (based on the Cockcroft-Gault formula using ideal body weight)
  16. ALT or AST >3x upper limit of normal or bilirubin >1.5x upper limit of normal (ULN)
  17. Neutropenia defined as an absolute neutrophil count <500/mm3
  18. Thrombocytopenia defined as a platelet count <50,000 cells/mm3
  19. 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
  20. Requiring concomitant administration of systemic corticosteroids greater than 40 mg/day of prednisolone (or equivalent)
  21. 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
  22. Concomitant therapy with medications known to lower seizure threshold or those patients with a history of seizure disorder
  23. Concomitant therapy with medications known to be associated with QTc prolongation potential (eg, Class IA and Class III anti-arrhythmic agents)
  24. 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
  25. History of any hypersensitivity or allergic reaction to beta-lactam drugs such as carbapenems, penicillins, or cephalosporins
  26. History of any hypersensitivity or allergic reaction to vancomycin or history of Red Man Syndrome
  27. Any planned medical intervention or personal event that might interfere with the ability to comply with the study requirements
  28. Any condition that, in the opinion of the principal investigator, would compromise the safety of the patient or the quality of the data
  29. Life expectancy of less than 3 months from the time of enrollment
  30. Use of an investigational drug or device (ie, a drug or device without an FDA approved indication) within the previous 30 days
  31. Prior participation in this protocol
  32. Unable or unwilling to adhere to the study-specified procedures and restrictions

Sites / Locations

  • eStudySite - Sharp Chula Vista
  • Novellus Research Site
  • Novellus Research Site
  • eStudySite - Tri-City Medical Center
  • eStudySite - Good Samaritan Hospital
  • Infectious Disease of Indiana, PSC
  • Gulf Coast Research, LLC
  • Henry Ford Hospital
  • University of Missouri Health Care
  • Truman Medical Center - Hospital Hill
  • Mercury Street Medical Group
  • Holy Name Hospital Institute for Clinical Research
  • Summa Health System
  • Remington-Davis, Inc.
  • NewBridge Medical Research

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Active Comparator

Arm Label

A

B

C

Arm Description

PZ-601

PZ-601

Standard of Care

Outcomes

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.

Secondary Outcome Measures

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

Full Information

First Posted
May 1, 2008
Last Updated
June 2, 2009
Sponsor
Protez Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00671580
Brief Title
Safety, Potential Efficacy, and Pharmacokinetics of PZ-601 in the Treatment of Complicated Skin and Skin Structure Infection
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 Type
Interventional

2. Study Status

Record Verification Date
June 2009
Overall Recruitment Status
Completed
Study Start Date
May 2008 (undefined)
Primary Completion Date
February 2009 (Actual)
Study Completion Date
February 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Protez Pharmaceuticals, Inc.

4. Oversight

Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Skin Infections
Keywords
Skin Infections, Complicated Skin and Skin Structure Infections

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
99 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
A
Arm Type
Experimental
Arm Description
PZ-601
Arm Title
B
Arm Type
Experimental
Arm Description
PZ-601
Arm Title
C
Arm Type
Active Comparator
Arm Description
Standard of Care
Intervention Type
Drug
Intervention Name(s)
PZ-601
Intervention Description
750 mg
Intervention Type
Drug
Intervention Name(s)
PZ-601
Intervention Description
1000 mg
Intervention Type
Drug
Intervention Name(s)
Standard of Care
Intervention Description
as directed
Primary Outcome Measure Information:
Title
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.
Time Frame
up to 6 weeks
Secondary Outcome Measure Information:
Title
Clinical Response in the Clinically Evaluable (CE) population at the End of Treatment (EOT) visit
Time Frame
Up to 4 weeks
Title
Clinical Response in the Intent-to-Treat (ITT), Microbiological ITT (mITT), and Microbiologically Evaluable (ME) populations at the Test of Cure (TOC) visit
Time Frame
Up to 4 weeks
Title
Clinical Response in the Intent-to-Treat (ITT), Microbiological ITT (mITT), and Microbiologically Evaluable (ME) populations at the End of Treatment (EOT) visit
Time Frame
Up to 4 weeks
Title
By-pathogen and by-patient Microbiological Response in the Microbiological ITT (mITT) and Microbiologically Evaluable (ME) populations at the Test of Cure (TOC) visit
Time Frame
Up to 4 weeks
Title
By-pathogen and by-patient Microbiological Response in the Microbiological ITT (mITT) and Microbiologically Evaluable (ME) populations at the End of Treatment (EOT) visit
Time Frame
Up to 4 weeks
Title
Overall combined Clinical and Microbiological Response in the Microbiological ITT (mITT) and Microbiologically Evaluable (ME) populations at the Test of Cure (TOC) visit
Time Frame
Up to 4 weeks
Title
Overall combined Clinical and Microbiological Response in the Microbiological ITT (mITT) and Microbiologically Evaluable (ME) populations at the End of Therapy (EOT) visit
Time Frame
Up to 4 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
eStudySite - Sharp Chula Vista
City
Chula Vista
State/Province
California
ZIP/Postal Code
91911
Country
United States
Facility Name
Novellus Research Site
City
Fountain Valley
State/Province
California
ZIP/Postal Code
92708
Country
United States
Facility Name
Novellus Research Site
City
Long Beach
State/Province
California
ZIP/Postal Code
90806
Country
United States
Facility Name
eStudySite - Tri-City Medical Center
City
Oceanside
State/Province
California
ZIP/Postal Code
92056
Country
United States
Facility Name
eStudySite - Good Samaritan Hospital
City
San Jose
State/Province
California
ZIP/Postal Code
95124
Country
United States
Facility Name
Infectious Disease of Indiana, PSC
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46280
Country
United States
Facility Name
Gulf Coast Research, LLC
City
Baton Rouge
State/Province
Louisiana
ZIP/Postal Code
70808
Country
United States
Facility Name
Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
University of Missouri Health Care
City
Columbia
State/Province
Missouri
ZIP/Postal Code
65212
Country
United States
Facility Name
Truman Medical Center - Hospital Hill
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
Mercury Street Medical Group
City
Butte
State/Province
Montana
ZIP/Postal Code
59701
Country
United States
Facility Name
Holy Name Hospital Institute for Clinical Research
City
Teaneck
State/Province
New Jersey
ZIP/Postal Code
07666
Country
United States
Facility Name
Summa Health System
City
Akron
State/Province
Ohio
ZIP/Postal Code
44304
Country
United States
Facility Name
Remington-Davis, Inc.
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43215
Country
United States
Facility Name
NewBridge Medical Research
City
Warren
State/Province
Pennsylvania
ZIP/Postal Code
16365
Country
United States

12. IPD Sharing Statement

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

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