Clinical trial NCT01283581: A Study to Assess Objective Endpoint Measurements of Response in Bacterial Skin Infections
Official title: A Phase 2 Exploratory Study of Objective Endpoints in Subjects With Acute Bacterial Skin and Skin Structure Infections Treated With Delafloxacin, Vancomycin, or Linezolid
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Skin and Subcutaneous Tissue Bacterial Infections
Lead sponsor: Melinta Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2011-01-26
Enrollment: 256
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare clinical response to the measurement techniques of several objective measures of clinical efficacy for use in future ABSSSI (Acute Bacterial Skin and Skin Structure Infection) clinical trials


Eligibility criteria: Inclusion Criteria:

* Adult (≥ 18 years of age) men or women
* Sexually active women and men with partners of childbearing potential must agree to use an acceptable form of contraception as determined by the investigator during participation in the study and for 30 days after the final dose of study drug
* Female partners of male subjects should also use an additional reliable method of contraception during study and for 30 days after the final dose of study drug
* Subjects must have a diagnosis of ABSSSI - one or more of the following 4 infection types: cellulitis/erysipelas, wound infection, major cutaneous abscess, or burn infection
* Subjects must have lymph node enlargement due to the present infection or at least one of the following symptoms of systemic infection: fever ≥ 38°C, lymphangitis, WBC (white blood cell) count ≥ 15,000 cells/μL, elevated C-reactive protein (\> 5.0mg/L)
* In the opinion of the investigator, the subject must require and be a suitable candidate for IV antibiotic therapy

Exclusion Criteria:

* A medical history of significant hypersensitivity or allergic reaction to quinolones, linezolid, vancomycin, or vancomycin derivatives
* Women who are pregnant or lactating
* Any chronic or underlying skin condition at the site of infection that may complicate the assessment of response
* Subjects with any of the following: infection involving prosthetic materials or foreign bodies, infection associated with a human or animal bite, osteomyelitis, decubitus ulcer, diabetic foot ulcer, septic arthritis, mediastinitis, necrotizing fasciitis, anaerobic cellulitis, or synergistic necrotizing cellulitis, myositis, tendinitis, endocarditis, toxic shock syndrome, gangrene, burns covering ≥ 10% of body surface area, severely impaired arterial blood supply, current evidence of deep vein thrombosis or superficial thrombophlebitis
* Minor abscesses, unless present with one of the ABSSSI types
* Any infection expected to require other antimicrobial agents in addition to study drug
* Receipt of \> 24 hours of systemic antibiotic therapy in the 14 days before enrollment unless one of the following is documented: the subject received a single dose of a short-acting antibacterial drug 3 or more days before clinical trial enrollment for surgical prophylaxis or recently completed treatment with an antibacterial drug for an infection other than ABSSSI and the drug does not have antibacterial activity against bacterial pathogens that cause ABSSSI
* Receipt of more than 1 dose of a potentially effective antibacterial agent for treatment of the ABSSSI under study prior to enrollment
* Receipt of chronic anti-inflammatory therapy for longer than 14 days before enrollment
* Severely compromised immune systems
* Subjects taking any medicinal product which inhibits monoamine oxidases A or B or within 2 weeks of Screening
* Hypertension as defined by a systolic blood pressure of ≥ 180 mmHg or a diastolic blood pressure of ≥110 mmHg with confirmed re-check within 20 minutes of initial reading
* Subjects with pheochromocytoma, thyrotoxicosis and/or subjects taking any of the following types of medications: sympathomimetic agents, vasopressive agents, dopaminergic agents, or other agents with the potential for serotonergic interactions
* Subjects with carcinoid syndrome and/or subjects taking any of the following medications: serotonin re-uptake inhibitors, tricyclic antidepressants, serotonin 5-HT1 (serotonin receptor) receptor agonists, meperidine, or buspirone
* Known history of liver disease
* History of severe renal impairment
* Life expectancy of \< 3 months
* Any underlying disease that, in the opinion of the investigator, could interfere with the subject's ability to participate in the study
* Subjects previously randomized in this study or in who have received a dose of an investigational drug within 30 days of randomization
* Subjects \> 140 kg in body weight

Primary outcomes:
measure: Investigator's Assessment of Clinical Response in the ITT (Intent-to-treat) Population at Follow-up
timeFrame: Follow-up (Day 14 ± 1)
Secondary outcomes:
measure: Erythema Clinical Success
timeFrame: 48 - 72 hours
measure: Pharmacokinetic (PK) Parameter, Area Under Curve, (AUCinf, ug*h/mL), in Subjects Administered Delafloxacin, Vancomycin, and Linezolid
timeFrame: Through Day 3 (± 1 day)
measure: The Levels of Inflammation Were Examined by Measuring a Surrogate, C-Reactive Protein (CRP)
timeFrame: Baseline, Days 1, 5, Follow-up (FU), and late Follow-up (LFU)
measure: Microbiological Response Rate in All Subjects (Microbiological Evaluable Population)
timeFrame: Follow-up (Day 14 ± 1)
measure: Microbiological Response Rate in Subjects With MRSA (Methicillin Resistant Staphylococcus Aureus) in Microbiological Evaluable (ME) Population
timeFrame: Follow-up (Day 14 ± 1)
measure: Clinical Response in Subjects With Infections Caused by MRSA - Microbiological ITT (MITT) Population
timeFrame: Follow-up (Day 14 ± 1)
Other outcomes:
Locations:
city: Mobile
country: United States
facility: University of South Alabama Medical Center
state: Alabama
city: Montgomery
country: United States
facility: Drug Research and Analysis Corp
state: Alabama
city: Buena Park
country: United States
facility: Southbay Pharma Research
state: California
city: Chula Vista
country: United States
facility: eStudySite
state: California
city: La Mesa
country: United States
facility: eStudySite
state: California
city: Los Angeles
country: United States
facility: HealthCare Partners Medical Group
state: California
city: Oceanside
country: United States
facility: eStudySite
state: California
city: Pasadena
country: United States
facility: HealthCare Partners Medical Group
state: California
city: Newark
country: United States
facility: Christiana Care Health Services
state: Delaware
city: Edgewater
country: United States
facility: Riverside Clinical Research
state: Florida
city: Jacksonville
country: United States
facility: River City Clinical Research
state: Florida
city: Kissimmee
country: United States
facility: Central Florida Internists
state: Florida
city: Orlando
country: United States
facility: Central Florida Internists Medical
state: Florida
city: Saint Cloud
country: United States
facility: Central Florida Internists
state: Florida
city: Temple Terrace
country: United States
facility: Ronald Barbour, MD
state: Florida
city: Columbus
country: United States
facility: Southeast Regional Research Group
state: Georgia
city: Decatur
country: United States
facility: Atlanta Institute for Medical Research, Inc
state: Georgia
city: Savannah
country: United States
facility: Southeast Regional Research Group
state: Georgia
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Paducah
country: United States
facility: Four Rivers Clinical Research, Inc
state: Kentucky
city: Baton Rouge
country: United States
facility: Medical Development Centers, LLC
state: Louisiana
city: Columbia
country: United States
facility: University of Missouri Health Care
state: Missouri
city: Butte
country: United States
facility: Mercury Street Medical Group, PLLC
state: Montana
city: Las Vegas
country: United States
facility: eStudySite
state: Nevada
city: Somers Point
country: United States
facility: South Jersey Infectious Disease
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Columbus
country: United States
facility: Remington-Davis, Inc.
state: Ohio
city: Lima
country: United States
facility: Ravi Kamepalli, MD
state: Ohio
city: Rapid City
country: United States
facility: Health Concepts
state: South Dakota
city: Houston
country: United States
facility: Jennifer Johnson-Caldwell, MD
state: Texas
city: Houston
country: United States
facility: Alan Nolasco, MD
state: Texas
Study officials:
name: Scott Hopkins, MD
role: STUDY_DIRECTOR
References:
citation: Results of a Phase 2 Study of Delafloxacin (DLX) Compared to Vancomycin (VAN) and Linezolid (LNZ) in Acute Bacterial Skin and Skin Structure Infections (ABSSSI) J. Longcor 1 , S. Hopkins 1 , L. Lawrence 1 , S. Green 2 , P. Mehra 2 , P. Manos 2 , W. Sears 2 , W. O'Riordan 2 1 Rib - X Pharmaceuticals, Inc., New Haven, CT; 2 eStudySite, San Diego, CA 52nd ICAAC, San Francisco, CA 2012
citation: Characterization and In Vitro Activity of Delafloxacin (DLX) Against Isolates from a Phase 2 Study of Acute Bacterial Skin and Skin Structure Infections (ABSSSI) L. Lawrence 1 , S. Hopkins 1 , D. Sahm 2 , Jennifer Deane 2 , E. Burak 1 , J. Longcor 1 1 Rib - X Pharmaceuticals, Inc., New Haven, CT; 2 Eurofins Medinet, Chantilly, VA 52nd ICAAC, San Franciso, 2012
citation: Pharmacokinetics (PK) of Delafloxacin (DLX), Vancomycin (VAN), and Linezolid (LNZ) in a Phase 2 Exploratory Study in Subjects with Acute Bacterial Skin and Skin Structure Infections (ABSSSI) R. Hoover 1 , L. Lawrence 1 , J. Longcor 1 , J. Greenfield 2 1 Rib - X Pharmaceuticals, New Haven, CT; 2 PharmaNet/i3, The Woodlands, TX 52nd ICAAC, San Francisco, CA, 2012
citation: Kingsley J, Mehra P, Lawrence LE, Henry E, Duffy E, Cammarata SK, Pullman J. A randomized, double-blind, Phase 2 study to evaluate subjective and objective outcomes in patients with acute bacterial skin and skin structure infections treated with delafloxacin, linezolid or vancomycin. J Antimicrob Chemother. 2016 Mar;71(3):821-9. doi: 10.1093/jac/dkv411. Epub 2015 Dec 17.