A Study to Assess Objective Endpoint Measurements of Response in Bacterial Skin Infections

Skin and Subcutaneous Tissue Bacterial Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01283581
• Other study ID #: RX-3341-202
• Status: Completed
• Phase: Phase 2
• Start date: January 2011
• Est. completion date: November 2011

Study information

• Verified date: September 2019
• Source: Melinta Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 256
• Est. completion date: November 2011
• Est. primary completion date: November 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bacterial Infections
• Communicable Diseases
• Infection
• Skin and Subcutaneous Tissue Bacterial Infections

Intervention

Drug:
• Delafloxacin
300mg IV every 12 hours for 5-14 days
• Linezolid
600mg IV every 12 hours for 5-14 days
• Vancomycin
15mg/kg, up to 1250 mg, IV every 12 hours for 5-14 days

Locations

Country	Name	City	State
United States	Medical Development Centers, LLC	Baton Rouge	Louisiana
United States	Montefiore Medical Center	Bronx	New York
United States	Southbay Pharma Research	Buena Park	California
United States	Mercury Street Medical Group, PLLC	Butte	Montana
United States	eStudySite	Chula Vista	California
United States	University of Missouri Health Care	Columbia	Missouri
United States	Remington-Davis, Inc.	Columbus	Ohio
United States	Southeast Regional Research Group	Columbus	Georgia
United States	Atlanta Institute for Medical Research, Inc	Decatur	Georgia
United States	Riverside Clinical Research	Edgewater	Florida
United States	Alan Nolasco, MD	Houston	Texas
United States	Jennifer Johnson-Caldwell, MD	Houston	Texas
United States	River City Clinical Research	Jacksonville	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Central Florida Internists	Kissimmee	Florida
United States	eStudySite	La Mesa	California
United States	eStudySite	Las Vegas	Nevada
United States	Ravi Kamepalli, MD	Lima	Ohio
United States	HealthCare Partners Medical Group	Los Angeles	California
United States	University of South Alabama Medical Center	Mobile	Alabama
United States	Drug Research and Analysis Corp	Montgomery	Alabama
United States	Christiana Care Health Services	Newark	Delaware
United States	eStudySite	Oceanside	California
United States	Central Florida Internists Medical	Orlando	Florida
United States	Four Rivers Clinical Research, Inc	Paducah	Kentucky
United States	HealthCare Partners Medical Group	Pasadena	California
United States	Health Concepts	Rapid City	South Dakota
United States	Central Florida Internists	Saint Cloud	Florida
United States	Southeast Regional Research Group	Savannah	Georgia
United States	South Jersey Infectious Disease	Somers Point	New Jersey
United States	Ronald Barbour, MD	Temple Terrace	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Melinta Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (3)

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

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 R

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Investigator's Assessment of Clinical Response in the ITT (Intent-to-treat) Population at Follow-up	The primary efficacy endpoint was the success rate, defined as (cure)/(cure + failure), and expressed as a percentage. Cure was defined as the complete resolution of all baseline signs and symptoms of ABSSSI and follow-up and late follow-up. If erythema was the only sign of infection present at follow-up and it was then absent at late follow-up, the case was classified as a Cure.	Follow-up (Day 14 ± 1)
Secondary	Erythema Clinical Success	The number of ITT subjects who had cessation of erythema within 48-72 hours, based on digital measurements, as well as resolution/absence of fever. Cessation was defined as a percentage change from baseline in total area of erythema/induration that is less than or equal to 0%.	48 - 72 hours
Secondary	Pharmacokinetic (PK) Parameter, Area Under Curve, (AUCinf, ug*h/mL), in Subjects Administered Delafloxacin, Vancomycin, and Linezolid	Blood samples for pharmacokinetic analyses were drawn from all subjects on Day 3 (± 1 day) of treatment within 2 hours before the first study drug infusion and at 1, 2, 3, 5, and 12 hours (ie, immediately before the second dose) after the start of the first study drug infusion. An analytical, validated method was used to analyze samples and determine human plasma concentrations. The primary pharmacokinetic parameter calculated was area under the plasma concentration - time curve from time 0 extrapolated to infinity (AUCinf, ug*h/mL).	Through Day 3 (± 1 day)
Secondary	The Levels of Inflammation Were Examined by Measuring a Surrogate, C-Reactive Protein (CRP)	CRP Levels (g/m3) were analyzed from blood samples collected from subjects at Baseline and various time points throughout the study. Change in baseline values were analyzed using an analysis of covariance (ANCOVA) model with treatment, infection category, and prior antimicrobial therapy as fixed effects and the baseline measure as the covariate.	Baseline, Days 1, 5, Follow-up (FU), and late Follow-up (LFU)
Secondary	Microbiological Response Rate in All Subjects (Microbiological Evaluable Population)	Based on the results of the baseline and follow up cultures and susceptibility testing, together with the clinical response assigned by the investigator, the sponsor determined a microbiological response for subjects in the ME population.	Follow-up (Day 14 ± 1)
Secondary	Microbiological Response Rate in Subjects With MRSA (Methicillin Resistant Staphylococcus Aureus) in Microbiological Evaluable (ME) Population	Based on the results of the baseline and follow up cultures and susceptibility testing, together with the clinical response assigned by the investigator, the sponsor determined a microbiological response for subjects in the ME population.	Follow-up (Day 14 ± 1)
Secondary	Clinical Response in Subjects With Infections Caused by MRSA - Microbiological ITT (MITT) Population	The success rate, defined as (cure)/(cure + failure), and expressed as a percentage. Cure was defined as the complete resolution of all baseline signs and symptoms of ABSSSI and follow-up and late follow-up. If erythema was the only sign of infection present at follow-up and it was then absent at late follow-up, the case was classified as a Cure.	Follow-up (Day 14 ± 1)