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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Melinta Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT01283581
First received: January 24, 2011
Last updated: October 29, 2013
Last verified: October 2013
  Purpose

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 Infections) clinical trials


Condition Intervention Phase
Skin and Subcutaneous Tissue Bacterial Infections
Drug: Delafloxacin
Drug: Linezolid
Drug: Vancomycin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Melinta Therapeutics, Inc.:

Primary Outcome Measures:
  • Investigator's Assessment of Clinical Response in the ITT (Intent-to-treat) Population at Follow-up and Late Follow-up. [ Time Frame: Follow-up (Day 14 ± 1) and late follow-up (Day 21-28) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Erythema Clinical Success [ Time Frame: 48 - 72 hours ] [ Designated as safety issue: No ]
    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%.

  • Steady State Pharmacokinetic Parameters in Subjects Administered Delafloxacin, Vancomycin, and Linezolid [ Time Frame: Through Day 3 (± 1 day) ] [ Designated as safety issue: No ]
  • The Levels of Biochemical Markers of Inflammation [ Time Frame: on Days 1, 5, Follow-up, and late Follow-up ] [ Designated as safety issue: No ]
  • Microbiological Response Rate in All Subjects and in Subjects With Infections Caused by MRSA [ Time Frame: up to Late Follow-up ] [ Designated as safety issue: No ]
  • Clinical Response Rate in Subjects With Infections Caused by MRSA [ Time Frame: up to Late Follow-up ] [ Designated as safety issue: No ]

Enrollment: 256
Study Start Date: January 2011
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Delafloxacin
300 mg IV every 12 hours for 5-14 days
Drug: Delafloxacin
300mg IV every 12 hours for 5-14 days
Other Name: RX-3341
Active Comparator: Vancomycin
15 mg/kg, up to 1250 mg, IV every 12 hours for 5-14 dyas
Drug: Vancomycin
15mg/kg, up to 1250 mg, IV every 12 hours for 5-14 days
Other Name: Vancocin
Active Comparator: Linezolid
600 mg IV every 12 hours for 5-14 days
Drug: Linezolid
600mg IV every 12 hours for 5-14 days
Other Name: Zyvox

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01283581

  Show 31 Study Locations
Sponsors and Collaborators
Melinta Therapeutics, Inc.
Investigators
Study Director: Scott Hopkins, MD
  More Information

No publications provided

Responsible Party: Melinta Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT01283581     History of Changes
Other Study ID Numbers: RX-3341-202
Study First Received: January 24, 2011
Results First Received: August 23, 2013
Last Updated: October 29, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Bacterial Infections
Skin Diseases, Bacterial
Skin Diseases, Infectious
Infection
Skin Diseases
Vancomycin
Fluoroquinolones
Linezolid
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on April 15, 2014