Delafloxacin vs Vancomycin and Aztreonam for the Treatment of Acute Bacterial Skin and Skin Structure Infections

A Phase 3, Multicenter, Randomized, Double-blind, Active Controlled Study to Evaluate the Efficacy + Safety of IV + Oral Delafloxacin Compared With Vancomycin + Aztreonam in Patients With Acute Bacterial Skin and Skin Structure Infections (ABSSSI)

The purpose of this study is to evaluate the effects of Delafloxacin versus Vancomycin plus Aztreonam in the treatment of patients with acute bacterial skin and soft tissue infections.

Study Overview

• Status: Completed
• Conditions: Skin and Subcutaneous Tissue Bacterial Infections; Skin Structures and Soft Tissue Infections
• Intervention / Treatment: Drug: vancomycin; Drug: delafloxacin; Drug: aztreonam

Detailed Description

The purpose of this study is to determine if delafloxacin, an investigational drug, is safe and effective in the treatment of skin and nearby tissue infections compared with a combination of other antibiotics, vancomycin and aztreonam.

• Study Type: Interventional
• Enrollment (Actual): 850
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Cordoba, Argentina
    • Melinta 303 Study Site
  • Santa Fe, Argentina
    • Melinta 303 Study Site
  • Buenos Aires
    • La Plata, Buenos Aires, Argentina
      • Melinta 303 Study Site
  • Santa Fe
    • Rosario, Santa Fe, Argentina
      • Melinta 303 Study Site
• Brazil
  • Sao Paulo, Brazil
    • Melinta 303 Study Site
  • Bahia
    • Salvador, Bahia, Brazil
      • Melinta 303 Study Site
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil
      • Melinta 303 Study Site
    • Lavras, Minas Gerais, Brazil
      • Melinta 303 Study Site
  • Rio Grande Do Sul
    • Passo Fundo, Rio Grande Do Sul, Brazil
      • Melinta 303 Study Site
  • Sao Paulo
    • Campinas, Sao Paulo, Brazil
      • Melinta 303 Study Site
    • São José Do Rio Preto, Sao Paulo, Brazil
      • Melinta 303 Study Site
• Bulgaria
  • Pleven, Bulgaria
    • Melinta 303 Study Site
  • Plovdiv, Bulgaria
    • Melinta 303 Study Site
  • Ruse, Bulgaria
    • Melinta 303 Study Site
  • Sofia, Bulgaria
    • Melinta 303 Study Site
  • Varna, Bulgaria
    • Melinta 303 Study Site
• Chile
  • Santiago, Chile
    • Melinta 303 Study Site
  • Temuco, Chile
    • Melinta 303 Study Site
• Estonia
  • Kohtla-Järve, Estonia
    • Melinta 303 Study Site
  • Tallinn, Estonia
    • Melinta 303 Study Site
  • Tartu, Estonia
    • Melinta 303 Study Site
  • Voru, Estonia
    • Melinta 303 Study Site
• Georgia
  • Batumi, Georgia
    • Melinta 303 Study Site
  • Kutaisi, Georgia
    • Melinta 303 Study Site
  • Tbilisi, Georgia
    • Melinta 303 Study Site
  • Zugdidi, Georgia
    • Melinta 303 Study Site
• Hungary
  • Kaposvar, Hungary
    • Melinta 303 Study Site
  • Kecskemét, Hungary
    • Melinta 303 Study Site
  • Nyiregyhaza, Hungary
    • Melinta 303 Study Site
  • Szeged, Hungary
    • Melinta 303 Study Site
  • Veszprem, Hungary
    • Melinta 303 Study Site
• Korea, Republic of
  • Daegu, Korea, Republic of
    • Melinta 303 Study Site
  • Daejeon, Korea, Republic of
    • Melinta 303 Study Site
  • Gwangju, Korea, Republic of
    • Melinta 303 Study Site
  • Incheon, Korea, Republic of
    • Melinta 303 Study Site
  • Seoul, Korea, Republic of
    • Melinta 303 Study Site
  • Gang'weondo
    • Wŏnju, Gang'weondo, Korea, Republic of
      • Melinta 303 Study Site
  • Gyeonggido
    • Ansan, Gyeonggido, Korea, Republic of
      • Melinta 303 Study Site
    • Goyang, Gyeonggido, Korea, Republic of
      • Melinta 303 Study Site
• Latvia
  • Daugavpils, Latvia
    • Melinta 303 Study Site
  • Liepaja, Latvia
    • Melinta 303 Study Site
  • Rezekne, Latvia
    • Melinta 303 Study Site
  • Riga, Latvia
    • Melinta 303 Study Site
• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico
      • Melinta 303 Study Site
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico
      • Melinta 303 Study Site
• Moldova, Republic of
  • Chisinau, Moldova, Republic of
    • Melinta 303 Study Site
• Peru
  • Cusco, Peru
    • Melinta 303 Study Site
  • Lima, Peru
    • Melinta 303 Study Site
  • Loreto, Peru
    • Melinta 303 Study Site
  • La Libertad
    • Trujillo, La Libertad, Peru
      • Melinta 303 Study Site
• Romania
  • Bucharest, Romania
    • Melinta 303 Study Site
  • Targu mures, Romania
    • Melinta 303 Study Site
  • Cluj
    • Cluj-Napoca, Cluj, Romania
      • Melinta 303 Study Site
  • Dolj
    • Craiova, Dolj, Romania
      • Melinta 303 Study Site
  • Timis
    • Timisoara, Timis, Romania
      • Melinta 303 Study Site
• Slovakia
  • Banska Bystrica, Slovakia
    • Melinta 303 Study Site
  • Presov, Slovakia
    • Melinta 303 Study Site
• Taiwan
  • Kaohsiung, Taiwan
    • Melinta 303 Study Site
  • New Taipei City, Taiwan
    • Melinta 303 Study Site
  • Taichung, Taiwan
    • Melinta 303 Study Site
  • Tainan City, Taiwan
    • Melinta 303 Study Site
  • Taipei, Taiwan
    • Melinta 303 Study Site
  • Zhonghe, Taiwan
    • Melinta 303 Study Site
• United States
  • Alabama
    • Mobile, Alabama, United States, 36607
      • Melinta 303 Study Site
    • Montgomery, Alabama, United States
      • Melinta 303 Study Site
  • California
    • Anaheim, California, United States
      • Melinta 303 Study Site
    • Chula Vista, California, United States, 91911
      • Melinta 303 Study Site
    • La Mesa, California, United States, 91942
      • Melinta 303 Study Site
    • Long Beach, California, United States
      • Melinta 303 Study Site
    • Modesto, California, United States
      • Melinta 303 Study Site
    • Oceanside, California, United States, 92056
      • Melinta 303 Study Site
    • San Diego, California, United States, 92114
      • Melinta 303 Study Site
    • Stockton, California, United States
      • Melinta 303 Study Site
    • Torrance, California, United States, 90509
      • Melinta 303 Study Site
  • Florida
    • DeLand, Florida, United States
      • Melinta 303 Study Site
    • Orlando, Florida, United States
      • Melinta 303 Study Site
  • Georgia
    • Columbus, Georgia, United States, 31904
      • Melinta 303 Study Site
    • Savannah, Georgia, United States, 31405
      • Melinta 303 Study Site
  • Louisiana
    • Eunice, Louisiana, United States, 70535
      • Melinta 303 Study Site
  • Massachusetts
    • Springfield, Massachusetts, United States
      • Melinta 303 Study Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55422
      • Melinta 303 Study Site
  • Montana
    • Butte, Montana, United States
      • Melinta 303 Study Site
  • Nebraska
    • Lincoln, Nebraska, United States
      • Melinta 303 Study Site
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Melinta 303 Study Site
  • New Jersey
    • Somers Point, New Jersey, United States, 08244
      • Melinta 303 Study Site
    • Teaneck, New Jersey, United States
      • Melinta 303 Study Site
  • Ohio
    • Columbus, Ohio, United States
      • Melinta 303 Study Site
    • Toledo, Ohio, United States
      • Melinta 303 Study Site
  • South Dakota
    • Rapid City, South Dakota, United States
      • Melinta 303 Study Site
  • Tennessee
    • Jackson, Tennessee, United States
      • Melinta 303 Study Site
    • Smyrna, Tennessee, United States
      • Melinta 303 Study Site
  • Texas
    • Channelview, Texas, United States, 77530
      • Melinta 303 Study Site
    • Houston, Texas, United States, 77024
      • Melinta 303 Study Site
    • San Antonio, Texas, United States
      • Melinta 303 Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult (≥ 18 years of age) men or women with a diagnosis of ABSSSI (cellulitis/erysipelas, wound infection, major cutaneous abscess, or burn infection) with surrounding redness of a minimum surface area of 75 cm^2 and at least two signs of systemic infection
• In the opinion of the investigator, the subject must require and be a suitable candidate for IV antibiotic therapy, and the subject must be able and willing to comply with protocol requirements

Exclusion Criteria:

• A medical history of significant hypersensitivity or allergic reaction to quinolones, beta-lactams, vancomycin, or vancomycin derivatives according to the judgment of the investigator.
• Women who are pregnant or lactating.
• Any chronic or underlying skin condition at the site of infection that may complicate the assessment of response, including infection involving a prosthetic joint, human or animal bite, osteomyelitis, decubitus ulcer, diabetic foot ulcer, septic arthritis, mediastinitis, necrotizing fasciitis, anaerobic cellulitis, or synergistic necrotizing cellulitis, myositis, tendinitis, endocarditis, sustained shock, gangrene or gas gangrene; burns covering ≥10% of body surface area; severely compromised immune system, severely impaired arterial blood supply to an extremity with an ABSSSI, deep vein thrombosis or superficial thrombophlebitis, and requiring either an amputation or multiple debridement procedures.

• Receipt of systemic antibiotic therapy in the 14 days before enrollment unless 1 of the following was documented:

  • Received ≥ 48 hours of antibiotic therapy for ABSSSI AND clinical progression is documented (i.e., not by patient history alone).
  • Recently (within 14 days) completed a treatment course with an antibacterial drug for an infection other than ABSSSI and the drug does not have activity against bacterial pathogens that cause ABSSSI.
  • Received only 1 dose of either a single, potentially effective, short-acting antimicrobial drug or drug regimen for ABSSSI.
• Any underlying disease that, in the opinion of the investigator, could interfere with the subject's ability to participate in the study including severe cardiac disease, known history of liver disease, end-stage renal disease, malignancy, psychiatric disorder, ongoing treatment for seizures or untreated history of seizures, or life expectancy of < 3 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Delafloxacin; Delafloxacin 300 mg IV Q12H for 6 doses, then Delafloxacin 450 mg oral tablet Q12H for a minimum of 10 up to a maximum of 28 doses total	Drug: delafloxacin; Other Names: RX-3341
Active Comparator: Vancomycin plus Aztreonam; Vancomycin 15 mg/kg IV plus two grams Aztreonam every 12 hours for a minimum of 10 up to a maximum of 28 doses total (Aztreonam was discontinued as soon as possible if a gram-negative organism was not identified in baseline cultures)	Drug: vancomycin; Drug: aztreonam

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response of ≥20% Reduction in Lesion Erythema Area Compared to Baseline at 48 to 72 Hours After Initiation of Treatment as Determined by Digital Measurements of the Leading Edge.	A patient was considered a responder if s/he had a ≥20% reduction in size of the area of erythema associated with the baseline ABSSSI, as determined by digital planimetry of the leading edge and had none of the reasons for clinical failure; a patient was considered a non-responder (failure) if s/he had <20% reduction in size of the area of erythema associated with the baseline ABSSSI as determined by digital planimetry of the leading edge, or had major intervention such as another antibiotic or surgical intervention or died within 74 hours after initiation of study drug.	48 to 72 hrs after starting treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigator-assessed Response of Signs and Symptoms of Infection at the Follow up Visit (European Medicines Agency [EMA] Primary Endpoint)	A patient was considered a Cure if all baseline signs and symptoms of ABSSSI had resolved; if some symptoms remained, but the patient was improved to the extent that no additional antibiotic treatment was necessary, the response was Improved. A patient was considered a Failure for any of the following reasons: nonstudy antibacterial drug therapy was required because of lack of efficacy after at least 4 doses of study drug or for a treatment-related AE; study antibacterial drug therapy was required for longer than 28 doses; and/or unplanned surgical intervention was needed after study entry except for limited bedside debridement and standard wound care. Improved and Indeterminate responses were considered failures in the primary analysis. A sensitivity analysis was also performed, in which the assigned responses were Success (Cure + Improved) or Failure (Failure + Indeterminate/Missing).	Study Day 14 ± 1
Investigator-assessed Response of Signs and Symptoms of Infection at the Late Follow-up Visit	A patient was considered a Cure if all baseline signs and symptoms of ABSSSI had resolved; if some symptoms remained, but the patient was improved to the extent that no additional antibiotic treatment was necessary, the response was Improved. A patient was considered a Failure for any of the following reasons: nonstudy antibacterial drug therapy was required because of lack of efficacy after at least 4 doses of study drug or for a treatment-related AE; study antibacterial drug therapy was required for longer than 28 doses; and/or unplanned surgical intervention was needed after study entry except for limited bedside debridement and standard wound care. Improved and Indeterminate responses were considered failures in the primary analysis. A sensitivity analysis was also performed, in which the assigned responses were Success (Cure + Improved) or Failure (Failure + Indeterminate/Missing).	Study Day 21 to 28

Collaborators and Investigators

• Sponsor: Melinta Therapeutics, Inc.
• Investigators: Study Director: Sue K Cammarata, MD, Melinta Therapeutics, Inc.

Publications and helpful links

General Publications

• Lodise T, Corey R, Hooper D, Cammarata S. Safety of Delafloxacin: Focus on Adverse Events of Special Interest. Open Forum Infect Dis. 2018 Sep 10;5(10):ofy220. doi: 10.1093/ofid/ofy220. eCollection 2018 Oct.
• O'Riordan W, McManus A, Teras J, Poromanski I, Cruz-Saldariagga M, Quintas M, Lawrence L, Liang S, Cammarata S; PROCEED Study Group. A Comparison of the Efficacy and Safety of Intravenous Followed by Oral Delafloxacin With Vancomycin Plus Aztreonam for the Treatment of Acute Bacterial Skin and Skin Structure Infections: A Phase 3, Multinational, Double-Blind, Randomized Study. Clin Infect Dis. 2018 Aug 16;67(5):657-666. doi: 10.1093/cid/ciy165.
• McCurdy S, Lawrence L, Quintas M, Woosley L, Flamm R, Tseng C, Cammarata S. In Vitro Activity of Delafloxacin and Microbiological Response against Fluoroquinolone-Susceptible and Nonsusceptible Staphylococcus aureus Isolates from Two Phase 3 Studies of Acute Bacterial Skin and Skin Structure Infections. Antimicrob Agents Chemother. 2017 Aug 24;61(9):e00772-17. doi: 10.1128/AAC.00772-17. Print 2017 Sep.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2014
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: November 8, 2013
• First Submitted That Met QC Criteria: November 14, 2013
• First Posted (Estimate): November 15, 2013

Study Record Updates

• Last Update Posted (Actual): November 17, 2017
• Last Update Submitted That Met QC Criteria: November 13, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: skin; Anti-Infective Agents; infection; bacterial infection; vancomycin; aztreonam; Bacterial skin infection; delafloxacin; methicillin-resistant Staphylococcus aureus (MRSA) bacteria
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections and Mycoses; Infections; Communicable Diseases; Soft Tissue Infections; Bacterial Infections; Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin; Aztreonam
• Other Study ID Numbers: RX-3341-303

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO