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

NCT01984684 | Completed Phase 3 Results

• 1 other identifier: RX-3341-303
• Study Type: interventional
• Target: 850
• Locations: 16 countries
• Sites: 94

Brief Summary

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.

Conditions

Skin and Subcutaneous Tissue Bacterial Infections; Skin Structures and Soft Tissue Infections

Keywords

Bacterial skin infection; infection; skin; delafloxacin; vancomycin; aztreonam; methicillin-resistant Staphylococcus aureus (MRSA) bacteria; bacterial infection; Anti-Infective Agents

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Investigator-assessed Response of Signs and Symptoms of Infection at the Follow up Visit (European Medicines Agency [EMA] Primary Endpoint)

  Study Day 14 ± 1

• Investigator-assessed Response of Signs and Symptoms of Infection at the Late Follow-up Visit

  Study Day 21 to 28

Study Arms (2)

Delafloxacin

EXPERIMENTAL

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

Vancomycin plus Aztreonam

ACTIVE COMPARATOR

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

Interventions

delafloxacin DRUG

Also known as: RX-3341

Delafloxacin

vancomycin DRUG

Vancomycin plus Aztreonam

aztreonam DRUG

Vancomycin plus Aztreonam

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Melinta Therapeutics, Inc.: lead

Study Sites (94)

Melinta 303 Study Site

Mobile, Alabama, 36607, United States

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Montgomery, Alabama, United States

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Anaheim, California, United States

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Chula Vista, California, 91911, United States

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La Mesa, California, 91942, United States

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Long Beach, California, United States

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Modesto, California, United States

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Oceanside, California, 92056, United States

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San Diego, California, 92114, United States

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Stockton, California, United States

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Torrance, California, 90509, United States

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DeLand, Florida, United States

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Orlando, Florida, United States

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Columbus, Georgia, 31904, United States

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Savannah, Georgia, 31405, United States

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Eunice, Louisiana, 70535, United States

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Springfield, Massachusetts, United States

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Minneapolis, Minnesota, 55422, United States

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Butte, Montana, United States

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Lincoln, Nebraska, United States

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Las Vegas, Nevada, 89109, United States

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Somers Point, New Jersey, 08244, United States

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Teaneck, New Jersey, United States

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Columbus, Ohio, United States

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Toledo, Ohio, United States

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Rapid City, South Dakota, United States

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Jackson, Tennessee, United States

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Smyrna, Tennessee, United States

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Channelview, Texas, 77530, United States

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Houston, Texas, 77024, United States

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San Antonio, Texas, United States

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La Plata, Buenos Aires, Argentina

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Rosario, Santa Fe Province, Argentina

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Córdoba, Argentina

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Santa Fe, Argentina

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Salvador, Estado de Bahia, Brazil

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Belo Horizonte, Minas Gerais, Brazil

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Lavras, Minas Gerais, Brazil

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Passo Fundo, Rio Grande do Sul, Brazil

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Campinas, São Paulo, Brazil

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São José do Rio Preto, São Paulo, Brazil

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São Paulo, Brazil

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Pleven, Bulgaria

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Plovdiv, Bulgaria

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Rousse, Bulgaria

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Sofia, Bulgaria

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Varna, Bulgaria

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Santiago, Chile

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Temuco, Chile

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Kohtla-Järve, Estonia

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Tallinn, Estonia

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Tartu, Estonia

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Võru, Estonia

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Batumi, Georgia

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Kutaisi, Georgia

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Tbilisi, Georgia

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Zugdidi, Georgia

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Kaposvár, Hungary

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Kecskemét, Hungary

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Nyíregyháza, Hungary

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Szeged, Hungary

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Veszprém, Hungary

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Daugavpils, Latvia

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Liepāja, Latvia

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Rēzekne, Latvia

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Riga, Latvia

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Guadalajara, Jalisco, Mexico

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Monterrey, Nuevo León, Mexico

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Chisinau, Moldova

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Trujillo, La Libertad, Peru

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Cusco, Peru

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Lima, Peru

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Loreto, Peru

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Cluj-Napoca, Cluj, Romania

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Craiova, Dolj, Romania

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Timișoara, Timiș County, Romania

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Bucharest, Romania

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Târgu Mureş, Romania

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Banská Bystrica, Slovakia

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Prešov, Slovakia

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Wŏnju, Gang'weondo, South Korea

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Ansan, Gyeonggido, South Korea

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Goyang, Gyeonggido, South Korea

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Daegu, South Korea

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Daejeon, South Korea

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Gwangju, South Korea

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Incheon, South Korea

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Seoul, South Korea

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Kaohsiung City, Taiwan

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New Taipei City, Taiwan

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Taichung, Taiwan

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Tainan, Taiwan

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Taipei, Taiwan

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Zhonghe, Taiwan

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Related Publications (3)

• 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.

  PMID: 30349845 DERIVED

• 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.

  PMID: 29518178 DERIVED

• 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.

  PMID: 28630189 DERIVED

MeSH Terms

Conditions

Soft Tissue Infections; Skin Diseases, Bacterial; Infections; Bacterial Infections

Interventions

delafloxacin; Vancomycin; Aztreonam

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins; Monobactams; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Sue Cammarata (Chief Medical Officer)
• Organization: Melinta Therapeutics, Inc.

clinicaltrials@melinta.com

1-844-MELINTA (1-844-635-4682)

Study Officials

• Sue K Cammarata, MD

  Melinta Therapeutics, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2013
• First Posted: November 15, 2013
• Study Start: May 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: January 1, 2016
• Last Updated: November 17, 2017
• Results First Posted: August 28, 2017

Record last verified: 2017-11

Data Sharing

• IPD Sharing: Will not share

Locations

GE (4); CL (2); SL (2); ME (2); HU (5); LA (4); RO (5); MO (1); US (31); BR (7); KR (8); PE (4); AR (4); BU (5); TW (6); ES (4)