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

Skin and Subcutaneous Tissue Bacterial Infections Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01984684
• Other study ID #: RX-3341-303
• Status: Completed
• Phase: Phase 3
• First received: November 8, 2013
• Last updated: November 13, 2017
• Start date: May 2014
• Est. completion date: January 2016

Study information

• Verified date: November 2017
• Source: Melinta Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 850
• Est. completion date: January 2016
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• delafloxacin

• vancomycin

• aztreonam

Locations

Country	Name	City	State
Argentina	Melinta 303 Study Site	Cordoba
Argentina	Melinta 303 Study Site	La Plata	Buenos Aires
Argentina	Melinta 303 Study Site	Rosario	Santa Fe
Argentina	Melinta 303 Study Site	Santa Fe
Brazil	Melinta 303 Study Site	Belo Horizonte	Minas Gerais
Brazil	Melinta 303 Study Site	Campinas	Sao Paulo
Brazil	Melinta 303 Study Site	Lavras	Minas Gerais
Brazil	Melinta 303 Study Site	Passo Fundo	Rio Grande Do Sul
Brazil	Melinta 303 Study Site	Salvador	Bahia
Brazil	Melinta 303 Study Site	São José Do Rio Preto	Sao Paulo
Brazil	Melinta 303 Study Site	Sao Paulo
Bulgaria	Melinta 303 Study Site	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
Chile	Melinta 303 Study Site	Santiago
Chile	Melinta 303 Study Site	Temuco
Estonia	Melinta 303 Study Site	Kohtla-Järve
Estonia	Melinta 303 Study Site	Tallinn
Estonia	Melinta 303 Study Site	Tartu
Estonia	Melinta 303 Study Site	Voru
Georgia	Melinta 303 Study Site	Batumi
Georgia	Melinta 303 Study Site	Kutaisi
Georgia	Melinta 303 Study Site	Tbilisi
Georgia	Melinta 303 Study Site	Zugdidi
Hungary	Melinta 303 Study Site	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
Korea, Republic of	Melinta 303 Study Site	Ansan	Gyeonggido
Korea, Republic of	Melinta 303 Study Site	Daegu
Korea, Republic of	Melinta 303 Study Site	Daejeon
Korea, Republic of	Melinta 303 Study Site	Goyang	Gyeonggido
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	Wonju	Gang'weondo
Latvia	Melinta 303 Study Site	Daugavpils
Latvia	Melinta 303 Study Site	Liepaja
Latvia	Melinta 303 Study Site	Rezekne
Latvia	Melinta 303 Study Site	Riga
Mexico	Melinta 303 Study Site	Guadalajara	Jalisco
Mexico	Melinta 303 Study Site	Monterrey	Nuevo Leon
Moldova, Republic of	Melinta 303 Study Site	Chisinau
Peru	Melinta 303 Study Site	Cusco
Peru	Melinta 303 Study Site	Lima
Peru	Melinta 303 Study Site	Loreto
Peru	Melinta 303 Study Site	Trujillo	La Libertad
Romania	Melinta 303 Study Site	Bucharest
Romania	Melinta 303 Study Site	Cluj-Napoca	Cluj
Romania	Melinta 303 Study Site	Craiova	Dolj
Romania	Melinta 303 Study Site	Targu mures
Romania	Melinta 303 Study Site	Timisoara	Timis
Slovakia	Melinta 303 Study Site	Banska Bystrica
Slovakia	Melinta 303 Study Site	Presov
Taiwan	Melinta 303 Study Site	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
United States	Melinta 303 Study Site	Anaheim	California
United States	Melinta 303 Study Site	Butte	Montana
United States	Melinta 303 Study Site	Channelview	Texas
United States	Melinta 303 Study Site	Chula Vista	California
United States	Melinta 303 Study Site	Columbus	Georgia
United States	Melinta 303 Study Site	Columbus	Ohio
United States	Melinta 303 Study Site	DeLand	Florida
United States	Melinta 303 Study Site	Eunice	Louisiana
United States	Melinta 303 Study Site	Houston	Texas
United States	Melinta 303 Study Site	Jackson	Tennessee
United States	Melinta 303 Study Site	La Mesa	California
United States	Melinta 303 Study Site	Las Vegas	Nevada
United States	Melinta 303 Study Site	Lincoln	Nebraska
United States	Melinta 303 Study Site	Long Beach	California
United States	Melinta 303 Study Site	Minneapolis	Minnesota
United States	Melinta 303 Study Site	Mobile	Alabama
United States	Melinta 303 Study Site	Modesto	California
United States	Melinta 303 Study Site	Montgomery	Alabama
United States	Melinta 303 Study Site	Oceanside	California
United States	Melinta 303 Study Site	Orlando	Florida
United States	Melinta 303 Study Site	Rapid City	South Dakota
United States	Melinta 303 Study Site	San Antonio	Texas
United States	Melinta 303 Study Site	San Diego	California
United States	Melinta 303 Study Site	Savannah	Georgia
United States	Melinta 303 Study Site	Smyrna	Tennessee
United States	Melinta 303 Study Site	Somers Point	New Jersey
United States	Melinta 303 Study Site	Springfield	Massachusetts
United States	Melinta 303 Study Site	Stockton	California
United States	Melinta 303 Study Site	Teaneck	New Jersey
United States	Melinta 303 Study Site	Toledo	Ohio
United States	Melinta 303 Study Site	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
Melinta Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Bulgaria,  Chile,  Estonia,  Georgia,  Hungary,  Korea, Republic of,  Latvia,  Mexico,  Moldova, Republic of,  Peru,  Romania,  Slovakia,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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