Skin Structure Infections, Bacterial Skin Diseases, Staphylococcal Skin Infections
Conditions
Keywords
complicated, skin
Brief summary
The purpose of this study is to assess the efficacy, safety and tolerability of RX-3341 (delafloxacin), a fluoroquinolone, versus tigecycline, a glycylcycline antibacterial drug, in the treatment of complicated skin and skin structure infections.
Interventions
DRUGdelafloxacin
300 mg intravenous every 12 hours
DRUGtigecycline
100 mg then 50 mg intravenous tigecycline every 12 hours
Sponsors
Melinta Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult (≥18 years of age) men or women with cSSSI * Diagnosis of one of the following 3 types of cSSSI: wound infection that has developed within 30 days of surgery, trauma, or a bite injury; abscess that has developed in the 7 days before enrollment; or cellulitis that has developed in the 7 days before enrollment * Sexually active men and women 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 * The patient must be willing to comply with protocol requirements
Exclusion criteria
* Medical history of hypersensitivity or allergic reaction to quinolones, tetracycline or tetracycline derivatives * Chronic or underlying skin condition at the site of infection * Infection involving prosthetic materials or foreign bodies (unless prosthetic material will be removed within 24 hours), infection associated with a human bite, osteomyelitis, decubitus ulcer, diabetic foot ulcer, septic arthritis, mediastinitis, necrotizing fasciitis, myositis, tendinitis, endocarditis, toxic shock syndrome, gangrene or gas gangrene, burns covering ≥10% of body surface area, severely impaired arterial blood supply, current evidence of deep vein thrombosis or superficial thrombophlebitis * An infection that would normally have a high cure rate after surgical incision alone * Any infection expected to require other antimicrobial agents in addition to study drug * Receipt of \>24 hours of systemic antibiotic therapy in the 7 days before enrollment * A severely compromised immune system * History of Child-Pugh Class B or C liver disease or severe renal impairment (creatinine clearance of \<30 mL/minute) * Pregnancy or lactation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Response at Test of Cure (TOC) in the Clinically Evaluable (CE) Population | 14-21 days after the last dose of study drug | A Cure was defined as resolution of baseline signs and symptoms, or improvement to an extent that no additional antibiotic treatment is necessary. Failure was defined as the need for additional antibiotics, either because of lack of efficacy after at least 2 days (i.e., 4 doses) of study treatment or because of treatment-related adverse events (AEs), and/or the need for surgical intervention greater than 48 hours after study entry. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Response in Patients With Methicillin-resistant Staphylococcus Aureus (MRSA) | 14-21 days after the last dose of study drug | A Cure was defined as resolution of baseline signs and symptoms, or improvement to an extent that no additional antibiotic treatment is necessary. Failure was defined as the need for additional antibiotics, either because of lack of efficacy after at least 2 days (i.e., 4 doses) of study treatment or because of treatment-related adverse events (AEs), and/or the need for surgical intervention greater than 48 hours after study entry. |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
This study targeted participants with complicated skin and skin structure infections (cSSSI), i.e. infections involving subcutaneous tissues or requiring surgical intervention. Patients could have one of three infection types: wound infection, abscess, or cellulitis.
Participants by arm
| Arm | Count |
|---|---|
| Delafloxacin 300 mg IV q12h | 49 |
| Delafloxacin 450 mg IV q12h | 51 |
| Tigecycline 100 mg IV x 1, Followed by 50 mg IV q12h | 50 |
| Total | 150 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 3 |
| Overall Study | Lost to Follow-up | 2 | 0 | 3 |
| Overall Study | Physician Decision | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 2 |
Baseline characteristics
| Characteristic | Delafloxacin 300 mg IV q12h | Delafloxacin 450 mg IV q12h | Tigecycline 100 mg IV x 1, Followed by 50 mg IV q12h | Total |
|---|---|---|---|---|
| Age, Continuous | 42.7 years STANDARD_DEVIATION 15.1 | 37.2 years STANDARD_DEVIATION 14.35 | 40.4 years STANDARD_DEVIATION 13.83 | 40.1 years STANDARD_DEVIATION 14.51 |
| Sex: Female, Male Female | 18 Participants | 15 Participants | 15 Participants | 48 Participants |
| Sex: Female, Male Male | 31 Participants | 36 Participants | 35 Participants | 102 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 14 / 49 | 32 / 51 | 36 / 50 |
| serious Total, serious adverse events | 1 / 49 | 3 / 51 | 3 / 50 |
Outcome results
Primary
Clinical Response at Test of Cure (TOC) in the Clinically Evaluable (CE) Population
A Cure was defined as resolution of baseline signs and symptoms, or improvement to an extent that no additional antibiotic treatment is necessary. Failure was defined as the need for additional antibiotics, either because of lack of efficacy after at least 2 days (i.e., 4 doses) of study treatment or because of treatment-related adverse events (AEs), and/or the need for surgical intervention greater than 48 hours after study entry.
Time frame: 14-21 days after the last dose of study drug
Population: The CE population included patients with a diagnosis of cSSSI who received at least 80% of study drug, had a test of cure (TOC) visit 14-21 days after the last dose of study drug, and who did not receive any concomitant, systemic antibacterial therapy with activity against the causative pathogen.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Delafloxacin 300 mg IV q12h | Clinical Response at Test of Cure (TOC) in the Clinically Evaluable (CE) Population | 33 Participants |
| Delafloxacin 450 mg IV q12h | Clinical Response at Test of Cure (TOC) in the Clinically Evaluable (CE) Population | 37 Participants |
| Tigecycline 100 mg IV x 1, Followed by 50 mg IV q12h | Clinical Response at Test of Cure (TOC) in the Clinically Evaluable (CE) Population | 31 Participants |
Secondary
Clinical Response in Patients With Methicillin-resistant Staphylococcus Aureus (MRSA)
A Cure was defined as resolution of baseline signs and symptoms, or improvement to an extent that no additional antibiotic treatment is necessary. Failure was defined as the need for additional antibiotics, either because of lack of efficacy after at least 2 days (i.e., 4 doses) of study treatment or because of treatment-related adverse events (AEs), and/or the need for surgical intervention greater than 48 hours after study entry.
Time frame: 14-21 days after the last dose of study drug
Population: Clinically Evaluable (CE) patients (see previous definition) with MRSA isolated from screening culture of primary infection.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Delafloxacin 300 mg IV q12h | Clinical Response in Patients With Methicillin-resistant Staphylococcus Aureus (MRSA) | 13 Participants |
| Delafloxacin 450 mg IV q12h | Clinical Response in Patients With Methicillin-resistant Staphylococcus Aureus (MRSA) | 19 Participants |
| Tigecycline 100 mg IV x 1, Followed by 50 mg IV q12h | Clinical Response in Patients With Methicillin-resistant Staphylococcus Aureus (MRSA) | 12 Participants |