Abscess, Bacterial Skin Diseases, Infectious Skin Diseases, Staphylococcal Skin Infections, Streptococcal Infections
Conditions
Brief summary
The purpose of this study is to assess the efficacy, safety and tolerability of RX-1741, an oxazolidinone, versus linezolid, another oxazolidinone, in the treatment of uncomplicated skin and skin structure infections
Interventions
DRUGRadezolid
450mg PO QD
DRUGLinezolid
600mg PO BID
Sponsors
Melinta Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients with uSSSI * Adult (men and women) ≥18 years * Females must be post-menopausal for at least 1 year or surgically sterile * Sexually active males must use a barrier method of birth control during and for 30 days after the study * Acceptable clinical diagnoses of uSSSI include, but are not limited to: Simple abscess, Impetiginous lesions, Folliculitis, Furunculosis, Carbuncles, Cellulitis * The infection is accompanied by 2 or more of the following local signs and symptoms: Pain/tenderness, Swelling, Erythema, Localized warmth, Purulent drainage/discharge, Induration, Regional lymph node swelling or tenderness, Extension of redness * A sample for microbiologic culture must be obtained from the primary infection site at the screening visit * The patient must require and be a suitable candidate for oral antibiotic therapy in the opinion of the Investigator and be able to swallow tablets or capsules intact * A written, voluntarily signed informed consent must be obtained from the patient prior to the initiation of any study-related procedures
Exclusion criteria
* Cellulitis (area greater than 10cm2), chronic or recurrent furunculosis, postoperative wound infection, leg ulcer, decubitus ulcer(s), erysipelas, progressive lymphangitis, acute paronychia or a deep tissue abscess such as pilonidal or breast abscess. Also excluded are skin infections resulting from animal bites * Patients with a complicated skin and skin structure infection as judged by the Investigator * Infections that can be treated by surgical incision alone according to the judgment of the Investigator * Treatment with the following anti-infective agents prior to study drug administration: systemic antibiotic within 7 days; azithromycin within 14 days; a long-acting injectable antibiotic within 30 days * Any infection which requires the use of a concomitant antimicrobial agent, in addition to study drug * Concomitant topical therapy at the infection site for the period within 48 hours prior to study drug administration through TOC * A chronic or underlying skin condition at the site of infection or infections involving prosthetic materials * A wound secondary to burn injury or acne vulgaris * Any infection site that requires: intraoperative surgical debridement; excision of infected area * Documented or suspected bacteremia * Fungal infection involving the nail bed or scalp at the primary uSSSI site * Significant peripheral vascular disease * An abscess at an anatomical location where the incidence of anaerobic pathogen involvement is increased * Patient receiving a daily dose of \> 15 mg of systemic prednisone or equivalent, for \> 10 days within the period starting 14 days prior to study drug administration or anticipated through TOC * Patient with known human immunodeficiency virus (HIV) infection. * Medical history of hypersensitivity or allergic reaction to linezolid according to the judgment of the Investigator * Patients receiving serotonergic agents, selective serotonin reuptake inhibitors (SSRIs), or monoamine oxidase inhibitors (MAOIs) * Patients who have severe liver disease * History of pheochromocytoma, untreated hyperthyroidism, untreated or uncontrolled hypertension, carcinoid syndrome * Evidence of uncontrolled, clinically significant (according to the judgment of the Investigator) cardiovascular, pulmonary, metabolic, gastrointestinal, neurological, or endocrine disease; malignancy or psychiatric disorder * Current evidence of deep vein thrombosis or superficial thrombophlebitis * Experienced a recent clinically significant coagulopathy * Evidence of clinically significant immunosuppression * Patient who previously enrolled in this study * Patient who has previously enrolled in any other clinical trial within 4 weeks of enrollment through TOC. Treatment with an investigational drug within 4 weeks prior to study drug administration * Patient residing in a chronic care facility * Any underlying condition or disease state that would interfere with the completion of the study procedures and evaluation of the absorption of study drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Clinical Response of Cure | Test of Cure (TOC), day 10-20 | To qualify as a Cure, participants were required to fulfill the following criteria: all systemic signs and symptoms of uSSSI present at screening were improved or resolved; no further antibiotic therapy was necessary for treatment of uSSSI; and there was no worsening or appearance of new signs and symptoms of uSSSI. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Per-Patient Microbiologic Response of Eradicated | Test of Cure (TOC), day 10-20 | The microbiological response at the patient level was considered Eradicated (documented or presumed)if no pathogens were present in repeat cultures taken from the original site of infection or a clinical response of cure precluded the ability to obtain a culturable specimen. |
Countries
United States
Participant flow
Recruitment details
This study targeted participants with uncomplicated skin and soft tissue infections (uSSSI) for which oral, outpatient treatment was appropriate. Eligible uSSSIs included simple abscesses, impetigo, folliculitis, furunculosis, carbuncles, and cellulitis (area \<10 cm2).
Participants by arm
| Arm | Count |
|---|---|
| Radezolid QD 450 mg by mouth (PO) once daily (QD) | 51 |
| Radezolid BID 450 mg by mouth (PO) twice daily (BID) | 50 |
| Linezolid BID 600 mg by mouth (PO) BID | 49 |
| Total | 150 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Abnormal screening lab tests | 1 | 1 | 0 |
| Overall Study | Adverse Event | 4 | 0 | 0 |
| Overall Study | Did not receive study drug | 2 | 0 | 2 |
| Overall Study | Lack of Efficacy | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 5 | 7 |
| Overall Study | Protocol Violation | 1 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 0 |
Baseline characteristics
| Characteristic | Radezolid QD | Radezolid BID | Linezolid BID | Total |
|---|---|---|---|---|
| Age, Continuous | 42.8 years STANDARD_DEVIATION 12.43 | 43.6 years STANDARD_DEVIATION 13.65 | 43.7 years STANDARD_DEVIATION 16.33 | 43.3 years STANDARD_DEVIATION 14.1 |
| Sex: Female, Male Female | 14 Participants | 14 Participants | 13 Participants | 41 Participants |
| Sex: Female, Male Male | 37 Participants | 36 Participants | 36 Participants | 109 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 | 20 / 49 | 17 / 50 | 10 / 47 |
| serious Total, serious adverse events | 0 / 49 | 0 / 50 | 0 / 47 |
Outcome results
Primary
Number of Participants With a Clinical Response of Cure
To qualify as a Cure, participants were required to fulfill the following criteria: all systemic signs and symptoms of uSSSI present at screening were improved or resolved; no further antibiotic therapy was necessary for treatment of uSSSI; and there was no worsening or appearance of new signs and symptoms of uSSSI.
Time frame: Test of Cure (TOC), day 10-20
Population: Clinically Evaluable participants were those that met the entry criteria, received a certain amount of drug, did not receive any additional antibiotics before Test of Cure (TOC), and who presented for a TOC evaluation in the appropriate window.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Radezolid QD | Number of Participants With a Clinical Response of Cure | 38 Participants |
| Radezolid BID | Number of Participants With a Clinical Response of Cure | 34 Participants |
| Linezolid BID | Number of Participants With a Clinical Response of Cure | 37 Participants |
Secondary
Number of Patients With Per-Patient Microbiologic Response of Eradicated
The microbiological response at the patient level was considered Eradicated (documented or presumed)if no pathogens were present in repeat cultures taken from the original site of infection or a clinical response of cure precluded the ability to obtain a culturable specimen.
Time frame: Test of Cure (TOC), day 10-20
Population: Microbiologically Evaluable patients were those that met the entry criteria, received a certain amount of drug, did not receive any additional antibiotics before TOC, presented for a TOC evaluation in the appropriate window, and who had a baseline pathogen that was susceptible to study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Radezolid QD | Number of Patients With Per-Patient Microbiologic Response of Eradicated | 20 Participants |
| Radezolid BID | Number of Patients With Per-Patient Microbiologic Response of Eradicated | 23 Participants |
| Linezolid BID | Number of Patients With Per-Patient Microbiologic Response of Eradicated | 21 Participants |