Oritavancin Versus IV Vancomycin for the Treatment of Patients With Acute Bacterial Skin and Skin Structure Infection

Condition(s) targeted: Wound Infection; Abscess; Systemic Inflammation; Cellulitis

Intervention: Single-Dose IV Oritavancin Diphosphate (Drug); IV Vancomycin (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: The Medicines Company

Official(s) and/or principal investigator(s):
G. Ralph Corey, MD, Principal Investigator, Affiliation: Duke Clinical Research Institute

The purpose of this Phase 3 trial is to evaluate the efficacy, safety, and tolerability of oritavancin in ABSSSIs, including those caused by MRSA and to evaluate the potential economic benefit of oritavancin administered as a single 1200 mg IV dose.

Official title: A Multicenter, Double-Blind, Randomized Study to Evaluate the Efficacy and Safety of Single-Dose IV Oritavancin Versus IV Vancomycin for the Treatment of Patients With Acute Bacterial Skin and Skin Structure Infection (SOLO I)

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Cessation of spread or reduction in size of baseline lesion, absence of fever, and no rescue antibiotic medication at ECE (48 to 72 hours)

Secondary outcome:

Clinical cure determined by the investigator at EOT, Day 10 and PTE visits

Safety of oritavancin assessed according to vital signs, laboratory abnormalities, ECG, all-cause mortality and the incidence of adverse events (AEs) and SAEs

The clinical cure determined by the investigator, overall, and by pathogen, at the EOT visit, Day 10, and at the PTE visit

Pharmacokinetics of oritavancin including area under the plasma concentration-time curve (AUC), half-life (t1/2), clearance (CL), Cmax, and steady state volume of distribution (Vss)

The microbiological response, overall and by pathogen, at the EOT visit, at Day 10, and at the PTE visit

The microbiological relapse (or recurrence) at the PTE visit

Clinical response cessation of spread or reduction in size of baseline lesion, absence of fever & no rescue antibiotic medication & clinical cure & microbiological response within the CE population & MicroE population meeting SIRS criteria at screening.

Detailed description: This is a Phase 3, multicenter, randomized, double-blind, parallel, comparative efficacy and safety study of single-dose IV oritavancin/IV placebo versus IV vancomycin for 7 to 10 days in adults with acute bacterial skin and skin structure infection (ABSSSI) suspected or proven to be caused by Gram-positive pathogens. Approximately 960 patients will be randomized at 100 centers globally. In addition, this study will characterize the PK and PK/PD properties of a single 1200 mg IV dose of oritavancin and evaluate the potential health economic benefits offered by this dosing strategy.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria: Subjects may be included in the study if they meet all of the following inclusion criteria: 1. Males or females ≥18 years old 2. Diagnosis of ABSSSI suspected or confirmed to be caused by a Gram-positive pathogen requiring at least 7 days of IV therapy 3. An ABSSSI includes one of the following infections Wound infections, Cellulitis/erysipelas, Major cutaneous abscess 4. ABSSSI must present with at least 2 signs and symptoms 5. Able to give informed consent and willing to comply with all required study procedures Exclusion Criteria: Subjects will be excluded from the study if any of the following exclusion criteria apply prior to randomization: 1. Prior systemic or topical antibacterial therapy with activity against suspected or proven Gram-positive pathogens within the preceding 14 days

- The causative Gram-positive pathogen(s)isolated from the ABSSSI site is

resistant in vitro to the antibacterial(s) that was administered with documented clinical progression, or

- Documented failure to previous ABSSSI antibiotic therapy is available.

Documentation of treatment failure must be recorded

- Patient received a single dose of a short- acting antibacterial therapy three or

more days before randomization 2. Infections associated with, or in close proximity to, a prosthetic device 3. Severe sepsis or refractory shock 4. Known or suspected bacteremia at time of screening 5. ABSSSI due to or associated with any of the following:

- Infections suspected or documented to be caused by Gram-negative pathogens --

Wound infections (surgical or traumatic) and abscesses with only Gram-negative pathogens

- Diabetic foot infections

- Concomitant infection at another site not including a secondary ABSSSI lesion

- Infected burns

- A primary infection secondary to a pre-existing skin disease with associated

inflammatory changes

- Decubitus or chronic skin ulcer, or ischemic ulcer due to peripheral vascular

disease

- Any evolving necrotizing process gangrene or infection suspected or proven to be

caused by Clostridium species

- Infections known to be caused by a Gram-positive organism with a vancomycin MIC

>2 μg/mL or clinically failing prior therapy with glycopeptides

- Catheter site infections

6. Allergy or intolerance to aztreonam or metronidazole in a patient with suspected or proven polymicrobial wound infection involving Gram-negative and/or anaerobic bacteria 7. Currently receiving chronic systemic immunosuppressive therapy 8. AIDS with CD4 count < 200 cells/mm3 9. Neutropenia 10. Significant or life-threatening condition that would confound or interfere with the assessment of the ABSSSI 11. Women who are pregnant or nursing 12. History of immune-related hypersensitivity reaction to glycopeptides 13. Patients that require anticoagulant monitoring with an aPTT 14. Contraindication to vancomycin 15. Patients unwilling to forego blood and/or blood product donation 16. Treatment with investigational medicinal product within 30 days before enrollment and for the duration of the study 17. Investigational device present, or removed <30 days before enrollment, or presence of device-related infection 18. Patients unlikely to adhere to the protocol, comply with study drug administration, or complete the clinical study 19. Severe hepatic disease 20. Presence of hyperuricemia 21. Unwilling to refrain from chronic use of any medication with antipyretic properties

Sharp Chula Vista Medical Center, Chula Vista, California 91911, United States

Starting date: December 2010
Last updated: November 9, 2012