Oritavancin Versus IV Vancomycin for the Treatment of Participants With Acute Bacterial Skin and Skin Structure Infection (SOLO I)

Melinta Therapeutics

Status and phase: Completed; Phase 3

Conditions: Cellulitis; Systemic Inflammation; Wound Infection; Abscess

Treatments: Drug: Single-Dose IV Oritavancin Diphosphate; Drug: Placebo; Drug: IV Vancomycin

Study type: Interventional

Funder types: Industry

Identifiers

NCT01252719

TMC-ORI-10-01

Details and patient eligibility

About

The purpose of this Phase 3 trial was to evaluate the efficacy, safety, and tolerability of oritavancin in acute bacterial skin and skin structure infections (ABSSSIs), including those caused by methicillin-resistant staphylococcus aureus (MRSA), and to evaluate the potential economic benefit of oritavancin administered as a single 1200-milligram (mg) intravenous (IV) dose.

Full description

This was 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 ABSSSI suspected or proven to be caused by gram-positive pathogens. Approximately 960 participants were to be randomized at 100 centers globally.

In addition, this study characterized the pharmacokinetics (PK) and PK/pharmacodynamics (PD) properties of a single 1200-mg IV dose of oritavancin and evaluated the potential health economic benefits offered by this dosing strategy.

Enrollment: 968 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Participants were included in the study if they met 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 included 1 of the following infections: wound infections, cellulitis/erysipelas, major cutaneous abscess
4. ABSSSI must have presented with at least 2 local signs and symptoms and at least 1 sign of systemic inflammation (unless >70 years of age).
5. Able to give informed consent and willing to comply with all required study procedures

Exclusion criteria

Participants were excluded from the study if any of the following exclusion criteria applied prior to randomization:

1. Prior systemic or topical antibacterial therapy with activity against suspected or proven gram-positive pathogens within the preceding 14 days unless:

   • The causative gram-positive pathogen(s) isolated from the ABSSSI site was/were resistant in vitro to the antibacterial(s) that was/were administered with documented clinical progression.
   • Documented failure to previous ABSSSI antibiotic therapy was available. Documentation of treatment failure must have been recorded.
   • Participant received a single dose of a short-acting antibacterial therapy 3 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 minimum inhibitory concentration >2 micrograms/milliliter or clinically failing prior therapy with glycopeptides
   • Catheter site infections

6. Allergy or intolerance to aztreonam or metronidazole in a participant with suspected or proven polymicrobial wound infection involving gram-negative and/or anaerobic bacteria

7. Was currently receiving chronic systemic immunosuppressive therapy

8. Acquired immunodeficiency syndrome with cluster of differentiation 4 count <200 cells/cubic millimeter

9. Neutropenia

10. Significant or life-threatening condition that would confound or interfere with the assessment of the ABSSSI

11. Women who were pregnant or nursing

12. History of immune-related hypersensitivity reaction to glycopeptides

13. Participants that required anticoagulant monitoring with an activated partial thromboplastin time

14. Contraindication to vancomycin

15. Participants 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. Participants 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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968 participants in 2 patient groups

Single-Dose IV Oritavancin Diphosphate

Experimental group

Treatment:

Drug: Placebo

Drug: Single-Dose IV Oritavancin Diphosphate

IV Vancomycin

Active Comparator group

Treatment:

Drug: IV Vancomycin