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

• ClinicalTrials.gov Identifier: NCT01252719
• Recruitment Status: Completed
• First Posted: December 3, 2010
• Results First Posted: August 1, 2022
• Last Update Posted: August 1, 2022
• Sponsor: Melinta Therapeutics, Inc.
• Information provided by (Responsible Party): Melinta Therapeutics, Inc.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Wound Infection; Abscess; Systemic Inflammation; Cellulitis	Drug: Single-Dose IV Oritavancin Diphosphate; Drug: IV Vancomycin; Drug: Placebo	Phase 3

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 968 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: December 2010
• Actual Primary Completion Date: October 2012
• Actual Study Completion Date: November 30, 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: Single-Dose IV Oritavancin Diphosphate	Drug: Single-Dose IV Oritavancin Diphosphate; Oritavancin was administered as a single IV dose.; Drug: Placebo; Intravenous placebo was administered thereafter, for a minimum of 7 days and up to a maximum of 10 days (oritavancin and placebo).
Active Comparator: IV Vancomycin	Drug: IV Vancomycin; Intravenous vancomycin was administered for a minimum of 7 days and up to a maximum of 10 days.

Outcome Measures

Primary Outcome Measures :

1. Cessation Of Spread Or Reduction In Size Of Baseline Lesion, Absence Of Fever, And No Rescue Antibiotic Medication At Early Clinical Evaluation (ECE) (48 To 72 Hours) [ Time Frame: 48-72 hours after the initiation of study therapy ]

   Clinical response at the ECE visit (48-72 hours following initiation of study drug administration). Early clinical response was defined as a composite outcome based on cessation of spreading or reduction in the size of baseline lesion, absence of fever and no rescue antibiotic medication.

   A participant was classified as "success" if all of the following were met: cessation of spread or reduction of the lesion (defined as cessation of spread of the redness, edema, and/or induration or reduction in size [length, width, and area] of the redness, edema, and/or induration such that the size of the lesion was less than or equal to the size at baseline); resolution (absence) of fever (temperature <37.7°Celsius at the last 3 consecutive recordings by the same route of administration taken 4 times per day, for example every 6 hours between 48 and 72 hours); no rescue antibiotic medication.

Secondary Outcome Measures :

1. Investigator Assessed Clinical Cure Of Treatment With Single-dose IV Oritavancin Compared With IV Vancomycin For 7 To 10 Days At Post-therapy Evaluation (Key Secondary Endpoint) [ Time Frame: 7-14 days after end of therapy ]
   Compared the clinical efficacy at the post therapy evaluation of oritavancin and vancomycin based on the Investigator examination of the signs and symptoms of the primary acute bacterial skin and skin structure infection (ABSSSI). Investigator assessment of clinical cure was complete or nearly complete resolution of baseline signs and symptoms of the primary infection such that no further treatment with antibiotics was needed.
2. Number Of Participants With A Lesion Size Reduction ≥20% From Baseline At ECE [ Time Frame: 48-72 hours after the initiation of study therapy ]
   Clinical response at the ECE visit (48-72 hours following initiation of study drug administration) based on changes in ABSSSI lesion size measurements from baseline. Participants with a ≥20% reduction in size of baseline lesion were classified a 'success', while those with missing data or those without a reduction in size of baseline lesion ≥20% were classified a 'failure'.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, California

Sharp Chula Vista Medical Center

Chula Vista, California, United States, 91911

Sponsors and Collaborators

Melinta Therapeutics, Inc.

Investigators

• Principal Investigator: G. Ralph Corey, MD; Duke Clinical Research Institute

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Corey GR, Loutit J, Moeck G, Wikler M, Dudley MN, O'Riordan W; SOLO I and SOLO II investigators. Single Intravenous Dose of Oritavancin for Treatment of Acute Skin and Skin Structure Infections Caused by Gram-Positive Bacteria: Summary of Safety Analysis from the Phase 3 SOLO Studies. Antimicrob Agents Chemother. 2018 Mar 27;62(4):e01919-17. doi: 10.1128/AAC.01919-17. Print 2018 Apr.

Deck DH, Jordan JM, Holland TL, Fan W, Wikler MA, Sulham KA, Ralph Corey G. Single-Dose Oritavancin Treatment of Acute Bacterial Skin and Skin Structure Infections: SOLO Trial Efficacy by Eron Severity and Management Setting. Infect Dis Ther. 2016 Sep;5(3):353-61. doi: 10.1007/s40121-016-0119-9. Epub 2016 Jul 1. Erratum In: Infect Dis Ther. 2016 Sep;5(3):363-5.

Corey GR, Kabler H, Mehra P, Gupta S, Overcash JS, Porwal A, Giordano P, Lucasti C, Perez A, Good S, Jiang H, Moeck G, O'Riordan W; SOLO I Investigators. Single-dose oritavancin in the treatment of acute bacterial skin infections. N Engl J Med. 2014 Jun 5;370(23):2180-90. doi: 10.1056/NEJMoa1310422.

• Responsible Party: Melinta Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT01252719
• Other Study ID Numbers: TMC-ORI-10-01
• First Posted: December 3, 2010
• Results First Posted: August 1, 2022
• Last Update Posted: August 1, 2022
• Last Verified: July 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Melinta Therapeutics, Inc.:

ABSSSI; Skin Infection; Abscess

Additional relevant MeSH terms:

Oritavancin; Infections; Communicable Diseases; Wound Infection; Abscess; Cellulitis; Inflammation; Disease Attributes; Pathologic Processes; Suppuration; Skin Diseases, Infectious; Connective Tissue Diseases; Vancomycin; Anti-Bacterial Agents; Anti-Infective Agents