Safety of Either a Single or Two Intravenous Doses of Orbactiv in Participants With Acute Bacterial Skin and Skin Structure Infection

A Double-Blind, Randomized Study to Evaluate the Safety of Either a Single 1200-mg Intravenous (IV) Dose of Orbactiv™ (Oritavancin) and Placebo or Two IV Doses of Orbactiv™ in Subjects Being Treated for Acute Bacterial Skin and Skin Structure Infection (ABSSSI)

The purpose of this study was to evaluate the safety and tolerability of two 1200 milligram (mg) intravenous (IV) infusions of oritavancin when administered one week apart.

Study Overview

• Status: Completed
• Conditions: Skin Diseases, Bacterial
• Intervention / Treatment: Drug: Oritavancin; Drug: Placebo (D5W)

Detailed Description

Clinical studies in adult participants with acute bacterial skin and skin structure infection (ABSSSI) have demonstrated that a single 1200-mg IV dose of oritavancin was clinically non-inferior, well tolerated, and had a similar safety profile to 7 to 10 days of IV vancomycin treatment. The 1200-mg dose of oritavancin is the United States approved therapeutic dose.

Participants with ABSSSI were enrolled in this study to obtain safety information of two 1200-mg IV infusions of oritavancin when administered one week apart.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Somers Point, New Jersey, United States, 08244
      • South Jersey Infectious Disease

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Diagnosis of ABSSSI (wound infections, cellulitis/erysipelas, or cutaneous abscess) suspected or confirmed to be caused by a Gram-positive pathogen requiring IV therapy
• Able to give informed consent and willing to comply with all required study procedures

Exclusion Criteria:

• Infections associated with, or in close proximity to, a prosthetic device
• Severe sepsis or refractory shock
• Known or suspected bacteremia at time of screening

• ABSSSI due to or associated with any of the following:

  • Infections suspected or documented to be caused by Gram-negative pathogens (i.e., human or animal bites, injuries contaminated with fresh or salt water, external malignant otitis)
  • Wound infections (surgical or traumatic) and abscesses with only Gram-negative pathogens
  • Diabetic foot infections (infection extending distal to the malleoli in a participant with diabetes mellitus and peripheral neuropathy and/or vascular insufficiency or any ulceration of their foot)
  • Concomitant infection at another site not including a secondary ABSSSI lesion (e.g., septic arthritis, endocarditis, osteomyelitis)
  • Infected burns
  • A primary infection secondary to a pre-existing skin disease with associated inflammatory changes such as atopic dermatitis, eczema, or hidradenitis suppurativa
  • Decubitus or chronic skin ulcer, or ischemic ulcer due to peripheral vascular disease (arterial or venous)
  • Any evolving necrotizing process (i.e., necrotizing fasciitis), gangrene, or infection suspected or proven to be caused by Clostridium species (e.g., crepitance on examination of the ABSSSI site and/or surrounding tissue(s) or radiographic evidence of subcutaneous gas in proximity to the infection)
  • Infections known to be caused by a Gram-positive organism with a vancomycin minimum inhibitory concentration (MIC) >2 μg/mL or clinically failing prior therapy with glycopeptides
  • Catheter site infections
• Currently receiving chronic systemic immunosuppressive therapy such as chemotherapy or prednisone (prednisone at non-immunosuppressive doses of ≤15 mg/day is permitted)
• Participants who are likely to need treatment with IV unfractionated heparin sodium within 48 hours after oritavancin administration
• Last known cluster of differentiation 4 (CD4) count <200 cells/mm^3 in participants with known human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS)
• Neutropenia with absolute neutrophil count (ANC) <500 cells/mm^3
• Significant or life-threatening condition (e.g., endocarditis) that would confound or interfere with the assessment of safety
• Women who are pregnant or nursing, or who are of childbearing potential and unwilling to use at least 2 acceptable methods of birth control: (e.g., prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, barrier method(s) or male partner sterilization). Women ≥2 years postmenopausal or surgically sterile are exempt from this exclusion
• History of immune-related hypersensitivity reaction to glycopeptides (such as vancomycin, televancin, daptomycin, or dalbavancin) or any of their excipients. Note: participants who have had histamine-like infusion reactions to a glycopeptide are not excluded
• Participants unwilling to forego blood and/or blood product donation for at least 1 month from initiation of oritavancin dose
• Treatment with investigational medicinal product within 30 days or 5 half-lives, whichever is longer, before enrollment and for the duration of the study
• Investigational device present, or removed within 30 days before enrollment, or presence of device-related infection
• Participants who the investigator considers unlikely to adhere to the protocol, comply with oritavancin administration, or complete the clinical study (e.g., unlikely to survive 90 days from initiation of oritavancin dosing)
• Prior exposure to oritavancin alone or in combination with another product.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oritavancin/Oritavancin; On Day 1, participants were administered a single 1200-mg IV dose of oritavancin in 1000 milliliters (mL) diluted in 5% dextrose in water (D5W). On Day 7, an additional 1200-mg IV dose of oritavancin in 1000 mL of D5W was administered.	Drug: Oritavancin; Administered intravenously; Other Names: Orbactiv
Other: Oritavancin/Placebo; On Day 1, participants were administered a single 1200-mg IV dose of oritavancin in 1000 mL of D5W. On Day 7, a placebo was administered IV in 1000 mL of D5W.	Drug: Oritavancin; Administered intravenously; Other Names: Orbactiv; Drug: Placebo (D5W); Administered intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment, including abnormal vital signs or laboratory assessments. Treatment emergent adverse events (TEAE) were AEs which occurred or whose severities worsened on or after the initiation of study drug. An SAE was defined as any untoward medical occurrence that at any dose resulted in any of the following outcomes as fatal, life-threatening, required in-participant hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect, an important medical event. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.	Up to Day 21 after first administration of oritavancin

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With a Clinical Response of Cure	Participants were classified by investigator assessment as "success" for clinical response of cure if there was a complete or nearly complete resolution of baseline signs and symptoms of the primary infection such that no further treatment with antibiotics was needed.	Up to Day 8 after first administration of oritavancin

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Potential for antibody development	A composite measure of multiple laboratory results (direct and indirect antiglobulin test, immunoglobulin panel assays, assay for oritavancin antibodies) assessing the potential for antibody development following single and multiple doses of oritavancin	From screening (≤24 hours from 1st dose) until day 21 follow up

Collaborators and Investigators

• Sponsor: The Medicines Company
• Investigators: Study Director: Medical Information, Melinta Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2017
• Primary Completion (Actual): June 20, 2017
• Study Completion (Actual): June 20, 2017

Study Registration Dates

• First Submitted: October 4, 2016
• First Submitted That Met QC Criteria: October 4, 2016
• First Posted (Estimated): October 5, 2016

Study Record Updates

• Last Update Posted (Estimated): February 1, 2024
• Last Update Submitted That Met QC Criteria: January 30, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Skin Diseases, Infectious; Skin Diseases; Skin Diseases, Bacterial; Anti-Infective Agents; Anti-Bacterial Agents; Oritavancin
• Other Study ID Numbers: MDCO-ORI-16-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No