Safety of Either a Single or Two IV Doses of Orbactiv in Subjects With ABSSSI

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and tolerability of two 1200-mg IV infusions of oritavancin when administered one week apart.

Detailed Description
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Clinical studies in adult subjects with 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 (US) approved therapeutic dose. Subjects with ABSSSI will be enrolled in this study to obtain safety information of two 1200-mg IV infusions of oritavancin when administered one week apart. The safety information will include the potential for antibody production following two 1200-mg IV infusions of oritavancin. This study will be a randomized, double-blind study. Subjects will be randomized to receive either two doses of oritavancin or one dose of oritavancin and a single dose of placebo one week apart in order to obtain safety information. This safety information will include information regarding the potential for antibody production following one or two doses of 1200 mg oritavancin.

Official Title
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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)

Conditions
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Skin Diseases, Bacterial

Intervention / Treatment
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* Drug: oritavancin
* Drug: placebo (D5W)


Participation Criteria
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Eligibility Criteria
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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 subject 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) Subjects 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/mm3 in subjects with known human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) Neutropenia with absolute neutrophil count (ANC) <500 cells/mm3 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: subjects who have had histamine-like infusion reactions to a glycopeptide are not excluded Subjects 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 Subjects 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Two doses oritavancin<br>On Day 1 of the study, subjects will be administered a single 1200-mg IV dose of oritavancin in 1000 mL D5W. On Day 7, an additional 1200-mg IV dose of oritavancin in 1000 mL D5W will be administered. | Drug: oritavancin<br> <br> |
| Other: One dose oritavancin, one dose placebo<br>On Day 1 of the study, subjects will be administered a single 1200-mg IV dose of oritavancin in 1000 mL D5W. On Day 7, a placebo (D5W) will be administered. | Drug: oritavancin<br> <br> Drug: placebo (D5W)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: AEs/SAEs | a composite measure of the number and types of AEs/SAEs encountered and relationship to time of dosing | From consent until day 21 follow up | 
| Safety: clinical safety laboratory results | A composite measure of multiple laboratory results assessing the clinical significance of any changes from baseline | From consent until day 21 follow up | 
| Safety: vital sign measurements | A composite of multiple vital sign measurements, assessing the clinical significance of any changes from baseline | From consent until day 21 follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Cure - Resolution of fever | Resolution (absence) of fever (temperature <37.7°C) | Determined by the investigator at Day 7 | 
| Clinical Cure - Cessation of spread or reduction of the lesion | Cessation of spread, or reduction in size (length, width, and area) such that the size of the lesion is less than or equal to the size at baseline | Determined by the investigator at Day 7 | 
| Clinical Cure - No rescue antibiotic medication | No rescue antibiotic medication was needed | Determined by the investigator at Day 7 |