Skin Diseases, Bacterial
Conditions
Brief summary
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.
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.
Interventions
DRUGOritavancin
Administered intravenously
DRUGPlacebo (D5W)
Administered intravenously
Sponsors
The Medicines Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to Day 21 after first administration of oritavancin | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Clinical Response of Cure | Up to Day 8 after first administration of oritavancin | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Oritavancin/Oritavancin Participants received an IV infusion of 1200 mg of oritavancin on Day 1 and Day 7 | 17 |
| Oritavancin/Placebo Participants received an IV infusion of 1200 mg of oritavancin on Day 1 and placebo on Day 7 | 5 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
Baseline characteristics
| Characteristic | Oritavancin/Oritavancin | Oritavancin/Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 3 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 2 Participants | 14 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 17 Participants | 5 Participants | 22 Participants |
| Race/Ethnicity, Customized White | 15 Participants | 5 Participants | 20 Participants |
| Sex: Female, Male Female | 11 Participants | 4 Participants | 15 Participants |
| Sex: Female, Male Male | 6 Participants | 1 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 5 |
| other Total, other adverse events | 14 / 17 | 4 / 5 |
| serious Total, serious adverse events | 0 / 17 | 0 / 5 |
Outcome results
Primary
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.
Time frame: Up to Day 21 after first administration of oritavancin
Population: Safety population included all participants who were dosed with a dose of IV oritavancin
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Oritavancin/Oritavancin | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | At least 1 TEAE | 16 Participants |
| Oritavancin/Oritavancin | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | At least 1 SAE | 0 Participants |
| Oritavancin/Placebo | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | At least 1 TEAE | 4 Participants |
| Oritavancin/Placebo | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | At least 1 SAE | 0 Participants |
Secondary
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.
Time frame: Up to Day 8 after first administration of oritavancin
Population: Safety population included all participants who were dosed with a dose of IV oritavancin
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Oritavancin/Oritavancin | Number of Participants With a Clinical Response of Cure | 15 Participants |
| Oritavancin/Placebo | Number of Participants With a Clinical Response of Cure | 5 Participants |