Osteomyelitis
Conditions
Keywords
Osteomyelitis, dalbavancin, antibiotic
Brief summary
This clinical study will be a single-center, randomized, open-label, active-controlled, parallel-group study comparing dalbavancin to standard of care (SOC) therapy in osteomyelitis.
Interventions
DRUGDalbavancin
DRUGComparator
Sponsors
Durata Therapeutics Inc., an affiliate of Allergan plc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* A diagnosis of osteomyelitis (first episode) defined by: * Pain or point tenderness upon palpation or probing to bone * Plain radiograph or Magnetic resonance imaging (MRI) consistent with osteomyelitis (indistinctly marginated edema-like pattern of bone marrow hypointensity on unenhanced T1-weighted sequences, hyperintensity on fat-saturated T2-weighted and Short tau inversion recovery (STIR) sequences and/or abnormal enhancement on gadolinium-enhanced fat-saturated T2-weighted sequences, with or without visible periostitis or cortical bone destruction) OR Gram-positive cocci documented on a baseline Gram-stain from a bone specimen * Elevated C-reactive protein (CRP) (low sensitivity) above the upper limit of normal (ULN) (reference range for low sensitivity CRP is 3-10 mg/L) * Participants must be willing and able, if discharged from the hospital, to return to the hospital or a designated clinic for scheduled visits, treatment, laboratory tests, and other outpatient procedures as required by the protocol.
Exclusion criteria
* Treatment with an investigational drug within 30 days preceding the first dose of investigational product. * Receipt of \> 24 hours of potentially effective IV antibacterial therapy for osteomyelitis within 96 hours of randomization, unless the pathogen isolated was documented to be Methicillin-resistant Staphylococcus aureus (MRSA) that was resistant to the administered antibiotic. * A prior episode of osteomyelitis, or a failed course of therapy for osteomyelitis. * Infection associated with a burn wound, with a sacral decubitus ulcer, or with multiple sites of osteomyelitis. * Septic arthritis that is non-contiguous to osteomyelitis, as diagnosed by isolation of a pathogen from synovial fluid culture. * Immunosuppression/immune deficiency * Evidence of Gram-negative bacteria by Gram stain in the absence of Gram-positive organisms. * Gram-negative bacteremia * Patients with concomitant endocarditis, necrotizing fasciitis, or prosthetic material at the site of infection at the time of study initiation. * Infection due to an organism known prior to study entry to not be susceptible to dalbavancin (dalbavancin mean inhibitory concentration \[MIC\] \> 0.12 μg/mL) or vancomycin (vancomycin MIC \> 2 μg/mL). * Concomitant systemic antibacterial therapy for Gram-positive infections (eg, rifampin, gentamicin). * Known or suspected hypersensitivity to glycopeptide antibiotics. * Patients with a rapidly fatal illness, who are not expected to survive for 3 months. * Pregnant or nursing females; positive urine (or serum) pregnancy test at Screening (pre-menopausal females only) or after admission (prior to dosing) * Sexually active females of childbearing potential who are unwilling or unable to use an acceptable method of contraception from at least the first dose of study drug until the last pregnancy test.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Clinical Response at Day 42 in the Clinically Evaluable (CE) Population | Day 42 | Clinical response was either cure, failure or indeterminate. A cure was defined as recovery without need for additional antibiotic therapy. A failure was defined as the requirement of additional antibiotic therapy for no response or worsening after improvement, new purulence, amputation due to progression of infection (from initiation of study drug to outcome assessment visit), requiring \>6 weeks of antibiotic therapy for participants in the standard of care arm or death (for any reason). Indeterminate was defined as lost to follow-up or amputation due to vascular insufficiency (from initiation of study drug to outcome assessment visit). |
| Percentage of Participants With Clinical Response at Day 365 in the CE Population | Day 365 | Clinical response was either cure, failure or indeterminate. A cure was defined as recovery without need for additional antibiotic therapy. A failure was defined as the requirement of additional antibiotic therapy for no response or worsening after improvement, new purulence, amputation due to progression of infection (from initiation of study drug to outcome assessment visit), requiring \>6 weeks of antibiotic therapy for participants in the standard of care arm or death (for any reason). Indeterminate was defined as lost to follow-up or amputation due to vascular insufficiency (from initiation of study drug to outcome assessment visit). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Clinical Response at Day 42 in the mITT Population | Day 42 | Clinical response was either cure, failure or indeterminate. A cure was defined as recovery without need for additional antibiotic therapy. A failure was defined as the requirement of additional antibiotic therapy for no response or worsening after improvement, new purulence, amputation due to progression of infection (from initiation of study drug to outcome assessment visit), requiring \>6 weeks of antibiotic therapy for participants in the standard of care arm or death (for any reason). Indeterminate was defined as lost to follow-up or amputation due to vascular insufficiency (from initiation of study drug to outcome assessment visit). |
| Percentage of Participants With Clinical Response at Day 42 in the Microbiological Modified Intent-to-Treat (Micro-mITT) Population | Day 42 | Clinical response was either cure, failure or indeterminate. A cure was defined as recovery without need for additional antibiotic therapy. A failure was defined as the requirement of additional antibiotic therapy for no response or worsening after improvement, new purulence, amputation due to progression of infection (from initiation of study drug to outcome assessment visit), requiring \>6 weeks of antibiotic therapy for participants in the standard of care arm or death (for any reason). Indeterminate was defined as lost to follow-up or amputation due to vascular insufficiency (from initiation of study drug to outcome assessment visit). |
| Percentage of Participant With Clinical Response at Day 180 in the mITT Population | Day 180 | Clinical response was either cure, failure or indeterminate. A cure was defined as recovery without need for additional antibiotic therapy. A failure was defined as the requirement of additional antibiotic therapy for no response or worsening after improvement, new purulence, amputation due to progression of infection (from initiation of study drug to outcome assessment visit), requiring \>6 weeks of antibiotic therapy for participants in the standard of care arm or death (for any reason). Indeterminate was defined as lost to follow-up or amputation due to vascular insufficiency (from initiation of study drug to outcome assessment visit). |
| Percentage of Participants With Clinical Improvement at Day 21 in the mITT Population | Baseline to Day 21 | Clinical improvement was defined as no worsening of pain from baseline, if present (subjective pain and/or point tenderness), and improvement in inflammation (as measured by C-reactive protein \[CRP\]). |
| Percentage of Participants With Clinical Response at Day 365 in the mITT Population | Day 365 | Clinical response was either cure, failure or indeterminate. A cure was defined as recovery without need for additional antibiotic therapy. A failure was defined as the requirement of additional antibiotic therapy for no response or worsening after improvement, new purulence, amputation due to progression of infection (from initiation of study drug to outcome assessment visit), requiring \>6 weeks of antibiotic therapy for participants in the standard of care arm or death (for any reason). Indeterminate was defined as lost to follow-up or amputation due to vascular insufficiency (from initiation of study drug to outcome assessment visit). |
| Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Day 42 | Clinical response was either cure, failure or indeterminate. A cure was defined as recovery without need for additional antibiotic therapy. A failure was defined as the requirement of additional antibiotic therapy for no response or worsening after improvement, new purulence, amputation due to progression of infection (from initiation of study drug to outcome assessment visit), requiring \>6 weeks of antibiotic therapy for participants in the standard of care arm or death (for any reason). Indeterminate was defined as lost to follow-up or amputation due to vascular insufficiency (from initiation of study drug to outcome assessment visit). |
| Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Day 180 | Clinical response was either cure, failure or indeterminate. A cure was defined as recovery without need for additional antibiotic therapy. A failure was defined as the requirement of additional antibiotic therapy for no response or worsening after improvement, new purulence, amputation due to progression of infection (from initiation of study drug to outcome assessment visit), requiring \>6 weeks of antibiotic therapy for participants in the standard of care arm or death (for any reason). Indeterminate was defined as lost to follow-up or amputation due to vascular insufficiency (from initiation of study drug to outcome assessment visit). |
| Percentage of Participants With Clinical Response at Day 180 in the CE Population | Day 180 | Clinical response was either cure, failure or indeterminate. A cure was defined as recovery without need for additional antibiotic therapy. A failure was defined as the requirement of additional antibiotic therapy for no response or worsening after improvement, new purulence, amputation due to progression of infection (from initiation of study drug to outcome assessment visit), requiring \>6 weeks of antibiotic therapy for participants in the standard of care arm or death (for any reason). Indeterminate was defined as lost to follow-up or amputation due to vascular insufficiency (from initiation of study drug to outcome assessment visit). |
| Percentage of Participants With Clinical Improvement at Day 21 in the CE Population | Baseline to Day 21 | Clinical improvement was defined as no worsening of pain from baseline, if present (subjective pain and/or point tenderness), and improvement in inflammation (as measured by C-reactive protein \[CRP\]). |
Countries
Ukraine
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dalbavancin Dalbavancin 1500 mg, intravenous (IV) administration over 30 minutes on Day 1 and Day 8. If creatinine clearance was \< 30 milliliters per minute (mL/min) and participant was not receiving regular hemodialysis or peritoneal dialysis, dalbavancin dose was decreased to 1000 mg. | 70 |
| Standard of Care Antibiotic consistent with Standard of Care (SOC), based on baseline pathogen, for 4 to 6 weeks. | 10 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Withdrawal of Consent | 0 | 1 |
Baseline characteristics
| Characteristic | Dalbavancin | Standard of Care | Total |
|---|---|---|---|
| Age, Continuous | 49.2 years STANDARD_DEVIATION 13.3 | 54.4 years STANDARD_DEVIATION 15.3 | 49.8 years STANDARD_DEVIATION 13.6 |
| Race/Ethnicity, Customized Not Hispanic or Latino | 70 Participants | 10 Participants | 80 Participants |
| Race/Ethnicity, Customized White | 70 Participants | 10 Participants | 80 Participants |
| Sex: Female, Male Female | 11 Participants | 5 Participants | 16 Participants |
| Sex: Female, Male Male | 59 Participants | 5 Participants | 64 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 70 | 0 / 10 |
| other Total, other adverse events | 0 / 70 | 0 / 10 |
| serious Total, serious adverse events | 2 / 70 | 0 / 10 |
Outcome results
Primary
Percentage of Participants With Clinical Response at Day 365 in the CE Population
Clinical response was either cure, failure or indeterminate. A cure was defined as recovery without need for additional antibiotic therapy. A failure was defined as the requirement of additional antibiotic therapy for no response or worsening after improvement, new purulence, amputation due to progression of infection (from initiation of study drug to outcome assessment visit), requiring \>6 weeks of antibiotic therapy for participants in the standard of care arm or death (for any reason). Indeterminate was defined as lost to follow-up or amputation due to vascular insufficiency (from initiation of study drug to outcome assessment visit).
Time frame: Day 365
Population: CE-D365 population included all mITT participants who met specific conditions for evaluability at Day 365 (D365).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dalbavancin | Percentage of Participants With Clinical Response at Day 365 in the CE Population | Clinical Cure | 95.5 percentage of participants |
| Dalbavancin | Percentage of Participants With Clinical Response at Day 365 in the CE Population | Clinical Failure | 1.5 percentage of participants |
| Dalbavancin | Percentage of Participants With Clinical Response at Day 365 in the CE Population | Indeterminate | 3.0 percentage of participants |
| Standard of Care | Percentage of Participants With Clinical Response at Day 365 in the CE Population | Clinical Cure | 87.5 percentage of participants |
| Standard of Care | Percentage of Participants With Clinical Response at Day 365 in the CE Population | Clinical Failure | 0 percentage of participants |
| Standard of Care | Percentage of Participants With Clinical Response at Day 365 in the CE Population | Indeterminate | 12.5 percentage of participants |
Primary
Percentage of Participants With Clinical Response at Day 42 in the Clinically Evaluable (CE) Population
Clinical response was either cure, failure or indeterminate. A cure was defined as recovery without need for additional antibiotic therapy. A failure was defined as the requirement of additional antibiotic therapy for no response or worsening after improvement, new purulence, amputation due to progression of infection (from initiation of study drug to outcome assessment visit), requiring \>6 weeks of antibiotic therapy for participants in the standard of care arm or death (for any reason). Indeterminate was defined as lost to follow-up or amputation due to vascular insufficiency (from initiation of study drug to outcome assessment visit).
Time frame: Day 42
Population: CE-D42 population included all modified intent-to-treat (mITT) participants who met specific conditions for evaluability at Day 42 (D42).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dalbavancin | Percentage of Participants With Clinical Response at Day 42 in the Clinically Evaluable (CE) Population | Clinical Cure | 97.0 percentage of participants |
| Dalbavancin | Percentage of Participants With Clinical Response at Day 42 in the Clinically Evaluable (CE) Population | Clinical Failure | 0.0 percentage of participants |
| Dalbavancin | Percentage of Participants With Clinical Response at Day 42 in the Clinically Evaluable (CE) Population | Indeterminate | 3.0 percentage of participants |
| Standard of Care | Percentage of Participants With Clinical Response at Day 42 in the Clinically Evaluable (CE) Population | Clinical Cure | 87.5 percentage of participants |
| Standard of Care | Percentage of Participants With Clinical Response at Day 42 in the Clinically Evaluable (CE) Population | Clinical Failure | 12.5 percentage of participants |
| Standard of Care | Percentage of Participants With Clinical Response at Day 42 in the Clinically Evaluable (CE) Population | Indeterminate | 0.0 percentage of participants |
Secondary
Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population
Clinical response was either cure, failure or indeterminate. A cure was defined as recovery without need for additional antibiotic therapy. A failure was defined as the requirement of additional antibiotic therapy for no response or worsening after improvement, new purulence, amputation due to progression of infection (from initiation of study drug to outcome assessment visit), requiring \>6 weeks of antibiotic therapy for participants in the standard of care arm or death (for any reason). Indeterminate was defined as lost to follow-up or amputation due to vascular insufficiency (from initiation of study drug to outcome assessment visit).
Time frame: Day 180
Population: CE-D180 population included all mITT participants who met specific conditions for evaluability at Day 180 (D180). Includes participants who had baseline pathogens. Participants who had more than one pathogen at Baseline were counted in each category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Prevotella species | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Pluralibacter gergoviae | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Acinetobacter calcoaceticus | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Bacteroides fragilis | 2 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Bacteroides thetaiotaomicron | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Bacteroides vulgatus | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Porphyromonas asaccharolytica | 2 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Prevotella melaninogenica | 2 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Prevotella disiens | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Prevotella intermedia | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Staphylococcus aureus | 39 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Staphylococcus epidermidis | 6 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Staphylococcus haemolyticus | 3 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Staphylococcus pasteuri | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Staphylococcus hominis | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Staphylococcus simulans | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Enterococcus faecalis | 7 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Enterococcus faecium | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Streptococcus agalactiae | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Streptococcus dysgalactiae | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Streptococcus pyogenes | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Corynebacterium striatum | 2 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Aerococcus viridans | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Globicatella species | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Micrococcus luteus | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Peptoniphilus harei | 2 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Anaerococcus prevotii | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Finegoldia magna | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Peptostrep. anaerobius | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Escherichia coli | 3 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Klebsiella pneumoniae | 2 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Pseudomonas aeruginosa | 2 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Enterobacter cloacae complex | 2 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Morganella morganii | 2 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Proteus mirabilis | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Raoultella planticola | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Escherichia hermannii | 1 participants |
| Standard of Care | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Staphylococcus aureus | 5 participants |
| Standard of Care | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Pseudomonas aeruginosa | 1 participants |
| Standard of Care | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Staphylococcus epidermidis | 2 participants |
| Standard of Care | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Streptococcus agalactiae | 1 participants |
| Standard of Care | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Proteus mirabilis | 1 participants |
| Standard of Care | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Serratia marcescens | 1 participants |
| Standard of Care | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Klebsiella pneumoniae | 1 participants |
| Standard of Care | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Corynebacterium striatum | 1 participants |
| Standard of Care | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Enterococcus faecalis | 0 participants |
| Standard of Care | Number of Participants With Clinical Cure by Baseline Pathogen at Day 180 in the CE Population | Raoultella planticola | 1 participants |
Secondary
Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population
Clinical response was either cure, failure or indeterminate. A cure was defined as recovery without need for additional antibiotic therapy. A failure was defined as the requirement of additional antibiotic therapy for no response or worsening after improvement, new purulence, amputation due to progression of infection (from initiation of study drug to outcome assessment visit), requiring \>6 weeks of antibiotic therapy for participants in the standard of care arm or death (for any reason). Indeterminate was defined as lost to follow-up or amputation due to vascular insufficiency (from initiation of study drug to outcome assessment visit).
Time frame: Day 42
Population: CE-D42 population included all mITT participants who met specific conditions for evaluability at Day 42 (D42). Includes participants who had baseline pathogens. Participants who had more than one pathogen at Baseline were counted in each category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Prevotella species | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Pluralibacter gergoviae | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Acinetobacter calcoaceticus | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Bacteroides fragilis | 2 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Bacteroides thetaiotaomicron | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Bacteroides vulgatus | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Porphyromonas asaccharolytica | 2 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Prevotella melaninogenica | 2 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Prevotella disiens | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Prevotella intermedia | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Staphylococcus aureus | 41 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Staphylococcus epidermidis | 6 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Staphylococcus haemolyticus | 3 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Enterococcus faecalis | 7 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Escherichia hermannii | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Staphylococcus pasteuri | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Staphylococcus hominis | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Staphylococcus simulans | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Enterococcus faecium | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Streptococcus agalactiae | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Streptococcus dysgalactiae | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Streptococcus pyogenes | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Corynebacterium striatum | 2 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Aerococcus viridans | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Globicatella species | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Micrococcus luteus | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Peptoniphilus harei | 2 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Anaerococcus prevotii | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Finegoldia magna | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Peptostrep. anaerobius | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Escherichia coli | 3 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Klebsiella pneumoniae | 2 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Pseudomonas aeruginosa | 2 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Enterobacter cloacae complex | 2 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Morganella morganii | 2 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Proteus mirabilis | 1 participants |
| Dalbavancin | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Raoultella planticola | 1 participants |
| Standard of Care | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Staphylococcus aureus | 5 participants |
| Standard of Care | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Raoultella planticola | 0 participants |
| Standard of Care | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Staphylococcus epidermidis | 2 participants |
| Standard of Care | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Pseudomonas aeruginosa | 0 participants |
| Standard of Care | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Streptococcus agalactiae | 1 participants |
| Standard of Care | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Proteus mirabilis | 1 participants |
| Standard of Care | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Serratia marcescens | 0 participants |
| Standard of Care | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Klebsiella pneumoniae | 1 participants |
| Standard of Care | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Corynebacterium striatum | 1 participants |
| Standard of Care | Number of Participants With Clinical Cure by Baseline Pathogen at Day 42 in the CE Population | Enterococcus faecalis | 1 participants |
Secondary
Percentage of Participants With Clinical Improvement at Day 21 in the CE Population
Clinical improvement was defined as no worsening of pain from baseline, if present (subjective pain and/or point tenderness), and improvement in inflammation (as measured by C-reactive protein \[CRP\]).
Time frame: Baseline to Day 21
Population: CE-D21 population included all mITT (modified intent-to-treat) participants who met specific conditions for evaluability at Day 21 (D21).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dalbavancin | Percentage of Participants With Clinical Improvement at Day 21 in the CE Population | 94.0 percentage of participants |
| Standard of Care | Percentage of Participants With Clinical Improvement at Day 21 in the CE Population | 62.5 percentage of participants |
Secondary
Percentage of Participants With Clinical Improvement at Day 21 in the mITT Population
Clinical improvement was defined as no worsening of pain from baseline, if present (subjective pain and/or point tenderness), and improvement in inflammation (as measured by C-reactive protein \[CRP\]).
Time frame: Baseline to Day 21
Population: mITT population included all ITT participants who received any amount of randomized medication and met the criteria for known or suspected Gram-positive osteomyelitis. Participants from whom only a Gram-negative pathogen was isolated from blood and/or bone culture were excluded.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dalbavancin | Percentage of Participants With Clinical Improvement at Day 21 in the mITT Population | 94.0 percentage of participants |
| Standard of Care | Percentage of Participants With Clinical Improvement at Day 21 in the mITT Population | 62.5 percentage of participants |
Secondary
Percentage of Participants With Clinical Response at Day 180 in the CE Population
Clinical response was either cure, failure or indeterminate. A cure was defined as recovery without need for additional antibiotic therapy. A failure was defined as the requirement of additional antibiotic therapy for no response or worsening after improvement, new purulence, amputation due to progression of infection (from initiation of study drug to outcome assessment visit), requiring \>6 weeks of antibiotic therapy for participants in the standard of care arm or death (for any reason). Indeterminate was defined as lost to follow-up or amputation due to vascular insufficiency (from initiation of study drug to outcome assessment visit).
Time frame: Day 180
Population: CE-D180 population included all mITT participants who met specific conditions for evaluability at Day 180 (D180).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dalbavancin | Percentage of Participants With Clinical Response at Day 180 in the CE Population | Clinical Cure | 95.5 percentage of participants |
| Dalbavancin | Percentage of Participants With Clinical Response at Day 180 in the CE Population | Clinical Failure | 1.5 percentage of participants |
| Dalbavancin | Percentage of Participants With Clinical Response at Day 180 in the CE Population | Indeterminate | 3.0 percentage of participants |
| Standard of Care | Percentage of Participants With Clinical Response at Day 180 in the CE Population | Clinical Cure | 87.5 percentage of participants |
| Standard of Care | Percentage of Participants With Clinical Response at Day 180 in the CE Population | Clinical Failure | 0.0 percentage of participants |
| Standard of Care | Percentage of Participants With Clinical Response at Day 180 in the CE Population | Indeterminate | 12.5 percentage of participants |
Secondary
Percentage of Participants With Clinical Response at Day 365 in the mITT Population
Clinical response was either cure, failure or indeterminate. A cure was defined as recovery without need for additional antibiotic therapy. A failure was defined as the requirement of additional antibiotic therapy for no response or worsening after improvement, new purulence, amputation due to progression of infection (from initiation of study drug to outcome assessment visit), requiring \>6 weeks of antibiotic therapy for participants in the standard of care arm or death (for any reason). Indeterminate was defined as lost to follow-up or amputation due to vascular insufficiency (from initiation of study drug to outcome assessment visit).
Time frame: Day 365
Population: mITT population included all ITT participants who received any amount of randomized medication and met the criteria for known or suspected Gram-positive osteomyelitis. Participants from whom only a Gram-negative pathogen was isolated from blood and/or bone culture were excluded.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dalbavancin | Percentage of Participants With Clinical Response at Day 365 in the mITT Population | Clinical Cure | 94.0 percentage of participants |
| Dalbavancin | Percentage of Participants With Clinical Response at Day 365 in the mITT Population | Clinical Failure | 3.0 percentage of participants |
| Dalbavancin | Percentage of Participants With Clinical Response at Day 365 in the mITT Population | Indeterminate | 3.0 percentage of participants |
| Standard of Care | Percentage of Participants With Clinical Response at Day 365 in the mITT Population | Clinical Cure | 87.5 percentage of participants |
| Standard of Care | Percentage of Participants With Clinical Response at Day 365 in the mITT Population | Clinical Failure | 0 percentage of participants |
| Standard of Care | Percentage of Participants With Clinical Response at Day 365 in the mITT Population | Indeterminate | 12.5 percentage of participants |
Secondary
Percentage of Participants With Clinical Response at Day 42 in the Microbiological Modified Intent-to-Treat (Micro-mITT) Population
Clinical response was either cure, failure or indeterminate. A cure was defined as recovery without need for additional antibiotic therapy. A failure was defined as the requirement of additional antibiotic therapy for no response or worsening after improvement, new purulence, amputation due to progression of infection (from initiation of study drug to outcome assessment visit), requiring \>6 weeks of antibiotic therapy for participants in the standard of care arm or death (for any reason). Indeterminate was defined as lost to follow-up or amputation due to vascular insufficiency (from initiation of study drug to outcome assessment visit).
Time frame: Day 42
Population: Micro-mITT population included mITT participants with a Gram-positive pathogen isolated from blood and/or bone specimen. Participants whose cultures included both a Gram-positive and a Gram-negative pathogen are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dalbavancin | Percentage of Participants With Clinical Response at Day 42 in the Microbiological Modified Intent-to-Treat (Micro-mITT) Population | Clinical Cure | 96.8 percentage of participants |
| Dalbavancin | Percentage of Participants With Clinical Response at Day 42 in the Microbiological Modified Intent-to-Treat (Micro-mITT) Population | Clinical Failure | 0.0 percentage of participants |
| Dalbavancin | Percentage of Participants With Clinical Response at Day 42 in the Microbiological Modified Intent-to-Treat (Micro-mITT) Population | Indeterminate | 3.2 percentage of participants |
| Standard of Care | Percentage of Participants With Clinical Response at Day 42 in the Microbiological Modified Intent-to-Treat (Micro-mITT) Population | Clinical Cure | 87.5 percentage of participants |
| Standard of Care | Percentage of Participants With Clinical Response at Day 42 in the Microbiological Modified Intent-to-Treat (Micro-mITT) Population | Clinical Failure | 12.5 percentage of participants |
| Standard of Care | Percentage of Participants With Clinical Response at Day 42 in the Microbiological Modified Intent-to-Treat (Micro-mITT) Population | Indeterminate | 0.0 percentage of participants |
Secondary
Percentage of Participants With Clinical Response at Day 42 in the mITT Population
Clinical response was either cure, failure or indeterminate. A cure was defined as recovery without need for additional antibiotic therapy. A failure was defined as the requirement of additional antibiotic therapy for no response or worsening after improvement, new purulence, amputation due to progression of infection (from initiation of study drug to outcome assessment visit), requiring \>6 weeks of antibiotic therapy for participants in the standard of care arm or death (for any reason). Indeterminate was defined as lost to follow-up or amputation due to vascular insufficiency (from initiation of study drug to outcome assessment visit).
Time frame: Day 42
Population: mITT population included all ITT participants who received any amount of randomized medication and met the criteria for known or suspected Gram-positive osteomyelitis. Participants from whom only a Gram-negative pathogen was isolated from blood and/or bone culture were excluded.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dalbavancin | Percentage of Participants With Clinical Response at Day 42 in the mITT Population | Clinical Cure | 97.0 percentage of participants |
| Dalbavancin | Percentage of Participants With Clinical Response at Day 42 in the mITT Population | Clinical Failure | 0.0 percentage of participants |
| Dalbavancin | Percentage of Participants With Clinical Response at Day 42 in the mITT Population | Indeterminate | 3.0 percentage of participants |
| Standard of Care | Percentage of Participants With Clinical Response at Day 42 in the mITT Population | Clinical Cure | 87.5 percentage of participants |
| Standard of Care | Percentage of Participants With Clinical Response at Day 42 in the mITT Population | Clinical Failure | 12.5 percentage of participants |
| Standard of Care | Percentage of Participants With Clinical Response at Day 42 in the mITT Population | Indeterminate | 0.0 percentage of participants |
Secondary
Percentage of Participant With Clinical Response at Day 180 in the mITT Population
Clinical response was either cure, failure or indeterminate. A cure was defined as recovery without need for additional antibiotic therapy. A failure was defined as the requirement of additional antibiotic therapy for no response or worsening after improvement, new purulence, amputation due to progression of infection (from initiation of study drug to outcome assessment visit), requiring \>6 weeks of antibiotic therapy for participants in the standard of care arm or death (for any reason). Indeterminate was defined as lost to follow-up or amputation due to vascular insufficiency (from initiation of study drug to outcome assessment visit).
Time frame: Day 180
Population: mITT population included all ITT participants who received any amount of randomized medication and met the criteria for known or suspected Gram-positive osteomyelitis. Participants from whom only a Gram-negative pathogen was isolated from blood and/or bone culture were excluded.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dalbavancin | Percentage of Participant With Clinical Response at Day 180 in the mITT Population | Clinical Cure | 94.0 percentage of participants |
| Dalbavancin | Percentage of Participant With Clinical Response at Day 180 in the mITT Population | Clinical Failure | 3.0 percentage of participants |
| Dalbavancin | Percentage of Participant With Clinical Response at Day 180 in the mITT Population | Indeterminate | 3.0 percentage of participants |
| Standard of Care | Percentage of Participant With Clinical Response at Day 180 in the mITT Population | Clinical Cure | 87.5 percentage of participants |
| Standard of Care | Percentage of Participant With Clinical Response at Day 180 in the mITT Population | Clinical Failure | 0.0 percentage of participants |
| Standard of Care | Percentage of Participant With Clinical Response at Day 180 in the mITT Population | Indeterminate | 12.5 percentage of participants |