A Phase 2 Randomized Study Investigating the Safety, Efficacy and Pharmacokinetics of Daptomycin 6 mg/kg and 8 mg/kg Versus Comparator in the Treatment of Subjects Undergoing Surgical Standard of Care for Osteomyelitis Associated With an Infected Prosthetic Hip or Knee Joint Caused by Staphylococci
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Enrollment
- 75
- Locations
- 26
- Primary Endpoint
- Any Creatine Phosphokinase (CPK) Elevation > 500 Units Per Liter (U/L)
Study Overview
Brief Summary
This is a research study designed to look at the efficacy and safety of daptomycin given at a dose of 6 mg/kg or 8 mg/kg in subjects being treated for prosthetic hip or knee infections caused by Staphylococci. These types of bacteria are among the most common types of bacteria causing infections of prosthetic joints.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Subject must be between the ages of 18 and 80, inclusive
- •Subject must have a diagnosis of prosthetic joint infection (PJI) in a hip or knee joint which has never previously been totally revised because of an infection and for which they are anticipated to undergo a two-stage replacement surgery
- •Subject must have a positive microbiological identifier of staphylococci.
- •If Subject is female of childbearing potential, must be willing to practice reliable birth control
Exclusion Criteria
- •Subject has permanent intravascular prosthetic material such as heart valves or pacemakers
- •Subject has a creatinine clearance (CLCR) <30 mL/min as determined by the Cockcroft-Gault equation using actual body weight.
- •Subject has significant hepatic dysfunction
- •Subject has a fungal or mycobacterial PJI
- •Subject is known to be HIV-infected with CD4 count ≤ 200 cells/ mm3
- •Subject has an abnormal creatine phosphokinase (CPK) (elevated CPK level ≥ 2x ULN) at baseline as measured by central laboratory
- •Subject is currently under treatment with chemotherapeutic agents excluding chronic maintenance therapy (e.g. tamoxifen to prevent relapse of primary breast cancer)
- •Subject is pregnant, nursing, or lactating.
- •Subject is receiving or is expected to receive chronic immunosuppressive therapy during the study.
Arms & Interventions
Daptomycin 6 mg/kg
Daptomycin (6 mg/kg every 24 hours [q24h]) as a 30 minute intravenous (IV) infusion for 6 weeks (± one week).
Intervention: daptomycin (Drug)
Daptomycin 8 mg/kg
Daptomycin (8 mg/kg q24h) as a 30 minute IV infusion for 6 weeks (± one week).
Intervention: daptomycin (Drug)
Comparator
Vancomycin was administered at 1 gram every 12 hours (q12h) as a 60-minute infusion and teicoplanin was administered 6 mg/kg q24h as a 30-minute infusion also for 6 weeks (±1 week). Semi-synthetic penicillin (nafcillin, oxacillin, or flucloxacillin) was administered according to standard of care for 6 weeks (±1 week).
Intervention: vancomycin (Drug)
Comparator
Vancomycin was administered at 1 gram every 12 hours (q12h) as a 60-minute infusion and teicoplanin was administered 6 mg/kg q24h as a 30-minute infusion also for 6 weeks (±1 week). Semi-synthetic penicillin (nafcillin, oxacillin, or flucloxacillin) was administered according to standard of care for 6 weeks (±1 week).
Intervention: teicoplanin (Drug)
Comparator
Vancomycin was administered at 1 gram every 12 hours (q12h) as a 60-minute infusion and teicoplanin was administered 6 mg/kg q24h as a 30-minute infusion also for 6 weeks (±1 week). Semi-synthetic penicillin (nafcillin, oxacillin, or flucloxacillin) was administered according to standard of care for 6 weeks (±1 week).
Intervention: nafcillin (Drug)
Comparator
Vancomycin was administered at 1 gram every 12 hours (q12h) as a 60-minute infusion and teicoplanin was administered 6 mg/kg q24h as a 30-minute infusion also for 6 weeks (±1 week). Semi-synthetic penicillin (nafcillin, oxacillin, or flucloxacillin) was administered according to standard of care for 6 weeks (±1 week).
Intervention: oxacillin (Drug)
Comparator
Vancomycin was administered at 1 gram every 12 hours (q12h) as a 60-minute infusion and teicoplanin was administered 6 mg/kg q24h as a 30-minute infusion also for 6 weeks (±1 week). Semi-synthetic penicillin (nafcillin, oxacillin, or flucloxacillin) was administered according to standard of care for 6 weeks (±1 week).
Intervention: flucloxacillin (Drug)
Outcomes
Primary Outcomes
Any Creatine Phosphokinase (CPK) Elevation > 500 Units Per Liter (U/L)
Time Frame: From the 3rd day of therapy to 1 week post last dose (approximately week 7)
Number of subjects with CPK \>500 U/L between Day 3 and 7 days following the last dose of study medication (Day 7P) as measured by the central laboratory.
Secondary Outcomes
- Safety - Notable Laboratory Abnormalities(From the 1st day of therapy to maximum of 23 weeks post last dose (up to maximum of week 30))
- Overall Clinical Outcome(Approximately 6 weeks post last dose (approximately week 12))
- Microbiological Response(Approximately 6 weeks post last dose (approximately week 12))
- Pharmacokinetic Parameter: Maximum Plasma Concentration (Cmax)(Day 4 (steady state))
- Pharmacokinetic Parameter: Area Under the Concentration-time Curve During a Dosing Interval at Steady State (AUCss)(Day 4 (steady state))