Study of Daptomycin in Subjects Undergoing Surgery for Osteomyelitis Associated With an Infected Prosthetic Caused by Staphylococci
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:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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|
- 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) ] [ Designated as safety issue: Yes ]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.
- Safety - Notable Laboratory Abnormalities [ Time Frame: From the 1st day of therapy to maximum of 23 weeks post last dose (up to maximum of week 30) ] [ Designated as safety issue: Yes ]Summary of Notable Laboratory Abnormalities - description of the proportion of subjects within each treatment group that had clinical laboratory values outside the reference range.
- Overall Clinical Outcome [ Time Frame: Approximately 6 weeks post last dose (approximately week 12) ] [ Designated as safety issue: No ]The sponsor determined overall clinical outcome based on blinded review of clinical, microbiological, and radiological response of the subject including, but not limited to, clinical signs and symptoms of PJI, microbiological assessments, radiographic findings, and surgical procedures performed. Subjects were a success if both clinical and microbiological responses were success. A subject who failed to respond clinically or microbiologically was a failure. If microbiological response was non-evaluable and/or clinical evaluation at TOC was not performed, the subject was non-evaluable.
- Microbiological Response [ Time Frame: Approximately 6 weeks post last dose (approximately week 12) ] [ Designated as safety issue: No ]Sponsor's assessment of subject-level microbiological response at the test-of-cure visit for the modified Intent-to-Treat (mITT) population.
- Pharmacokinetic Parameter: Maximum Plasma Concentration (Cmax) [ Time Frame: Day 4 (steady state) ] [ Designated as safety issue: No ]The pharmacokinetic (PK) parameters of daptomycin at steady state for the 6 mg/kg and 8 mg/kg dose groups. On treatment day 4, PK samples for daptomycin levels were to be obtained prior to start of daptomycin infusion (0 hr) and at 0.5 hr (end of infusion), 1-1.5 hr, 3-5 hr, 8-12 hr, and 24 hr after the start of daptomycin infusion.
- Pharmacokinetic Parameter: Area Under the Concentration-time Curve During a Dosing Interval at Steady State (AUCss) [ Time Frame: Day 4 (steady state) ] [ Designated as safety issue: No ]The pharmacokinetic (PK) parameters of daptomycin at steady state for the 6 mg/kg and 8 mg/kg dose groups. On treatment day 4, PK samples for daptomycin levels were to be obtained prior to start of daptomycin infusion (0 hr) and at 0.5 hr (end of infusion), 1-1.5 hr, 3-5 hr, 8-12 hr, and 24 hr after the start of daptomycin infusion.
|Study Start Date:||January 2007|
|Study Completion Date:||June 2010|
|Primary Completion Date:||March 2010 (Final data collection date for primary outcome measure)|
Experimental: Daptomycin 6 mg/kg
Daptomycin (6 mg/kg every 24 hours [q24h]) as a 30 minute intravenous (IV) infusion for 6 weeks (± one week).
Other Name: Cubicin
Experimental: Daptomycin 8 mg/kg
Daptomycin (8 mg/kg q24h) as a 30 minute IV infusion for 6 weeks (± one week).
Other Name: Cubicin
Active Comparator: 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).
Other Name: VancocinDrug: teicoplanin
6 mg/kg; used only at UK sites
Other Name: TargocidDrug: nafcillin
Other Name: UnipenDrug: oxacillin
Other Name: BactocillDrug: flucloxacillin
Other Name: Fluclox
Show 26 Study Locations
|Study Director:||Alistair Wheeler, MD||Cubist Pharmaceuticals, 65 Hayden Ave, Lexington, MA 02421, USA|