Treatment of subjects undergoing surgical standard of care for osteomyelitis associated with an infected prosthetic hip or knee joint caused by methicillin-resistant Staphylococcus Aureus and/or coagulase-negative Staphylococci. MedDRA version: 9.1 Level: LLT Classification code 10064250 Term: Staphylococcal osteomyelitis
Conditions
Interventions
Product Name: Cubicin
Pharmaceutical Form: Powder for injection*
INN or Proposed INN: Daptomycin
CAS Number: 103060-53-3
Current Sponsor code: CB-109187
Concentration unit: mg milligram(s)
Concentrati
Sponsors
Cubist Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Informed consent has been obtained; 2.Between the ages of 18 and 80, inclusive; 3.Subject must have a diagnosis of 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; 4.Has one of the following microbiological identifiers of PJI: a. Two confirmatory deep intra-operative cultures obtained at Surgery #1 from 4 or more independent surgical sites for staphylococci (e.g. S. aureus or CoNS); or b. One culture positive for staphylococci (e.g. S. aureus or CoNS) from affected joint synovial fluid aspirate obtained within 6 weeks (42 days) prior to Surgery #1 with a confirmatory positive culture from 1 or more deep intra-operative surgical sites within 72 hours of Surgery #1; or c. In the event intra-operative cultures are negative or remain pending after 72 hours, a patient may be considered for study participation if 2 Gram stains show Gram-positive pathogens or histopathological evidence of staphylococci is obtained within 72 hours following Surgery #1; or d. Two positive blood cultures for staphylococci (e.g. S. aureus or CoNS) obtained from two independent peripheral sites within 48 hours prior to Surgery #1. 5.Subject, if female of childbearing potential, must be willing to practice reliable birth control measures (e.g., condoms or diaphragms together with a spermicidal foam or gel) during study treatment and for at least 28 days after completion of study medication and has a documented negative pregnancy test result within 72 hours prior to study medication administration 6.Subject must be willing to participate in the study, follow protocol study treatment regimen, and comply with all planned assessments. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Subject is anticipated to have retention of the infected prosthetic joint, a one-stage prosthetic joint replacement procedure, or resection of the prosthetic joint and arthrodesis; 2.Subject has undergone a total revision for previous infection of the joint under study; 3. Subject has permanent intravascular prosthetic material in a site or sites other than the joint under study, includingsuch as heart valves, or pacemakers, and any other metalwork or prosthetic implant unless deemed acceptable by the Medical Monitor; 4.Subject is likely to require non-study systemic antibiotics effective against staphylococci for any other reason during the trial period from first dose of study medication through discharge from the hospital following Surgery #2; 5.Subject is anticipated to require oral antibiotic step-down or suppressive antibiotic therapy after EOT and through discharge from the hospital following Surgery #2; 6.Subject has a Creatinine Clearance <30 mL/min as determined by the Cockcroft-Gault equation using actual body weight;[Note: If CRCL drops below 30 mL/min while on treatment the Medical Monitor must be contacted. A decision will be made between the Medical Monitor and the Investigator on a case-by-case basis whether to discontinue a patient from the study.]; 7.Subject has a significant hepatic dysfunction (AST/ALT =5 x ULN or total bilirubin =3.0mg/dL); 8.Subject is unable to discontinue HMG CoA reductase inhibitor therapy from randomization through the EOT visit; 9.Subject has a mixed Gram-positive and Gram-negative PJI or a pure Gram-negative PJI; 10. Subject has a mixed Gram-positive PJI other than staphylococci; 11. Cultures positive for staphylococci that have a non-susceptible MIC to daptomycin, vancomycin or teicoplanin; 12. Subject has a fungal or mycobacterial PJI; 13. Subject is known to be HIV-infected with CD4 count =200 cells/ mm3; 14. Subject has an abnormal CPK (elevated CPK level =2 x ULN) at baseline as measured by central laboratory; 15. Subject is currently under treatment with chemotherapeutic agents, excluding chronic maintenance therapy (e.g. tamoxifen to prevent relapse of primary breast cancer); 16. Subject is severely neutropenic (absolute neutrophil count <0.500x103/µL); 17. Subject has been previously enrolled in the study; 18. Subject has a documented history of significant allergy or intolerance to daptomycin, vancomycin, teicoplanin, or semi-synthetic penicillins; 19. Subject has pneumonia; 20. Subject has prior exposure to daptomycin (either investigational or commercial) within the past 30 days; 21. Subject is currently receiving another investigational drug; 22. Subject is pregnant, nursing, or lactating; 23. Subject is receiving or is expected to receive chronic immunosuppressive therapy during the study. Corticosteroids at doses greater than 10 mg daily for longer than 8 weeks duration will be considered immunosuppressive.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety parameter of CPK levels >500 in PJI subjects treated with daptomycin at 6mg/kg or 8mg/kg versus comparator (vancomycin or teicoplanin);Secondary Objective: Safety: To evaluate the safety parameters, including vital signs, laboratory analytes and adverse events in subjects treated with daptomycin at 6 mg/kg and 8 mg/kg versus those treated with comparator Clinical Efficacy: To evaluate the clinical efficacy of daptomycin at 6 mg/kg and 8 mg/kg versus comparator at the TOC visit Microbiological Response: To evaluate the microbiological response rate of daptomycin at 6 mg/kg and 8 mg/kg versus comparator at the TOC visit Pharmacokinetics: To assess the PK of daptomycin at 6 mg/kg versus 8 mg/kg ;Primary end point(s): The primary endpoint for the study is the incidence of elevated CPK (defined as any CPK value above 500 U/L based on central laboratory assessments) in the CPK safety population at any time point from Day 3 of study medication through 7 days following the last dose of study drug (Day 7P). These data will be analyzed as a dichotomous variable: “No CPK > 500U/L” versus “Any CPK >500U/L”. | — |
Countries
United Kingdom
Outcome results
None listed