Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

Comparative Evaluation of the Safety & Efficacy of Daptomycin Versus SOC in 1 - 17 Year Olds With Staphylococcus Aureus Bacteremia (MK-3009-005)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Cubist Pharmaceuticals LLC
ClinicalTrials.gov Identifier:
NCT01728376
First received: November 5, 2012
Last updated: February 2, 2016
Last verified: February 2016
  Purpose
The intent of this study is to describe the safety and efficacy of daptomycin versus standard of care (SOC) in pediatric participants aged 1-17 years with bacteremia caused by Staphylococcus aureus (S. aureus).

Condition Intervention Phase
Bacteremia
Drug: Daptomycin
Drug: Comparator (Vancomycin, Semi-synthetic penicillin, First-generation cephalosporins, Clindamycin)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Comparative Evaluation of the Safety and Efficacy of Daptomycin Versus Standard of Care in Pediatric Subjects One - Seventeen Years of Age With Bacteremia Caused by Staphylococcus Aureus.

Resource links provided by NLM:


Further study details as provided by Cubist Pharmaceuticals LLC:

Primary Outcome Measures:
  • Number of participants with one or more Adverse Events [ Time Frame: Administration of first dose through the last follow-up visit (up to 77 days) ] [ Designated as safety issue: Yes ]
  • Number of participants with one or more Serious Adverse Events [ Time Frame: Administration of first dose through the last follow-up visit (up to 77 days) ] [ Designated as safety issue: Yes ]
  • Levels of serum creatine phosphokinase (CPK) [ Time Frame: Baseline up to end of therapy visit (up to 44 days) ] [ Designated as safety issue: Yes ]
  • Change from baseline in number of participants with abnormal focused (peripheral) neurological assessments [ Time Frame: Baseline and up to Test of Cure (TOC) Safety Visit (up to 56 days) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Percentage of participants with clinical success at TOC/Safety visit [ Time Frame: 7-14 days after the last dose of study medication (up to 56 days) ] [ Designated as safety issue: No ]
  • Trough plasma concentration of daptomycin [ Time Frame: Days 3, 4 or 5 of treatment at pre-dose ] [ Designated as safety issue: No ]
  • Maximum plasma concentration (Cmax) of daptomycin [ Time Frame: Days 3, 4 or 5 of treatment at end of infusion ] [ Designated as safety issue: No ]
  • Percentage of participants with overall success at TOC visit [ Time Frame: 7-14 days after the last dose of study medication (up to 56 days) ] [ Designated as safety issue: No ]

Enrollment: 82
Study Start Date: November 2012
Study Completion Date: January 2016
Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Daptomycin - 12 to 17 year olds
12-17 year olds: administered daptomycin 7 mg/kg, infused once daily, intravenously, over 30 minutes
Drug: Daptomycin
Intravenous daptomycin given at 7 mg/kg (ages 12-17 years); 9 mg/kg (ages 7-11 years); 12 mg/kg (ages 1-6 years) infused once daily, intravenously, over 30 or 60 minutes
Other Name: Cubicin
Active Comparator: Standard of care; comparator
vancomycin, Semi-synthetic penicillin, First-generation cephalosporins, Clindamycin
Drug: Comparator (Vancomycin, Semi-synthetic penicillin, First-generation cephalosporins, Clindamycin)
Administered per standard of care
Other Name: Vancomycin, Semi-synthetic penicillin, First-generation cephalosporins, Clindamycin
Experimental: Daptomycin - 7 to 11 year olds
7-11 year olds: administered daptomycin 9 mg/kg, infused once daily, intravenously, over 30 minutes
Drug: Daptomycin
Intravenous daptomycin given at 7 mg/kg (ages 12-17 years); 9 mg/kg (ages 7-11 years); 12 mg/kg (ages 1-6 years) infused once daily, intravenously, over 30 or 60 minutes
Other Name: Cubicin
Experimental: Daptomycin - 1 to 6 year olds
1-6 year olds: administered daptomycin 12 mg/kg, infused once daily, intravenously, over 60 minutes
Drug: Daptomycin
Intravenous daptomycin given at 7 mg/kg (ages 12-17 years); 9 mg/kg (ages 7-11 years); 12 mg/kg (ages 1-6 years) infused once daily, intravenously, over 30 or 60 minutes
Other Name: Cubicin

Detailed Description:

S. aureus causes a series of invasive diseases in adults and children, including bacteremia. Infections due to S. aureus in children, particularly those due to methicillin resistant S. aureus (MRSA), are a growing world-wide public health concern.

Daptomycin, a cyclic lipopeptide antibacterial agent, shows rapid in vitro bactericidal activity with concentration-dependent killing for Gram-positive organisms, including S. aureus. Surveillance studies have demonstrated a daptomycin MIC90 of 0.5µg/ml for both methicillin-susceptible S. aureus (MSSA) and MRSA with >99% of MRSA isolates being categorized as susceptible by the Food and Drug Administration (FDA), European Committee of antimicrobial susceptibility testing (EUCAST) and Clinical and Laboratory Standards Institute (CLSI) breakpoints (5). Clinical trials in adults demonstrated that daptomycin was safe and efficacious in complicated skin and skin structure infections (cSSSI) and bloodstream infections caused by S. aureus, including right-sided infective endocarditis (RIE). However, information on the safety and efficacy of daptomycin for use in children is lacking.

The intent of this study in children is to confirm the safety of daptomycin at mean steady state systemic exposures (AUC) similar to those reported for adults treated at 6 mg/kg for bacteremia.

  Eligibility

Ages Eligible for Study:   1 Year to 17 Years   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

To be included in this study, participants must:

  • Sign a parental consent form; if appropriate, sign an assent form
  • Be between 1 and 17 years of age
  • Have proven or probable bacteremia caused by S. aureus based on the traditional culture result, rapid diagnostic test or Gram stain
  • If female of childbearing potential, must not be pregnant or nursing and take appropriate measures to not get pregnant during the study
  • If male, must take appropriate measures to not get partner pregnant
  • Able to comply with the protocol requirements

Exclusion Criteria:

Participants will not be allowed into the study if they:

  • Have received a certain amount of antibacterial therapy specific for current bacteremia unless it is demonstrated that the organism is resistant to the given antibacterial;
  • Anticipate to require other antibiotics that may be potentially effective against S. aureus;
  • Have shock or hypotension unresponsive to standard therapy;
  • Have received an investigational product or have participated in an experimental procedure within 30 days;
  • Have an intolerance or hypersensitivity to daptomycin;
  • Have renal insufficiency;
  • Have prior history or current evidence of muscle damage (rhabdomyolysis; significant CPK elevation);
  • Have history of clinically significant muscular disease, nervous system or seizure disorder, including unexplained muscular weakness, history of peripheral neuropathy, Guillain-Barré or spinal cord injury;
  • Have S. aureus pneumonia, empyema, meningitis, or endocarditis
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01728376

Sponsors and Collaborators
Cubist Pharmaceuticals LLC
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Responsible Party: Cubist Pharmaceuticals LLC
ClinicalTrials.gov Identifier: NCT01728376     History of Changes
Other Study ID Numbers: 3009-005  DAP-PEDBAC-11-02 
Study First Received: November 5, 2012
Last Updated: February 2, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Bacteremia
Bacterial Infections
Sepsis
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Vancomycin
Clindamycin
Clindamycin palmitate
Clindamycin phosphate
Daptomycin
Penicillins
Cephalosporins
Anti-Bacterial Agents
Anti-Infective Agents
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 23, 2016