Safety and Efficacy Study of Daptomycin Compared to Active Comparator in Pediatric Participants With Acute Hematogenous Osteomyelitis (AHO) (MK-3009-006)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2015 by Cubist Pharmaceuticals Holdings LLC
Information provided by (Responsible Party):
Cubist Pharmaceuticals Holdings LLC Identifier:
First received: August 9, 2013
Last updated: October 8, 2015
Last verified: October 2015

The purpose of the study is to determine whether daptomycin is effective and safe in the treatment of pediatric participants with AHO when compared to vancomycin (or equivalent) or nafcillin (or β-lactam equivalent).

Condition Intervention Phase
Acute Hematogenous Osteomyelitis
Drug: Daptomycin
Drug: Vancomycin (or equivalent)
Drug: Nafcillin (or equivalent)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-Blinded Comparative Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Daptomycin Versus Active Comparator in Pediatric Subjects With Acute Hematogenous Osteomyelitis Due to Gram-Positive Organisms

Resource links provided by NLM:

Further study details as provided by Cubist Pharmaceuticals Holdings LLC:

Primary Outcome Measures:
  • Percentage of participants with clinical improvement in the 3 general categories of Pain, Inflammation, and Limb Function based on the Investigator's overall assessment of severity of each of the symptom categories. [ Time Frame: Study Day 5 ] [ Designated as safety issue: No ]
    The Investigator will assess the general categories and clinical symptom parameters of AHO

Secondary Outcome Measures:
  • Percentage of participants with clinical improvement measured as a composite end point of pain, inflammation, limb function, body temperature, and C-reactive protein [ Time Frame: Up to study Day 5 ] [ Designated as safety issue: No ]
  • Percentage of participants with a favorable clinical outcome [ Time Frame: Baseline (within 48 hours prior to first dose of IV study drug) - and up to Test of Cure (21-35 days after last dose of IV study drug) (up to Day 77) ] [ Designated as safety issue: No ]
  • Percentage of participants with a clinical cure or a favorable microbiological response by baseline pathogen at Test of Cure [ Time Frame: Baseline (within 48 hours prior to first dose of IV study drug) - and Test of Cure (21-35 days after last dose of IV study drug) (up to Day 77) ] [ Designated as safety issue: No ]
  • Percentage of participants with sustained clinical improvement [ Time Frame: Baseline (within 48 hours prior to first dose of IV study drug) - up to Test of Cure (21-35 days after last dose of IV study drug) (up to Day 77) ] [ Designated as safety issue: No ]
  • Percentage of participants with a a favorable microbiological response at Test of Cure [ Time Frame: Baseline (within 48 hours prior to first dose of IV study drug) - and Test of Cure (21-35 days after last dose of IV study drug) (up to Day 77) ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Number of participants with 1 or more Adverse Events [ Time Frame: Administration of first dose through Test of Cure Visit (up to Day 77) ] [ Designated as safety issue: Yes ]
  • Number of participants with 1 or more Serious Adverse Events [ Time Frame: Administration of first dose through the last follow-up visit; an expected time of up to 6.5 months ] [ Designated as safety issue: Yes ]
  • Concentration of serum creatine kinase (CK); [ Time Frame: Baseline up to end of IV study drug (up to Day 42) ] [ 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 (21-35 days after last dose of IV study drug) (up to Day 77) ] [ Designated as safety issue: Yes ]
  • Plasma concentration of daptomycin [ Time Frame: Day 3 up to Day 42 ] [ Designated as safety issue: No ]

Estimated Enrollment: 144
Study Start Date: September 2013
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Intervention Drug: Daptomycin
IV daptomycin dosed at 7, 9, or 12 mg/kg infused over 60 minutes ± 10 minutes once daily followed by up to 3 dummy infusions every 6 hours (q6h) infused over 60 (± 10) min to maintain the blind.
Drug: Daptomycin
Active Comparator: Vancomycin (or equivalent), or nafcillin (or equivalent)
IV vancomycin (or equivalent), 10 to 15 mg/kg, infused over 60 (± 10) minutes q6h (± 1 hour) or IV nafcillin (or β-lactam equivalent) at 100-200 mg/kg/day, in divided doses infused over 60 (± 10) min q6h (± 1 hour)
Drug: Vancomycin (or equivalent) Drug: Nafcillin (or equivalent)

Detailed Description:

Acute hematogenous osteomyelitis is a common problem in the pediatric population, affecting approximately 5/10,000 children each year and accounting for approximately 1% of all pediatric hospitalizations. In children, osteomyelitis arises from bacteremic seeding of the bone metaphysis.

Daptomycin, is a cyclic lipopeptide antibacterial active against most clinically significant gram-positive pathogens including drug-resistant strains such as Methicillin Resistant Staphylococcus (S.) aureus (MRSA) and Methicillin Susceptible S. aureus (MSSA). Daptomycin has proven clinical efficacy in adults in the treatment of complicated skin and skin structure infections (cSSSI) caused by aerobic gram-positive pathogens and the treatment of S. aureus bloodstream infections (bacteremia; SAB), including those complicated by right-sided infective endocarditis, caused by MSSA and MRSA. Although not indicated for osteomyelitis, daptomycin has been successfully used to treat osteoarticular infections in adults and children as salvage therapy and at medical centers with increasingly high rates of vancomycin resistant organisms.

In addition, more comparative clinical trials are needed in pediatric AHO to better elucidate the optimal treatment regimen and clinical response.


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

Inclusion Criteria:

  • Obtain Informed Consent;
  • Be 1 year to < 18 years old; a stepwise approach will be implemented to gate enrollment as follows: enrollment will begin with children aged 2-17 years; after an external Drug Safety Monitoring Board (DSMB) review, enrollment will be broadened to 1-17 years.
  • Have diagnosis of suspected or confirmed AHO warranting IV antibacterial therapy as inpatient, based on clinical, imaging and/or microbiological evidence as outlined below:

I. Clinical evidence of fever accompanied by symptoms on the affected limb that include but it is not limited to pain, tenderness on palpation, inflammation, warmth, swelling, difficulty bearing weight, motion restriction, loss of function

II. Radiologic imaging (magnetic resonance imaging [MRI], bone scan, x-ray, or computed tomography [CT] scan) consistent with osteomyelitis OR Microbiological evidence (gram stain, culture or polymerase chain reaction (PCR)) from a bone biopsy or bone aspirate (if available), or blood

III. Laboratory evidence: C-reactive protein (CRP) elevated, Erythrocyte sedimentation rate (ESR) elevated, leukocytosis or leukopenia, immature neutrophils

•Confirmed (I, II, and III) OR suspected (I and III) that must be confirmed post-randomization

Participants will not be allowed into the study if they:

  • Have documented history of any hypersensitivity or allergic reaction to daptomycin
  • Have septic arthritis only (without AHO)
  • Have acute hematogenous osteomyelitis that is located in the spine
  • Have chronic osteomyelitis (i.e. symptoms of osteomyelitis > 21 days) or osteomyelitis with complications requiring non-routine surgical treatment (i.e. sequestration).
  • Have major trauma, penetrating trauma (including a puncture wound of the foot), postoperative osteomyelitis, foreign body in or adjacent to affected bone or joint, or other iatrogenic bone or joint infections present at the site of infection
  • Have acute hematogenous osteomyelitis due to a proven gram-negative organism
  • Have transient tenosynovitis, juvenile rheumatoid arthritis (JRA), reactive arthritis, bony tumors, and other osteoarticular diseases suspected to be due to a nonbacterial (eg, fungal or mycobacterial) etiology
  • Receive more than 24 hours of effective intravenous antibacterial therapy for osteomyelitis within 96 hours before randomization unless microbiological or clinical failure is documented
  • Require any potentially effective concomitant systemic antibacterial therapy for gram-positive infections
  • Have history of seizures (except febrile seizure of childhood)
  • Have peripheral neuropathy
  • Have history of rhabdomyolysis (with the exception of muscle injury due to trauma)
  • Have Sickle cell anemia
  • Cannot be assessed clinically during the study
  • Have any condition (eg, cystic fibrosis, current septic shock) that would make the subject, in the opinion of the Investigator, unsuitable for the study
  • Have significant reduced creatinine clearance (CrCl) < 50 mL/min/1.73 m2
  • Have evidence of significant hepatic, hematologic, or immunologic dysfunction
  • Have Creatine kinase (CK) elevation ≥ 10 × ULN (upper limit of normal) without symptoms or ≥ 5 × ULN with symptoms
  • If female, must not be pregnant or nursing and if required by age and life style take appropriate measures to not get pregnant during the study.
  • Have participated in any study involving administration of an investigational agent or device or daptomycin within 30 days
  • Are unable or unwilling to adhere to the study-specified procedures and restrictions
  • Has suspected or confirmed 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 identifier: NCT01922011

Contact: Toll Free Number 1-888-577-8839

  Show 47 Study Locations
Sponsors and Collaborators
Cubist Pharmaceuticals Holdings LLC
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Cubist Pharmaceuticals Holdings LLC Identifier: NCT01922011     History of Changes
Other Study ID Numbers: 3009-006, DAP-PEDOST-11-03, 2013-000864-28
Study First Received: August 9, 2013
Last Updated: October 8, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Bone Diseases
Bone Diseases, Infectious
Musculoskeletal Diseases
Anti-Bacterial Agents
Anti-Infective Agents
Pharmacologic Actions
Therapeutic Uses processed this record on October 09, 2015