Safety and Efficacy Study of Daptomycin in Pediatric Participants (1 to 17 Years-old) With Skin and Skin Structure Infections

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Cubist Pharmaceuticals Holdings LLC ( Cubist Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00711802
First received: July 7, 2008
Last updated: May 27, 2015
Last verified: May 2015
  Purpose

This is a multi-center, evaluator-blinded, randomized, comparative study designed to assess the safety, efficacy, and pharmacokinetics (PK) of daptomycin in pediatric subjects ages 1 to 17 years, inclusive, with complicated skin and skin structure infections (cSSSI) caused by Gram-positive pathogens.


Condition Intervention Phase
Skin Diseases, Infectious
Drug: Daptomycin
Drug: Standard of Care (SOC)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: An Evaluation of the Safety, Efficacy and Pharmacokinetics of Daptomycin in Pediatric Subjects Aged One to Seventeen Years With Complicated Skin and Skin Structure Infections Caused by Gram-Positive Pathogens

Resource links provided by NLM:


Further study details as provided by Cubist Pharmaceuticals Holdings LLC:

Primary Outcome Measures:
  • Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Baseline through 14 days after last dose of study drug ] [ Designated as safety issue: No ]
    A TEAE was defined as any treatment-emergent adverse event (AE) that occurred from the time of first dose of the study drug through the last study evaluation or pre-existing adverse AEs that were aggravated in severity or frequency during the dosing period. The percentage of participants with at least 1 TEAE, with at least one drug-related AE (drug-related included "possibly related" or "related" as deemed by the Investigator; it also included events if causality was missing), and who discontinued from treatment due to a TEAE is presented. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.


Secondary Outcome Measures:
  • Percentage of Participants With an Overall Therapeutic Response at Test of Cure Visit [ Time Frame: Baseline through 14 days after last dose of study drug ] [ Designated as safety issue: No ]
    The assessment of therapeutic response was determined by comparing a participant's signs and symptoms at the test of cure visit (up to 14 days after last dose) to those recorded at baseline. Participants were classified as "Success" or "Failure" by combining their clinical and microbiological efficacy responses. Resolution of clinically significant signs and symptoms associated with the skin infection present at study baseline was considered "Success" by the Investigator. These participants were deemed both clinically cured and microbiologically eradicated. For participants whose clinical course could not be clearly defined as improved, a clinical outcome of "Failure" was rendered. In addition, if it was determined that the primary site of infection required additional antibiotic treatment, the assessment of clinical response was "Failure." If the Investigator was unable to determine a response because the participant was lost to follow-up, the assessment was "Unable to evaluate."

  • Pharmacokinetics (PK): Area Under the Plasma Concentration-Time Curve for Daptomycin From 0 to the Last Sampling Time Point (AUC[0-t]) [ Time Frame: Predose and 5 timepoints according to age group (up to 12 hours postdose) ] [ Designated as safety issue: No ]

    Participants who volunteered for PK sampling had a blood sample collected for analysis at the following time points:

    Age Group 1; Day 3: Predose, 0.25 hour (hr), 1 hr, 4 hr, and12 hr postdose. Age Group 2; Day 3: Predose, 0.25 hr, 1 hr, 6 hr, and 10 hr postdose. Age Group 3; Day 1, 2, or 3: Predose, 0.25 hr, 1 hr, 6 hr, and 8 hr postdose. Age Group 4; Day 1, 2, or 3: 0, 1, 2, 4, and 6 hr relative to end of infusion.



Enrollment: 396
Study Start Date: July 2008
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Daptomycin

Administered intravenously (IV) every 24 hours for up to 14 days at the following age-dependent dosages.

Participants ages 7 to 17 years: daptomycin was dissolved in a volume of 50 milliliters (mL) 0.9% sodium chloride for injection over 30 minutes (min) with an infusion rate of 1.67 mL/min.

Participants 1 to 6 years-old: daptomycin was dissolved in a volume of 25 mL 0.9% sodium chloride for injection over 60 min with an infusion rate was 0.42 mL/min.

Age Group 1 (for ages 12 to 17 years): 5 milligrams/kilogram (mg/kg)

Age Group 2 (for ages 7 to 11 years): 7 mg/kg

Age Group 3 (for ages 2 to 6 years): 9 mg/kg

Age Group 4 (for ages 1 to <2 years): 10 mg/kg

Drug: Daptomycin
Other Name: Cubicin
Active Comparator: Standard of Care (SOC)
The comparator agent for this study was the SOC treatment and dosage deemed appropriate by the Investigator. The recommended SOC agents were IV vancomycin, IV clindamycin, and IV semisynthetic penicillins every 24 hours for up to 14 days.
Drug: Standard of Care (SOC)
Other Name: nafcillin, oxacillin, cloxacillin

Detailed Description:

This is a multi-center, evaluator-blinded, randomized, comparative study designed to assess the safety, efficacy, and PK of daptomycin in pediatric participants ages 1 to 17 years, inclusive, with cSSSI caused by Gram-positive pathogens. Participants will be enrolled into age groups and given age-dependent doses over a period of up to 14 days. Participants will be stratified by age group to receive either daptomycin or SOC (recommended as vancomycin, clindamycin or semisynthetic penicillin) in a ratio of 2:1, respectively. Participants may continue on oral therapy following completion of IV study drug administration and provided that the participant meets all criteria for conversion to oral therapy, including clear clinical improvement and availability of an oral agent to which the pathogen is susceptible. The choice of oral therapy will be left to the discretion of the Investigator. February 11, 2015 released from post marketing requirement to include subjects aged 3 months - < 1 year. Ref ID: 3701325

  Eligibility

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

Inclusion Criteria:

  • Written parental (or appropriate legal representative) informed consent prior to any study-related procedure not part of normal medical care
  • Written participant assent (as appropriate)
  • Male or female between the ages of 1 and 17 years old, inclusive
  • If female of childbearing potential (defined as post-menarche), not lactating or pregnant, documented negative pregnancy test result within 48 hours prior to study medication administration and willing to practice reliable birth control measures (at the discretion of the Principal Investigator) during study treatment and for at least 28 days after study completion
  • Able to comply with the protocol for the duration of the study
  • Skin and skin structure infections of a complicated nature known or suspected to be caused by Gram-positive pathogen(s) that require IV antibiotic treatment. Complicated infections are defined as infections either involving deep soft tissue or requiring significant surgical intervention (such as, infected ulcers, burns, and major abscesses) or infections in which the participant has a significant underlying disease state that complicates the response to treatment. The Investigator may contact the Medical Monitor to discuss infections not meeting this definition but which otherwise appear appropriate for inclusion
  • At least three of the following clinical signs and symptoms associated with the cSSSI: pain; tenderness to palpation; temperature >37.5 degrees Celsius (C) (99.5 degrees Fahrenheit [F]) oral or >38 degrees C (100.4 degrees F) rectal; white blood count (WBC) >12,000/cubic millimeter (mm^3) or ≥10% bands; swelling and/or induration; erythema (>1 centimeter [cm] beyond edge of wound or abscess); or pus formation

Exclusion Criteria:

  • Investigational drug use (including daptomycin) or participation in any experimental procedure in the 30 days preceding study entry
  • Known allergy/hypersensitivity to daptomycin
  • Known infection caused solely by Gram-negative pathogen(s), fungus(i), or virus(es)
  • Previous systemic antimicrobial therapy exceeding 24 hours in duration administered anytime during the 48 hours prior to the first dose of study drug (exception: a participant is eligible if on previous antibiotics without any clinical improvement and/or a wound culture is available and the pathogen is not sensitive to prior therapy)
  • Known or suspected pneumonia, osteomyelitis, meningitis, or endocarditis
  • Known bacteremia (exception: any participant enrolled in the study that is subsequently found to have a blood culture positive for bacteremia may be continued)
  • Participant with current or known clinically significant abnormal laboratory test results (including electrocardiograms [ECGs]) that would expose the participant to unacceptable risk as determined by Investigator
  • History of clinically significant cardiovascular, renal, hepatic, pulmonary (well-controlled asthma is acceptable), gastrointestinal, endocrine, hematological, autoimmune disease, or primary immune deficiency (unless the Investigator considers that the subject would not be at risk by participating in the study [Note: human immunodeficiency virus-infected participants must not be enrolled])
  • History of or current clinically significant (at the discretion of the Investigator) muscular disease, nervous system, or seizure disorder
  • Unexplained muscular weakness, history of peripheral neuropathy, Guillain-Barre syndrome or spinal cord injury
  • Known or suspected renal insufficiency (that is, estimated creatinine clearance rate [CLcr]<80 mL/min/1.73 squared meter [m^2]
  • History of or current rhabdomyolysis
  • History of (within 1 year prior to first dose of study drug) or current myositis
  • Current septic shock
  • Known or suspected creatine phosphokinase (CPK) elevation
  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: NCT00711802

  Show 30 Study Locations
Sponsors and Collaborators
Cubist Pharmaceuticals
Investigators
Study Director: Ellie Hershberger Cubist Pharmaceuticals
  More Information

No publications provided

Responsible Party: Cubist Pharmaceuticals Holdings LLC ( Cubist Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00711802     History of Changes
Other Study ID Numbers: DAP-PEDS-07-03
Study First Received: July 7, 2008
Results First Received: May 27, 2015
Last Updated: May 27, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Cubist Pharmaceuticals Holdings LLC:
Complicated
Skin
Structure

Additional relevant MeSH terms:
Communicable Diseases
Infection
Skin Diseases
Skin Diseases, Infectious
Daptomycin
Anti-Bacterial Agents
Anti-Infective Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on July 30, 2015