Clinical trial NCT00711802: Safety and Efficacy Study of Daptomycin in Pediatric Participants (1 to 17 Years-old) With Skin and Skin Structure Infections
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Skin Diseases, Infectious
Keywords: Complicated
Skin
Structure
Lead sponsor: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Sponsor class: INDUSTRY
First posted: 2008-07-09
Enrollment: 396
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Baseline through 14 days after last dose of study drug
Secondary outcomes:
measure: Percentage of Participants With an Overall Therapeutic Response at Test of Cure Visit
timeFrame: Baseline through 14 days after last dose of study drug
measure: Pharmacokinetics (PK): Area Under the Plasma Concentration-Time Curve for Daptomycin From 0 to the Last Sampling Time Point (AUC[0-t])
timeFrame: Predose and 5 timepoints according to age group (up to 12 hours postdose)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Oakland
country: United States
facility: Children's Hospital Research Center Oakland
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital - San Diego
state: California
city: Tampa
country: United States
facility: University of South Florida College of Medicine
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Detroit
country: United States
facility: Children's Hospital of Michigan
state: Michigan
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: New Brunswick
country: United States
facility: Robert Wood Johnson Medical School
state: New Jersey
city: Bronx
country: United States
facility: Montifiore Medical Center
state: New York
city: Brooklyn
country: United States
facility: SUNY Downstate Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Akron
country: United States
facility: Children's Hospital Medical Center of Akron
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Toledo
country: United States
facility: Toledo Children's Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Memphis
country: United States
facility: LeBonheur Children's Medical Center
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center and Children's Hospital
state: Tennessee
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Houston
country: United States
facility: The University of Texas Health Science Center
state: Texas
city: Bangalore
country: India
facility: Medisys Hospital
city: Bangalore
country: India
facility: MS Ramaiah
city: Lucknow
country: India
facility: MV Hospital and Research Center
city: Mumbai
country: India
facility: BYL Nair Hospital
city: Mumbai
country: India
facility: Lokmanya Tilak Municipal Medical College
city: Pune
country: India
facility: KEM Hospital
city: Pune
country: India
facility: Ruby Hall Clinic
city: Panama
country: Panama
facility: Hospital Del Nino
Study officials:
affiliation: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
name: Ellie Hershberger
role: STUDY_DIRECTOR
References:
citation: Bradley J, Glasser C, Patino H, Arnold SR, Arrieta A, Congeni B, Daum RS, Kojaoghlanian T, Yoon M, Anastasiou D, Wolf DJ, Bokesch P. Daptomycin for Complicated Skin Infections: A Randomized Trial. Pediatrics. 2017 Mar;139(3):e20162477. doi: 10.1542/peds.2016-2477. Epub 2017 Feb 15.