Safety and Efficacy Study of Daptomycin in Pediatric Subjects (2-17 Years)With Skin and Skin Structure Infections

Condition(s) targeted: Skin Diseases, Infectious

Intervention: Daptomycin (Drug); Vancomycin, Clindamycin or semi-synthetic Penicillins (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Cubist Pharmaceuticals

Official(s) and/or principal investigator(s):
Hernando Patino, MD, Study Director, Affiliation: Cubist Pharmaceuticals

Overall contact:
Claudia Abbes, Phone: 781-860-8201, Email: claudia.abbes@cubist.com

This is a multi-center, evaluator-blinded, randomized, comparative study designed to assess the safety, efficacy and pharmacokinetics of daptomycin in pediatric subjects ages 2-17 years, inclusive, with cSSSI caused by Gram-positive pathogens.

Official title: An Evaluation of the Safety, Efficacy and Pharmacokinetics of Daptomycin in Pediatric Subjects Aged Two to Seventeen Years With Complicated Skin and Skin Structure Infections Caused by Gram-Positive Pathogens

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Safety of daptomycin

Secondary outcome:

Efficacy of daptomycin

Pharmacokinetics of daptomycin

Detailed description: This is a multi-center, evaluator-blinded, randomized, comparative study designed to assess the safety, efficacy and pharmacokinetics of daptomycin in pediatric subjects ages 2-17 years, inclusive, with cSSSI caused by Gram-positive pathogens. Subjects will be enrolled into two age groups and given age dependant doses over a period of up to 14 days. Subjects will be stratified by age group to receive either daptomycin or standard of care (recommended as vancomycin, clindamycin or semi-synthetic penicillin) in a ratio of 2: 1, respectively. Subjects may continue on oral therapy following completion of i. v. study drug administration and provided that the subject 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.

Minimum age: 1 Year. Maximum age: 17 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Written parental (or appropriate legal representative) informed consent prior to any

study-related procedure not part of normal medical care;

- Written subject 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 intravenous antibiotic treatment. Complicated infections are defined as infections either involving deep soft tissue or requiring significant surgical intervention (e. g. infected ulcers, burns, and major abscesses) or infections in which the subject 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 C (99. 5 degrees F) oral or >38 degrees C (100. 4 degrees F) rectal; white blood count (WBC) >12,000/mm3 or ≥10% bands; swelling and/or induration;erythema (>1 cm beyond edge of wound or abscess); 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 duration administered

anytime during the 48 hours prior to the first dose of study drug (exception: a subject 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 subject enrolled in the study that is subsequently

found to have a blood culture positive for bacteremia may be continued as described in section 10. 4.4);

- Subjects with current or known clinically significant abnormal laboratory test

results (including ECGs) that would expose the subject 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: HIV infected subjects 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 or

spinal cord injury;

- Known renal insufficiency (i. e. estimated creatinine clearance rate (CLcr)<80

mL/min/1. 73m2, or suspected;

- History of or current rhabdomyolysis;

- History of (within one year prior to first dose of study drug) or current myositis;

- Current septic shock;

- Known or suspected CPK elevation

Claudia Abbes, Phone: 781-860-8201, Email: claudia.abbes@cubist.com

MS Ramaiah, Bangalore, India; Terminated

Citi Hospital, Bangalore, India; Withdrawn

Medisys Hospital, Bangalore, India; Terminated

MV Hospital and Research Center, Lucknow, India; Terminated

BYL Nair Hospital, Mumbai, India; Terminated

Lokmanya Tilak Municipal Medical College, Mumbai, India; Terminated

Ruby Hall Clinic, Pune, India; Terminated

KEM Hospital, Pune, India; Terminated

JOSHA Research, Bloemfontein, South Africa; Withdrawn

Middleburg Hospital, Middleburg, South Africa; Withdrawn

GCT-Mercantile Clinical Trial Centre, Port Elizabeth, South Africa; Withdrawn

Global Clinical Trials (Pty) Ltd, Temba, South Africa; Withdrawn

University of Alabama at Birmingham, Birmingham, Alabama 35233, United States; Recruiting
David Kimberlin, MD, Principal Investigator

Miller Children's Hospital, Long Beach, California 90806, United States; Withdrawn

Children's Hospital Reseach Center Oakland, Oakland, California 94606, United States; Terminated

Children's Hospital of Orange County, Orange, California 92868, United States; Terminated

Rady Children's Hospital - San Diego, San Diego, California 92123, United States; Recruiting
John Bradley, MD, Principal Investigator

Lee Memorial Health System, Fort Myers, Florida 33908, United States; Withdrawn

University of South Florida College of Medicine, Tampa, Florida 33606, United States; Terminated

Emory University, Atlanta, Georgia 30322, United States; Terminated

University of Chicago, Chicago, Illinois 60637, United States; Recruiting
Robert Daum, MD, Principal Investigator

University of Louisiana at Monroe, Shreveport, Louisiana 71103, United States; Withdrawn

Boston Medical Center, Boston, Massachusetts 02118, United States; Withdrawn

Children's Hospital of Michigan, Detroit, Michigan 48201, United States; Recruiting
Nahed Abdel-Haq, MD, Principal Investigator

Children's Mercy Hospital, Kansas City, Missouri 64108, United States; Withdrawn

University of Nebraska Medical Center, Omaha, Nebraska 68198, United States; Recruiting
Kari Simonsen, MD, Principal Investigator

Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901, United States; Recruiting
Amisha Malhotra, MD, Principal Investigator

Montifiore Medical Center, Bronx, New York 10467, United States; Recruiting
Tsoline Kojaoghlanian, MD, Principal Investigator

SUNY Downstate Medical Center, Brooklyn, New York 11203, United States; Terminated

Duke University Medical Center, Durham, North Carolina 27710, United States; Recruiting
Coleen Cunningham, MD, Principal Investigator

Children's Hospital Medical Center of Akron, Akron, Ohio 44308, United States; Terminated

University Hospitals Case Medical Center, Cleveland, Ohio 44106, United States; Recruiting
Philip Toltzis, MD, Principal Investigator

Nationwide Children's Hospital, Columbus, Ohio 43205, United States; Withdrawn

Toledo Children's Hospital, Toledo, Ohio 43606, United States; Recruiting

University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, United States; Terminated

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States; Withdrawn

LeBonheur Children's Medical Center, Memphis, Tennessee 38105, United States; Recruiting
Sandra Arnold, MD, Principal Investigator

Vanderbuilt University Medical Center and Children's Hospital, Nashville, Tennessee 37232, United States; Terminated

Cook Children's Medical Center, Fort Worth, Texas 76104, United States; Recruiting
Lynne Eger, MD, Principal Investigator

The University of Texas Health Science Center, Houston, Texas 77030, United States; Recruiting
Gloria Heresi, MD, Principal Investigator

Texas Children's Hospital, Houston, Texas 77030, United States; Recruiting
Sheldon Kaplan, MD, Principal Investigator

Starting date: July 2008
Last updated: February 8, 2012