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

NCT00711802 | Completed Phase 4 Results

• 2 other identifiers: 3009-017DAP-PEDS-07-03
• Study Type: interventional
• Target: 396
• Locations: 3 countries
• Sites: 30

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.

Conditions

Skin Diseases, Infectious

Keywords

Complicated; Skin; Structure

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)

  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.

  Baseline through 14 days after last dose of study drug

Secondary Outcomes (2)

• Percentage of Participants With an Overall Therapeutic Response at Test of Cure Visit

  Baseline through 14 days after last dose of study drug

• Pharmacokinetics (PK): Area Under the Plasma Concentration-Time Curve for Daptomycin From 0 to the Last Sampling Time Point (AUC[0-t])

  Predose and 5 timepoints according to age group (up to 12 hours postdose)

Study Arms (2)

Daptomycin

EXPERIMENTAL

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

Standard of Care (SOC)

ACTIVE COMPARATOR

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)

Interventions

Daptomycin DRUG

Also known as: Cubicin

Daptomycin

Standard of Care (SOC) DRUG

Also known as: nafcillin, oxacillin, cloxacillin

Standard of Care (SOC)

Eligibility Criteria

• Age: 1 Year - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA): lead

Study Sites (30)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Children's Hospital Research Center Oakland

Oakland, California, 94606, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

Rady Children's Hospital - San Diego

San Diego, California, 92123, United States

Location

University of South Florida College of Medicine

Tampa, Florida, 33606, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Children's Hospital of Michigan

Detroit, Michigan, 48201, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Robert Wood Johnson Medical School

New Brunswick, New Jersey, 08901, United States

Location

SUNY Downstate Medical Center

Brooklyn, New York, 11203, United States

Location

Montifiore Medical Center

The Bronx, New York, 10467, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Children's Hospital Medical Center of Akron

Akron, Ohio, 44308, United States

Location

University Hospitals Case Medical Center

Cleveland, Ohio, 44106, United States

Location

Toledo Children's Hospital

Toledo, Ohio, 43606, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

LeBonheur Children's Medical Center

Memphis, Tennessee, 38105, United States

Location

Vanderbilt University Medical Center and Children's Hospital

Nashville, Tennessee, 37232, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

The University of Texas Health Science Center

Houston, Texas, 77030, United States

Location

Medisys Hospital

Bangalore, India

Location

MS Ramaiah

Bangalore, India

Location

MV Hospital and Research Center

Lucknow, India

Location

BYL Nair Hospital

Mumbai, India

Location

Lokmanya Tilak Municipal Medical College

Mumbai, India

Location

KEM Hospital

Pune, India

Location

Ruby Hall Clinic

Pune, India

Location

Hospital Del Nino

Panama City, Panama

Location

Related Publications (1)

• 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.

  PMID: 28202770 RESULT

MeSH Terms

Conditions

Skin Diseases, Infectious

Interventions

Daptomycin; Standard of Care; Nafcillin; Oxacillin; Cloxacillin

Condition Hierarchy (Ancestors)

Infections; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Lipopeptides; Lipids; Peptides; Amino Acids, Peptides, and Proteins; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Vice President, Clinical Research
• Organization: Cubist Pharmaceuticals

(781) 860-8660

Study Officials

• Ellie Hershberger

  Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2008
• First Posted: July 9, 2008
• Study Start: July 23, 2008
• Primary Completion: October 11, 2013
• Study Completion: October 11, 2013
• Last Updated: September 5, 2018
• Results First Posted: June 10, 2015

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share

Locations

PA (1); US (22); IN (7)