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

Skin Diseases, Infectious Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00711802
• Other study ID #: 3009-017
• Secondary ID: DAP-PEDS-07-03
• Status: Completed
• Phase: Phase 4
• Start date: July 23, 2008
• Est. completion date: October 11, 2013

Study information

• Verified date: August 2018
• Source: Cubist Pharmaceuticals LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 396
• Est. completion date: October 11, 2013
• Est. primary completion date: October 11, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Communicable Diseases
• Infection
• Skin Diseases
• Skin Diseases, Infectious

Intervention

Drug:
• Daptomycin

• Standard of Care (SOC)

Locations

Country	Name	City	State
India	Medisys Hospital	Bangalore
India	MS Ramaiah	Bangalore
India	MV Hospital and Research Center	Lucknow
India	BYL Nair Hospital	Mumbai
India	Lokmanya Tilak Municipal Medical College	Mumbai
India	KEM Hospital	Pune
India	Ruby Hall Clinic	Pune
Panama	Hospital Del Nino	Panama
United States	Children's Hospital Medical Center of Akron	Akron	Ohio
United States	Emory University	Atlanta	Georgia
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Montifiore Medical Center	Bronx	New York
United States	SUNY Downstate Medical Center	Brooklyn	New York
United States	University of Chicago	Chicago	Illinois
United States	University Hospitals Case Medical Center	Cleveland	Ohio
United States	Children's Hospital of Michigan	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	Texas Children's Hospital	Houston	Texas
United States	The University of Texas Health Science Center	Houston	Texas
United States	LeBonheur Children's Medical Center	Memphis	Tennessee
United States	Vanderbilt University Medical Center and Children's Hospital	Nashville	Tennessee
United States	Robert Wood Johnson Medical School	New Brunswick	New Jersey
United States	Children's Hospital Research Center Oakland	Oakland	California
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Children's Hospital of Orange County	Orange	California
United States	Rady Children's Hospital - San Diego	San Diego	California
United States	University of South Florida College of Medicine	Tampa	Florida
United States	Toledo Children's Hospital	Toledo	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Cubist Pharmaceuticals LLC

Countries where clinical trial is conducted

United States,  India,  Panama, 

References & 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). pii: e20162477. doi: 10.1542/ — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Percentage of Participants With an Overall Therapeutic Response at Test of Cure Visit	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."	Baseline through 14 days after last dose of study drug
Secondary	Pharmacokinetics (PK): Area Under the Plasma Concentration-Time Curve for Daptomycin From 0 to the Last Sampling Time Point (AUC[0-t])	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.	Predose and 5 timepoints according to age group (up to 12 hours postdose)