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

ID: NCT00711802
Status: Completed
Phase: Phase 4
Start Date: July 23, 2008
First Submitted: July 07, 2008
Last Updated: May 26, 2017
Results: Available
Success Rate: 88%
Sponsors & Collaborators: Cubist Pharmaceuticals LLC
Location: India, Panama, United States
Conditions: Skin Diseases, Infectious
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Study Description

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
Condition or disease Intervention/treatment Phase

Skin Diseases, Infectious

Drug: Daptomycin
Other Names
Cubicin
Drug: Standard of Care (SOC)
Other Names
nafcillin, oxacillin, cloxacillin
Phase 4

Tracking Information

First Submitted DateJuly 07, 2008
Last Update Posted DateMay 26, 2017
Actual Start DateJuly 23, 2008
Actual Completion DateOctober 11, 2013
Actual Primary Completion DateOctober 11, 2013
Results First Submitted DateMay 27, 2015
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) [Time Frame: Baseline through 14 days after last dose of study drug]

    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.

Original Primary Outcome Measures

  • 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.

Current 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]

    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)]

    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.

Original Secondary Outcome Measures

  • 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.

  • 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."

Study Design

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

Study TypeInterventional
Study PhasePhase 4
Estimated Enrollment
396
Allocation
Randomized
Interventional Model
Parallel Assignment
Masking
Single
Primary Purpose
Treatment
Conditions
Skin Diseases, Infectious
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: Daptomycin

Other Names
Cubicin
Drug: Standard of Care (SOC)

Other Names
nafcillin, oxacillin, cloxacillin
Study Groups/Cohorts
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

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.

Study Arms
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

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)

Arm Intervention/Treatment
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
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)

Recruitment Information

Recruitment Status:Completed
Enrollment396
Completion DateOctober 11, 2013
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
GenderAll
Age1 Year to 17 Years
Accepts Healthy VolunteersNo
Contacts
Not Available
Listed Location Countries
India
Panama
United States
Guatemala
South Africa

Administrative Information

NCT Number:NCT00711802
Other Study ID Numbers
3009-017
DAP-PEDS-07-03
Has Data Monitoring CommitteeNo
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Plan to Share IPD: Yes
Plan Description: http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf http://engagezone.msd.com/ds_documentation.php
Responsible Party,
Study Sponsor
Cubist Pharmaceuticals LLC
Collaborators
Not Available
Investigators
Study Director
Ellie Hershberger
Cubist Pharmaceuticals LLC

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Not Available

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Not Available

Reporting Groups

TitleDescription
Age Group 1: Daptomycin
Daptomycin: 5 milligrams/kilogram (mg/kg) administered intravenously (IV) every 24 hours for up to 14 days Age Group 1: Participants ages 12 to 17 years
Age Group 1: Standard of Care (SOC)
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. Age Group 1: Participants ages 12 to 17 years
Age Group 2: Daptomycin
Daptomycin: 7 mg/kg administered IV every 24 hours for up to 14 days Age Group 2: Participants ages 7 to 11 years
Age Group 2: SOC
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. Age Group 2: Participants ages 7 to 11 years
Age Group 3: Daptomycin
Daptomycin: 9 mg/kg administered IV every 24 hours for up to 14 days Age Group 3: Participants ages 2 to 6 years
Age Group 3: SOC
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. Age Group 3: Participants ages 2 to 6 years
Age Group 4: Daptomycin
Daptomycin: 10 mg/kg administered IV every 24 hours for up to 14 days Age Group 4: Participants ages 1 to <2 years
Age Group 4: SOC
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. Age Group 4: Participants ages 1 to <2 years

Participant Flow: Overall

Age Group 1: DaptomycinAge Group 1: Standard of Care (SOC)Age Group 2: DaptomycinAge Group 2: SOCAge Group 3: DaptomycinAge Group 3: SOCAge Group 4: DaptomycinAge Group 4: SOC
7337733881423015
Started7538753883423015
Completed7332693569342513
Not Completed266314852
Adverse Event00001100
Lost to Follow-up003110642
Microbiological failure01000100
Not treated (no further detail)21202000
Physician Decision02000000
Protocol Violation00010000
Reason not reported01101010
Withdrawal by Subject01010000

Baseline Characteristics

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who received at least 1 dose of study drug

Reporting Groups

TitleDescription
Age Group 1: Daptomycin
Daptomycin: 5 mg/kg administered IV every 24 hours for up to 14 days Age Group 1: Participants ages 12 to 17 years
Age Group 1: Standard of Care (SOC)
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. Age Group 1: Participants ages 12 to 17 years
Age Group 2: Daptomycin
Daptomycin: 7 mg/kg administered IV every 24 hours for up to 14 days Age Group 2: Participants ages 7 to 11 years
Age Group 2: SOC
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. Age Group 2: Participants ages 7 to 11 years
Age Group 3: Daptomycin
Daptomycin: 9 mg/kg administered IV every 24 hours for up to 14 days Age Group 3: Participants ages 2 to 6 years
Age Group 3: SOC
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. Age Group 3: Participants ages 2 to 6 years
Age Group 4: Daptomycin
Daptomycin: 10 mg/kg administered IV every 24 hours for up to 14 days Age Group 4: Participants ages 1 to <2 years
Age Group 4: SOC
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. Age Group 4: Participants ages 1 to <2 years
Total
Total of all reporting groups

Baseline Measures

Age Group 1: DaptomycinAge Group 1: Standard of Care (SOC)Age Group 2: DaptomycinAge Group 2: SOCAge Group 3: DaptomycinAge Group 3: SOCAge Group 4: DaptomycinAge Group 4: SOCTotal
Overall Participants Analyzed
Units: Participants
Participants Analyzed
7337733881423015389
7337733881423015389
Age
Units: years - Mean (Standard Deviation)
Participants Analyzed
7337733881423015389
15.02 (1.584)14.84 (1.735)9.05 (1.443)8.98 (1.305)3.92 (1.556)3.86 (1.555)1.46 (0.299)1.43 (0.299)8.21 (5.134)
Sex: Female, Male
Units: Participants - Count of Participants
Participants Analyzed
7337733881423015389
Female2915281548202112188
Male44224523332293201
Race (NIH/OMB)
Units: Participants - Count of Participants
Participants Analyzed
7337733881423015389
American Indian or Alaska Native000000000
Asian331649251001125
Black or African American12685331012490
More than one race000101002
Native Hawaiian or Other Pacific Islander000000000
Unknown or Not Reported011040017
White28141574331189165

Outcome Measures

1. Primary: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)

Measure Type
Primary
Measure Title
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
Measure Description
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.
Time Frame
Baseline through 14 days after last dose of study drug

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants who received at least 1 dose of study drug with evaluable post-baseline TEAE data.

Reporting Groups

TitleDescription
Age Group 1: Daptomycin
Daptomycin: 5 mg/kg administered IV every 24 hours for up to 14 days Age Group 1: Participants ages 12 to 17 years
Age Group 1: Standard of Care (SOC)
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. Age Group 1: Participants ages 12 to 17 years
Age Group 2: Daptomycin
Daptomycin: 7 mg/kg administered IV every 24 hours for up to 14 days Age Group 2: Participants ages 7 to 11 years
Age Group 2: SOC
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. Age Group 2: Participants ages 7 to 11 years
Age Group 3: Daptomycin
Daptomycin: 9 mg/kg administered IV every 24 hours for up to 14 days Age Group 3: Participants ages 2 to 6 years
Age Group 3: SOC
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. Age Group 3: Participants ages 2 to 6 years
Age Group 4: Daptomycin
Daptomycin: 10 mg/kg administered IV every 24 hours for up to 14 days Age Group 4: Participants ages 1 to <2 years
Age Group 4: SOC
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. Age Group 4: Participants ages 1 to <2 years

Outcome Measures

Age Group 1: DaptomycinAge Group 1: Standard of Care (SOC)Age Group 2: DaptomycinAge Group 2: SOCAge Group 3: DaptomycinAge Group 3: SOCAge Group 4: DaptomycinAge Group 4: SOC
Participants Analyzed
Units: Participants
7238733881423015
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
Units: percentage of participants - Number
At least 1 drug-related TEAE13.910.55.510.522.221.410.033.3
At least 1 TEAE36.136.823.318.450.638.146.773.3
Discontinued treatment due to a TEAE2.801.403.714.33.36.7

2. Secondary: Percentage of Participants With an Overall Therapeutic Response at Test of Cure Visit

Measure Type
Secondary
Measure Title
Percentage of Participants With an Overall Therapeutic Response at Test of Cure Visit
Measure Description
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."
Time Frame
Baseline through 14 days after last dose of study drug

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants who received at least 1 dose of study drug with evaluable test-of-cure visit data.

Reporting Groups

TitleDescription
Age Group 1: Daptomycin
Daptomycin: 5 mg/kg administered IV every 24 hours for up to 14 days Age Group 1: Participants ages 12 to 17 years
Age Group 1: Standard of Care (SOC)
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. Age Group 1: Participants ages 12 to 17 years
Age Group 2: Daptomycin
Daptomycin: 7 mg/kg administered IV every 24 hours for up to 14 days Age Group 2: Participants ages 7 to 11 years
Age Group 2: SOC
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. Age Group 2: Participants ages 7 to 11 years
Age Group 3: Daptomycin
Daptomycin: 9 mg/kg administered IV every 24 hours for up to 14 days Age Group 3: Participants ages 2 to 6 years
Age Group 3: SOC
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. Age Group 3: Participants ages 2 to 6 years
Age Group 4: Daptomycin
Daptomycin: 10 mg/kg administered IV every 24 hours for up to 14 days Age Group 4: Participants ages 1 to <2 years
Age Group 4: SOC
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. Age Group 4: Participants ages 1 to <2 years

Outcome Measures

Age Group 1: DaptomycinAge Group 1: Standard of Care (SOC)Age Group 2: DaptomycinAge Group 2: SOCAge Group 3: DaptomycinAge Group 3: SOCAge Group 4: DaptomycinAge Group 4: SOC
Participants Analyzed
Units: Participants
7337733881423015
Percentage of Participants With an Overall Therapeutic Response at Test of Cure Visit
Units: percentage of participants - Number
Clinical failure02.72.701.2000
Clinical success95.991.990.492.182.776.280.086.7
Unable to evaluate4.15.46.97.916.123.820.013.3

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

Measure Type
Secondary
Measure Title
Pharmacokinetics (PK): Area Under the Plasma Concentration-Time Curve for Daptomycin From 0 to the Last Sampling Time Point (AUC[0-t])
Measure Description
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.
Time Frame
Predose and 5 timepoints according to age group (up to 12 hours postdose)

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants who received at least 1 dose of study drug with evaluable daptomycin AUC(0-t) data.

Reporting Groups

TitleDescription
Age Group 1: Daptomycin
Daptomycin: 5 mg/kg administered IV every 24 hours for up to 14 days Age Group 1: Participants ages 12 to 17 years
Age Group 2: Daptomycin
Daptomycin: 7 mg/kg administered IV every 24 hours for up to 14 days Age Group 2: Participants ages 7 to 11 years
Age Group 3: Daptomycin
Daptomycin: 9 mg/kg administered IV every 24 hours for up to 14 days Age Group 3: Participants ages 2 to 6 years
Age Group 4: Daptomycin
Daptomycin: 10 mg/kg administered IV every 24 hours for up to 14 days Age Group 4: Participants ages 1 to <2 years

Outcome Measures

Age Group 1: DaptomycinAge Group 2: DaptomycinAge Group 3: DaptomycinAge Group 4: Daptomycin
Participants Analyzed
Units: Participants
62730
Pharmacokinetics (PK): Area Under the Plasma Concentration-Time Curve for Daptomycin From 0 to the Last Sampling Time Point (AUC[0-t])
Units: microgram*hour per milliliter (μg*hr/mL) - Mean (Standard Deviation)
318 (62.2)NA318 (68.6)466

Serious Adverse Events

Time Frame
Baseline through 14 days after last dose of study drug
Additional Description
Participants who received at least 1 dose of study drug with evaluable post-baseline TEAE data are included. Participants who experience more than one event are counted only once per System Organ Class and Preferred Term.
Frequency Threshold0% (Threshold above which other adverse events are reported)

Reporting Groups

TitleDescription
Age Group 1: Daptomycin
Daptomycin: 5 mg/kg administered IV every 24 hours for up to 14 days Age Group 1: Participants ages 12 to 17 years
Age Group 1: Standard of Care (SOC)
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. Age Group 1: Participants ages 12 to 17 years
Age Group 2: Daptomycin
Daptomycin: 7 mg/kg administered IV every 24 hours for up to 14 days Age Group 2: Participants ages 7 to 11 years
Age Group 2: SOC
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. Age Group 2: Participants ages 7 to 11 years
Age Group 3: Daptomycin
Daptomycin: 9 mg/kg administered IV every 24 hours for up to 14 days Age Group 3: Participants ages 2 to 6 years
Age Group 3: SOC
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. Age Group 3: Participants ages 2 to 6 years
Age Group 4: Daptomycin
Daptomycin: 10 mg/kg administered IV every 24 hours for up to 14 days Age Group 4: Participants ages 1 to <2 years
Age Group 4: SOC
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. Age Group 4: Participants ages 1 to <2 years

Serious Adverse Events

Age Group 1: DaptomycinAge Group 1: Standard of Care (SOC)Age Group 2: DaptomycinAge Group 2: SOCAge Group 3: DaptomycinAge Group 3: SOCAge Group 4: DaptomycinAge Group 4: SOC
Total, serious adverse events
No. of participants affected / at risk3/72 (0.00%)1/38 (0.00%)1/73 (0.00%)1/38 (0.00%)2/81 (0.00%)1/42 (0.00%)0/30 (0.00%)0/15 (0.00%)
Chest pain
No. of participants affected / at risk1/72 (0.00%)0/38 (0.00%)0/73 (0.00%)0/38 (0.00%)0/81 (0.00%)0/42 (0.00%)0/30 (0.00%)0/15 (0.00%)
Pyrexia
No. of participants affected / at risk0/72 (0.00%)0/38 (0.00%)1/73 (0.00%)0/38 (0.00%)1/81 (0.00%)0/42 (0.00%)0/30 (0.00%)0/15 (0.00%)
Abscess
No. of participants affected / at risk0/72 (0.00%)0/38 (0.00%)1/73 (0.00%)0/38 (0.00%)0/81 (0.00%)0/42 (0.00%)0/30 (0.00%)0/15 (0.00%)
Bacteraemia
No. of participants affected / at risk0/72 (0.00%)0/38 (0.00%)0/73 (0.00%)0/38 (0.00%)0/81 (0.00%)1/42 (0.00%)0/30 (0.00%)0/15 (0.00%)
Osteomyelitis
No. of participants affected / at risk0/72 (0.00%)0/38 (0.00%)0/73 (0.00%)1/38 (0.00%)0/81 (0.00%)0/42 (0.00%)0/30 (0.00%)0/15 (0.00%)
Subcutaneous abscess
No. of participants affected / at risk1/72 (0.00%)0/38 (0.00%)0/73 (0.00%)0/38 (0.00%)0/81 (0.00%)0/42 (0.00%)0/30 (0.00%)0/15 (0.00%)
Toxic shock syndrome
No. of participants affected / at risk0/72 (0.00%)1/38 (0.00%)0/73 (0.00%)0/38 (0.00%)0/81 (0.00%)0/42 (0.00%)0/30 (0.00%)0/15 (0.00%)
Blood creatine phosphokinase increased
No. of participants affected / at risk1/72 (0.00%)0/38 (0.00%)0/73 (0.00%)0/38 (0.00%)0/81 (0.00%)0/42 (0.00%)0/30 (0.00%)0/15 (0.00%)
Myopathy
No. of participants affected / at risk1/72 (0.00%)0/38 (0.00%)0/73 (0.00%)0/38 (0.00%)0/81 (0.00%)0/42 (0.00%)0/30 (0.00%)0/15 (0.00%)
Status asthmaticus
No. of participants affected / at risk0/72 (0.00%)0/38 (0.00%)0/73 (0.00%)0/38 (0.00%)1/81 (0.00%)0/42 (0.00%)0/30 (0.00%)0/15 (0.00%)
Wound drainage
No. of participants affected / at risk0/72 (0.00%)0/38 (0.00%)1/73 (0.00%)0/38 (0.00%)0/81 (0.00%)0/42 (0.00%)0/30 (0.00%)0/15 (0.00%)

Other Adverse Events

Time Frame
Baseline through 14 days after last dose of study drug
Additional Description
Participants who received at least 1 dose of study drug with evaluable post-baseline TEAE data are included. Participants who experience more than one event are counted only once per System Organ Class and Preferred Term.
Frequency Threshold1% (Threshold above which other adverse events are reported)

Reporting Groups

TitleDescription
Age Group 1: Daptomycin
Daptomycin: 5 mg/kg administered IV every 24 hours for up to 14 days Age Group 1: Participants ages 12 to 17 years
Age Group 1: Standard of Care (SOC)
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. Age Group 1: Participants ages 12 to 17 years
Age Group 2: Daptomycin
Daptomycin: 7 mg/kg administered IV every 24 hours for up to 14 days Age Group 2: Participants ages 7 to 11 years
Age Group 2: SOC
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. Age Group 2: Participants ages 7 to 11 years
Age Group 3: Daptomycin
Daptomycin: 9 mg/kg administered IV every 24 hours for up to 14 days Age Group 3: Participants ages 2 to 6 years
Age Group 3: SOC
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. Age Group 3: Participants ages 2 to 6 years
Age Group 4: Daptomycin
Daptomycin: 10 mg/kg administered IV every 24 hours for up to 14 days Age Group 4: Participants ages 1 to <2 years
Age Group 4: SOC
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. Age Group 4: Participants ages 1 to <2 years

Other Adverse Events

Age Group 1: DaptomycinAge Group 1: Standard of Care (SOC)Age Group 2: DaptomycinAge Group 2: SOCAge Group 3: DaptomycinAge Group 3: SOCAge Group 4: DaptomycinAge Group 4: SOC
Total, other adverse events
No. of participants affected / at risk15/72 (0.00%)9/38 (0.00%)7/73 (0.00%)2/38 (0.00%)27/81 (0.00%)10/42 (0.00%)11/30 (0.00%)11/15 (0.00%)
Cheilitis
No. of participants affected / at risk0/72 (0.00%)1/38 (0.00%)0/73 (0.00%)0/38 (0.00%)0/81 (0.00%)0/42 (0.00%)0/30 (0.00%)1/15 (0.00%)
Diarrhoea
No. of participants affected / at risk3/72 (0.00%)1/38 (0.00%)3/73 (0.00%)1/38 (0.00%)12/81 (0.00%)4/42 (0.00%)0/30 (0.00%)1/15 (0.00%)
Nausea
No. of participants affected / at risk2/72 (0.00%)0/38 (0.00%)1/73 (0.00%)0/38 (0.00%)0/81 (0.00%)0/42 (0.00%)0/30 (0.00%)1/15 (0.00%)
Vomiting
No. of participants affected / at risk0/72 (0.00%)0/38 (0.00%)1/73 (0.00%)0/38 (0.00%)4/81 (0.00%)1/42 (0.00%)2/30 (0.00%)0/15 (0.00%)
Infusion site extravasation
No. of participants affected / at risk1/72 (0.00%)1/38 (0.00%)0/73 (0.00%)0/38 (0.00%)0/81 (0.00%)0/42 (0.00%)0/30 (0.00%)1/15 (0.00%)
Infusion site pain
No. of participants affected / at risk1/72 (0.00%)2/38 (0.00%)1/73 (0.00%)0/38 (0.00%)1/81 (0.00%)0/42 (0.00%)0/30 (0.00%)0/15 (0.00%)
Pyrexia
No. of participants affected / at risk2/72 (0.00%)0/38 (0.00%)4/73 (0.00%)0/38 (0.00%)1/81 (0.00%)1/42 (0.00%)2/30 (0.00%)3/15 (0.00%)
Abscess neck
No. of participants affected / at risk0/72 (0.00%)0/38 (0.00%)0/73 (0.00%)0/38 (0.00%)0/81 (0.00%)0/42 (0.00%)0/30 (0.00%)1/15 (0.00%)
Candida nappy rash
No. of participants affected / at risk0/72 (0.00%)0/38 (0.00%)0/73 (0.00%)0/38 (0.00%)0/81 (0.00%)0/42 (0.00%)1/30 (0.00%)1/15 (0.00%)
Cellulitis
No. of participants affected / at risk1/72 (0.00%)0/38 (0.00%)0/73 (0.00%)0/38 (0.00%)1/81 (0.00%)0/42 (0.00%)2/30 (0.00%)0/15 (0.00%)
Fungal infection
No. of participants affected / at risk0/72 (0.00%)0/38 (0.00%)0/73 (0.00%)0/38 (0.00%)1/81 (0.00%)0/42 (0.00%)0/30 (0.00%)1/15 (0.00%)
Genital candidiasis
No. of participants affected / at risk0/72 (0.00%)0/38 (0.00%)0/73 (0.00%)0/38 (0.00%)0/81 (0.00%)0/42 (0.00%)0/30 (0.00%)1/15 (0.00%)
Hand-foot-and-mouth disease
No. of participants affected / at risk0/72 (0.00%)0/38 (0.00%)0/73 (0.00%)0/38 (0.00%)0/81 (0.00%)0/42 (0.00%)0/30 (0.00%)1/15 (0.00%)
Rhinitis
No. of participants affected / at risk0/72 (0.00%)0/38 (0.00%)0/73 (0.00%)0/38 (0.00%)0/81 (0.00%)0/42 (0.00%)0/30 (0.00%)1/15 (0.00%)
Upper respiratory tract infection
No. of participants affected / at risk0/72 (0.00%)0/38 (0.00%)0/73 (0.00%)1/38 (0.00%)0/81 (0.00%)1/42 (0.00%)0/30 (0.00%)1/15 (0.00%)
Blood creatine phosphokinase increased
No. of participants affected / at risk4/72 (0.00%)2/38 (0.00%)0/73 (0.00%)1/38 (0.00%)8/81 (0.00%)2/42 (0.00%)1/30 (0.00%)2/15 (0.00%)
Blood phosphorus increased
No. of participants affected / at risk0/72 (0.00%)0/38 (0.00%)0/73 (0.00%)0/38 (0.00%)1/81 (0.00%)0/42 (0.00%)1/30 (0.00%)1/15 (0.00%)
Lymphocyte percentage increase
No. of participants affected / at risk0/72 (0.00%)0/38 (0.00%)0/73 (0.00%)0/38 (0.00%)0/81 (0.00%)0/42 (0.00%)0/30 (0.00%)1/15 (0.00%)
Neutrophil count decreased
No. of participants affected / at risk0/72 (0.00%)0/38 (0.00%)0/73 (0.00%)0/38 (0.00%)0/81 (0.00%)0/42 (0.00%)0/30 (0.00%)1/15 (0.00%)
Platelet count increased
No. of participants affected / at risk0/72 (0.00%)0/38 (0.00%)0/73 (0.00%)0/38 (0.00%)0/81 (0.00%)0/42 (0.00%)0/30 (0.00%)1/15 (0.00%)
Red blood cells urine
No. of participants affected / at risk0/72 (0.00%)0/38 (0.00%)0/73 (0.00%)0/38 (0.00%)0/81 (0.00%)0/42 (0.00%)0/30 (0.00%)1/15 (0.00%)
Hyperphosphataemia
No. of participants affected / at risk0/72 (0.00%)0/38 (0.00%)0/73 (0.00%)0/38 (0.00%)1/81 (0.00%)0/42 (0.00%)2/30 (0.00%)0/15 (0.00%)
Headache
No. of participants affected / at risk5/72 (0.00%)3/38 (0.00%)2/73 (0.00%)0/38 (0.00%)0/81 (0.00%)0/42 (0.00%)0/30 (0.00%)0/15 (0.00%)
Pharyngeal lesion
No. of participants affected / at risk0/72 (0.00%)0/38 (0.00%)0/73 (0.00%)0/38 (0.00%)0/81 (0.00%)0/42 (0.00%)0/30 (0.00%)1/15 (0.00%)
Rhinorrhoea
No. of participants affected / at risk0/72 (0.00%)0/38 (0.00%)0/73 (0.00%)1/38 (0.00%)2/81 (0.00%)0/42 (0.00%)2/30 (0.00%)0/15 (0.00%)
Dermatitis diaper
No. of participants affected / at risk0/72 (0.00%)0/38 (0.00%)0/73 (0.00%)0/38 (0.00%)0/81 (0.00%)1/42 (0.00%)2/30 (0.00%)2/15 (0.00%)
Rash
No. of participants affected / at risk0/72 (0.00%)1/38 (0.00%)0/73 (0.00%)0/38 (0.00%)1/81 (0.00%)2/42 (0.00%)0/30 (0.00%)1/15 (0.00%)
Rash papular
No. of participants affected / at risk1/72 (0.00%)0/38 (0.00%)0/73 (0.00%)0/38 (0.00%)0/81 (0.00%)1/42 (0.00%)2/30 (0.00%)0/15 (0.00%)
Urticaria
No. of participants affected / at risk0/72 (0.00%)0/38 (0.00%)0/73 (0.00%)0/38 (0.00%)0/81 (0.00%)1/42 (0.00%)0/30 (0.00%)1/15 (0.00%)

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

Results Point of Contact

Name/TitleOrganizationPhoneEmail
Vice President, Clinical Research
Cubist Pharmaceuticals
(781) 860-8660