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Safety and Efficacy Study of Daptomycin Compared to Active Comparator in Pediatric Participants With Acute Hematogenous Osteomyelitis (AHO) (MK-3009-006)

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ClinicalTrials.gov Identifier: NCT01922011
Recruitment Status : Completed
First Posted : August 14, 2013
Results First Posted : June 23, 2017
Last Update Posted : August 28, 2018
Sponsor:
Information provided by (Responsible Party):
Cubist Pharmaceuticals LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Acute Hematogenous Osteomyelitis
Interventions Drug: Daptomycin
Drug: Vancomycin (or equivalent)
Drug: Nafcillin (or equivalent)
Enrollment 149
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Daptomycin Vancomycin or Nafcillin
Hide Arm/Group Description Intravenous (IV) daptomycin 7, 9, or 12 mg/kg once daily and ≤3 dummy infusions daily IV vancomycin (or equivalent), 10 to 15 mg/kg every six hours (q6h), or IV nafcillin (or β-lactam equivalent) 100-200 mg/kg/day, in divided doses q6h.
Period Title: Overall Study
Started 75 [1] 74 [1]
Treated 73 [2] 73 [2]
Treatment Actually Received 74 [3] 72 [3]
Completed 69 69
Not Completed 6 5
Reason Not Completed
Protocol Violation             0             1
Physician Decision             0             1
Parent/Guardian Decision             3             0
Lost to Follow-up             0             1
Missed Test-of-Cure Visit             0             2
Not Treated             1             0
Lack of willing home health agency             1             0
Randomized in error             1             0
[1]
Randomized participants
[2]
Treated Participants
[3]
One participant intended for treatment with Vancomycin or Nafcillin was treated with Daptomycin
Arm/Group Title Daptomycin Vancomycin or Nafcillin Total
Hide Arm/Group Description IV daptomycin 7, 9, or 12 mg/kg once daily and ≤3 dummy infusions daily IV vancomycin (or equivalent), 10 to 15 mg/kg q6h, or IV nafcillin (or β-lactam equivalent) 100-200 mg/kg/day, in divided doses q6h. Total of all reporting groups
Overall Number of Baseline Participants 75 74 149
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 75 participants 74 participants 149 participants
9.1  (4.4) 9.2  (4.1) 9.2  (4.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 75 participants 74 participants 149 participants
Female
31
  41.3%
25
  33.8%
56
  37.6%
Male
44
  58.7%
49
  66.2%
93
  62.4%
1.Primary Outcome
Title Percentage of Participants With Clinical Improvement in the 3 General Categories of Pain, Inflammation, and Limb Function Based on the Investigator's Overall Assessment of Severity of Each of the Symptom Categories.
Hide Description Clinical improvement was based on the Investigator’s overall assessment of severity of each of the 3 general symptom categories of Pain, Inflammation, and Limb Function. Based on this evaluation, a participant was considered to have met criteria for clinical improvement according to the following definition: If 3 general categories are present at baseline: at least a 1-point improvement (i.e. severe to moderate, moderate to mild, mild to absent) in at least 2 of the general categories and no worsening in the other. If 2 general categories are present at baseline: at least a 2-point improvement (i.e. severe to mild, moderate to absent) in at least 1 of the general categories and no worsening or new findings in the others OR at least a 1-point improvement in both and no new findings in the other. If 1 general category is present at baseline: at least a 2-point improvement (i.e., severe to mild, moderate to absent) in that category and no new findings in the others.
Time Frame Up to study Day 5
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received any amount of IV study drug and who had a confirmed or suspected diagnosis of AHO, excluding those with confirmed culture of a gram-negative organism from any baseline specimen.
Arm/Group Title Daptomycin Vancomycin or Nafcillin
Hide Arm/Group Description:
IV daptomycin 7, 9, or 12 mg/kg once daily and ≤3 dummy infusions daily
IV vancomycin (or equivalent), 10 to 15 mg/kg q6h, or IV nafcillin (or β-lactam equivalent) 100-200 mg/kg/day, in divided doses q6h
Overall Number of Participants Analyzed 71 70
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
77.5
(67.7 to 87.2)
82.9
(74.0 to 91.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Daptomycin, Vancomycin or Nafcillin
Comments 95% confidence interval of the common difference was based on stratified Newcombe confidence interval (CI) with minimum risk weights, with age cohort as the stratification factor.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority was concluded if the lower bound of the 2-sided 95% CI is greater than -15%
Statistical Test of Hypothesis P-Value 0.421
Comments [Not Specified]
Method Wald
Comments [Not Specified]
Method of Estimation Estimation Parameter Common Difference
Estimated Value -6.1
Confidence Interval (2-Sided) 95%
-19.4 to 7.4
Estimation Comments Daptomycin – Comparator
2.Secondary Outcome
Title Percentage of Participants With Clinical Improvement Measured as a Composite End Point of Pain, Inflammation, Limb Function, Body Temperature, and C-reactive Protein at End-of IV (EOIV) Therapy Visit.
Hide Description A participant had a favorable outcome in this composite endpoint if all 3 of the following criteria were met: Clinical improvement in the general symptom categories of Pain, Inflammation, and Limb Function on or before Study Day 5; Body temperature ≤ 38°C (100.4°F) over the preceding 24 hours; and C-reactive Protein (CRP) decreased from baseline for participants who had a baseline CRP >ULN (upper limit of normal)) or remain <=ULN for participants who had a baseline <=ULN on or before Study Day 5. The EOIV visit is within 24 hours after the last dose of IV study drug and before switch to optional open label (PO) therapy, if applicable.
Time Frame Up to study Day 5
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received any amount of IV study drug and who had a confirmed diagnosis of AHO (Categories I, II and III), excluding participants with confirmed culture of a gram-negative organism from any baseline specimen and who did not have all clinical assessments performed at the time point.
Arm/Group Title Daptomycin Vancomycin or Nafcillin
Hide Arm/Group Description:
IV daptomycin 7, 9, or 12 mg/kg once daily and ≤3 dummy infusions daily
IV vancomycin (or equivalent), 10 to 15 mg/kg q6h, or IV nafcillin (or β-lactam equivalent) 100-200 mg/kg/day, in divided doses q6h
Overall Number of Participants Analyzed 69 68
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
71.0
(60.3 to 81.7)
76.5
(66.4 to 86.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Daptomycin, Vancomycin or Nafcillin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.467
Comments [Not Specified]
Method Wald
Comments [Not Specified]
Method of Estimation Estimation Parameter Common difference
Estimated Value -7.1
Confidence Interval (2-Sided) 95%
-21.6 to 7.9
Estimation Comments 95% confidence interval of the common difference ( Daptomycin minus Vancomycin or Nafcillin) is based on stratified Newcombe confidence interval (CI) with minimum risk weights, with age cohort as the stratification factor.
3.Secondary Outcome
Title Percentage of Participants With a Favorable Clinical Outcome
Hide Description Favorable clinical outcomes are clinical recovery and clinical cure. Clinical cure is defined as resolution of all acute symptoms of AHO or improvement to such an extent that no further intravenous antibacterial therapy is required. Clinical recovery is defined as clinical improvement in the composite end point three general categories of Pain, Inflammation, and Limb Function on or before Study Day 5, and no development of new symptoms of AHO; body temperature ≤ 38°C (100.4°F) for 24 hours; no new or additional bone or joint infection (e.g., abscess, spreading to other osseous or articular locations) such that no further antibacterial therapy or surgery are required; no hematogenous metastatic infection (e.g., abscess in liver, spleen, lung; other bones) or bacteremia.. The End of Therapy (EOT) visit is within 48 hours of last dose of PO therapy.
Time Frame Baseline (within 48 hours prior to first dose of IV study drug) - and up to Test of Cure (21-35 days after last dose of IV study drug) (up to Day 77)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received any amount of IV study drug and who had a confirmed diagnosis of AHO (Categories I, II and III), excluding participants with confirmed culture of a gram-negative organism from any baseline specimen
Arm/Group Title Daptomycin Vancomycin or Nafcillin
Hide Arm/Group Description:
IV daptomycin 7, 9, or 12 mg/kg once daily and ≤3 dummy infusions daily.
IV vancomycin (or equivalent), 10 to 15 mg/kg q6h, or IV nafcillin (or β-lactam equivalent) 100-200 mg/kg/day, in divided doses q6h
Overall Number of Participants Analyzed 71 70
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
At End of IV (EOIV) Therapy (n= 71,69)
85.9
(77.8 to 94.0)
91.3
(84.7 to 98.0)
At End of Therapy (EOT) (n= 71,69)
83.1
(74.4 to 91.8)
89.9
(82.7 to 97.0)
At Test Of Cure (TOC) (n= 71,70)
81.7
(72.7 to 90.7)
87.1
(79.3 to 95.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Daptomycin, Vancomycin or Nafcillin
Comments At EOIV visit
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.313
Comments [Not Specified]
Method Wald
Comments [Not Specified]
Method of Estimation Estimation Parameter Common difference
Estimated Value -6.2
Confidence Interval (2-Sided) 95%
-17.5 to 5.0
Estimation Comments 95% confidence interval of the common difference ( Daptomycin minus Vancomycin or Nafcillin) is based on stratified Newcombe confidence interval (CI) with minimum risk weights, with age cohort as the stratification factor.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Daptomycin, Vancomycin or Nafcillin
Comments At EOT visit
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.239
Comments [Not Specified]
Method Wald
Comments [Not Specified]
Method of Estimation Estimation Parameter Common difference
Estimated Value -7.9
Confidence Interval (2-Sided) 95%
-19.8 to 4.0
Estimation Comments 95% confidence interval of the common difference ( Daptomycin minus Vancomycin or Nafcillin) is based on stratified Newcombe confidence interval (CI) with minimum risk weights, with age cohort as the stratification factor.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Daptomycin, Vancomycin or Nafcillin
Comments At TOC visit
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.370
Comments [Not Specified]
Method Wald
Comments [Not Specified]
Method of Estimation Estimation Parameter Common difference
Estimated Value -6.7
Confidence Interval (2-Sided) 95%
-19.1 to 5.8
Estimation Comments 95% confidence interval of the common difference ( Daptomycin minus Vancomycin or Nafcillin) is based on stratified Newcombe confidence interval (CI) with minimum risk weights, with age cohort as the stratification factor.
4.Secondary Outcome
Title Percentage of Participants With a Clinical Cure Categorized by Baseline Pathogen at Test of Cure
Hide Description At Test Of Cure (TOC) clinical cure is defined as resolution of all acute symptoms of AHO or improvement to such an extent that no further antibacterial therapy is required. Favorable microbiological outcomes are either eradication where the source specimen demonstrated absence of the original baseline pathogen; or presumed eradication where the source specimen was not available to culture, and the subject was assessed as a clinical cure. To have a favorable microbiological response, the outcome for each participant's baseline pathogen must be favorable (eradicated or presumed eradicated). Other pathogens include Arcanobacterium haemolyticum, Gram positive cocci, Staphylococcus epidermidis, Streptococcus dysgalactiae, Streptococcus mitis group and Streptococcus pyogenes.
Time Frame Baseline (within 48 hours prior to first dose of IV study drug) - and Test of Cure (21-35 days after last dose of IV study drug) (up to Day 77)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received IV study drug and had a confirmed diagnosis of AHO, excluding participants with confirmed culture of a gram-negative organism; but including those where at least one bacterial pathogen was isolated from an appropriate microbiological specimen at baseline.
Arm/Group Title Daptomycin Vancomycin or Nafcillin
Hide Arm/Group Description:
IV daptomycin 7, 9, or 12 mg/kg once daily and ≤3 dummy infusions daily.
IV vancomycin (or equivalent), 10 to 15 mg/kg q6h, or IV nafcillin (or β-lactam equivalent) 100-200 mg/kg/day, in divided doses q6h
Overall Number of Participants Analyzed 45 47
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Overall Baseline Infecting Pathogen (n =45,47)
77.8
(65.6 to 89.9)
87.2
(77.7 to 96.8)
Staphylococcus Aureus (SA) (n= 43,42)
76.7
(64.1 to 89.4)
88.1
(78.3 to 97.9)
Methicillin Susceptible SA (MSSA) (n= 39,37)
79.5
(66.8 to 92.2)
94.6
(87.3 to 100)
Methicillin Resistant SA (MRSA) (n= 4,4)
50.0
(1.0 to 99.0)
25.0
(0.0 to 67.4)
Other Pathogens (n= 2,7)
100
(100 to 100)
85.7
(59.8 to 100)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Daptomycin, Vancomycin or Nafcillin
Comments Overall Baseline Infecting Pathogen
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.230
Comments [Not Specified]
Method Wald
Comments [Not Specified]
Method of Estimation Estimation Parameter Common difference
Estimated Value -10.5
Confidence Interval (2-Sided) 95%
-26.3 to 5.4
Estimation Comments 95% confidence interval of the common difference ( Daptomycin minus Vancomycin or Nafcillin) is based on stratified Newcombe confidence interval (CI) with minimum risk weights, with age cohort as the stratification factor.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Daptomycin, Vancomycin or Nafcillin
Comments SA
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.164
Comments [Not Specified]
Method Wald
Comments [Not Specified]
Method of Estimation Estimation Parameter Common difference
Estimated Value -12.3
Confidence Interval (2-Sided) 95%
-28.5 to 4.4
Estimation Comments 95% confidence interval of the common difference ( Daptomycin minus Vancomycin or Nafcillin) is based on stratified Newcombe confidence interval (CI) with minimum risk weights, with age cohort as the stratification factor.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Daptomycin, Vancomycin or Nafcillin
Comments MSSA
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.043
Comments [Not Specified]
Method Wald
Comments [Not Specified]
Method of Estimation Estimation Parameter Common difference
Estimated Value -15.5
Confidence Interval (2-Sided) 95%
-31.2 to 1.1
Estimation Comments 95% confidence interval of the common difference ( Daptomycin minus Vancomycin or Nafcillin) is based on stratified Newcombe confidence interval (CI) with minimum risk weights, with age cohort as the stratification factor.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Daptomycin, Vancomycin or Nafcillin
Comments MRSA
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.450
Comments [Not Specified]
Method Wald
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Daptomycin, Vancomycin or Nafcillin
Comments Other Pathogen
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.280
Comments [Not Specified]
Method Wald
Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants With Sustained Clinical Improvement
Hide Description Sustained clinical improvement was defined as participants with clinical improvement who further met the definition of clinical cure. Clinical improvement was in the three general categories of Pain, Inflammation, and Limb Function on or before Study Day 5. Clinical cure is defined as resolution of all acute symptoms of AHO or improvement to such an extent that no further intravenous antibacterial therapy is required. The EOT visit is within 48 hours of last dose of PO therapy.
Time Frame Baseline (within 48 hours prior to first dose of IV study drug) - up to Test of Cure (21-35 days after last dose of IV study drug) (up to Day 77)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received any amount of IV study drug and who had a confirmed or suspected diagnosis of AHO, excluding those with confirmed culture of a gram-negative organism from any baseline specimen; and had non-missing clinical outcome.
Arm/Group Title Daptomycin Vancomycin or Nafcillin
Hide Arm/Group Description:
IV daptomycin 7, 9, or 12 mg/kg once daily and ≤3 dummy infusions daily.
IV vancomycin (or equivalent), 10 to 15 mg/kg q6h, or IV nafcillin (or β-lactam equivalent) 100-200 mg/kg/day, in divided doses q6h
Overall Number of Participants Analyzed 71 70
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
EOT (n= 55,57)
89.1
(80.9 to 97.3)
94.7
(88.9 to 100.0)
TOC (n= 55,58)
87.3
(78.5 to 96.1)
91.4
(84.2 to 98.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Daptomycin, Vancomycin or Nafcillin
Comments EOT
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.272
Comments [Not Specified]
Method Wald
Comments [Not Specified]
Method of Estimation Estimation Parameter Common difference
Estimated Value -6.3
Confidence Interval (2-Sided) 95%
-18.2 to 5.5
Estimation Comments 95% confidence interval of the common difference ( Daptomycin minus Vancomycin or Nafcillin) is based on stratified Newcombe confidence interval (CI) with minimum risk weights, with age cohort as the stratification factor.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Daptomycin, Vancomycin or Nafcillin
Comments TOC
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.480
Comments [Not Specified]
Method Wald
Comments [Not Specified]
Method of Estimation Estimation Parameter Common difference
Estimated Value -4.8
Confidence Interval (2-Sided) 95%
-17.6 to 7.9
Estimation Comments 95% confidence interval of the common difference ( Daptomycin minus Vancomycin or Nafcillin) is based on stratified Newcombe confidence interval (CI) with minimum risk weights, with age cohort as the stratification factor.
6.Secondary Outcome
Title Percentage of Participants With a Favorable Microbiological Response Categorized by Baseline Pathogen at Test of Cure
Hide Description Favorable microbiological outcomes are either eradication where the source specimen demonstrated absence of the original baseline pathogen; or presumed eradication where the source specimen was not available to culture, and the subject was assessed as a clinical cure. For a favorable microbiological response, the outcome for each baseline pathogen must be eradicated or presumed eradicated. Other pathogens include Arcanobacterium haemolyticum, Gram positive cocci, Staphylococcus epidermidis, Streptococcus dysgalactiae, Streptococcus mitis group and Streptococcus pyogenes.
Time Frame Baseline (within 48 hours prior to first dose of IV study drug) - and Test of Cure (21-35 days after last dose of IV study drug) (up to Day 77)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received IV study drug and had a confirmed diagnosis of AHO, excluding participants with confirmed culture of a gram-negative organism; but including those where at least one bacterial pathogen was isolated from an appropriate microbiological specimen at baseline.
Arm/Group Title Daptomycin Vancomycin or Nafcillin
Hide Arm/Group Description:
IV daptomycin 7, 9, or 12 mg/kg once daily and ≤3 dummy infusions daily.
IV vancomycin (or equivalent), 10 to 15 mg/kg q6h, or IV nafcillin (or β-lactam equivalent) 100-200 mg/kg/day, in divided doses q6h
Overall Number of Participants Analyzed 45 47
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Overall Baseline Infecting Pathogen (n =45,47)
82.2
(71.1 to 93.4)
91.5
(83.5 to 99.5)
SA (n= 43,42)
81.4
(69.8 to 93.0)
92.9
(85.1 to 100.0)
MSSA (n= 39,37)
84.6
(73.3 to 95.9)
94.6
(87.3 to 100.0)
MRSA (n= 4,4)
50.0
(1.0 to 99.0)
75.0
(32.6 to 100.0)
Other Pathogens (n= 2,7)
100
(100.0 to 100.0)
85.7
(59.8 to 100.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Daptomycin, Vancomycin or Nafcillin
Comments Overall Baseline Infecting Pathogen
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Common difference
Estimated Value -10.1
Confidence Interval (2-Sided) 95%
-24.8 to 4.2
Estimation Comments 95% confidence interval of the common difference ( Daptomycin minus Vancomycin or Nafcillin) is based on stratified Newcombe confidence interval (CI) with minimum risk weights, with age cohort as the stratification factor.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Daptomycin, Vancomycin or Nafcillin
Comments SA
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Common difference
Estimated Value -12.2
Confidence Interval (2-Sided) 95%
-27.2 to 2.8
Estimation Comments 95% confidence interval of the common difference ( Daptomycin minus Vancomycin or Nafcillin) is based on stratified Newcombe confidence interval (CI) with minimum risk weights, with age cohort as the stratification factor.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Daptomycin, Vancomycin or Nafcillin
Comments MSSA
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Common difference
Estimated Value -10.4
Confidence Interval (2-Sided) 95%
-25.4 to 5.2
Estimation Comments 95% confidence interval of the common difference ( Daptomycin minus Vancomycin or Nafcillin) is based on stratified Newcombe confidence interval (CI) with minimum risk weights, with age cohort as the stratification factor.
7.Other Pre-specified Outcome
Title Number of Participants With 1 or More Adverse Events (AEs)
Hide Description An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, clinically significant laboratory finding, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product
Time Frame Administration of first dose up to approximately six and a half months after last dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
Treated participants based on the treatment received
Arm/Group Title Daptomycin Vancomycin or Nafcillin
Hide Arm/Group Description:
IV daptomycin 7, 9, or 12 mg/kg once daily and ≤3 dummy infusions daily.
IV vancomycin (or equivalent), 10 to 15 mg/kg q6h, or IV nafcillin (or β-lactam equivalent) 100-200 mg/kg/day, in divided doses q6h
Overall Number of Participants Analyzed 74 72
Measure Type: Number
Unit of Measure: Participants
34 45
8.Other Pre-specified Outcome
Title Number of Participants With 1 or More Serious Adverse Events (SAEs)
Hide Description An SAE is any untoward medical occurrence that at any dose results in death; is life threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; or is a congenital anomaly/birth defect.
Time Frame Administration of first dose through the last follow-up visit; an expected time of up to 6.5 months
Hide Outcome Measure Data
Hide Analysis Population Description
Treated participants based on the treatment received
Arm/Group Title Daptomycin Vancomycin or Nafcillin
Hide Arm/Group Description:
IV daptomycin 7, 9, or 12 mg/kg once daily and ≤3 dummy infusions daily.
IV vancomycin (or equivalent), 10 to 15 mg/kg q6h, or IV nafcillin (or β-lactam equivalent) 100-200 mg/kg/day, in divided doses q6h
Overall Number of Participants Analyzed 74 72
Measure Type: Number
Unit of Measure: Participants
5 4
9.Other Pre-specified Outcome
Title Concentration of Serum Creatine Kinase (CK)
Hide Description Serum was collected at Baseline and at End of Therapy IV, from which the concentration of CK was determined.
Time Frame Baseline and End of Therapy IV (up to Day 42)
Hide Outcome Measure Data
Hide Analysis Population Description
Treated participants based on the treatment received
Arm/Group Title Daptomycin Vancomycin or Nafcillin
Hide Arm/Group Description:
IV daptomycin 7, 9, or 12 mg/kg once daily and ≤3 dummy infusions daily.
IV vancomycin (or equivalent), 10 to 15 mg/kg q6h, or IV nafcillin (or β-lactam equivalent) 100-200 mg/kg/day, in divided doses q6h
Overall Number of Participants Analyzed 74 72
Mean (Standard Deviation)
Unit of Measure: U/L
Baseline (n = 68,72) 141.7  (188.70) 99.9  (95.00)
End of Therapy IV (n= 35,41) 89.4  (66.55) 82.4  (95.03)
10.Other Pre-specified Outcome
Title Change From Baseline in Number of Participants With Abnormal Focused (Peripheral) Neurological Assessments
Hide Description Focused neurological examinations include assessments of alertness, sensation, pupillary reflex and tracking, peripheral reflexes (biceps, patellar tendon, ankle jerk, and plantar response), muscle tone and strength (upper and lower limbs), coordination (finger to nose), and tremor of the hands/fingers.
Time Frame Baseline and up to Test of Cure (21-35 days after last dose of IV study drug) (up to Day 77)
Hide Outcome Measure Data
Hide Analysis Population Description
Data were only summarized for each visit; but not analyzed.
Arm/Group Title Daptomycin Vancomycin or Nafcillin
Hide Arm/Group Description:
IV daptomycin 7, 9, or 12 mg/kg once daily and ≤3 dummy infusions daily.
IV vancomycin (or equivalent), 10 to 15 mg/kg q6h, or IV nafcillin (or β-lactam equivalent) 100-200 mg/kg/day, in divided doses q6h
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
11.Other Pre-specified Outcome
Title Plasma Concentration of Daptomycin at the End of IV Infusion
Hide Description Blood samples were collected, after infusion of IV study drug between the end of infusion on study day 3, up to Day 42
Time Frame Day 3 up to Day 42
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received a known amount of daptomycin and who had at least one blood sample collected. Participants treated with vancomycin, nafcillin or equivalent were not analyzed.
Arm/Group Title Daptomycin 12 - < 24 Months Old Daptomycin 24 Months - < 7 Yrs Old Daptomycin 7 - < 12 Yrs Old Daptomycin 12 - < 18 Yrs Old
Hide Arm/Group Description:
IV daptomycin 12 mg/kg once daily and ≤3 dummy infusions daily for ages 12 - < 24 months old only.
IV daptomycin 12 mg/kg once daily and ≤3 dummy infusions daily for ages 24 months - < 7 yrs old only.
IV daptomycin 9 mg/kg once daily and ≤3 dummy infusions daily for ages 7 - < 12 yrs old only.
IV daptomycin 7 mg/kg once daily and ≤3 dummy infusions daily for ages 12 - < 18 yrs old only.
Overall Number of Participants Analyzed 1 6 5 10
Mean (Standard Deviation)
Unit of Measure: µg/mL
36.800  (0) 75.772  (39.1156) 58.940  (27.4149) 68.907  (56.6695)
12.Other Pre-specified Outcome
Title Plasma Concentration of Daptomycin at 15 Minutes to 1 Hour After the End of IV Infusion
Hide Description Blood samples were collected, after infusion of IV study drug between the end of infusion on study day 3, up to Day 42
Time Frame Day 3 up to Day 42
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received a known amount of daptomycin and who had at least one blood sample collected. Participants treated with vancomycin, nafcillin or equivalent were not analyzed.
Arm/Group Title Daptomycin 12 - < 24 Months Old Daptomycin 24 Months - < 7 Yrs Old Daptomycin 7 - < 12 Yrs Old Daptomycin 12 - < 18 Yrs Old
Hide Arm/Group Description:
IV daptomycin 12 mg/kg once daily and ≤3 dummy infusions daily for ages 12 - < 24 months old only.
IV daptomycin 12 mg/kg once daily and ≤3 dummy infusions daily for ages 24 months - < 7 yrs old only.
IV daptomycin 9 mg/kg once daily and ≤3 dummy infusions daily for ages 7 - < 12 yrs old only.
IV daptomycin 7 mg/kg once daily and ≤3 dummy infusions daily for ages 12 - < 18 yrs old only.
Overall Number of Participants Analyzed 3 8 12 10
Mean (Standard Deviation)
Unit of Measure: µg/mL
65.533  (30.8468) 84.564  (35.0179) 70.342  (35.0196) 57.370  (61.5616)
13.Other Pre-specified Outcome
Title Plasma Concentration of Daptomycin at 2 to 3 Hours After the End of IV Infusion
Hide Description Blood samples were collected, after infusion of IV study drug between the end of infusion on study day 3, up to Day 42
Time Frame Day 3 up to Day 42
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received a known amount of daptomycin and who had at least one blood sample collected. Participants treated with vancomycin, nafcillin or equivalent were not analyzed.
Arm/Group Title Daptomycin 12 - < 24 Months Old Daptomycin 24 Months - < 7 Yrs Old Daptomycin 7 - < 12 Yrs Old Daptomycin 12 - < 18 Yrs Old
Hide Arm/Group Description:
IV daptomycin 12 mg/kg once daily and ≤3 dummy infusions daily for ages 12 - < 24 months old only.
IV daptomycin 12 mg/kg once daily and ≤3 dummy infusions daily for ages 24 months - < 7 yrs old only.
IV daptomycin 9, mg/kg once daily and ≤3 dummy infusions daily for ages 7 - < 12 yrs old only.
IV daptomycin 7 mg/kg once daily and ≤3 dummy infusions daily for ages 12 - < 18 yrs old only.
Overall Number of Participants Analyzed 0 6 5 9
Mean (Standard Deviation)
Unit of Measure: µg/mL
51.150  (16.1179) 31.200  (14.7027) 46.756  (51.2678)
14.Other Pre-specified Outcome
Title Plasma Concentration of Daptomycin at 4 to 5 Hours After the End of IV Infusion
Hide Description Blood samples were collected, after infusion of IV study drug between the end of infusion on study day 3, up to Day 42
Time Frame Day 3 up to Day 42
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received a known amount of daptomycin and who had at least one blood sample collected. Participants treated with vancomycin, nafcillin or equivalent were not analyzed.
Arm/Group Title Daptomycin 12 - < 24 Months Old Daptomycin 24 Months - < 7 Yrs Old Daptomycin 7 - < 12 Yrs Old Daptomycin 12 - < 18 Yrs Old
Hide Arm/Group Description:
IV daptomycin 12 mg/kg once daily and ≤3 dummy infusions daily for ages 12 - < 24 months old only.
IV daptomycin 12 mg/kg once daily and ≤3 dummy infusions daily for ages 24 months - < 7 yrs old only.
IV daptomycin 9 mg/kg once daily and ≤3 dummy infusions daily for ages 7 - < 12 yrs old only.
IV daptomycin 7 mg/kg once daily and ≤3 dummy infusions daily for ages 12 - < 18 yrs old only.
Overall Number of Participants Analyzed 3 7 11 10
Mean (Standard Deviation)
Unit of Measure: µg/mL
35.933  (6.3956) 53.059  (21.8879) 50.809  (26.0469) 41.447  (57.8657)
Time Frame Serious Adverse Events (AEs): Up to approximately six and a half months after last dose of study drug. Non-serious AEs (NSAEs): Up to 35 days after last dose of study drug
Adverse Event Reporting Description Treated participants based on the treatment received
 
Arm/Group Title Daptomycin Vancomycin or Nafcillin
Hide Arm/Group Description IV daptomycin 7, 9, or 12 mg/kg once daily and ≤3 dummy infusions daily IV vancomycin (or equivalent), 10 to 15 mg/kg q6h, or IV nafcillin (or β-lactam equivalent) 100-200 mg/kg/day, in divided doses q6h.
All-Cause Mortality
Daptomycin Vancomycin or Nafcillin
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Daptomycin Vancomycin or Nafcillin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/74 (6.76%)      4/72 (5.56%)    
General disorders     
Pyrexia  1  0/74 (0.00%)  0 1/72 (1.39%)  1
Infections and infestations     
Device related infection  1  0/74 (0.00%)  0 1/72 (1.39%)  1
Osteomyelitis  1  1/74 (1.35%)  1 0/72 (0.00%)  0
Sepsis  1  1/74 (1.35%)  1 0/72 (0.00%)  0
Viral infection  1  0/74 (0.00%)  0 1/72 (1.39%)  1
Injury, poisoning and procedural complications     
Femur fracture  1  1/74 (1.35%)  1 0/72 (0.00%)  0
Joint injury  1  0/74 (0.00%)  0 1/72 (1.39%)  1
Musculoskeletal and connective tissue disorders     
Myalgia  1  1/74 (1.35%)  1 0/72 (0.00%)  0
Pain in extremity  1  1/74 (1.35%)  1 0/72 (0.00%)  0
Pathological fracture  1  1/74 (1.35%)  1 0/72 (0.00%)  0
Skin and subcutaneous tissue disorders     
Drug reaction with eosinophilia and systemic symptoms  1  0/74 (0.00%)  0 1/72 (1.39%)  1
Red man syndrome  1  0/74 (0.00%)  0 1/72 (1.39%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Daptomycin Vancomycin or Nafcillin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/74 (8.11%)      24/72 (33.33%)    
Gastrointestinal disorders     
Constipation  1  1/74 (1.35%)  1 6/72 (8.33%)  6
Diarrhoea  1  1/74 (1.35%)  1 4/72 (5.56%)  4
Vomiting  1  3/74 (4.05%)  3 6/72 (8.33%)  6
General disorders     
Pyrexia  1  2/74 (2.70%)  2 5/72 (6.94%)  6
Infections and infestations     
Nasopharyngitis  1  0/74 (0.00%)  0 4/72 (5.56%)  5
Nervous system disorders     
Headache  1  0/74 (0.00%)  0 4/72 (5.56%)  4
Skin and subcutaneous tissue disorders     
Rash  1  1/74 (1.35%)  1 5/72 (6.94%)  5
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The data generated in this clinical study are the exclusive property of the Sponsor and are confidential. The Sponsor will make all reasonable efforts to publish the results of the study in an appropriate peer-reviewed journal. Authorship on the primary publication of the results from this study will be based on contributions to study design, enrollment, data analysis, and interpretation of results.
Results Point of Contact
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
Responsible Party: Cubist Pharmaceuticals LLC
ClinicalTrials.gov Identifier: NCT01922011     History of Changes
Other Study ID Numbers: 3009-006
DAP-PEDOST-11-03 ( Other Identifier: Cubist Pharmaceuticals, Inc. Protocol Number )
2013-000864-28 ( EudraCT Number )
First Submitted: August 9, 2013
First Posted: August 14, 2013
Results First Submitted: June 2, 2017
Results First Posted: June 23, 2017
Last Update Posted: August 28, 2018