Trial Outcomes & Findings for Safety and Efficacy Study of Daptomycin Compared to Active Comparator in Pediatric Participants With Acute Hematogenous Osteomyelitis (AHO) (MK-3009-006) (NCT NCT01922011)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

149 participants

Primary outcome timeframe

Up to study Day 5

Results posted on

2018-08-28

Participant Flow

Participant milestones

Participant milestones
Measure	Daptomycin Intravenous (IV) daptomycin 7, 9, or 12 mg/kg once daily and ≤3 dummy infusions daily	Vancomycin or Nafcillin 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.
Overall Study STARTED	75	74
Overall Study Treated	73	73
Overall Study Treatment Actually Received	74	72
Overall Study COMPLETED	69	69
Overall Study NOT COMPLETED	6	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Daptomycin Intravenous (IV) daptomycin 7, 9, or 12 mg/kg once daily and ≤3 dummy infusions daily	Vancomycin or Nafcillin 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.
Overall Study Protocol Violation	0	1
Overall Study Physician Decision	0	1
Overall Study Parent/Guardian Decision	3	0
Overall Study Lost to Follow-up	0	1
Overall Study Missed Test-of-Cure Visit	0	2
Overall Study Not Treated	1	0
Overall Study Lack of willing home health agency	1	0
Overall Study Randomized in error	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Daptomycin n=75 Participants IV daptomycin 7, 9, or 12 mg/kg once daily and ≤3 dummy infusions daily	Vancomycin or Nafcillin n=74 Participants 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 n=149 Participants Total of all reporting groups
Age, Continuous	9.1 Years STANDARD_DEVIATION 4.4 • n=5 Participants	9.2 Years STANDARD_DEVIATION 4.1 • n=7 Participants	9.2 Years STANDARD_DEVIATION 4.2 • n=5 Participants
Sex: Female, Male Female	31 Participants n=5 Participants	25 Participants n=7 Participants	56 Participants n=5 Participants
Sex: Female, Male Male	44 Participants n=5 Participants	49 Participants n=7 Participants	93 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to study Day 5

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Daptomycin n=71 Participants IV daptomycin 7, 9, or 12 mg/kg once daily and ≤3 dummy infusions daily	Vancomycin or Nafcillin n=70 Participants 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	Daptomycin 7 - < 12 Yrs Old IV daptomycin 9 mg/kg once daily and ≤3 dummy infusions daily for ages 7 - \< 12 yrs old only.	Daptomycin 12 - < 18 Yrs Old IV daptomycin 7 mg/kg once daily and ≤3 dummy infusions daily for ages 12 - \< 18 yrs old only.
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.	77.5 Percentage of participants Interval 67.7 to 87.2	82.9 Percentage of participants Interval 74.0 to 91.7	—	—

SECONDARY outcome

Timeframe: Up to study Day 5

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Daptomycin n=69 Participants IV daptomycin 7, 9, or 12 mg/kg once daily and ≤3 dummy infusions daily	Vancomycin or Nafcillin n=68 Participants 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	Daptomycin 7 - < 12 Yrs Old IV daptomycin 9 mg/kg once daily and ≤3 dummy infusions daily for ages 7 - \< 12 yrs old only.	Daptomycin 12 - < 18 Yrs Old IV daptomycin 7 mg/kg once daily and ≤3 dummy infusions daily for ages 12 - \< 18 yrs old only.
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.	71.0 Percentage of participants Interval 60.3 to 81.7	76.5 Percentage of participants Interval 66.4 to 86.6	—	—

SECONDARY outcome

Timeframe: 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)

Population: 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

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.

Outcome measures

Outcome measures
Measure	Daptomycin n=71 Participants IV daptomycin 7, 9, or 12 mg/kg once daily and ≤3 dummy infusions daily	Vancomycin or Nafcillin n=70 Participants 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	Daptomycin 7 - < 12 Yrs Old IV daptomycin 9 mg/kg once daily and ≤3 dummy infusions daily for ages 7 - \< 12 yrs old only.	Daptomycin 12 - < 18 Yrs Old IV daptomycin 7 mg/kg once daily and ≤3 dummy infusions daily for ages 12 - \< 18 yrs old only.
Percentage of Participants With a Favorable Clinical Outcome At End of IV (EOIV) Therapy (n= 71,69)	85.9 Percentage of participants Interval 77.8 to 94.0	91.3 Percentage of participants Interval 84.7 to 98.0	—	—
Percentage of Participants With a Favorable Clinical Outcome At End of Therapy (EOT) (n= 71,69)	83.1 Percentage of participants Interval 74.4 to 91.8	89.9 Percentage of participants Interval 82.7 to 97.0	—	—
Percentage of Participants With a Favorable Clinical Outcome At Test Of Cure (TOC) (n= 71,70)	81.7 Percentage of participants Interval 72.7 to 90.7	87.1 Percentage of participants Interval 79.3 to 95.0	—	—

SECONDARY outcome

Timeframe: 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)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Daptomycin n=45 Participants IV daptomycin 7, 9, or 12 mg/kg once daily and ≤3 dummy infusions daily	Vancomycin or Nafcillin n=47 Participants 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	Daptomycin 7 - < 12 Yrs Old IV daptomycin 9 mg/kg once daily and ≤3 dummy infusions daily for ages 7 - \< 12 yrs old only.	Daptomycin 12 - < 18 Yrs Old IV daptomycin 7 mg/kg once daily and ≤3 dummy infusions daily for ages 12 - \< 18 yrs old only.
Percentage of Participants With a Clinical Cure Categorized by Baseline Pathogen at Test of Cure Overall Baseline Infecting Pathogen (n =45,47)	77.8 Percentage of participants Interval 65.6 to 89.9	87.2 Percentage of participants Interval 77.7 to 96.8	—	—
Percentage of Participants With a Clinical Cure Categorized by Baseline Pathogen at Test of Cure Staphylococcus Aureus (SA) (n= 43,42)	76.7 Percentage of participants Interval 64.1 to 89.4	88.1 Percentage of participants Interval 78.3 to 97.9	—	—
Percentage of Participants With a Clinical Cure Categorized by Baseline Pathogen at Test of Cure Methicillin Susceptible SA (MSSA) (n= 39,37)	79.5 Percentage of participants Interval 66.8 to 92.2	94.6 Percentage of participants Interval 87.3 to 100.0	—	—
Percentage of Participants With a Clinical Cure Categorized by Baseline Pathogen at Test of Cure Methicillin Resistant SA (MRSA) (n= 4,4)	50.0 Percentage of participants Interval 1.0 to 99.0	25.0 Percentage of participants Interval 0.0 to 67.4	—	—
Percentage of Participants With a Clinical Cure Categorized by Baseline Pathogen at Test of Cure Other Pathogens (n= 2,7)	100 Percentage of participants Interval 100.0 to 100.0	85.7 Percentage of participants Interval 59.8 to 100.0	—	—

SECONDARY outcome

Timeframe: 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)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Daptomycin n=71 Participants IV daptomycin 7, 9, or 12 mg/kg once daily and ≤3 dummy infusions daily	Vancomycin or Nafcillin n=70 Participants 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	Daptomycin 7 - < 12 Yrs Old IV daptomycin 9 mg/kg once daily and ≤3 dummy infusions daily for ages 7 - \< 12 yrs old only.	Daptomycin 12 - < 18 Yrs Old IV daptomycin 7 mg/kg once daily and ≤3 dummy infusions daily for ages 12 - \< 18 yrs old only.
Percentage of Participants With Sustained Clinical Improvement EOT (n= 55,57)	89.1 Percentage of participants Interval 80.9 to 97.3	94.7 Percentage of participants Interval 88.9 to 100.0	—	—
Percentage of Participants With Sustained Clinical Improvement TOC (n= 55,58)	87.3 Percentage of participants Interval 78.5 to 96.1	91.4 Percentage of participants Interval 84.2 to 98.6	—	—

SECONDARY outcome

Timeframe: 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)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Daptomycin n=45 Participants IV daptomycin 7, 9, or 12 mg/kg once daily and ≤3 dummy infusions daily	Vancomycin or Nafcillin n=47 Participants 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	Daptomycin 7 - < 12 Yrs Old IV daptomycin 9 mg/kg once daily and ≤3 dummy infusions daily for ages 7 - \< 12 yrs old only.	Daptomycin 12 - < 18 Yrs Old IV daptomycin 7 mg/kg once daily and ≤3 dummy infusions daily for ages 12 - \< 18 yrs old only.
Percentage of Participants With a Favorable Microbiological Response Categorized by Baseline Pathogen at Test of Cure Overall Baseline Infecting Pathogen (n =45,47)	82.2 Percentage of participants Interval 71.1 to 93.4	91.5 Percentage of participants Interval 83.5 to 99.5	—	—
Percentage of Participants With a Favorable Microbiological Response Categorized by Baseline Pathogen at Test of Cure SA (n= 43,42)	81.4 Percentage of participants Interval 69.8 to 93.0	92.9 Percentage of participants Interval 85.1 to 100.0	—	—
Percentage of Participants With a Favorable Microbiological Response Categorized by Baseline Pathogen at Test of Cure MSSA (n= 39,37)	84.6 Percentage of participants Interval 73.3 to 95.9	94.6 Percentage of participants Interval 87.3 to 100.0	—	—
Percentage of Participants With a Favorable Microbiological Response Categorized by Baseline Pathogen at Test of Cure MRSA (n= 4,4)	50.0 Percentage of participants Interval 1.0 to 99.0	75.0 Percentage of participants Interval 32.6 to 100.0	—	—
Percentage of Participants With a Favorable Microbiological Response Categorized by Baseline Pathogen at Test of Cure Other Pathogens (n= 2,7)	100 Percentage of participants Interval 100.0 to 100.0	85.7 Percentage of participants Interval 59.8 to 100.0	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Administration of first dose up to approximately six and a half months after last dose of study drug

Population: Treated participants based on the treatment received

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

Outcome measures

Outcome measures
Measure	Daptomycin n=74 Participants IV daptomycin 7, 9, or 12 mg/kg once daily and ≤3 dummy infusions daily	Vancomycin or Nafcillin n=72 Participants 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	Daptomycin 7 - < 12 Yrs Old IV daptomycin 9 mg/kg once daily and ≤3 dummy infusions daily for ages 7 - \< 12 yrs old only.	Daptomycin 12 - < 18 Yrs Old IV daptomycin 7 mg/kg once daily and ≤3 dummy infusions daily for ages 12 - \< 18 yrs old only.
Number of Participants With 1 or More Adverse Events (AEs)	34 Participants	45 Participants	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Administration of first dose through the last follow-up visit; an expected time of up to 6.5 months

Population: Treated participants based on the treatment received

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.

Outcome measures

Outcome measures
Measure	Daptomycin n=74 Participants IV daptomycin 7, 9, or 12 mg/kg once daily and ≤3 dummy infusions daily	Vancomycin or Nafcillin n=72 Participants 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	Daptomycin 7 - < 12 Yrs Old IV daptomycin 9 mg/kg once daily and ≤3 dummy infusions daily for ages 7 - \< 12 yrs old only.	Daptomycin 12 - < 18 Yrs Old IV daptomycin 7 mg/kg once daily and ≤3 dummy infusions daily for ages 12 - \< 18 yrs old only.
Number of Participants With 1 or More Serious Adverse Events (SAEs)	5 Participants	4 Participants	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and End of Therapy IV (up to Day 42)

Population: Treated participants based on the treatment received

Serum was collected at Baseline and at End of Therapy IV, from which the concentration of CK was determined.

Outcome measures

Outcome measures
Measure	Daptomycin n=74 Participants IV daptomycin 7, 9, or 12 mg/kg once daily and ≤3 dummy infusions daily	Vancomycin or Nafcillin n=72 Participants 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	Daptomycin 7 - < 12 Yrs Old IV daptomycin 9 mg/kg once daily and ≤3 dummy infusions daily for ages 7 - \< 12 yrs old only.	Daptomycin 12 - < 18 Yrs Old IV daptomycin 7 mg/kg once daily and ≤3 dummy infusions daily for ages 12 - \< 18 yrs old only.
Concentration of Serum Creatine Kinase (CK) Baseline (n = 68,72)	141.7 U/L Standard Deviation 188.70	99.9 U/L Standard Deviation 95.00	—	—
Concentration of Serum Creatine Kinase (CK) End of Therapy IV (n= 35,41)	89.4 U/L Standard Deviation 66.55	82.4 U/L Standard Deviation 95.03	—	—

Adverse Events

Daptomycin

Serious events: 5 serious events

Other events: 6 other events

Deaths: 0 deaths

Vancomycin or Nafcillin

Serious events: 4 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Daptomycin n=74 participants at risk IV daptomycin 7, 9, or 12 mg/kg once daily and ≤3 dummy infusions daily	Vancomycin or Nafcillin n=72 participants at risk 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.
General disorders Pyrexia	0.00% 0/74 • 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 Treated participants based on the treatment received	1.4% 1/72 • Number of events 1 • 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 Treated participants based on the treatment received
Infections and infestations Device related infection	0.00% 0/74 • 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 Treated participants based on the treatment received	1.4% 1/72 • Number of events 1 • 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 Treated participants based on the treatment received
Infections and infestations Osteomyelitis	1.4% 1/74 • Number of events 1 • 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 Treated participants based on the treatment received	0.00% 0/72 • 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 Treated participants based on the treatment received
Infections and infestations Sepsis	1.4% 1/74 • Number of events 1 • 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 Treated participants based on the treatment received	0.00% 0/72 • 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 Treated participants based on the treatment received
Infections and infestations Viral infection	0.00% 0/74 • 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 Treated participants based on the treatment received	1.4% 1/72 • Number of events 1 • 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 Treated participants based on the treatment received
Injury, poisoning and procedural complications Femur fracture	1.4% 1/74 • Number of events 1 • 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 Treated participants based on the treatment received	0.00% 0/72 • 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 Treated participants based on the treatment received
Injury, poisoning and procedural complications Joint injury	0.00% 0/74 • 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 Treated participants based on the treatment received	1.4% 1/72 • Number of events 1 • 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 Treated participants based on the treatment received
Musculoskeletal and connective tissue disorders Myalgia	1.4% 1/74 • Number of events 1 • 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 Treated participants based on the treatment received	0.00% 0/72 • 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 Treated participants based on the treatment received
Musculoskeletal and connective tissue disorders Pain in extremity	1.4% 1/74 • Number of events 1 • 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 Treated participants based on the treatment received	0.00% 0/72 • 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 Treated participants based on the treatment received
Musculoskeletal and connective tissue disorders Pathological fracture	1.4% 1/74 • Number of events 1 • 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 Treated participants based on the treatment received	0.00% 0/72 • 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 Treated participants based on the treatment received
Skin and subcutaneous tissue disorders Drug reaction with eosinophilia and systemic symptoms	0.00% 0/74 • 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 Treated participants based on the treatment received	1.4% 1/72 • Number of events 1 • 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 Treated participants based on the treatment received
Skin and subcutaneous tissue disorders Red man syndrome	0.00% 0/74 • 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 Treated participants based on the treatment received	1.4% 1/72 • Number of events 1 • 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 Treated participants based on the treatment received

Other adverse events

Other adverse events
Measure	Daptomycin n=74 participants at risk IV daptomycin 7, 9, or 12 mg/kg once daily and ≤3 dummy infusions daily	Vancomycin or Nafcillin n=72 participants at risk 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.
Gastrointestinal disorders Constipation	1.4% 1/74 • Number of events 1 • 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 Treated participants based on the treatment received	8.3% 6/72 • Number of events 6 • 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 Treated participants based on the treatment received
Gastrointestinal disorders Diarrhoea	1.4% 1/74 • Number of events 1 • 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 Treated participants based on the treatment received	5.6% 4/72 • Number of events 4 • 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 Treated participants based on the treatment received
Gastrointestinal disorders Vomiting	4.1% 3/74 • Number of events 3 • 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 Treated participants based on the treatment received	8.3% 6/72 • Number of events 6 • 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 Treated participants based on the treatment received
General disorders Pyrexia	2.7% 2/74 • Number of events 2 • 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 Treated participants based on the treatment received	6.9% 5/72 • Number of events 6 • 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 Treated participants based on the treatment received
Infections and infestations Nasopharyngitis	0.00% 0/74 • 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 Treated participants based on the treatment received	5.6% 4/72 • Number of events 5 • 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 Treated participants based on the treatment received
Nervous system disorders Headache	0.00% 0/74 • 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 Treated participants based on the treatment received	5.6% 4/72 • Number of events 4 • 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 Treated participants based on the treatment received
Skin and subcutaneous tissue disorders Rash	1.4% 1/74 • Number of events 1 • 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 Treated participants based on the treatment received	6.9% 5/72 • Number of events 5 • 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 Treated participants based on the treatment received

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER