Study of Daptomycin in Subjects Undergoing Surgery for Osteomyelitis Associated With an Infected Prosthetic Caused by Staphylococci

ID: NCT00428844
Status: Completed
Phase: Phase 2
Start Date: January 01, 2007
First Submitted: January 26, 2007
Last Updated: January 05, 2016
Results: Available
Success Rate: 83%
Sponsors & Collaborators: Cubist Pharmaceuticals LLC
Location: Russian Federation, United Kingdom, United States
Conditions: Osteomyelitis
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Study Description

Brief Summary

This is a research study designed to look at the efficacy and safety of daptomycin given at a dose of 6 mg/kg or 8 mg/kg in subjects being treated for prosthetic hip or knee infections caused by Staphylococci. These types of bacteria are among the most common types of bacteria causing infections of prosthetic joints.

Detailed Description

Condition or disease Intervention/treatment Phase

Osteomyelitis

Drug: daptomycin
Other Names
Cubicin
Drug: daptomycin
Other Names
Cubicin
Drug: vancomycin
Other Names
Vancocin
Drug: teicoplanin
Other Names
Targocid
Drug: nafcillin
Other Names
Unipen
Drug: oxacillin
Other Names
Bactocill
Drug: flucloxacillin
Other Names
Fluclox
Phase 2

Tracking Information

First Submitted DateJanuary 26, 2007
Last Update Posted DateJanuary 05, 2016
Start DateJanuary 01, 2007
Actual Completion DateJune 01, 2010
Primary Completion DateMarch 01, 2010
Results First Submitted DateMarch 16, 2011
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Any Creatine Phosphokinase (CPK) Elevation > 500 Units Per Liter (U/L) [Time Frame: From the 3rd day of therapy to 1 week post last dose (approximately week 7)]

    Number of subjects with CPK >500 U/L between Day 3 and 7 days following the last dose of study medication (Day 7P) as measured by the central laboratory.

Original Primary Outcome Measures

  • Any Creatine Phosphokinase (CPK) Elevation > 500 Units Per Liter (U/L)

    Number of subjects with CPK >500 U/L between Day 3 and 7 days following the last dose of study medication (Day 7P) as measured by the central laboratory.

Current Secondary Outcome Measures

  • Safety - Notable Laboratory Abnormalities [Time Frame: From the 1st day of therapy to maximum of 23 weeks post last dose (up to maximum of week 30)]

    Summary of Notable Laboratory Abnormalities - description of the proportion of subjects within each treatment group that had clinical laboratory values outside the reference range.

  • Overall Clinical Outcome [Time Frame: Approximately 6 weeks post last dose (approximately week 12)]

    The sponsor determined overall clinical outcome based on blinded review of clinical, microbiological, and radiological response of the subject including, but not limited to, clinical signs and symptoms of PJI, microbiological assessments, radiographic findings, and surgical procedures performed. Subjects were a success if both clinical and microbiological responses were success. A subject who failed to respond clinically or microbiologically was a failure. If microbiological response was non-evaluable and/or clinical evaluation at TOC was not performed, the subject was non-evaluable.

  • Microbiological Response [Time Frame: Approximately 6 weeks post last dose (approximately week 12)]

    Sponsor's assessment of subject-level microbiological response at the test-of-cure visit for the modified Intent-to-Treat (mITT) population.

  • Pharmacokinetic Parameter: Maximum Plasma Concentration (Cmax) [Time Frame: Day 4 (steady state)]

    The pharmacokinetic (PK) parameters of daptomycin at steady state for the 6 mg/kg and 8 mg/kg dose groups. On treatment day 4, PK samples for daptomycin levels were to be obtained prior to start of daptomycin infusion (0 hr) and at 0.5 hr (end of infusion), 1-1.5 hr, 3-5 hr, 8-12 hr, and 24 hr after the start of daptomycin infusion.

  • Pharmacokinetic Parameter: Area Under the Concentration-time Curve During a Dosing Interval at Steady State (AUCss) [Time Frame: Day 4 (steady state)]

    The pharmacokinetic (PK) parameters of daptomycin at steady state for the 6 mg/kg and 8 mg/kg dose groups. On treatment day 4, PK samples for daptomycin levels were to be obtained prior to start of daptomycin infusion (0 hr) and at 0.5 hr (end of infusion), 1-1.5 hr, 3-5 hr, 8-12 hr, and 24 hr after the start of daptomycin infusion.

Original Secondary Outcome Measures

  • Pharmacokinetic Parameter: Area Under the Concentration-time Curve During a Dosing Interval at Steady State (AUCss)

    The pharmacokinetic (PK) parameters of daptomycin at steady state for the 6 mg/kg and 8 mg/kg dose groups. On treatment day 4, PK samples for daptomycin levels were to be obtained prior to start of daptomycin infusion (0 hr) and at 0.5 hr (end of infusion), 1-1.5 hr, 3-5 hr, 8-12 hr, and 24 hr after the start of daptomycin infusion.

  • Pharmacokinetic Parameter: Maximum Plasma Concentration (Cmax)

    The pharmacokinetic (PK) parameters of daptomycin at steady state for the 6 mg/kg and 8 mg/kg dose groups. On treatment day 4, PK samples for daptomycin levels were to be obtained prior to start of daptomycin infusion (0 hr) and at 0.5 hr (end of infusion), 1-1.5 hr, 3-5 hr, 8-12 hr, and 24 hr after the start of daptomycin infusion.

  • Microbiological Response

    Sponsor’s assessment of subject-level microbiological response at the test-of-cure visit for the modified Intent-to-Treat (mITT) population.

  • Overall Clinical Outcome

    The sponsor determined overall clinical outcome based on blinded review of clinical, microbiological, and radiological response of the subject including, but not limited to, clinical signs and symptoms of PJI, microbiological assessments, radiographic findings, and surgical procedures performed. Subjects were a success if both clinical and microbiological responses were success. A subject who failed to respond clinically or microbiologically was a failure. If microbiological response was non-evaluable and/or clinical evaluation at TOC was not performed, the subject was non-evaluable.

  • Safety - Notable Laboratory Abnormalities

    Summary of Notable Laboratory Abnormalities - description of the proportion of subjects within each treatment group that had clinical laboratory values outside the reference range.

Study Design

Brief TitleStudy of Daptomycin in Subjects Undergoing Surgery for Osteomyelitis Associated With an Infected Prosthetic Caused by Staphylococci
Official TitleA Phase 2 Randomized Study Investigating the Safety, Efficacy and Pharmacokinetics of Daptomycin 6 mg/kg and 8 mg/kg Versus Comparator in the Treatment of Subjects Undergoing Surgical Standard of Care for Osteomyelitis Associated With an Infected Prosthetic Hip or Knee Joint Caused by Staphylococci
Brief Summary

This is a research study designed to look at the efficacy and safety of daptomycin given at a dose of 6 mg/kg or 8 mg/kg in subjects being treated for prosthetic hip or knee infections caused by Staphylococci. These types of bacteria are among the most common types of bacteria causing infections of prosthetic joints.

Detailed Description

Study TypeInterventional
Study PhasePhase 2
Estimated Enrollment
75
Allocation
Randomized
Interventional Model
Parallel Assignment
Masking
None
Primary Purpose
Treatment
Conditions
Osteomyelitis
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: daptomycin

6 mg/kg

Other Names
Cubicin
Drug: daptomycin

8 mg/kg

Other Names
Cubicin
Drug: vancomycin

1 gram

Other Names
Vancocin
Drug: teicoplanin

6 mg/kg; used only at UK sites

Other Names
Targocid
Drug: nafcillin

1-2 gram

Other Names
Unipen
Drug: oxacillin

1-2 gram

Other Names
Bactocill
Drug: flucloxacillin

1-2 mg

Other Names
Fluclox
Study Groups/Cohorts
Daptomycin 6 mg/kg
Daptomycin (6 mg/kg every 24 hours [q24h]) as a 30 minute intravenous (IV) infusion for 6 weeks (± one week).

Daptomycin 8 mg/kg
Daptomycin (8 mg/kg q24h) as a 30 minute IV infusion for 6 weeks (± one week).

Comparator
Vancomycin was administered at 1 gram every 12 hours (q12h) as a 60-minute infusion and teicoplanin was administered 6 mg/kg q24h as a 30-minute infusion also for 6 weeks (±1 week). Semi-synthetic penicillin (nafcillin, oxacillin, or flucloxacillin) was administered according to standard of care for 6 weeks (±1 week).

Study Arms
Active Comparator Comparator
Vancomycin was administered at 1 gram every 12 hours (q12h) as a 60-minute infusion and teicoplanin was administered 6 mg/kg q24h as a 30-minute infusion also for 6 weeks (±1 week). Semi-synthetic penicillin (nafcillin, oxacillin, or flucloxacillin) was administered according to standard of care for 6 weeks (±1 week).
Drug : vancomycin
1 gram

Active Comparator Comparator
Vancomycin was administered at 1 gram every 12 hours (q12h) as a 60-minute infusion and teicoplanin was administered 6 mg/kg q24h as a 30-minute infusion also for 6 weeks (±1 week). Semi-synthetic penicillin (nafcillin, oxacillin, or flucloxacillin) was administered according to standard of care for 6 weeks (±1 week).
Drug : teicoplanin
6 mg/kg; used only at UK sites

Active Comparator Comparator
Vancomycin was administered at 1 gram every 12 hours (q12h) as a 60-minute infusion and teicoplanin was administered 6 mg/kg q24h as a 30-minute infusion also for 6 weeks (±1 week). Semi-synthetic penicillin (nafcillin, oxacillin, or flucloxacillin) was administered according to standard of care for 6 weeks (±1 week).
Drug : nafcillin
1-2 gram

Active Comparator Comparator
Vancomycin was administered at 1 gram every 12 hours (q12h) as a 60-minute infusion and teicoplanin was administered 6 mg/kg q24h as a 30-minute infusion also for 6 weeks (±1 week). Semi-synthetic penicillin (nafcillin, oxacillin, or flucloxacillin) was administered according to standard of care for 6 weeks (±1 week).
Drug : oxacillin
1-2 gram

Active Comparator Comparator
Vancomycin was administered at 1 gram every 12 hours (q12h) as a 60-minute infusion and teicoplanin was administered 6 mg/kg q24h as a 30-minute infusion also for 6 weeks (±1 week). Semi-synthetic penicillin (nafcillin, oxacillin, or flucloxacillin) was administered according to standard of care for 6 weeks (±1 week).
Drug : flucloxacillin
1-2 mg

Experimental Daptomycin 6 mg/kg
Daptomycin (6 mg/kg every 24 hours [q24h]) as a 30 minute intravenous (IV) infusion for 6 weeks (± one week).
Drug : daptomycin
6 mg/kg

Experimental Daptomycin 8 mg/kg
Daptomycin (8 mg/kg q24h) as a 30 minute IV infusion for 6 weeks (± one week).
Drug : daptomycin
8 mg/kg

Arm Intervention/Treatment
Active Comparator Comparator
Vancomycin was administered at 1 gram every 12 hours (q12h) as a 60-minute infusion and teicoplanin was administered 6 mg/kg q24h as a 30-minute infusion also for 6 weeks (±1 week). Semi-synthetic penicillin (nafcillin, oxacillin, or flucloxacillin) was administered according to standard of care for 6 weeks (±1 week).
Drug : vancomycin
Active Comparator Comparator
Vancomycin was administered at 1 gram every 12 hours (q12h) as a 60-minute infusion and teicoplanin was administered 6 mg/kg q24h as a 30-minute infusion also for 6 weeks (±1 week). Semi-synthetic penicillin (nafcillin, oxacillin, or flucloxacillin) was administered according to standard of care for 6 weeks (±1 week).
Drug : teicoplanin
Active Comparator Comparator
Vancomycin was administered at 1 gram every 12 hours (q12h) as a 60-minute infusion and teicoplanin was administered 6 mg/kg q24h as a 30-minute infusion also for 6 weeks (±1 week). Semi-synthetic penicillin (nafcillin, oxacillin, or flucloxacillin) was administered according to standard of care for 6 weeks (±1 week).
Drug : nafcillin
Active Comparator Comparator
Vancomycin was administered at 1 gram every 12 hours (q12h) as a 60-minute infusion and teicoplanin was administered 6 mg/kg q24h as a 30-minute infusion also for 6 weeks (±1 week). Semi-synthetic penicillin (nafcillin, oxacillin, or flucloxacillin) was administered according to standard of care for 6 weeks (±1 week).
Drug : oxacillin
Active Comparator Comparator
Vancomycin was administered at 1 gram every 12 hours (q12h) as a 60-minute infusion and teicoplanin was administered 6 mg/kg q24h as a 30-minute infusion also for 6 weeks (±1 week). Semi-synthetic penicillin (nafcillin, oxacillin, or flucloxacillin) was administered according to standard of care for 6 weeks (±1 week).
Drug : flucloxacillin
Experimental Daptomycin 6 mg/kg
Daptomycin (6 mg/kg every 24 hours [q24h]) as a 30 minute intravenous (IV) infusion for 6 weeks (± one week).
Drug : daptomycin
Experimental Daptomycin 8 mg/kg
Daptomycin (8 mg/kg q24h) as a 30 minute IV infusion for 6 weeks (± one week).
Drug : daptomycin

Recruitment Information

Recruitment Status:Completed
Enrollment75
Completion DateJune 01, 2010
Eligibility Criteria: Inclusion Criteria:
- Subject must be between the ages of 18 and 80, inclusive
- Subject must have a diagnosis of prosthetic joint infection (PJI) in a hip or knee joint which has never previously been totally revised because of an infection and for which they are anticipated to undergo a two-stage replacement surgery
- Subject must have a positive microbiological identifier of staphylococci.
- If Subject is female of childbearing potential, must be willing to practice reliable birth control

Exclusion Criteria:
- Subject has permanent intravascular prosthetic material such as heart valves or pacemakers
- Subject has a creatinine clearance (CLCR) <30 mL/min as determined by the Cockcroft-Gault equation using actual body weight.
- Subject has significant hepatic dysfunction
- Subject has a fungal or mycobacterial PJI
- Subject is known to be HIV-infected with CD4 count ≤ 200 cells/ mm3
- Subject has an abnormal creatine phosphokinase (CPK) (elevated CPK level ≥ 2x ULN) at baseline as measured by central laboratory
- Subject is currently under treatment with chemotherapeutic agents excluding chronic maintenance therapy (e.g. tamoxifen to prevent relapse of primary breast cancer)
- Subject is pregnant, nursing, or lactating.
- Subject is receiving or is expected to receive chronic immunosuppressive therapy during the study.
GenderAll
Age18 Years to 80 Years
Accepts Healthy VolunteersNo
Contacts
Not Available
Listed Location Countries
Russian Federation
United Kingdom
United States

Administrative Information

NCT Number:NCT00428844
Other Study ID Numbers
3009-016
DAP-OST-06-02
Has Data Monitoring CommitteeYes
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
Not Available
Responsible Party,
Study Sponsor
Cubist Pharmaceuticals LLC
Collaborators
Not Available
Investigators
Study Director
Alistair Wheeler, MD
Cubist Pharmaceuticals, 65 Hayden Ave, Lexington, MA 02421, USA

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
Daptomycin 6 mg/kg
Daptomycin (6 mg/kg every 24 hours [q24h]) as a 30 minute intravenous (IV) infusion for 6 weeks (± one week).
Daptomycin 8 mg/kg
Daptomycin (8 mg/kg q24h) as a 30 minute IV infusion for 6 weeks (± one week).
Comparator
Vancomycin was administered at 1 gram (gm)every 12 hours (q12h) as a 60-minute infusion and teicoplanin was administered 6 mg/kg q24h as a 30-minute infusion also for 6 weeks (±1 week). Semi-synthetic penicillin (nafcillin, oxacillin, or flucloxacillin) was administered according to standard of care for 6 weeks (±1 week).

Participant Flow: Overall

Daptomycin 6 mg/kgDaptomycin 8 mg/kgComparator
252425
Started252324
Started182619
Completed232018
Completed161917
Not Completed236
Not Completed272
Adverse Event204
Adverse Event141
Lack of Efficacy200
Microbiologic failure010
Protocol Violation001
Protocol Violation011
Randomized Not Treated001
Withdrawal by Subject011
Withdrawal by Subject010

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.
Not Available

Reporting Groups

TitleDescription
Daptomycin 6 mg/kg
Daptomycin (6 mg/kg q24h) as a 30-minute IV infusion for 6 weeks (±1 week).
Daptomycin 8 mg/kg
Daptomycin (8 mg/kg q24h) as a 30-minute IV infusion for 6 weeks (±1 week).
Comparator
Vancomycin was administered at 1 gm q12h as a 60-minute infusion and teicoplanin was administered 6 mg/kg q24h as a 30-minute infusion also for 6 weeks (±1 week). Semi-synthetic penicillin (nafcillin, oxacillin, or flucloxacillin) was administered according to standard of care for 6 weeks (±1 week).
Total
Total of all reporting groups

Baseline Measures

Daptomycin 6 mg/kgDaptomycin 8 mg/kgComparatorTotal
Overall Participants Analyzed
Units: Participants
Participants Analyzed
25242574
25242574
Age
Units: participants - Number
Participants Analyzed
25242574
<=18 years0000
>=65 years15101035
Between 18 and 65 years10141539
Gender
Units: participants - Number
Participants Analyzed
25242574
Female14101135
Male11141439

Outcome Measures

1. Primary: Any Creatine Phosphokinase (CPK) Elevation > 500 Units Per Liter (U/L)

Measure Type
Primary
Measure Title
Any Creatine Phosphokinase (CPK) Elevation > 500 Units Per Liter (U/L)
Measure Description
Number of subjects with CPK >500 U/L between Day 3 and 7 days following the last dose of study medication (Day 7P) as measured by the central laboratory.
Time Frame
From the 3rd day of therapy to 1 week post last dose (approximately week 7)

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.
Safety Population

Reporting Groups

TitleDescription
Daptomycin 6 mg/kg
Daptomycin (6 mg/kg q24h) as a 30-minute IV infusion for 6 weeks (±1 week).
Daptomycin 8 mg/kg
Daptomycin (8 mg/kg q24h) as a 30-minute IV infusion for 6 weeks (±1 week).
Comparator
Vancomycin was administered at 1 gm q12h as a 60-minute infusion and teicoplanin was administered 6 mg/kg q24h as a 30-minute infusion also for 6 weeks (±1 week). Semi-synthetic penicillin (nafcillin, oxacillin, or flucloxacillin) was administered according to standard of care for 6 weeks (±1 week).

Outcome Measures

Daptomycin 6 mg/kgDaptomycin 8 mg/kgComparator
Participants Analyzed
Units: Participants
252425
Any Creatine Phosphokinase (CPK) Elevation > 500 Units Per Liter (U/L)
Units: Participants - Number
452

2. Secondary: Safety - Notable Laboratory Abnormalities

Measure Type
Secondary
Measure Title
Safety - Notable Laboratory Abnormalities
Measure Description
Summary of Notable Laboratory Abnormalities - description of the proportion of subjects within each treatment group that had clinical laboratory values outside the reference range.
Time Frame
From the 1st day of therapy to maximum of 23 weeks post last dose (up to maximum of week 30)

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.
Safety Population

Reporting Groups

TitleDescription
Daptomycin 6 mg/kg
Daptomycin (6 mg/kg q24h) as a 30-minute IV infusion for 6 weeks (±1 week).
Daptomycin 8 mg/kg
Daptomycin (8 mg/kg q24h) as a 30-minute IV infusion for 6 weeks (±1 week).
Comparator
Vancomycin was administered at 1 gm q12h as a 60-minute infusion and teicoplanin was administered 6 mg/kg q24h as a 30-minute infusion also for 6 weeks (±1 week). Semi-synthetic penicillin (nafcillin, oxacillin, or flucloxacillin) was administered according to standard of care for 6 weeks (±1 week).

Outcome Measures

Daptomycin 6 mg/kgDaptomycin 8 mg/kgComparator
Participants Analyzed
Units: Participants
252425
Safety - Notable Laboratory Abnormalities
Units: Participants - Number
Alanine aminotransferase (>235 U/L)000
Albumin (<3, >6 g/dL)744
Alkaline Phosphatase (>1350 U/L)000
Aspartate aminotransferase (>185 U/L)100
Blood Urea Nitrogen (>50 mg/dL)201
Creatinine (Female >2.0; Male>2.8 mg/dL)102
Hematocrit (<30%, >60%)121015
Hemoglobin (<9,>19 g/dL)101012
Platelets (<40, >450 x 10^9/L)131310
Red Blood Cell (Female <2.5,>6.0; Male <3.0, >6.5)243
Total bilirubin (>2.2 mg/dL)000
White Blood Cell (<2, >20 x 10^9/L)100

3. Secondary: Overall Clinical Outcome

Measure Type
Secondary
Measure Title
Overall Clinical Outcome
Measure Description
The sponsor determined overall clinical outcome based on blinded review of clinical, microbiological, and radiological response of the subject including, but not limited to, clinical signs and symptoms of PJI, microbiological assessments, radiographic findings, and surgical procedures performed. Subjects were a success if both clinical and microbiological responses were success. A subject who failed to respond clinically or microbiologically was a failure. If microbiological response was non-evaluable and/or clinical evaluation at TOC was not performed, the subject was non-evaluable.
Time Frame
Approximately 6 weeks post last dose (approximately week 12)

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.
Modified Intent-to-Treat Population. Six treated patients in the ITT population were not included in the mITT population, as they did not have confirmed baseline staphylococcal infection.

Reporting Groups

TitleDescription
Daptomycin 6 mg/kg
Daptomycin (6 mg/kg q24h) as a 30-minute IV infusion for 6 weeks (±1 week).
Daptomycin 8 mg/kg
Daptomycin (8 mg/kg q24h) as a 30-minute IV infusion for 6 weeks (±1 week).
Comparator
Vancomycin was administered at 1 gm q12h as a 60-minute infusion and teicoplanin was administered 6 mg/kg q24h as a 30-minute infusion also for 6 weeks (±1 week). Semi-synthetic penicillin (nafcillin, oxacillin, or flucloxacillin) was administered according to standard of care for 6 weeks (±1 week).

Outcome Measures

Daptomycin 6 mg/kgDaptomycin 8 mg/kgComparator
Participants Analyzed
Units: Participants
242321
Overall Clinical Outcome
Units: Participants - Number
Failure10811
Nonevaluable122
Success13138

4. Secondary: Microbiological Response

Measure Type
Secondary
Measure Title
Microbiological Response
Measure Description
Sponsor’s assessment of subject-level microbiological response at the test-of-cure visit for the modified Intent-to-Treat (mITT) population.
Time Frame
Approximately 6 weeks post last dose (approximately week 12)

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.
Modified Intent to Treat Population. Six treated patients in the ITT population were not included in the mITT population, as they did not have confirmed baseline staphylococcal infection.

Reporting Groups

TitleDescription
Daptomycin 6 mg/kg
Daptomycin (6 mg/kg q24h) as a 30-minute IV infusion for 6 weeks (±1 week).
Daptomycin 8 mg/kg
Daptomycin (8 mg/kg q24h) as a 30-minute IV infusion for 6 weeks (±1 week).
Comparator
Vancomycin was administered at 1 gm q12h as a 60-minute infusion and teicoplanin was administered 6 mg/kg q24h as a 30-minute infusion also for 6 weeks (±1 week). Semi-synthetic penicillin (nafcillin, oxacillin, or flucloxacillin) was administered according to standard of care for 6 weeks (±1 week).

Outcome Measures

Daptomycin 6 mg/kgDaptomycin 8 mg/kgComparator
Participants Analyzed
Units: Participants
242321
Microbiological Response
Units: Participants - Number
Failure836
Non-evaluable487
Success12128

5. Secondary: Pharmacokinetic Parameter: Maximum Plasma Concentration (Cmax)

Measure Type
Secondary
Measure Title
Pharmacokinetic Parameter: Maximum Plasma Concentration (Cmax)
Measure Description
The pharmacokinetic (PK) parameters of daptomycin at steady state for the 6 mg/kg and 8 mg/kg dose groups. On treatment day 4, PK samples for daptomycin levels were to be obtained prior to start of daptomycin infusion (0 hr) and at 0.5 hr (end of infusion), 1-1.5 hr, 3-5 hr, 8-12 hr, and 24 hr after the start of daptomycin infusion.
Time Frame
Day 4 (steady state)

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.
Pharmacokinetic evaluable population. Pharmacokinetics not analyzed for the comparator group.

Reporting Groups

TitleDescription
Daptomycin 6 mg/kg
Daptomycin (6 mg/kg q24h) as a 30-minute IV infusion for 6 weeks (±1 week).
Daptomycin 8 mg/kg
Daptomycin (8 mg/kg q24h) as a 30-minute IV infusion for 6 weeks (±1 week).

Outcome Measures

Daptomycin 6 mg/kgDaptomycin 8 mg/kg
Participants Analyzed
Units: Participants
2220
Pharmacokinetic Parameter: Maximum Plasma Concentration (Cmax)
Units: µg/mL - Median (Full Range)
59.192.3

6. Secondary: Pharmacokinetic Parameter: Area Under the Concentration-time Curve During a Dosing Interval at Steady State (AUCss)

Measure Type
Secondary
Measure Title
Pharmacokinetic Parameter: Area Under the Concentration-time Curve During a Dosing Interval at Steady State (AUCss)
Measure Description
The pharmacokinetic (PK) parameters of daptomycin at steady state for the 6 mg/kg and 8 mg/kg dose groups. On treatment day 4, PK samples for daptomycin levels were to be obtained prior to start of daptomycin infusion (0 hr) and at 0.5 hr (end of infusion), 1-1.5 hr, 3-5 hr, 8-12 hr, and 24 hr after the start of daptomycin infusion.
Time Frame
Day 4 (steady state)

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.
Pharmacokinetic evaluable population. Pharmacokinetics not analyzed for the comparator group.

Reporting Groups

TitleDescription
Daptomycin 6 mg/kg
Daptomycin (6 mg/kg q24h) as a 30-minute IV infusion for 6 weeks (±1 week).
Daptomycin 8 mg/kg
Daptomycin (8 mg/kg q24h) as a 30-minute IV infusion for 6 weeks (±1 week).

Outcome Measures

Daptomycin 6 mg/kgDaptomycin 8 mg/kg
Participants Analyzed
Units: Participants
2220
Pharmacokinetic Parameter: Area Under the Concentration-time Curve During a Dosing Interval at Steady State (AUCss)
Units: µg•hr/mL - Median (Full Range)
499821

Serious Adverse Events

Time Frame
From the 1st day of therapy to maximum of 23 weeks post last dose (up to maximum of week 30)
Additional Description
Subjects who prematurely discontinue study drug will undergo follow-up safety evaluations within 30 days (±5 days) of administration of the last dose of study drug.
Frequency Threshold0% (Threshold above which other adverse events are reported)

Reporting Groups

TitleDescription
Daptomycin 6 mg/kg
Daptomycin (6 mg/kg q24h) as a 30-minute IV infusion for 6 weeks (±1 week).
Daptomycin 8 mg/kg
Daptomycin (8 mg/kg q24h) as a 30-minute IV infusion for 6 weeks (±1 week).
Comparator
Vancomycin was administered at 1 gm q12h as a 60-minute infusion and teicoplanin was administered 6 mg/kg q24h as a 30-minute infusion also for 6 weeks (±1 week). Semi-synthetic penicillin (nafcillin, oxacillin, or flucloxacillin) was administered according to standard of care for 6 weeks (±1 week).

Serious Adverse Events

Daptomycin 6 mg/kgDaptomycin 8 mg/kgComparator
Total, serious adverse events
No. of participants affected / at risk8/25 (0.00%)4/24 (0.00%)8/25 (0.00%)
Anaemia
No. of participants affected / at risk0/25 (0.00%)0/24 (0.00%)1/25 (0.00%)
Cardiac arrest
No. of participants affected / at risk0/25 (0.00%)0/24 (0.00%)1/25 (0.00%)
Wound necrosis
No. of participants affected / at risk0/25 (0.00%)0/24 (0.00%)1/25 (0.00%)
Cholecystitis acute
No. of participants affected / at risk1/25 (0.00%)0/24 (0.00%)0/25 (0.00%)
Anaphylactic reaction
No. of participants affected / at risk0/25 (0.00%)1/24 (0.00%)0/25 (0.00%)
Hypersensitivity
No. of participants affected / at risk0/25 (0.00%)0/24 (0.00%)1/25 (0.00%)
Device related infection
No. of participants affected / at risk0/25 (0.00%)1/24 (0.00%)0/25 (0.00%)
Sepsis
No. of participants affected / at risk0/25 (0.00%)0/24 (0.00%)1/25 (0.00%)
Urinary tract infection
No. of participants affected / at risk1/25 (0.00%)0/24 (0.00%)2/25 (0.00%)
Viral infection
No. of participants affected / at risk1/25 (0.00%)0/24 (0.00%)0/25 (0.00%)
Device dislocation
No. of participants affected / at risk1/25 (0.00%)0/24 (0.00%)0/25 (0.00%)
Dislocation of joint prosthesis
No. of participants affected / at risk2/25 (0.00%)0/24 (0.00%)0/25 (0.00%)
Femur fracture
No. of participants affected / at risk1/25 (0.00%)0/24 (0.00%)0/25 (0.00%)
Joint dislocation
No. of participants affected / at risk1/25 (0.00%)0/24 (0.00%)0/25 (0.00%)
Subcutaneous haematoma
No. of participants affected / at risk1/25 (0.00%)0/24 (0.00%)0/25 (0.00%)
Arthropathy
No. of participants affected / at risk0/25 (0.00%)0/24 (0.00%)1/25 (0.00%)
Rhabdomyolysis
No. of participants affected / at risk1/25 (0.00%)1/24 (0.00%)0/25 (0.00%)
Renal failure
No. of participants affected / at risk1/25 (0.00%)0/24 (0.00%)1/25 (0.00%)
Pulmonary embolism
No. of participants affected / at risk0/25 (0.00%)0/24 (0.00%)1/25 (0.00%)
Respiratory failure
No. of participants affected / at risk0/25 (0.00%)0/24 (0.00%)1/25 (0.00%)
Decubitus ulcer
No. of participants affected / at risk1/25 (0.00%)0/24 (0.00%)0/25 (0.00%)
Rash
No. of participants affected / at risk1/25 (0.00%)0/24 (0.00%)0/25 (0.00%)
Deep vein thrombosis
No. of participants affected / at risk1/25 (0.00%)1/24 (0.00%)1/25 (0.00%)
Haematoma
No. of participants affected / at risk0/25 (0.00%)0/24 (0.00%)1/25 (0.00%)

Other Adverse Events

Time Frame
From the 1st day of therapy to maximum of 23 weeks post last dose (up to maximum of week 30)
Additional Description
Subjects who prematurely discontinue study drug will undergo follow-up safety evaluations within 30 days (±5 days) of administration of the last dose of study drug.
Frequency Threshold5% (Threshold above which other adverse events are reported)

Reporting Groups

TitleDescription
Daptomycin 6 mg/kg
Daptomycin (6 mg/kg q24h) as a 30-minute IV infusion for 6 weeks (±1 week).
Daptomycin 8 mg/kg
Daptomycin (8 mg/kg q24h) as a 30-minute IV infusion for 6 weeks (±1 week).
Comparator
Vancomycin was administered at 1 gm q12h as a 60-minute infusion and teicoplanin was administered 6 mg/kg q24h as a 30-minute infusion also for 6 weeks (±1 week). Semi-synthetic penicillin (nafcillin, oxacillin, or flucloxacillin) was administered according to standard of care for 6 weeks (±1 week).

Other Adverse Events

Daptomycin 6 mg/kgDaptomycin 8 mg/kgComparator
Total, other adverse events
No. of participants affected / at risk23/25 (0.00%)18/24 (0.00%)22/25 (0.00%)
Vision blurred
No. of participants affected / at risk0/25 (0.00%)0/24 (0.00%)2/25 (0.00%)
Constipation
No. of participants affected / at risk4/25 (0.00%)2/24 (0.00%)1/25 (0.00%)
Diarrhoea
No. of participants affected / at risk2/25 (0.00%)2/24 (0.00%)2/25 (0.00%)
Dyspepsia
No. of participants affected / at risk0/25 (0.00%)0/24 (0.00%)2/25 (0.00%)
Nausea
No. of participants affected / at risk5/25 (0.00%)3/24 (0.00%)4/25 (0.00%)
Stomach discomfort
No. of participants affected / at risk0/25 (0.00%)0/24 (0.00%)2/25 (0.00%)
Vomiting
No. of participants affected / at risk1/25 (0.00%)1/24 (0.00%)2/25 (0.00%)
Asthenia
No. of participants affected / at risk0/25 (0.00%)0/24 (0.00%)2/25 (0.00%)
Catheter related complication
No. of participants affected / at risk1/25 (0.00%)2/24 (0.00%)2/25 (0.00%)
Chest pain
No. of participants affected / at risk2/25 (0.00%)0/24 (0.00%)0/25 (0.00%)
Fatigue
No. of participants affected / at risk1/25 (0.00%)0/24 (0.00%)2/25 (0.00%)
Oedema peripheral
No. of participants affected / at risk2/25 (0.00%)2/24 (0.00%)4/25 (0.00%)
Pyrexia
No. of participants affected / at risk4/25 (0.00%)2/24 (0.00%)4/25 (0.00%)
Arthritis infective
No. of participants affected / at risk0/25 (0.00%)0/24 (0.00%)2/25 (0.00%)
Bacteriuria
No. of participants affected / at risk2/25 (0.00%)1/24 (0.00%)0/25 (0.00%)
Urinary tract infection
No. of participants affected / at risk3/25 (0.00%)1/24 (0.00%)2/25 (0.00%)
Blood alkaline phosphatase increased
No. of participants affected / at risk2/25 (0.00%)1/24 (0.00%)2/25 (0.00%)
Blood creatine phosphokinase increased
No. of participants affected / at risk3/25 (0.00%)2/24 (0.00%)1/25 (0.00%)
Blood pressure increased
No. of participants affected / at risk0/25 (0.00%)2/24 (0.00%)1/25 (0.00%)
Haematocrit decreased
No. of participants affected / at risk0/25 (0.00%)2/24 (0.00%)1/25 (0.00%)
Haemoglobin decreased
No. of participants affected / at risk0/25 (0.00%)2/24 (0.00%)1/25 (0.00%)
Urine output decreased
No. of participants affected / at risk0/25 (0.00%)2/24 (0.00%)0/25 (0.00%)
Hypokalaemia
No. of participants affected / at risk2/25 (0.00%)1/24 (0.00%)1/25 (0.00%)
Arthralgia
No. of participants affected / at risk1/25 (0.00%)0/24 (0.00%)2/25 (0.00%)
Pain in extremity
No. of participants affected / at risk0/25 (0.00%)1/24 (0.00%)2/25 (0.00%)
Dizziness
No. of participants affected / at risk2/25 (0.00%)0/24 (0.00%)2/25 (0.00%)
Headache
No. of participants affected / at risk3/25 (0.00%)0/24 (0.00%)2/25 (0.00%)
Tremor
No. of participants affected / at risk2/25 (0.00%)0/24 (0.00%)0/25 (0.00%)
Anxiety
No. of participants affected / at risk2/25 (0.00%)1/24 (0.00%)1/25 (0.00%)
Hallucination
No. of participants affected / at risk0/25 (0.00%)0/24 (0.00%)2/25 (0.00%)
Cough
No. of participants affected / at risk2/25 (0.00%)2/24 (0.00%)2/25 (0.00%)
Dyspnoea
No. of participants affected / at risk1/25 (0.00%)0/24 (0.00%)3/25 (0.00%)
Erythema
No. of participants affected / at risk2/25 (0.00%)1/24 (0.00%)2/25 (0.00%)
Pruritus
No. of participants affected / at risk1/25 (0.00%)3/24 (0.00%)2/25 (0.00%)
Rash
No. of participants affected / at risk0/25 (0.00%)3/24 (0.00%)2/25 (0.00%)
Deep vein thrombosis
No. of participants affected / at risk3/25 (0.00%)0/24 (0.00%)0/25 (0.00%)
Hypertension
No. of participants affected / at risk2/25 (0.00%)1/24 (0.00%)1/25 (0.00%)
Hypertensive crisis
No. of participants affected / at risk1/25 (0.00%)2/24 (0.00%)0/25 (0.00%)
Hypotension
No. of participants affected / at risk1/25 (0.00%)2/24 (0.00%)3/25 (0.00%)

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.
The first publication is initiated by Cubist. If first publication not published within 1 year of study conclusion or termination, Investigator has right to publish and disclose the Data. Prior to any submission for publication, presentation, or communication of results or information arising from the Study, Investigator shall provide Cubist at least 90 days for review and comment upon the manuscript or other material for such publication or presentation.

Results Point of Contact

Name/TitleOrganizationPhoneEmail
Ed Campanaro, VP Clinical Operations
Cubist Pharmaceuticals, Inc.
781-860-8318