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

• Sponsor: Cubist Pharmaceuticals LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00428844
• Collaborator: (none)
• Enrollment: 75
• Locations: 26
• Arms: 3
• Actual Duration (Months): 35.9
• Patients Per Site: 2.9
• Patients Per Site Per Month: 0.1

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Osteomyelitis	Drug: daptomycin; Drug: daptomycin; Drug: vancomycin; Drug: teicoplanin; Drug: nafcillin; Drug: oxacillin; Drug: flucloxacillin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 75 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 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
• Actual Study Start Date: Jun 26, 2007
• Actual Primary Completion Date: Mar 26, 2010
• Actual Study Completion Date: Jun 23, 2010

Arms and Interventions

Arm	Intervention/Treatment
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; Other Names: Cubicin
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; Other Names: Cubicin
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; 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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

1. Safety - Notable Laboratory Abnormalities [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.

2. Overall Clinical Outcome [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.

3. Microbiological Response [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.

4. Pharmacokinetic Parameter: Maximum Plasma Concentration (Cmax) [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.

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UAMS College of Medicine	Little Rock	Arkansas	United States	72205-7199
2	South Denver Infectious Disease Associates, PC	Englewood	Colorado	United States	80133
3	Kane and Davis Associates	Washington	District of Columbia	United States	20016
4	Infectious Disease Association of Tampa Bay	Tampa	Florida	United States	33606
5	Idaho Falls Infectious Diseases, PLLC	Idaho Falls	Idaho	United States	83404
6	Rush St. Luke's Medical Center	Chicago	Illinois	United States	60612
7	Southern Illinois University School of Medicine	Springfield	Illinois	United States	62794
8	Mayo Clinic	Rochester	Minnesota	United States	55905
9	Sierra Infectious Disease	Reno	Nevada	United States	89502
10	Dartmouth-Hitchcock Medical center	Lebanon	New Hampshire	United States	03756
11	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
12	Summa Health Systems	Akron	Ohio	United States	44304
13	Cleveland Clinic	Cleveland	Ohio	United States	44195
14	Regional Infectious Diseases-Infusion Center	Lima	Ohio	United States	45801
15	Lehigh Valley Hospital Trauma and Critical Care Research	Allentown	Pennsylvania	United States	18103
16	Rothman Institute	Philadelphia	Pennsylvania	United States	19107
17	Gundersen Clinic, LTD	La Crosse	Wisconsin	United States	54601
18	Federal National Institution of Science "Russian Ilizarov Scientific Center" "Restorative Traumatology and Orthopedics" of Rosmedtechnology	Kurgan		Russian Federation	640014
19	National Healthcare Institution of Moscow "City Clinical Hospital #64"	Moscow		Russian Federation	117292
20	Federal Healthcare Institute "Novosibirsk Scientific Research Institute of Traumatology and Orthopedy Rosmeditechnology"	Novosibirsk		Russian Federation	630091
21	National Educational Institution of Higher Professional Education "Saint Petersburg State Medical Academy n.a. Mechnikov of Roszdrav"	Saint Petersburg		Russian Federation	195067
22	Russian Research Institute of Traumatology and Orthopedy	Saint Petersburg		Russian Federation	197046
23	National Healthcare Institution "Samara Regional Clinical Hospital n.a. Kalinin"	Samara		Russian Federation	443095
24	Nuffield Orthopaedics Centre, Bone Infection Unit	Headington, Oxford	Oxfordshire	United Kingdom	OX37LD
25	The Royal Infirmary of Edinburgh at Little France	Edinburgh	Scotland	United Kingdom	EH164SA
26	Brownlee Centre - Gartnavel General Hospital	Glasgow	Scotland	United Kingdom	G120YN

Sponsors and Collaborators

• Cubist Pharmaceuticals LLC

Investigators

• Study Director: Alistair Wheeler, MD, Cubist Pharmaceuticals, 65 Hayden Ave, Lexington, MA 02421, USA

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Cubist Pharmaceuticals LLC
• ClinicalTrials.gov Identifier: NCT00428844
• Other Study ID Numbers: 3009-016; DAP-OST-06-02
• First Posted: Jan 30, 2007
• Last Update Posted: Jan 31, 2018
• Last Verified: Jan 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Cubist Pharmaceuticals LLC: Osteomyelitis; Prosthetic Hip; Prosthetic Knee; MRSA; Osteomyelitis Associated with an Infected Prosthetic Hip or Knee Joint; Staphylococci
• Additional relevant MeSH terms: Osteomyelitis; Vancomycin; Daptomycin; Teicoplanin; Floxacillin; Oxacillin; Nafcillin

Study Results

Participant Flow

Arm/Group Title	Daptomycin 6 mg/kg	Daptomycin 8 mg/kg	Comparator
Arm/Group Description	Daptomycin (6 mg/kg every 24 hours [q24h]) as a 30 minute intravenous (IV) infusion for 6 weeks (± one week).	Daptomycin (8 mg/kg q24h) as a 30 minute IV infusion for 6 weeks (± one week).	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).
Period Title: Completed Study Drug Treatment
STARTED	25	24	26
Received First Dose	25	24	25
COMPLETED	23	18	19
NOT COMPLETED	2	6	7
Period Title: Completed Study Drug Treatment
STARTED	23	18	19
COMPLETED	20	16	17
NOT COMPLETED	3	2	2

Baseline Characteristics

Arm/Group Title	Daptomycin 6 mg/kg	Daptomycin 8 mg/kg	Comparator	Total
Arm/Group Description	Daptomycin (6 mg/kg q24h) as a 30-minute IV infusion for 6 weeks (±1 week).	Daptomycin (8 mg/kg q24h) as a 30-minute IV infusion for 6 weeks (±1 week).	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 of all reporting groups
Overall Participants	25	24	25	74
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	10 40%	14 58.3%	15 60%	39 52.7%
>=65 years	15 60%	10 41.7%	10 40%	35 47.3%
Sex: Female, Male (Count of Participants)
Female	14 56%	10 41.7%	11 44%	35 47.3%
Male	11 44%	14 58.3%	14 56%	39 52.7%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Daptomycin 6 mg/kg	Daptomycin 8 mg/kg	Comparator
Arm/Group Description	Daptomycin (6 mg/kg q24h) as a 30-minute IV infusion for 6 weeks (±1 week).	Daptomycin (8 mg/kg q24h) as a 30-minute IV infusion for 6 weeks (±1 week).	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).
Measure Participants	25	24	25
Number [Participants]	4 16%	5 20.8%	2 8%

2. Secondary Outcome

Title	Safety - Notable Laboratory Abnormalities
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)

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Daptomycin 6 mg/kg	Daptomycin 8 mg/kg	Comparator
Arm/Group Description	Daptomycin (6 mg/kg q24h) as a 30-minute IV infusion for 6 weeks (±1 week).	Daptomycin (8 mg/kg q24h) as a 30-minute IV infusion for 6 weeks (±1 week).	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).
Measure Participants	25	24	25
Hematocrit (<30%, >60%)	12 48%	10 41.7%	15 60%
Hemoglobin (<9,>19 g/dL)	10 40%	10 41.7%	12 48%
Red Blood Cell (Female <2.5,>6.0; Male <3.0, >6.5)	2 8%	4 16.7%	3 12%
White Blood Cell (<2, >20 x 10^9/L)	1 4%	0 0%	0 0%
Platelets (<40, >450 x 10^9/L)	13 52%	13 54.2%	10 40%
Albumin (<3, >6 g/dL)	7 28%	4 16.7%	4 16%
Alkaline Phosphatase (>1350 U/L)	0 0%	0 0%	0 0%
Alanine aminotransferase (>235 U/L)	0 0%	0 0%	0 0%
Aspartate aminotransferase (>185 U/L)	1 4%	0 0%	0 0%
Total bilirubin (>2.2 mg/dL)	0 0%	0 0%	0 0%
Blood Urea Nitrogen (>50 mg/dL)	2 8%	0 0%	1 4%
Creatinine (Female >2.0; Male>2.8 mg/dL)	1 4%	0 0%	2 8%

3. Secondary Outcome

Title	Overall Clinical Outcome
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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Daptomycin 6 mg/kg	Daptomycin 8 mg/kg	Comparator
Arm/Group Description	Daptomycin (6 mg/kg q24h) as a 30-minute IV infusion for 6 weeks (±1 week).	Daptomycin (8 mg/kg q24h) as a 30-minute IV infusion for 6 weeks (±1 week).	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).
Measure Participants	24	23	21
Success	13 52%	13 54.2%	8 32%
Failure	10 40%	8 33.3%	11 44%
Nonevaluable	1 4%	2 8.3%	2 8%

4. Secondary Outcome

Title	Microbiological Response
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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Daptomycin 6 mg/kg	Daptomycin 8 mg/kg	Comparator
Arm/Group Description	Daptomycin (6 mg/kg q24h) as a 30-minute IV infusion for 6 weeks (±1 week).	Daptomycin (8 mg/kg q24h) as a 30-minute IV infusion for 6 weeks (±1 week).	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).
Measure Participants	24	23	21
Success	12 48%	12 50%	8 32%
Failure	8 32%	3 12.5%	6 24%
Non-evaluable	4 16%	8 33.3%	7 28%

5. Secondary Outcome

Title	Pharmacokinetic Parameter: Maximum Plasma Concentration (Cmax)
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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Daptomycin 6 mg/kg	Daptomycin 8 mg/kg
Arm/Group Description	Daptomycin (6 mg/kg q24h) as a 30-minute IV infusion for 6 weeks (±1 week).	Daptomycin (8 mg/kg q24h) as a 30-minute IV infusion for 6 weeks (±1 week).
Measure Participants	22	20
Median (Full Range) [µg/mL]	59.1	92.3

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Daptomycin 6 mg/kg	Daptomycin 8 mg/kg
Arm/Group Description	Daptomycin (6 mg/kg q24h) as a 30-minute IV infusion for 6 weeks (±1 week).	Daptomycin (8 mg/kg q24h) as a 30-minute IV infusion for 6 weeks (±1 week).
Measure Participants	22	20
Median (Full Range) [µg•hr/mL]	499	821

Adverse Events

Time Frame	From the 1st day of therapy to maximum of 23 weeks post last dose (up to maximum of week 30)
Adverse Event Reporting 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.
Arm/Group Title	Daptomycin 6 mg/kg		Daptomycin 8 mg/kg		Comparator
Arm/Group Description	Daptomycin (6 mg/kg q24h) as a 30-minute IV infusion for 6 weeks (±1 week).		Daptomycin (8 mg/kg q24h) as a 30-minute IV infusion for 6 weeks (±1 week).		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).
All Cause Mortality
	Daptomycin 6 mg/kg		Daptomycin 8 mg/kg		Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Daptomycin 6 mg/kg		Daptomycin 8 mg/kg		Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/25 (32%)		4/24 (16.7%)		8/25 (32%)
Blood and lymphatic system disorders
Anaemia	0/25 (0%)	0	0/24 (0%)	0	1/25 (4%)	1
Cardiac disorders
Cardiac arrest	0/25 (0%)	0	0/24 (0%)	0	1/25 (4%)	3
General disorders
Wound necrosis	0/25 (0%)	0	0/24 (0%)	0	1/25 (4%)	1
Hepatobiliary disorders
Cholecystitis acute	1/25 (4%)	1	0/24 (0%)	0	0/25 (0%)	0
Immune system disorders
Anaphylactic reaction	0/25 (0%)	0	1/24 (4.2%)	1	0/25 (0%)	0
Hypersensitivity	0/25 (0%)	0	0/24 (0%)	0	1/25 (4%)	1
Infections and infestations
Device related infection	0/25 (0%)	0	1/24 (4.2%)	1	0/25 (0%)	0
Sepsis	0/25 (0%)	0	0/24 (0%)	0	1/25 (4%)	1
Urinary tract infection	1/25 (4%)	1	0/24 (0%)	0	2/25 (8%)	2
Viral infection	1/25 (4%)	1	0/24 (0%)	0	0/25 (0%)	0
Injury, poisoning and procedural complications
Device dislocation	1/25 (4%)	1	0/24 (0%)	0	0/25 (0%)	0
Dislocation of joint prosthesis	2/25 (8%)	2	0/24 (0%)	0	0/25 (0%)	0
Femur fracture	1/25 (4%)	1	0/24 (0%)	0	0/25 (0%)	0
Joint dislocation	1/25 (4%)	1	0/24 (0%)	0	0/25 (0%)	0
Subcutaneous haematoma	1/25 (4%)	1	0/24 (0%)	0	0/25 (0%)	0
Musculoskeletal and connective tissue disorders
Arthropathy	0/25 (0%)	0	0/24 (0%)	0	1/25 (4%)	1
Rhabdomyolysis	1/25 (4%)	1	1/24 (4.2%)	1	0/25 (0%)	0
Renal and urinary disorders
Renal failure	1/25 (4%)	1	0/24 (0%)	0	1/25 (4%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	0/25 (0%)	0	0/24 (0%)	0	1/25 (4%)	1
Respiratory failure	0/25 (0%)	0	0/24 (0%)	0	1/25 (4%)	1
Skin and subcutaneous tissue disorders
Decubitus ulcer	1/25 (4%)	1	0/24 (0%)	0	0/25 (0%)	0
Rash	1/25 (4%)	1	0/24 (0%)	0	0/25 (0%)	0
Vascular disorders
Deep vein thrombosis	1/25 (4%)	1	1/24 (4.2%)	1	1/25 (4%)	1
Haematoma	0/25 (0%)	0	0/24 (0%)	0	1/25 (4%)	1
Other (Not Including Serious) Adverse Events
	Daptomycin 6 mg/kg		Daptomycin 8 mg/kg		Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/25 (92%)		18/24 (75%)		22/25 (88%)
Eye disorders
Vision blurred	0/25 (0%)	0	0/24 (0%)	0	2/25 (8%)	2
Gastrointestinal disorders
Constipation	4/25 (16%)	5	2/24 (8.3%)	2	1/25 (4%)	1
Diarrhoea	2/25 (8%)	2	2/24 (8.3%)	3	2/25 (8%)	3
Dyspepsia	0/25 (0%)	0	0/24 (0%)	0	2/25 (8%)	2
Nausea	5/25 (20%)	5	3/24 (12.5%)	3	4/25 (16%)	7
Stomach discomfort	0/25 (0%)	0	0/24 (0%)	0	2/25 (8%)	2
Vomiting	1/25 (4%)	1	1/24 (4.2%)	2	2/25 (8%)	5
General disorders
Asthenia	0/25 (0%)	0	0/24 (0%)	0	2/25 (8%)	2
Catheter related complication	1/25 (4%)	1	2/24 (8.3%)	3	2/25 (8%)	9
Chest pain	2/25 (8%)	2	0/24 (0%)	0	0/25 (0%)	0
Fatigue	1/25 (4%)	1	0/24 (0%)	0	2/25 (8%)	3
Oedema peripheral	2/25 (8%)	5	2/24 (8.3%)	4	4/25 (16%)	7
Pyrexia	4/25 (16%)	5	2/24 (8.3%)	2	4/25 (16%)	7
Infections and infestations
Arthritis infective	0/25 (0%)	0	0/24 (0%)	0	2/25 (8%)	2
Bacteriuria	2/25 (8%)	2	1/24 (4.2%)	1	0/25 (0%)	0
Urinary tract infection	3/25 (12%)	4	1/24 (4.2%)	1	2/25 (8%)	2
Investigations
Blood alkaline phosphatase increased	2/25 (8%)	2	1/24 (4.2%)	1	2/25 (8%)	2
Blood creatine phosphokinase increased	3/25 (12%)	3	2/24 (8.3%)	2	1/25 (4%)	1
Blood pressure increased	0/25 (0%)	0	2/24 (8.3%)	2	1/25 (4%)	1
Haematocrit decreased	0/25 (0%)	0	2/24 (8.3%)	2	1/25 (4%)	1
Haemoglobin decreased	0/25 (0%)	0	2/24 (8.3%)	2	1/25 (4%)	1
Urine output decreased	0/25 (0%)	0	2/24 (8.3%)	2	0/25 (0%)	0
Metabolism and nutrition disorders
Hypokalaemia	2/25 (8%)	2	1/24 (4.2%)	2	1/25 (4%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/25 (4%)	1	0/24 (0%)	0	2/25 (8%)	2
Pain in extremity	0/25 (0%)	0	1/24 (4.2%)	1	2/25 (8%)	2
Nervous system disorders
Dizziness	2/25 (8%)	2	0/24 (0%)	0	2/25 (8%)	3
Headache	3/25 (12%)	5	0/24 (0%)	0	2/25 (8%)	2
Tremor	2/25 (8%)	3	0/24 (0%)	0	0/25 (0%)	0
Psychiatric disorders
Anxiety	2/25 (8%)	2	1/24 (4.2%)	1	1/25 (4%)	1
Hallucination	0/25 (0%)	0	0/24 (0%)	0	2/25 (8%)	2
Respiratory, thoracic and mediastinal disorders
Cough	2/25 (8%)	2	2/24 (8.3%)	2	2/25 (8%)	2
Dyspnoea	1/25 (4%)	1	0/24 (0%)	0	3/25 (12%)	4
Skin and subcutaneous tissue disorders
Erythema	2/25 (8%)	2	1/24 (4.2%)	1	2/25 (8%)	3
Pruritus	1/25 (4%)	2	3/24 (12.5%)	3	2/25 (8%)	2
Rash	0/25 (0%)	0	3/24 (12.5%)	4	2/25 (8%)	2
Vascular disorders
Deep vein thrombosis	3/25 (12%)	3	0/24 (0%)	0	0/25 (0%)	0
Hypertension	2/25 (8%)	2	1/24 (4.2%)	2	1/25 (4%)	1
Hypertensive crisis	1/25 (4%)	1	2/24 (8.3%)	2	0/25 (0%)	0
Hypotension	1/25 (4%)	1	2/24 (8.3%)	2	3/25 (12%)	3

Limitations/Caveats

[Not Specified]

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.