A Study of MK-3009 in Japanese Patients With Skin or Blood Stream Infections Caused by Methicillin-resistant Staphylococcus Aureus (MK-3009-002)

A Phase III Randomized, Open-labeled Clinical Trial of MK-3009 (Daptomycin) in Patients With Skin and Soft Tissue Infections, Septicemia and Right-sided Infective Endocarditis Caused by MRSA

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00770341

Enrollment

122

Registered

2008-10-10

Start date

2008-09-30

Completion date

2010-02-28

Last updated

2017-03-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Staphylococcal Infection

Brief summary

The study investigates the efficacy and safety of MK-3009 in participants with skin infections, septicemia and right-sided infective endocarditis (RIE) caused by methicillin-resistant Staphylococcus aureus (MRSA).

Interventions

DRUGDaptomycin 4 mg/kg

MK3009 (daptomycin) once daily by intravenous (IV) drip, 4 mg/kg for 7-14 days for skin and soft tissue infections (SSTI)

DRUGComparator: vancomycin

vancomycin 1g, twice daily (b.i.d.) by IV drip, for 7-14 days

DRUGDaptomycin 6 mg/kg

MK-3009 (daptomycin) once daily by intravenous drip, 6 mg/kg for 14-42 days for septicemia or right-sided infective endocarditis

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

20 Years to No maximum

Healthy volunteers

Inclusion criteria

* Both Sexes, Aged 20 Years Or Older * Japanese Participants With Skin And Soft Tissue Infections, Septicemia, or RIE Known Or Suspected To Be Caused By MRSA * Written Informed Consent

Exclusion criteria

* Participants With Skin and Soft Tissue infections That Can Be Treated By Surgery Alone * Participants With Pneumonia

Design outcomes

Primary

Measure	Time frame	Description
Efficacy Adjudication Committee (EAC) Assessment of Number of Participants With Clinical Success at Test of Cure (TOC)	7-14 days for SSTI, 14-42 days for septicemia and right-sided infective endocarditis (RIE)	Clinical Success = Study investigator's Clinical Response confirmed by the EAC as either cured or improved at end of treatment (EOT). MITT-MRSA (modified intent-to-treat - methicillin-resistant Staphylococcus aureus) was a subset of allocated participants with participants who were excluded for any of the following reasons: no MRSA isolated + any 1 of the following: failure to receive ≥1 dose of study drug, lack of all post-allocation primary and secondary endpoint data after ≥1 dose of study drug, no gram (+) coccus isolated at baseline.
Efficacy Adjudication Committee (EAC) Assessment of Number of Participants With Microbiological Response at TOC	7-14 days for SSTI, 14-42 days for septicemia and RIE	Response = eradicated or presumed eradicated. Eradicated was defined as absence of the admission pathogen in a culture obtained in the absence of potentially effective antibiotics for the pathogen. Presumed eradicated was defined as no material for culture was available due to improvement of infection, but the admission pathogen was presumed to be eradicated because the participant was deemed Cured or Improved by the investigator and the participant did not receive potentially effective antibiotics for the pathogen.

Secondary

Measure	Time frame	Description
EAC Assessment of Number of Participants With Clinical Success at End of Treatment (EOT).	7-14 days for SSTI, 14-42 days for septicemia and RIE	Clinical Success = Study investigator's Clinical Response confirmed by the EAC as either cured or improved at EOT.
EAC Assessment of Number of Participants With Microbiological Response at End of Treatment (EOT).	7-14 days for SSTI, 14-42 days for septicemia and RIE	Response = eradicated or presumed eradicated. Eradicated was defined as absence of the admission pathogen in a culture obtained in the absence of potentially effective antibiotics for the pathogen. Presumed eradicated was defined as no material for culture was available due to improvement of infection, but the admission pathogen was presumed to be eradicated because the participant was deemed Cured or Improved by the investigator and the participant did not receive potentially effective antibiotics for the pathogen.
Study Investigators' Assessment of Clinical Response at EOT	7-14 days for SSTI, 14-42 days for septicemia and RIE	Clinical Success = Study investigator's Clinical Response confirmed by the EAC as either cured or improved at EOT.
Study Investigators' Assessment of Clinical Response at TOC	7-14 days for SSTI, 14-42 days for septicemia and RIE	Clinical Success = Study investigator's Clinical Response confirmed by the EAC as either cured or improved at EOT.

Participant flow

Participants by arm

Arm	Count
MK-3009 (Daptomycin) 4 mg/kg Intravenous (IV) Daptomycin 4 mg/kg once daily for skin & soft tissue infections (SSTI)	88
Vancomycin IV Vancomycin 1 g twice daily for SSTI	22
MK-3009 (Daptomycin) 6 mg/kg IV Daptomycin 6 mg/kg once daily for Septicemia and right-sided infective endocarditis (RIE)	11
Total	121

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Clinical Adverse Event	3	1	2
Overall Study	Did not meet eligibility criteria	1	0	0
Overall Study	Laboratory adverse event	3	3	0
Overall Study	Lack of Efficacy	3	0	1
Overall Study	Not treated	1	0	0
Overall Study	Other	1	0	0
Overall Study	Withdrawal by Subject	0	1	0

Baseline characteristics

Characteristic	MK-3009 (Daptomycin) 4 mg/kg	Vancomycin	MK-3009 (Daptomycin) 6 mg/kg	Total
Age, Continuous	65.6 years STANDARD_DEVIATION 16	61.7 years STANDARD_DEVIATION 17.1	77.7 years STANDARD_DEVIATION 10.9	66.0 years STANDARD_DEVIATION 16.2
Region of Enrollment Japan	88 participants	22 participants	11 participants	121 participants
Sex: Female, Male Female	41 Participants	7 Participants	9 Participants	57 Participants
Sex: Female, Male Male	47 Participants	15 Participants	2 Participants	64 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —
other Total, other adverse events	0 / 1	34 / 88	11 / 22	9 / 11
serious Total, serious adverse events	0 / 1	6 / 88	4 / 22	4 / 11

Outcome results

Primary

Efficacy Adjudication Committee (EAC) Assessment of Number of Participants With Clinical Success at Test of Cure (TOC)

Clinical Success = Study investigator's Clinical Response confirmed by the EAC as either cured or improved at end of treatment (EOT). MITT-MRSA (modified intent-to-treat - methicillin-resistant Staphylococcus aureus) was a subset of allocated participants with participants who were excluded for any of the following reasons: no MRSA isolated + any 1 of the following: failure to receive ≥1 dose of study drug, lack of all post-allocation primary and secondary endpoint data after ≥1 dose of study drug, no gram (+) coccus isolated at baseline.

Time frame: 7-14 days for SSTI, 14-42 days for septicemia and right-sided infective endocarditis (RIE)

Population: MITT-MRSA; One participant with possible MRSA RIE was enrolled. This participant was excluded from the efficacy population.

Arm	Measure	Value (NUMBER)
MK-3009 (Daptomycin) 4 mg/kg	Efficacy Adjudication Committee (EAC) Assessment of Number of Participants With Clinical Success at Test of Cure (TOC)	45 Participants
Vancomycin	Efficacy Adjudication Committee (EAC) Assessment of Number of Participants With Clinical Success at Test of Cure (TOC)	16 Participants
MK-3009 (Daptomycin) 6 mg/kg	Efficacy Adjudication Committee (EAC) Assessment of Number of Participants With Clinical Success at Test of Cure (TOC)	2 Participants

Primary

Efficacy Adjudication Committee (EAC) Assessment of Number of Participants With Microbiological Response at TOC

Response = eradicated or presumed eradicated. Eradicated was defined as absence of the admission pathogen in a culture obtained in the absence of potentially effective antibiotics for the pathogen. Presumed eradicated was defined as no material for culture was available due to improvement of infection, but the admission pathogen was presumed to be eradicated because the participant was deemed Cured or Improved by the investigator and the participant did not receive potentially effective antibiotics for the pathogen.