Trial Outcomes & Findings for A Study of MK-3009 in Japanese Patients With Skin or Blood Stream Infections Caused by Methicillin-resistant Staphylococcus Aureus (MK-3009-002) (NCT NCT00770341)
NCT ID: NCT00770341
Last Updated: 2017-03-24
Results Overview
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.
COMPLETED
PHASE3
122 participants
7-14 days for SSTI, 14-42 days for septicemia and right-sided infective endocarditis (RIE)
2017-03-24
Participant Flow
Participant milestones
| Measure |
MK-3009 (Daptomycin) 4 mg/kg
Intravenous (IV) Daptomycin 4 mg/kg once daily for skin \& soft tissue infections (SSTI)
|
Vancomycin
IV Vancomycin 1 g twice daily for SSTI
|
MK-3009 (Daptomycin) 6 mg/kg
IV Daptomycin 6 mg/kg once daily for Septicemia and right-sided infective endocarditis (RIE)
|
|---|---|---|---|
|
Overall Study
STARTED
|
89
|
22
|
11
|
|
Overall Study
COMPLETED
|
77
|
17
|
8
|
|
Overall Study
NOT COMPLETED
|
12
|
5
|
3
|
Reasons for withdrawal
| Measure |
MK-3009 (Daptomycin) 4 mg/kg
Intravenous (IV) Daptomycin 4 mg/kg once daily for skin \& soft tissue infections (SSTI)
|
Vancomycin
IV Vancomycin 1 g twice daily for SSTI
|
MK-3009 (Daptomycin) 6 mg/kg
IV Daptomycin 6 mg/kg once daily for Septicemia and right-sided infective endocarditis (RIE)
|
|---|---|---|---|
|
Overall Study
Did not meet eligibility criteria
|
1
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
0
|
|
Overall Study
Clinical Adverse Event
|
3
|
1
|
2
|
|
Overall Study
Laboratory adverse event
|
3
|
3
|
0
|
|
Overall Study
Lack of Efficacy
|
3
|
0
|
1
|
|
Overall Study
Other
|
1
|
0
|
0
|
|
Overall Study
Not treated
|
1
|
0
|
0
|
Baseline Characteristics
A Study of MK-3009 in Japanese Patients With Skin or Blood Stream Infections Caused by Methicillin-resistant Staphylococcus Aureus (MK-3009-002)
Baseline characteristics by cohort
| Measure |
MK-3009 (Daptomycin) 4 mg/kg
n=88 Participants
Intravenous (IV) Daptomycin 4 mg/kg once daily for skin \& soft tissue infections (SSTI)
|
Vancomycin
n=22 Participants
IV Vancomycin 1 g twice daily for SSTI
|
MK-3009 (Daptomycin) 6 mg/kg
n=11 Participants
IV Daptomycin 6 mg/kg once daily for Septicemia and right-sided infective endocarditis (RIE)
|
Total
n=121 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
65.6 years
STANDARD_DEVIATION 16.0 • n=99 Participants
|
61.7 years
STANDARD_DEVIATION 17.1 • n=107 Participants
|
77.7 years
STANDARD_DEVIATION 10.9 • n=206 Participants
|
66.0 years
STANDARD_DEVIATION 16.2 • n=7 Participants
|
|
Sex: Female, Male
Female
|
41 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
9 Participants
n=206 Participants
|
57 Participants
n=7 Participants
|
|
Sex: Female, Male
Male
|
47 Participants
n=99 Participants
|
15 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
64 Participants
n=7 Participants
|
|
Region of Enrollment
Japan
|
88 participants
n=99 Participants
|
22 participants
n=107 Participants
|
11 participants
n=206 Participants
|
121 participants
n=7 Participants
|
PRIMARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
MK-3009 (Daptomycin) 4 mg/kg
n=55 Participants
Intravenous (IV) Daptomycin 4 mg/kg once daily for skin \& soft tissue infections (SSTI)
|
Vancomycin
n=19 Participants
IV Vancomycin 1 g twice daily for SSTI
|
MK-3009 (Daptomycin) 6 mg/kg
n=4 Participants
IV Daptomycin 6 mg/kg once daily for Septicemia and right-sided infective endocarditis (RIE)
|
|---|---|---|---|
|
Efficacy Adjudication Committee (EAC) Assessment of Number of Participants With Clinical Success at Test of Cure (TOC)
|
45 Participants
|
16 Participants
|
2 Participants
|
PRIMARY outcome
Timeframe: 7-14 days for SSTI, 14-42 days for septicemia and RIEPopulation: MITT-MRSA; one participant with possible MRSA RIE was enrolled into this study. This participant was excluded from the efficacy population.
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.
Outcome measures
| Measure |
MK-3009 (Daptomycin) 4 mg/kg
n=55 Participants
Intravenous (IV) Daptomycin 4 mg/kg once daily for skin \& soft tissue infections (SSTI)
|
Vancomycin
n=19 Participants
IV Vancomycin 1 g twice daily for SSTI
|
MK-3009 (Daptomycin) 6 mg/kg
n=4 Participants
IV Daptomycin 6 mg/kg once daily for Septicemia and right-sided infective endocarditis (RIE)
|
|---|---|---|---|
|
Efficacy Adjudication Committee (EAC) Assessment of Number of Participants With Microbiological Response at TOC
|
31 Participants
|
9 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: 7-14 days for SSTI, 14-42 days for septicemia and RIEPopulation: MITT-MRSA; one participant with possible MRSA RIE was enrolled into this study. This participant was excluded from the efficacy population.
Clinical Success = Study investigator's Clinical Response confirmed by the EAC as either cured or improved at EOT.
Outcome measures
| Measure |
MK-3009 (Daptomycin) 4 mg/kg
n=54 Participants
Intravenous (IV) Daptomycin 4 mg/kg once daily for skin \& soft tissue infections (SSTI)
|
Vancomycin
n=19 Participants
IV Vancomycin 1 g twice daily for SSTI
|
MK-3009 (Daptomycin) 6 mg/kg
n=4 Participants
IV Daptomycin 6 mg/kg once daily for Septicemia and right-sided infective endocarditis (RIE)
|
|---|---|---|---|
|
EAC Assessment of Number of Participants With Clinical Success at End of Treatment (EOT).
|
46 Participants
|
16 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: 7-14 days for SSTI, 14-42 days for septicemia and RIEPopulation: MITT-MRSA; one participant with possible MRSA RIE was enrolled into this study. This participant was excluded from the efficacy population.
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.
Outcome measures
| Measure |
MK-3009 (Daptomycin) 4 mg/kg
n=55 Participants
Intravenous (IV) Daptomycin 4 mg/kg once daily for skin \& soft tissue infections (SSTI)
|
Vancomycin
n=19 Participants
IV Vancomycin 1 g twice daily for SSTI
|
MK-3009 (Daptomycin) 6 mg/kg
n=4 Participants
IV Daptomycin 6 mg/kg once daily for Septicemia and right-sided infective endocarditis (RIE)
|
|---|---|---|---|
|
EAC Assessment of Number of Participants With Microbiological Response at End of Treatment (EOT).
|
24 Participants
|
9 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: 7-14 days for SSTI, 14-42 days for septicemia and RIEPopulation: MITT-MRSA; One participant with possible MRSA RIE was enrolled into this study. This participant was excluded from the efficacy population.
Clinical Success = Study investigator's Clinical Response confirmed by the EAC as either cured or improved at EOT.
Outcome measures
| Measure |
MK-3009 (Daptomycin) 4 mg/kg
n=54 Participants
Intravenous (IV) Daptomycin 4 mg/kg once daily for skin \& soft tissue infections (SSTI)
|
Vancomycin
n=19 Participants
IV Vancomycin 1 g twice daily for SSTI
|
MK-3009 (Daptomycin) 6 mg/kg
n=4 Participants
IV Daptomycin 6 mg/kg once daily for Septicemia and right-sided infective endocarditis (RIE)
|
|---|---|---|---|
|
Study Investigators' Assessment of Clinical Response at EOT
|
47 Participants
|
18 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: 7-14 days for SSTI, 14-42 days for septicemia and RIEPopulation: MITT-MRSA; One participant with possible MRSA RIE was enrolled into this study. This participant was excluded from the efficacy population.
Clinical Success = Study investigator's Clinical Response confirmed by the EAC as either cured or improved at EOT.
Outcome measures
| Measure |
MK-3009 (Daptomycin) 4 mg/kg
n=55 Participants
Intravenous (IV) Daptomycin 4 mg/kg once daily for skin \& soft tissue infections (SSTI)
|
Vancomycin
n=19 Participants
IV Vancomycin 1 g twice daily for SSTI
|
MK-3009 (Daptomycin) 6 mg/kg
n=4 Participants
IV Daptomycin 6 mg/kg once daily for Septicemia and right-sided infective endocarditis (RIE)
|
|---|---|---|---|
|
Study Investigators' Assessment of Clinical Response at TOC
|
48 Participants
|
17 Participants
|
2 Participants
|
Adverse Events
NOT TREATED
DAPTOMYCIN (4 MG/KG)
VANCOMYCIN
DAPTOMYCIN (6 MG/KG)
Serious adverse events
| Measure |
NOT TREATED
n=1 participants at risk
|
DAPTOMYCIN (4 MG/KG)
n=88 participants at risk
|
VANCOMYCIN
n=22 participants at risk
|
DAPTOMYCIN (6 MG/KG)
n=11 participants at risk
|
|---|---|---|---|---|
|
Gastrointestinal disorders
DUODENAL ULCER HAEMORRHAGE
|
0.00%
0/1
|
0.00%
0/88
|
4.5%
1/22 • Number of events 1
|
0.00%
0/11
|
|
Gastrointestinal disorders
INTESTINAL OBSTRUCTION
|
0.00%
0/1
|
0.00%
0/88
|
0.00%
0/22
|
9.1%
1/11 • Number of events 1
|
|
Gastrointestinal disorders
INTRA-ABDOMINAL HAEMORRHAGE
|
0.00%
0/1
|
0.00%
0/88
|
0.00%
0/22
|
9.1%
1/11 • Number of events 1
|
|
Immune system disorders
ANAPHYLACTIC SHOCK
|
0.00%
0/1
|
1.1%
1/88 • Number of events 1
|
0.00%
0/22
|
0.00%
0/11
|
|
Infections and infestations
INFECTION
|
0.00%
0/1
|
0.00%
0/88
|
4.5%
1/22 • Number of events 1
|
0.00%
0/11
|
|
Infections and infestations
PNEUMONIA
|
0.00%
0/1
|
1.1%
1/88 • Number of events 1
|
0.00%
0/22
|
0.00%
0/11
|
|
Infections and infestations
SEPSIS
|
0.00%
0/1
|
2.3%
2/88 • Number of events 2
|
0.00%
0/22
|
0.00%
0/11
|
|
Infections and infestations
URINARY TRACT INFECTION
|
0.00%
0/1
|
1.1%
1/88 • Number of events 1
|
0.00%
0/22
|
9.1%
1/11 • Number of events 1
|
|
Injury, poisoning and procedural complications
SKELETAL INJURY
|
0.00%
0/1
|
1.1%
1/88 • Number of events 1
|
0.00%
0/22
|
0.00%
0/11
|
|
Investigations
ELECTROCARDIOGRAM ST SEGMENT DEPRESSION
|
0.00%
0/1
|
0.00%
0/88
|
4.5%
1/22 • Number of events 1
|
0.00%
0/11
|
|
Metabolism and nutrition disorders
HYPOALBUMINAEMIA
|
0.00%
0/1
|
0.00%
0/88
|
4.5%
1/22 • Number of events 1
|
0.00%
0/11
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
HYPOPHARYNGEAL CANCER
|
0.00%
0/1
|
0.00%
0/88
|
4.5%
1/22 • Number of events 1
|
0.00%
0/11
|
|
Vascular disorders
AORTIC ANEURYSM RUPTURE
|
0.00%
0/1
|
0.00%
0/88
|
0.00%
0/22
|
9.1%
1/11 • Number of events 1
|
Other adverse events
| Measure |
NOT TREATED
n=1 participants at risk
|
DAPTOMYCIN (4 MG/KG)
n=88 participants at risk
|
VANCOMYCIN
n=22 participants at risk
|
DAPTOMYCIN (6 MG/KG)
n=11 participants at risk
|
|---|---|---|---|---|
|
Investigations
BLOOD POTASSIUM INCREASED
|
0.00%
0/1
|
4.5%
4/88 • Number of events 4
|
0.00%
0/22
|
18.2%
2/11 • Number of events 2
|
|
Investigations
BLOOD URINE PRESENT
|
0.00%
0/1
|
2.3%
2/88 • Number of events 2
|
4.5%
1/22 • Number of events 1
|
9.1%
1/11 • Number of events 1
|
|
Investigations
C-REACTIVE PROTEIN INCREASED
|
0.00%
0/1
|
4.5%
4/88 • Number of events 4
|
9.1%
2/22 • Number of events 2
|
0.00%
0/11
|
|
Cardiac disorders
ARRHYTHMIA
|
0.00%
0/1
|
0.00%
0/88
|
0.00%
0/22
|
9.1%
1/11 • Number of events 1
|
|
Cardiac disorders
CARDIAC FAILURE
|
0.00%
0/1
|
0.00%
0/88
|
0.00%
0/22
|
9.1%
1/11 • Number of events 1
|
|
Cardiac disorders
CARDIAC FAILURE CONGESTIVE
|
0.00%
0/1
|
0.00%
0/88
|
0.00%
0/22
|
9.1%
1/11 • Number of events 1
|
|
Ear and labyrinth disorders
VERTIGO
|
0.00%
0/1
|
0.00%
0/88
|
0.00%
0/22
|
9.1%
1/11 • Number of events 1
|
|
Gastrointestinal disorders
CONSTIPATION
|
0.00%
0/1
|
3.4%
3/88 • Number of events 3
|
0.00%
0/22
|
9.1%
1/11 • Number of events 1
|
|
Gastrointestinal disorders
DENTAL CARIES
|
0.00%
0/1
|
0.00%
0/88
|
0.00%
0/22
|
9.1%
1/11 • Number of events 1
|
|
Gastrointestinal disorders
DIARRHOEA
|
0.00%
0/1
|
2.3%
2/88 • Number of events 2
|
9.1%
2/22 • Number of events 3
|
9.1%
1/11 • Number of events 1
|
|
Gastrointestinal disorders
GASTRIC VOLVULUS
|
0.00%
0/1
|
0.00%
0/88
|
0.00%
0/22
|
9.1%
1/11 • Number of events 1
|
|
Gastrointestinal disorders
ILEUS PARALYTIC
|
0.00%
0/1
|
0.00%
0/88
|
0.00%
0/22
|
9.1%
1/11 • Number of events 1
|
|
Gastrointestinal disorders
INTESTINAL OBSTRUCTION
|
0.00%
0/1
|
0.00%
0/88
|
0.00%
0/22
|
9.1%
1/11 • Number of events 1
|
|
Gastrointestinal disorders
PERITONITIS
|
0.00%
0/1
|
0.00%
0/88
|
0.00%
0/22
|
9.1%
1/11 • Number of events 1
|
|
Gastrointestinal disorders
VOMITING
|
0.00%
0/1
|
2.3%
2/88 • Number of events 2
|
0.00%
0/22
|
9.1%
1/11 • Number of events 1
|
|
General disorders
OEDEMA
|
0.00%
0/1
|
1.1%
1/88 • Number of events 1
|
0.00%
0/22
|
9.1%
1/11 • Number of events 1
|
|
General disorders
OEDEMA PERIPHERAL
|
0.00%
0/1
|
0.00%
0/88
|
4.5%
1/22 • Number of events 1
|
9.1%
1/11 • Number of events 1
|
|
General disorders
PAIN
|
0.00%
0/1
|
2.3%
2/88 • Number of events 2
|
0.00%
0/22
|
9.1%
1/11 • Number of events 1
|
|
General disorders
PYREXIA
|
0.00%
0/1
|
6.8%
6/88 • Number of events 6
|
9.1%
2/22 • Number of events 2
|
0.00%
0/11
|
|
Infections and infestations
ABSCESS
|
0.00%
0/1
|
0.00%
0/88
|
0.00%
0/22
|
9.1%
1/11 • Number of events 1
|
|
Infections and infestations
ABSCESS LIMB
|
0.00%
0/1
|
0.00%
0/88
|
0.00%
0/22
|
9.1%
1/11 • Number of events 1
|
|
Infections and infestations
ARTHRITIS INFECTIVE
|
0.00%
0/1
|
0.00%
0/88
|
0.00%
0/22
|
9.1%
1/11 • Number of events 1
|
|
Infections and infestations
CATHETER RELATED INFECTION
|
0.00%
0/1
|
0.00%
0/88
|
0.00%
0/22
|
9.1%
1/11 • Number of events 1
|
|
Infections and infestations
JOINT ABSCESS
|
0.00%
0/1
|
0.00%
0/88
|
0.00%
0/22
|
9.1%
1/11 • Number of events 1
|
|
Infections and infestations
MUSCLE ABSCESS
|
0.00%
0/1
|
0.00%
0/88
|
0.00%
0/22
|
9.1%
1/11 • Number of events 1
|
|
Infections and infestations
URINARY TRACT INFECTION
|
0.00%
0/1
|
2.3%
2/88 • Number of events 2
|
0.00%
0/22
|
9.1%
1/11 • Number of events 1
|
|
Investigations
ALANINE AMINOTRANSFERASE INCREASED
|
0.00%
0/1
|
10.2%
9/88 • Number of events 9
|
13.6%
3/22 • Number of events 3
|
9.1%
1/11 • Number of events 1
|
|
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED
|
0.00%
0/1
|
10.2%
9/88 • Number of events 9
|
13.6%
3/22 • Number of events 3
|
9.1%
1/11 • Number of events 1
|
|
Investigations
BLOOD BILIRUBIN INCREASED
|
0.00%
0/1
|
0.00%
0/88
|
0.00%
0/22
|
9.1%
1/11 • Number of events 1
|
|
Investigations
BLOOD CREATININE INCREASED
|
0.00%
0/1
|
0.00%
0/88
|
4.5%
1/22 • Number of events 1
|
9.1%
1/11 • Number of events 1
|
|
Investigations
EOSINOPHIL COUNT INCREASED
|
0.00%
0/1
|
4.5%
4/88 • Number of events 4
|
0.00%
0/22
|
9.1%
1/11 • Number of events 1
|
|
Investigations
GLUCOSE URINE PRESENT
|
0.00%
0/1
|
2.3%
2/88 • Number of events 2
|
0.00%
0/22
|
9.1%
1/11 • Number of events 1
|
|
Investigations
HAEMOGLOBIN DECREASED
|
0.00%
0/1
|
2.3%
2/88 • Number of events 2
|
0.00%
0/22
|
9.1%
1/11 • Number of events 1
|
|
Investigations
PLATELET COUNT DECREASED
|
0.00%
0/1
|
2.3%
2/88 • Number of events 2
|
4.5%
1/22 • Number of events 1
|
9.1%
1/11 • Number of events 1
|
|
Metabolism and nutrition disorders
MALNUTRITION
|
0.00%
0/1
|
0.00%
0/88
|
0.00%
0/22
|
9.1%
1/11 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
OSTEOARTHRITIS
|
0.00%
0/1
|
0.00%
0/88
|
0.00%
0/22
|
9.1%
1/11 • Number of events 1
|
|
Renal and urinary disorders
PYURIA
|
0.00%
0/1
|
0.00%
0/88
|
0.00%
0/22
|
9.1%
1/11 • Number of events 1
|
|
Renal and urinary disorders
RENAL FAILURE ACUTE
|
0.00%
0/1
|
0.00%
0/88
|
0.00%
0/22
|
9.1%
1/11 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
ATELECTASIS
|
0.00%
0/1
|
0.00%
0/88
|
0.00%
0/22
|
9.1%
1/11 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
HAEMOPTYSIS
|
0.00%
0/1
|
0.00%
0/88
|
0.00%
0/22
|
9.1%
1/11 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
PLEURAL EFFUSION
|
0.00%
0/1
|
0.00%
0/88
|
0.00%
0/22
|
9.1%
1/11 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
RESPIRATORY FAILURE
|
0.00%
0/1
|
0.00%
0/88
|
0.00%
0/22
|
9.1%
1/11 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
DRUG ERUPTION
|
0.00%
0/1
|
0.00%
0/88
|
0.00%
0/22
|
9.1%
1/11 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
ECZEMA
|
0.00%
0/1
|
2.3%
2/88 • Number of events 2
|
0.00%
0/22
|
9.1%
1/11 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
ERYTHEMA
|
0.00%
0/1
|
0.00%
0/88
|
9.1%
2/22 • Number of events 2
|
9.1%
1/11 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
PRURITUS
|
0.00%
0/1
|
2.3%
2/88 • Number of events 2
|
9.1%
2/22 • Number of events 2
|
0.00%
0/11
|
|
Vascular disorders
ANGIOPATHY
|
0.00%
0/1
|
0.00%
0/88
|
0.00%
0/22
|
9.1%
1/11 • Number of events 1
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp
Results disclosure agreements
- Principal investigator is a sponsor employee The SPONSOR must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the SPONSOR as confidential must be deleted prior to submission. SPONSOR review can be expedited to meet publication guidelines.
- Publication restrictions are in place
Restriction type: OTHER