Skin Diseases, Infectious
Conditions
Keywords
Methicillin Resistant Staphylococcus Aureus,, Skin and soft tissue infection,, Bacteremia,, Tedizolid
Brief summary
The aim of this study is to see the efficacy and safety of BAY1192631 in Japanese patients with methicillin-resistant staphylococcus aureus (MRSA) (skin and soft tissue infections (SSTI) and SSTI-related bacteremia).
Interventions
DRUGTedizolid Phosphate (Sivextro, BAY1192631)
BAY1192631 solution or tablet 200 mg, once daily, Intravenous (IV) or By Mouth (PO) for 7-14 days for skin and soft tissue infections (SSTI) or 7-21 days for bacteremia.
DRUGLinezolid
Linezolid solution or tablet 600 mg, twice daily, every 12 ±3 hours, Intravenous (IV) or By mouth (PO) 7-14 days for skin and soft tissue infections (SSTI) or 7-21 days for bacteremia.
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Suspected or confirmed Methicillin-resistant Staphylococcus aureus (MRSA) infection * Japanese Male and female patients aged 18 years or above * Diagnosis of Skin and soft tissue infection with MRSA either suspected or confirmed as the major cause of infection, with/without SSTI (skin and soft tissue infection)-derived MRSA bacteremia suspected
Exclusion criteria
* Having received any systemic antibacterial potentially effective against MRSA for \>/=24 hours within 3 days prior to the first infusion of a study drug, or having received/expected to receive the medication within 24 hours prior to the first infusion, unless antibacterial therapy for \>/=72 hours proves to be ineffective on or lack appropriate potency (resistant) to MRSA. * Moribund clinical condition such as death likely within the first 3 days of a study drug treatment * History of significant allergy or intolerance to linezolid or BAY1192631 * Known or suspected human immunodeficiency virus (HIV) infection with a CD4+ T-cell count \< 200/μL * Chronic treatment with immunosuppressive drugs * Active tuberculosis or non-tuberculous mycobacteriosis which need medical treatments * Current or anticipated neutropenia with neutrophil count \< 1,000/ mm\^3 * Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) \>/= 8 times the upper limit of reference range OR moderate to severe hepatic disease with Child Pugh score \>/=10.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Response at Test of Cure (TOC) | 7-14 days after the end of treatment (EOT) for skin and soft tissue infections (SSTI) and 4-6 weeks after EOT for bacteremia | Clinical response was evaluated by the masked investigator as clinical cure, clinical failure and indeterminate on the basis of the clinical symptoms/findings, vital sign and laboratory data from screening period to each evaluation point. Measurements for the assessment of clinical response included body temperature, pulse/heart rate, respiration rate, and white blood cell or band cell count. |
| Microbiological Response at Test of Cure (TOC) | 7-14 days after the end of treatment (EOT) for skin and soft tissue infections (SSTI) and 4-6 weeks after EOT for bacteremia | Microbiological response was assessed in accordance with the Guidance for the method of microbiological assessment by Japanese Chemotherapy Society. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Response at End of Treatment Visit (EOT) | 7-14 days for skin and soft tissue infections (SSTI) or 7-21 days for bacteremia from the study drug administration | Clinical response was evaluated by the masked investigator as effective, ineffective and indeterminate on the basis of the clinical symptoms/findings, vital sign and laboratory data from screening period to each evaluation point. Measurements for the assessment of clinical response included body temperature, pulse/heart rate, respiration rate, and white blood cell or band cell count. |
| Microbiological Response at End of Treatment (EOT) | 7-14 days for skin and soft tissue infections (SSTI) or 7-21 days for bacteremia from the study drug administration | Microbiological response was assessed in accordance with the Guidance for the method of microbiological assessment by Japanese Chemotherapy Society. |
| Change of the Lesion Size From the Screening Visit by Visit (Only Skin and Soft Tissue Infection [SSTI]) | Multiple time points up to 7-14 days after the end of treatment | Lesion size was measured by the masked investigators of erythema, edema, or induration whichever is largest. |
| Reduction Ratio of the Lesion Size From the Screening Visit to Day 3 to Day 4 Visit (Only Skin and Soft Tissue Infection [SSTI]) | Baseline and Day 3/4, Day 5/13, EOT, TOC | Lesion size was measured by the masked investigators of erythema, edema, or induration whichever is largest. Reduction ratio (%) = 100 \* (the post baseline value - baseline value) / baseline value. Negative values represent reduction of lesion size compared to baseline. |
Countries
Japan
Participant flow
Recruitment details
The study was conducted in 46 study centers in Japan from 23 November 2013 (first subject, first visit) to 28 October 2016 (last subject, last visit).
Pre-assignment details
Overall, 131 participants were screened. Among them, 6 participants failed screening. 125 participants were randomized to one of the 2 treatment groups.
Participants by arm
| Arm | Count |
|---|---|
| Tedizolid Phosphate (Sivextro, BAY1192631) - SSTI Participants who had skin and soft tissue infections (SSTI) including deep skin and soft tissue infection, chronic pyoderma, infection secondary to wound, burn and surgical wound, infected ulcer at baseline received 200 mg BAY1192631 solution or tablet once daily (intravenous (I.V.) or oral (PO)) | 79 |
| Linezoid - SSTI Participants who had skin and soft tissue infections (SSTI) including deep skin and soft tissue infection, chronic pyoderma, infection secondary to wound, burn and surgical wound, infected ulcer at baseline received 600 mg Linezolid solution or tablet twice daily, every 12 ± 3 hours (intravenous (I.V.) or oral (PO)) | 39 |
| Tedizolid Phosphate (Sivextro, BAY1192631) - Bacteremia Participants who had SSTI-related bacteremia at baseline received 200 mg BAY1192631 solution or tablet once daily (intravenous (I.V.) or oral (PO)) | 4 |
| Linezoid - Bacteremia Participants who had SSTI-related bacteremia at baseline received 600 mg Linezolid solution or tablet twice daily, every 12 ± 3 hours (intravenous (I.V.) or oral (PO)) | 2 |
| Total | 124 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 |
| Overall Study | Lack of Efficacy | 1 | 1 |
| Overall Study | Logistical difficulties | 1 | 0 |
| Overall Study | Protocol driven decision point | 1 | 0 |
| Overall Study | Protocol Violation | 2 | 0 |
| Overall Study | Switching to other therapy | 2 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Tedizolid Phosphate (Sivextro, BAY1192631) - SSTI | Linezoid - SSTI | Tedizolid Phosphate (Sivextro, BAY1192631) - Bacteremia | Linezoid - Bacteremia | Total |
|---|---|---|---|---|---|
| Age, Customized 65 - 75 years | 31 Participants | 9 Participants | 1 Participants | 2 Participants | 43 Participants |
| Age, Customized < 65 years | 31 Participants | 20 Participants | 3 Participants | 0 Participants | 54 Participants |
| Age, Customized > 75 years | 17 Participants | 10 Participants | 0 Participants | 0 Participants | 27 Participants |
| Body Mass Index (BMI) | 25.52 kg/m^2 STANDARD_DEVIATION 4.7 | 25.72 kg/m^2 STANDARD_DEVIATION 5.8 | 30.75 kg/m^2 STANDARD_DEVIATION 11.19 | 22.35 kg/m^2 STANDARD_DEVIATION 0.64 | 25.70 kg/m^2 STANDARD_DEVIATION 5.34 |
| Lesion area <=75 cm^2 | 25 Participants | 14 Participants | — | — | 39 Participants |
| Lesion area >75 cm^2 | 54 Participants | 25 Participants | — | — | 79 Participants |
| Primary diagnosis Bacteremia | 0 Participants | 0 Participants | 4 Participants | 2 Participants | 6 Participants |
| Primary diagnosis Chronic pyoderma | 3 Participants | 2 Participants | 0 Participants | 0 Participants | 5 Participants |
| Primary diagnosis Deep SSTI | 44 Participants | 22 Participants | 0 Participants | 0 Participants | 66 Participants |
| Primary diagnosis Infection secondary to ulcer | 17 Participants | 5 Participants | 0 Participants | 0 Participants | 22 Participants |
| Primary diagnosis Infection secondary to wound, burn, surgical wound | 15 Participants | 10 Participants | 0 Participants | 0 Participants | 25 Participants |
| Sex: Female, Male Female | 27 Participants | 12 Participants | 2 Participants | 1 Participants | 42 Participants |
| Sex: Female, Male Male | 52 Participants | 27 Participants | 2 Participants | 1 Participants | 82 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 64 / 83 | 31 / 41 |
| serious Total, serious adverse events | 7 / 83 | 4 / 41 |
Outcome results
Primary
Clinical Response at Test of Cure (TOC)
Clinical response was evaluated by the masked investigator as clinical cure, clinical failure and indeterminate on the basis of the clinical symptoms/findings, vital sign and laboratory data from screening period to each evaluation point. Measurements for the assessment of clinical response included body temperature, pulse/heart rate, respiration rate, and white blood cell or band cell count.
Time frame: 7-14 days after the end of treatment (EOT) for skin and soft tissue infections (SSTI) and 4-6 weeks after EOT for bacteremia
Population: This outcome measure was analyzed based on the microbiological evaluable population-methicillin-resistant Staphylococcus aureus (ME-MRSA) analysis set. The ME-MRSA consisted of clinical evaluable population at test of Cure (CE-TOC) analysis population who had an MRSA isolated as pathogen at the baseline.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tedizolid Phosphate (Sivextro, BAY1192631) - SSTI | Clinical Response at Test of Cure (TOC) | Clinical failure | 6.9 Percentage of participants |
| Tedizolid Phosphate (Sivextro, BAY1192631) - SSTI | Clinical Response at Test of Cure (TOC) | Clinical cure | 86.2 Percentage of participants |
| Tedizolid Phosphate (Sivextro, BAY1192631) - SSTI | Clinical Response at Test of Cure (TOC) | Indeterminate | 6.9 Percentage of participants |
| Linezoid - SSTI | Clinical Response at Test of Cure (TOC) | Clinical failure | 10.0 Percentage of participants |
| Linezoid - SSTI | Clinical Response at Test of Cure (TOC) | Clinical cure | 80.0 Percentage of participants |
| Linezoid - SSTI | Clinical Response at Test of Cure (TOC) | Indeterminate | 10.0 Percentage of participants |
| Linezoid - Bacteremia | Clinical Response at Test of Cure (TOC) | Clinical cure | 0.0 Percentage of participants |
| Linezoid - Bacteremia | Clinical Response at Test of Cure (TOC) | Indeterminate | 100.0 Percentage of participants |
| Linezoid - Bacteremia | Clinical Response at Test of Cure (TOC) | Clinical failure | 0.0 Percentage of participants |
Primary
Microbiological Response at Test of Cure (TOC)
Microbiological response was assessed in accordance with the Guidance for the method of microbiological assessment by Japanese Chemotherapy Society.
Time frame: 7-14 days after the end of treatment (EOT) for skin and soft tissue infections (SSTI) and 4-6 weeks after EOT for bacteremia
Population: This outcome measure was analyzed based on the microbiological evaluable population-methicillin-resistant Staphylococcus aureus (ME-MRSA) analysis set. The ME-MRSA consisted of clinical evaluable population at test of Cure (CE-TOC) analysis population who had an MRSA isolated as pathogen at the baseline.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tedizolid Phosphate (Sivextro, BAY1192631) - SSTI | Microbiological Response at Test of Cure (TOC) | Eradication | 93.1 Percentage of participants |
| Tedizolid Phosphate (Sivextro, BAY1192631) - SSTI | Microbiological Response at Test of Cure (TOC) | Persistence | 3.4 Percentage of participants |
| Tedizolid Phosphate (Sivextro, BAY1192631) - SSTI | Microbiological Response at Test of Cure (TOC) | Elimination(indeterminate) | 0.0 Percentage of participants |
| Tedizolid Phosphate (Sivextro, BAY1192631) - SSTI | Microbiological Response at Test of Cure (TOC) | Missing | 3.4 Percentage of participants |
| Linezoid - SSTI | Microbiological Response at Test of Cure (TOC) | Missing | 10.0 Percentage of participants |
| Linezoid - SSTI | Microbiological Response at Test of Cure (TOC) | Eradication | 90.0 Percentage of participants |
| Linezoid - SSTI | Microbiological Response at Test of Cure (TOC) | Elimination(indeterminate) | 0.0 Percentage of participants |
| Linezoid - SSTI | Microbiological Response at Test of Cure (TOC) | Persistence | 0.0 Percentage of participants |
| Linezoid - Bacteremia | Microbiological Response at Test of Cure (TOC) | Missing | 0.0 Percentage of participants |
| Linezoid - Bacteremia | Microbiological Response at Test of Cure (TOC) | Persistence | 0.0 Percentage of participants |
| Linezoid - Bacteremia | Microbiological Response at Test of Cure (TOC) | Elimination(indeterminate) | 0.0 Percentage of participants |
| Linezoid - Bacteremia | Microbiological Response at Test of Cure (TOC) | Eradication | 100.0 Percentage of participants |
Secondary
Change of the Lesion Size From the Screening Visit by Visit (Only Skin and Soft Tissue Infection [SSTI])
Lesion size was measured by the masked investigators of erythema, edema, or induration whichever is largest.
Time frame: Multiple time points up to 7-14 days after the end of treatment
Population: This outcome measure was analyzed based on the microbiological evaluable population-ME-MRSA analysis set. The ME-MRSA consisted of clinical evaluable population at test of Cure (CE-TOC) analysis population who had an MRSA isolated as pathogen at the baseline. Data of SSTI target participants were reported for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tedizolid Phosphate (Sivextro, BAY1192631) - SSTI | Change of the Lesion Size From the Screening Visit by Visit (Only Skin and Soft Tissue Infection [SSTI]) | Day 3/4 | -62.05 cm^2 | Standard Deviation 96.89 |
| Tedizolid Phosphate (Sivextro, BAY1192631) - SSTI | Change of the Lesion Size From the Screening Visit by Visit (Only Skin and Soft Tissue Infection [SSTI]) | Day 5 to 13 | -134.31 cm^2 | Standard Deviation 153.3 |
| Tedizolid Phosphate (Sivextro, BAY1192631) - SSTI | Change of the Lesion Size From the Screening Visit by Visit (Only Skin and Soft Tissue Infection [SSTI]) | End of treatment | -174.96 cm^2 | Standard Deviation 283.05 |
| Tedizolid Phosphate (Sivextro, BAY1192631) - SSTI | Change of the Lesion Size From the Screening Visit by Visit (Only Skin and Soft Tissue Infection [SSTI]) | Test of cure (n=28, 9) | -212.63 cm^2 | Standard Deviation 369.43 |
| Linezoid - SSTI | Change of the Lesion Size From the Screening Visit by Visit (Only Skin and Soft Tissue Infection [SSTI]) | Test of cure (n=28, 9) | -314.18 cm^2 | Standard Deviation 402.93 |
| Linezoid - SSTI | Change of the Lesion Size From the Screening Visit by Visit (Only Skin and Soft Tissue Infection [SSTI]) | Day 3/4 | -173.93 cm^2 | Standard Deviation 210.19 |
| Linezoid - SSTI | Change of the Lesion Size From the Screening Visit by Visit (Only Skin and Soft Tissue Infection [SSTI]) | End of treatment | -280.69 cm^2 | Standard Deviation 386.64 |
| Linezoid - SSTI | Change of the Lesion Size From the Screening Visit by Visit (Only Skin and Soft Tissue Infection [SSTI]) | Day 5 to 13 | -317.66 cm^2 | Standard Deviation 410.86 |
Secondary
Clinical Response at End of Treatment Visit (EOT)
Clinical response was evaluated by the masked investigator as effective, ineffective and indeterminate on the basis of the clinical symptoms/findings, vital sign and laboratory data from screening period to each evaluation point. Measurements for the assessment of clinical response included body temperature, pulse/heart rate, respiration rate, and white blood cell or band cell count.
Time frame: 7-14 days for skin and soft tissue infections (SSTI) or 7-21 days for bacteremia from the study drug administration
Population: This outcome measure was analyzed based on the microbiological evaluable population-methicillin-resistant Staphylococcus aureus (ME-MRSA) analysis set. The ME-MRSA consisted of clinical evaluable population at test of Cure (CE-TOC) analysis population who had an MRSA isolated as pathogen at the baseline.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tedizolid Phosphate (Sivextro, BAY1192631) - SSTI | Clinical Response at End of Treatment Visit (EOT) | Ineffective | 6.9 Percentage of participants |
| Tedizolid Phosphate (Sivextro, BAY1192631) - SSTI | Clinical Response at End of Treatment Visit (EOT) | Effective | 93.1 Percentage of participants |
| Tedizolid Phosphate (Sivextro, BAY1192631) - SSTI | Clinical Response at End of Treatment Visit (EOT) | Indeterminate | 0.0 Percentage of participants |
| Linezoid - SSTI | Clinical Response at End of Treatment Visit (EOT) | Ineffective | 10.0 Percentage of participants |
| Linezoid - SSTI | Clinical Response at End of Treatment Visit (EOT) | Effective | 90.0 Percentage of participants |
| Linezoid - SSTI | Clinical Response at End of Treatment Visit (EOT) | Indeterminate | 0.0 Percentage of participants |
| Linezoid - Bacteremia | Clinical Response at End of Treatment Visit (EOT) | Effective | 50.0 Percentage of participants |
| Linezoid - Bacteremia | Clinical Response at End of Treatment Visit (EOT) | Indeterminate | 50.0 Percentage of participants |
| Linezoid - Bacteremia | Clinical Response at End of Treatment Visit (EOT) | Ineffective | 0.0 Percentage of participants |
Secondary
Microbiological Response at End of Treatment (EOT)
Microbiological response was assessed in accordance with the Guidance for the method of microbiological assessment by Japanese Chemotherapy Society.
Time frame: 7-14 days for skin and soft tissue infections (SSTI) or 7-21 days for bacteremia from the study drug administration
Population: This outcome measure was analyzed based on the microbiological evaluable population-methicillin-resistant Staphylococcus aureus (ME-MRSA) analysis set. The ME-MRSA consisted of clinical evaluable population at test of Cure (CE-TOC) analysis population who had an MRSA isolated as pathogen at the baseline.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tedizolid Phosphate (Sivextro, BAY1192631) - SSTI | Microbiological Response at End of Treatment (EOT) | Elimination (indeterminate) | 0.0 Percentage of participants |
| Tedizolid Phosphate (Sivextro, BAY1192631) - SSTI | Microbiological Response at End of Treatment (EOT) | Eradication | 93.1 Percentage of participants |
| Tedizolid Phosphate (Sivextro, BAY1192631) - SSTI | Microbiological Response at End of Treatment (EOT) | Persistence | 6.9 Percentage of participants |
| Linezoid - SSTI | Microbiological Response at End of Treatment (EOT) | Persistence | 0.0 Percentage of participants |
| Linezoid - SSTI | Microbiological Response at End of Treatment (EOT) | Elimination (indeterminate) | 0.0 Percentage of participants |
| Linezoid - SSTI | Microbiological Response at End of Treatment (EOT) | Eradication | 100.0 Percentage of participants |
| Linezoid - Bacteremia | Microbiological Response at End of Treatment (EOT) | Eradication | 100.0 Percentage of participants |
| Linezoid - Bacteremia | Microbiological Response at End of Treatment (EOT) | Elimination (indeterminate) | 0.0 Percentage of participants |
| Linezoid - Bacteremia | Microbiological Response at End of Treatment (EOT) | Persistence | 0.0 Percentage of participants |
Secondary
Reduction Ratio of the Lesion Size From the Screening Visit to Day 3 to Day 4 Visit (Only Skin and Soft Tissue Infection [SSTI])
Lesion size was measured by the masked investigators of erythema, edema, or induration whichever is largest. Reduction ratio (%) = 100 \* (the post baseline value - baseline value) / baseline value. Negative values represent reduction of lesion size compared to baseline.
Time frame: Baseline and Day 3/4, Day 5/13, EOT, TOC
Population: This outcome measure was analyzed based on the microbiological evaluable population-ME-MRSA analysis set. The ME-MRSA consisted of clinical evaluable population at test of Cure (CE-TOC) analysis population who had an MRSA isolated as pathogen at the baseline. Data of SSTI target participants were reported for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tedizolid Phosphate (Sivextro, BAY1192631) - SSTI | Reduction Ratio of the Lesion Size From the Screening Visit to Day 3 to Day 4 Visit (Only Skin and Soft Tissue Infection [SSTI]) | Day3/4 | -32.32 Percentage | Standard Deviation 40.5 |
| Tedizolid Phosphate (Sivextro, BAY1192631) - SSTI | Reduction Ratio of the Lesion Size From the Screening Visit to Day 3 to Day 4 Visit (Only Skin and Soft Tissue Infection [SSTI]) | Day 5 to 13 | -53.30 Percentage | Standard Deviation 41.66 |
| Tedizolid Phosphate (Sivextro, BAY1192631) - SSTI | Reduction Ratio of the Lesion Size From the Screening Visit to Day 3 to Day 4 Visit (Only Skin and Soft Tissue Infection [SSTI]) | End of Treatment | -67.69 Percentage | Standard Deviation 32.4 |
| Tedizolid Phosphate (Sivextro, BAY1192631) - SSTI | Reduction Ratio of the Lesion Size From the Screening Visit to Day 3 to Day 4 Visit (Only Skin and Soft Tissue Infection [SSTI]) | Test of Cure | -81.82 Percentage | Standard Deviation 23.99 |
| Linezoid - SSTI | Reduction Ratio of the Lesion Size From the Screening Visit to Day 3 to Day 4 Visit (Only Skin and Soft Tissue Infection [SSTI]) | Test of Cure | -99.09 Percentage | Standard Deviation 2.08 |
| Linezoid - SSTI | Reduction Ratio of the Lesion Size From the Screening Visit to Day 3 to Day 4 Visit (Only Skin and Soft Tissue Infection [SSTI]) | Day3/4 | -61.46 Percentage | Standard Deviation 33.31 |
| Linezoid - SSTI | Reduction Ratio of the Lesion Size From the Screening Visit to Day 3 to Day 4 Visit (Only Skin and Soft Tissue Infection [SSTI]) | End of Treatment | -90.09 Percentage | Standard Deviation 26.38 |
| Linezoid - SSTI | Reduction Ratio of the Lesion Size From the Screening Visit to Day 3 to Day 4 Visit (Only Skin and Soft Tissue Infection [SSTI]) | Day 5 to 13 | -94.61 Percentage | Standard Deviation 6.32 |