Trial Outcomes & Findings for Safety and Efficacy of BAY1192631 in Japanese Patients With Methicillin-resistant Staphylococcus Aureus (MRSA) Infections (NCT NCT01967225)

NCT ID: NCT01967225

Last Updated: 2018-10-04

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

125 participants

Primary outcome timeframe

7-14 days after the end of treatment (EOT) for skin and soft tissue infections (SSTI) and 4-6 weeks after EOT for bacteremia

Results posted on

2018-10-04

Participant Flow

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).

Overall, 131 participants were screened. Among them, 6 participants failed screening. 125 participants were randomized to one of the 2 treatment groups.

Participant milestones

Participant milestones
Measure	Tedizolid Phosphate (Sivextro, BAY1192631) Participants received 200 mg BAY1192631 solution or tablet once daily (intravenous (I.V.) or oral (PO))	Linezolid Participants received 600 mg Linezolid solution or tablet twice daily, every 12 +- 3 hours (intravenous (I.V.) or oral (PO))
Overall Study STARTED	84	41
Overall Study Participants Received Treatment	83	41
Overall Study COMPLETED	72	38
Overall Study NOT COMPLETED	12	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Tedizolid Phosphate (Sivextro, BAY1192631) Participants received 200 mg BAY1192631 solution or tablet once daily (intravenous (I.V.) or oral (PO))	Linezolid Participants received 600 mg Linezolid solution or tablet twice daily, every 12 +- 3 hours (intravenous (I.V.) or oral (PO))
Overall Study Adverse Event	3	1
Overall Study Withdrawal by Subject	2	1
Overall Study Lack of Efficacy	1	1
Overall Study Switching to other therapy	2	0
Overall Study Protocol driven decision point	1	0
Overall Study Logistical difficulties	1	0
Overall Study Protocol Violation	2	0

Baseline Characteristics

Lesion area is not collected or analyzed for bacteremia participants.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tedizolid Phosphate (Sivextro, BAY1192631) - SSTI n=79 Participants 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))	Linezoid - SSTI n=39 Participants 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))	Tedizolid Phosphate (Sivextro, BAY1192631) - Bacteremia n=4 Participants Participants who had SSTI-related bacteremia at baseline received 200 mg BAY1192631 solution or tablet once daily (intravenous (I.V.) or oral (PO))	Linezoid - Bacteremia n=2 Participants 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))	Total n=124 Participants Total of all reporting groups
Age, Customized < 65 years	31 Participants n=79 Participants	20 Participants n=39 Participants	3 Participants n=4 Participants	0 Participants n=2 Participants	54 Participants n=124 Participants
Age, Customized 65 - 75 years	31 Participants n=79 Participants	9 Participants n=39 Participants	1 Participants n=4 Participants	2 Participants n=2 Participants	43 Participants n=124 Participants
Age, Customized > 75 years	17 Participants n=79 Participants	10 Participants n=39 Participants	0 Participants n=4 Participants	0 Participants n=2 Participants	27 Participants n=124 Participants
Sex: Female, Male Female	27 Participants n=79 Participants	12 Participants n=39 Participants	2 Participants n=4 Participants	1 Participants n=2 Participants	42 Participants n=124 Participants
Sex: Female, Male Male	52 Participants n=79 Participants	27 Participants n=39 Participants	2 Participants n=4 Participants	1 Participants n=2 Participants	82 Participants n=124 Participants
Body Mass Index (BMI)	25.52 kg/m^2 STANDARD_DEVIATION 4.70 • n=79 Participants	25.72 kg/m^2 STANDARD_DEVIATION 5.80 • n=39 Participants	30.75 kg/m^2 STANDARD_DEVIATION 11.19 • n=4 Participants	22.35 kg/m^2 STANDARD_DEVIATION 0.64 • n=2 Participants	25.70 kg/m^2 STANDARD_DEVIATION 5.34 • n=124 Participants
Lesion area <=75 cm^2	25 Participants n=79 Participants • Lesion area is not collected or analyzed for bacteremia participants.	14 Participants n=39 Participants • Lesion area is not collected or analyzed for bacteremia participants.	—	—	39 Participants n=118 Participants • Lesion area is not collected or analyzed for bacteremia participants.
Lesion area >75 cm^2	54 Participants n=79 Participants • Lesion area is not collected or analyzed for bacteremia participants.	25 Participants n=39 Participants • Lesion area is not collected or analyzed for bacteremia participants.	—	—	79 Participants n=118 Participants • Lesion area is not collected or analyzed for bacteremia participants.
Primary diagnosis Deep SSTI	44 Participants n=79 Participants	22 Participants n=39 Participants	0 Participants n=4 Participants	0 Participants n=2 Participants	66 Participants n=124 Participants
Primary diagnosis Chronic pyoderma	3 Participants n=79 Participants	2 Participants n=39 Participants	0 Participants n=4 Participants	0 Participants n=2 Participants	5 Participants n=124 Participants
Primary diagnosis Infection secondary to wound, burn, surgical wound	15 Participants n=79 Participants	10 Participants n=39 Participants	0 Participants n=4 Participants	0 Participants n=2 Participants	25 Participants n=124 Participants
Primary diagnosis Infection secondary to ulcer	17 Participants n=79 Participants	5 Participants n=39 Participants	0 Participants n=4 Participants	0 Participants n=2 Participants	22 Participants n=124 Participants
Primary diagnosis Bacteremia	0 Participants n=79 Participants	0 Participants n=39 Participants	4 Participants n=4 Participants	2 Participants n=2 Participants	6 Participants n=124 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Tedizolid Phosphate (Sivextro, BAY1192631) - SSTI n=29 Participants 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))	Linezoid - SSTI n=10 Participants 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))	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))	Linezoid - Bacteremia n=2 Participants 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))
Clinical Response at Test of Cure (TOC) Clinical cure	86.2 Percentage of participants Interval 75.7 to 99.1	80.0 Percentage of participants	—	0.0 Percentage of participants
Clinical Response at Test of Cure (TOC) Clinical failure	6.9 Percentage of participants	10.0 Percentage of participants	—	0.0 Percentage of participants
Clinical Response at Test of Cure (TOC) Indeterminate	6.9 Percentage of participants	10.0 Percentage of participants	—	100.0 Percentage of participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Tedizolid Phosphate (Sivextro, BAY1192631) - SSTI n=29 Participants 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))	Linezoid - SSTI n=10 Participants 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))	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))	Linezoid - Bacteremia n=2 Participants 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))
Microbiological Response at Test of Cure (TOC) Eradication	93.1 Percentage of participants	90.0 Percentage of participants	—	100.0 Percentage of participants
Microbiological Response at Test of Cure (TOC) Persistence	3.4 Percentage of participants	0.0 Percentage of participants	—	0.0 Percentage of participants
Microbiological Response at Test of Cure (TOC) Elimination(indeterminate)	0.0 Percentage of participants	0.0 Percentage of participants	—	0.0 Percentage of participants
Microbiological Response at Test of Cure (TOC) Missing	3.4 Percentage of participants	10.0 Percentage of participants	—	0.0 Percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Tedizolid Phosphate (Sivextro, BAY1192631) - SSTI n=29 Participants 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))	Linezoid - SSTI n=10 Participants 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))	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))	Linezoid - Bacteremia n=2 Participants 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))
Clinical Response at End of Treatment Visit (EOT) Effective	93.1 Percentage of participants	90.0 Percentage of participants	—	50.0 Percentage of participants
Clinical Response at End of Treatment Visit (EOT) Ineffective	6.9 Percentage of participants	10.0 Percentage of participants	—	0.0 Percentage of participants
Clinical Response at End of Treatment Visit (EOT) Indeterminate	0.0 Percentage of participants	0.0 Percentage of participants	—	50.0 Percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Tedizolid Phosphate (Sivextro, BAY1192631) - SSTI n=29 Participants 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))	Linezoid - SSTI n=10 Participants 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))	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))	Linezoid - Bacteremia n=2 Participants 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))
Microbiological Response at End of Treatment (EOT) Elimination (indeterminate)	0.0 Percentage of participants	0.0 Percentage of participants	—	0.0 Percentage of participants
Microbiological Response at End of Treatment (EOT) Eradication	93.1 Percentage of participants	100.0 Percentage of participants	—	100.0 Percentage of participants
Microbiological Response at End of Treatment (EOT) Persistence	6.9 Percentage of participants	0.0 Percentage of participants	—	0.0 Percentage of participants

SECONDARY outcome

Timeframe: 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.

Lesion size was measured by the masked investigators of erythema, edema, or induration whichever is largest.

Outcome measures

Outcome measures
Measure	Tedizolid Phosphate (Sivextro, BAY1192631) - SSTI n=29 Participants 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))	Linezoid - SSTI n=10 Participants 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))	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))	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))
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	-173.93 cm^2 Standard Deviation 210.19	—	—
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	-317.66 cm^2 Standard Deviation 410.86	—	—
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	-280.69 cm^2 Standard Deviation 386.64	—	—
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	-314.18 cm^2 Standard Deviation 402.93	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Tedizolid Phosphate (Sivextro, BAY1192631) - SSTI n=29 Participants 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))	Linezoid - SSTI n=10 Participants 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))	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))	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))
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 40.50	-61.46 Percentage Standard Deviation 33.31	—	—
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	-94.61 Percentage Standard Deviation 6.32	—	—
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 32.40	-90.09 Percentage Standard Deviation 26.38	—	—
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	-99.09 Percentage Standard Deviation 2.08	—	—

Adverse Events

Tedizolid Phosphate (Sivextro, BAY1192631)

Serious events: 7 serious events

Other events: 64 other events

Deaths: 0 deaths

Linezolid

Serious events: 4 serious events

Other events: 31 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Tedizolid Phosphate (Sivextro, BAY1192631) n=83 participants at risk Participants received 200 mg BAY1192631 solution or tablet once daily (intravenous (I.V.) or oral (PO))	Linezolid n=41 participants at risk Participants received 600 mg Linezolid solution or tablet twice daily, every 12 +- 3 hours (intravenous (I.V.) or oral (PO))
Blood and lymphatic system disorders Bone marrow failure	0.00% 0/83 • 25 days after the last study medication administration	2.4% 1/41 • Number of events 1 • 25 days after the last study medication administration
Infections and infestations Cellulitis	1.2% 1/83 • Number of events 1 • 25 days after the last study medication administration	4.9% 2/41 • Number of events 2 • 25 days after the last study medication administration
Infections and infestations Gas gangrene	1.2% 1/83 • Number of events 1 • 25 days after the last study medication administration	0.00% 0/41 • 25 days after the last study medication administration
Infections and infestations Necrotising fasciitis	1.2% 1/83 • Number of events 1 • 25 days after the last study medication administration	0.00% 0/41 • 25 days after the last study medication administration
Infections and infestations Osteomyelitis	2.4% 2/83 • Number of events 2 • 25 days after the last study medication administration	0.00% 0/41 • 25 days after the last study medication administration
Infections and infestations Pneumonia	1.2% 1/83 • Number of events 1 • 25 days after the last study medication administration	0.00% 0/41 • 25 days after the last study medication administration
Infections and infestations Sepsis	0.00% 0/83 • 25 days after the last study medication administration	2.4% 1/41 • Number of events 1 • 25 days after the last study medication administration
Infections and infestations Anal abscess	0.00% 0/83 • 25 days after the last study medication administration	2.4% 1/41 • Number of events 1 • 25 days after the last study medication administration
Infections and infestations Muscle abscess	0.00% 0/83 • 25 days after the last study medication administration	2.4% 1/41 • Number of events 1 • 25 days after the last study medication administration
Infections and infestations Sternitis	1.2% 1/83 • Number of events 1 • 25 days after the last study medication administration	0.00% 0/41 • 25 days after the last study medication administration
Injury, poisoning and procedural complications Lumbar vertebral fracture	1.2% 1/83 • Number of events 1 • 25 days after the last study medication administration	0.00% 0/41 • 25 days after the last study medication administration

Other adverse events

Additional Information

Therapeutic Area Head

Bayer

Phone: (+) 1-888-8422937

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60