Safety and Efficacy of BAY1192631 in Japanese Patients With Methicillin-resistant Staphylococcus Aureus (MRSA) Infections

A Prospective, Randomized, Open-label, Active-controlled, Multicenter Study to Evaluate the Efficacy and Safety of BAY 1192631 in Japanese Patients With MRSA Infections (Skin and Soft Tissue Infection [SSTI] and SSTI-related Bacteremia)

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).

Study Overview

• Status: Completed
• Conditions: Skin Diseases, Infectious
• Intervention / Treatment: Drug: Tedizolid Phosphate (Sivextro, BAY1192631); Drug: Linezolid

• Study Type: Interventional
• Enrollment (Actual): 125
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan, 810-0001
  • Gifu, Japan, 500-8513
  • Kochi, Japan, 781-8555
  • Kumamoto, Japan, 860-0008
  • Nagasaki, Japan, 852-8501
  • Osaka, Japan, 534-0021
  • Shizuoka, Japan, 424-8636
  • Shizuoka, Japan, 420-8527
  • Toyama, Japan, 930-0194
  • Aichi
    • Nagakute, Aichi, Japan, 480-1195
    • Nagoya, Aichi, Japan, 455-8530
    • Nagoya, Aichi, Japan, 457-8510
    • Toyoake, Aichi, Japan, 470-1192
  • Fukui
    • Yoshida, Fukui, Japan, 910-1193
  • Fukuoka
    • Kasuga, Fukuoka, Japan, 816-0864
    • Kitakyushu, Fukuoka, Japan, 802-0077
    • Miyako-gun, Fukuoka, Japan, 800-0344
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-0061
    • Sapporo, Hokkaido, Japan, 006-8555
  • Hyogo
    • Amagasaki, Hyogo, Japan, 660-8511
    • Kobe, Hyogo, Japan, 650-0017
  • Ibaraki
    • Inashiki-gun, Ibaraki, Japan, 300-0395
    • Tsukuba, Ibaraki, Japan, 305-8576
  • Kanagawa
    • Kamakura, Kanagawa, Japan, 247-8533
    • Sagamihara, Kanagawa, Japan, 252-0375
    • Yokohama, Kanagawa, Japan, 231-8682
  • Kumamoto
    • Koshi, Kumamoto, Japan, 861-1196
  • Mie
    • Tsu, Mie, Japan, 514-1101
  • Miyagi
    • Sendai, Miyagi, Japan, 983-8520
  • Okinawa
    • Nakagami-gun, Okinawa, Japan, 901-2393
    • Shimajiri, Okinawa, Japan, 901-0493
  • Shizuoka
    • Hamamatsu, Shizuoka, Japan, 430-0929
    • Iwata, Shizuoka, Japan, 438-8550
    • Numazu, Shizuoka, Japan, 410-8555
  • Tokyo
    • Meguro-ku, Tokyo, Japan, 152-8902
    • Musashimurayama, Tokyo, Japan, 208-0011
    • Ota-ku, Tokyo, Japan, 145-0065
    • Ota-ku, Tokyo, Japan, 143-8541
    • Ota-ku, Tokyo, Japan, 143-0013
    • Setagaya-ku, Tokyo, Japan, 158-8531
    • Shinagawa, Tokyo, Japan, 141-8625
    • Shinjuku-ku, Tokyo, Japan, 162-8655
    • Tachikawa, Tokyo, Japan, 190-0014
  • Tottori
    • Yonago, Tottori, Japan, 683-8605
  • Yamaguchi
    • Shimonoseki, Yamaguchi, Japan, 750-8520
  • Yamanashi
    • Kofu, Yamanashi, Japan, 400-8506

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tedizolid Phosphate (Sivextro, BAY1192631); Participants received 200 mg BAY1192631 solution or tablet once daily (intravenous (I.V.) or oral (PO))	Drug: Tedizolid 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.
Active Comparator: Linezolid; Participants received 600 mg Linezolid solution or tablet twice daily, every 12 ± 3 hours (intravenous (I.V.) or oral (PO))	Drug: Linezolid; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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 at Test of Cure (TOC)	Microbiological response was assessed in accordance with the Guidance for the method of microbiological assessment by Japanese Chemotherapy Society.	7-14 days after the end of treatment (EOT) for skin and soft tissue infections (SSTI) and 4-6 weeks after EOT for bacteremia

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	7-14 days for skin and soft tissue infections (SSTI) or 7-21 days for bacteremia from the study drug administration
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.	7-14 days for skin and soft tissue infections (SSTI) or 7-21 days for bacteremia from the study drug administration
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.	Multiple time points up to 7-14 days after the end of treatment
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.	Baseline and Day 3/4, Day 5/13, EOT, TOC

Collaborators and Investigators

• Sponsor: Bayer

Study record dates

Study Major Dates

• Study Start (Actual): November 23, 2013
• Primary Completion (Actual): October 28, 2016
• Study Completion (Actual): October 28, 2016

Study Registration Dates

• First Submitted: October 18, 2013
• First Submitted That Met QC Criteria: October 18, 2013
• First Posted (Estimate): October 22, 2013

Study Record Updates

• Last Update Posted (Actual): October 4, 2018
• Last Update Submitted That Met QC Criteria: September 6, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Tedizolid; Methicillin Resistant Staphylococcus Aureus,; Skin and soft tissue infection,; Bacteremia,
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Skin Diseases, Infectious; Soft Tissue Infections; Skin Diseases; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Linezolid; Tedizolid; Tedizolid phosphate
• Other Study ID Numbers: 16099 (Other Identifier: City of Hope Medical Center)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes