Submitted by: John Michael Dominic Go 2017-07-19 00:00:00 Last Updated by: John Michael Dominic Go 2018-02-01 09:36:52 Export to PDF

APEKS-NP

PHRR170721-001630

1615R2132

2017-CT0407

A Multicenter, Randomized, Double-blind, Parallel-group Clinical Study of S-649266 Compared with Meropenem for the Treatment of Hospital-acquired Bacterial Pneumonia, Ventilator-associated Bacterial Pneumonia, or Healthcare-associated Bacterial Pneumonia Caused by Gram negative Pathogens

This is a Phase 3, multicenter (multinational), double-blind, parallel-group, randomized, active-controlled study in approximately 300 subjects with documented nosocomial1 pneumonia caused by Gram-negative bacteria. Subjects meeting eligibility criteria and assessed by the investigator to require 7 to 14 days of intravenous treatment in hospital will be randomized (1:1) to either S-649266 2 g administered intravenously over 3 hours every 8 hours (q8h) or meropenem 2 g administered intravenously over 3 hours q8h. 
Linezolid will be administered to subjects in both arms to provide coverage for methicillin resistant Staphylococcus aureus (MRSA) and to maintain the study blind and, in the S-649266 arm, to provide coverage for Gram-positive bacteria
 

Regime Classification Priority
2010 - 2016 Health Technology Development Drug Discovery and Development
Start Date Duration in Months Target Completion Date Actual Completion Date
2017-11-07 22 2019-09-07 0000-00-00

Ongoing

Institution Classification Region LTO #
Shionogi & Co., Ltd. Private Business Japan N/A
Institution Classification Region LTO #
INC Research Pte. Ltd. Private Business NCR CDRR-NCR-CRO-1
Institution Amount Region
Shionogi & Co., Ltd. N/A Japan
Name E-Mail Phone Number Postal Address
Shionogi & Co., Ltd shionogiclintrials-admin@shionogi.co.jp +81-6-6485-5090 1-1-4, Shibata, Kita-ku, Osaka 530-0012, Japan
Name E-Mail Phone Number Postal Address
Shionogi & Co., Ltd shionogiclintrials-admin@shionogi.co.jp +81-6-6485-5090 1-1-4, Shibata, Kita-ku, Osaka 530-0012, Japan
Name Expertise Affiliation
Ronald Allan R. Payumo, MD Pulmonology Mary Johnston Hospital
Lalaine Llamido Mortera, MD Pulmonology Manila Central University - Filemon D. Tanchoco Medical Foundation
Malbar G. Ferrer, MD Pulmonology St. Paul's Hospital Iloilo
Joel M. Santiaguel, MD Pulmonology Quirino Memorial Medical Center
Marie Grace Dawn T. Isidro, MD Pulmonology West Visayas State University Medical Center
Ronnie Z. Samoro, MD Pulmonology West Visayas State University Medical Center
Joven Roque V. Gonong, MD Pulmonology Lung Center of the Philippines
Albert Albay, Jr. MD Pulmonology Philippine General Hospital
Myla M. Castillo, MD Pulmonology Dr. Jose N. Rodriguez Memorial Hospital
Project Location Institutional Ethics Review Board
Mary Johnston Hospital Mary Johnston Hospital Ethics & Review Committee
Manila Central University - Filemon D. Tanchoco Medical Foundation Manila Central University - Filemon D. Tanchoco Medical Foundation Institutional Review Board
St. Paul's Hospital Iloilo St. Paul’s Hospital Iloilo – Institutional Ethics Review Board
Quirino Memorial Medical Center Quirino Memorial Medical Center Hospital Ethics Committee
West Visayas State University Medical Center N/A
West Visayas State University Medical Center N/A
Lung Center of the Philippines Lung Center of the Philippines Ethics Review Committee
Philippine General Hospital Philippine General Hospital Ethics Review Board
Dr. Jose N. Rodriguez Memorial Hospital N/A

Nosocomial pneumonia caused by a Gram-negative pathogen(s)
 

To compare all-cause mortality at Day 14 of S-649266 with that of the comparator, meropenem, in adults with hospital-acquired bacterial pneumonia (HABP),ventilator-associated bacterial pneumonia (VABP), or healthcare-associated bacterial pneumonia (HCABP) caused by Gram-negative pathogens.

-To compare the clinical outcome of treatment with S-649266 with that of meropenem in subjects at test of cure (TOC)
-To compare the microbiologic outcome of treatment with S-649266 with that of meropenem at TOC 

Recruiting

  • Belgium
  • Brazil
  • Canada
  • Colombia
  • Czech Republic
  • Estonia
  • France
  • Georgia
  • Germany
  • Hungary
  • Israel
  • Japan
  • Latvia
  • Philippines
  • Russia
  • Serbia and Montenegro
  • Spain
  • Taiwan
  • Ukraine
  • United Kingdom
  • United States

Clinical Trial

20170405162852

2017-06-22

None

Key Inclusion Criteria: 
Subjects who fulfill the following criteria at screening will be included in the study: 
• Subjects 18 years or older at the time of signing informed consent 
• Subjects who have provided written informed consent or their informed consent has been provided by legal guardian (Note: Country-specific rules and local Ethics Committee approval for legal guardian informed consent will determine whether or not and how a subject unable to comprehend or sign the informed consent is allowed to be enrolled in the study) 
• Subjects who meet the clinical diagnosis criteria for HABP/VABP/HCABP 
a. HABP is defined as an acute bacterial pneumonia in a subject hospitalized for more than 48 hours or developing within 7 days after discharge from a hospital. Subjects may experience acute respiratory failure and require mechanical ventilation for HABP (ventilated-HABP). 
b. VABP is defined as an acute bacterial pneumonia in a subject receiving mechanical ventilation via an endotracheal tube for a minimum of 48 hours. 
c. HCABP is defined as an acute bacterial pneumonia in a subject who was hospitalized in an acute care hospital for 2 or more days within 90 days of the infection; has been residing in a nursing home or long-term care facility; received intravenous antibiotic therapy, chemotherapy, or wound care or attended a hospital clinic or hemodialysis clinic within the past 30 days of the current infection. 
• All subjects must fulfill at least 1 of the following clinical criteria at screening:
 a.  New onset or worsening of pulmonary symptoms or signs, such as cough, dyspnea, tachypnea (eg, respiratory rate greater than 25 breaths/minute), expectorated sputum production, or requirement for mechanical ventilation 
b. Hypoxemia (eg, a partial pressure of oxygen [PaO2] less than 60 mm Hg while the subject is breathing room air, as determined by arterial blood gas [ABG], or worsening of the ratio of the PaO2 to the fraction of inspired oxygen [PaO2/FiO2]) 
c. Need for acute changes in the ventilator support system to enhance oxygenation, as determined by worsening oxygenation (ABG or PaO2/FiO2) or needed changes in the amount of positive end-expiratory pressure 
d. New onset of or increase in (quantity or characteristics) suctioned respiratory secretions, demonstrating evidence of inflammation and absence of contamination 
• All subjects must have at least 1 of the following signs: 
a. Documented fever (eg, core body temperature [tympanic, rectal, esophageal] greater than or equal to 38°C [100.4°F]) 
b. Hypothermia (eg, core body temperature [tympanic, rectal, esophageal] less than or equal to 35°C [95.0°F]) 
c. Leukocytosis with total peripheral white blood cell (WBC) count greater than or equal to 10,000 cells/mm3 
d. Leukopenia with total peripheralWBC count less than or equal to 4500 cells/mm3 
e. Greater than 15% immature neutrophils (bands) noted on peripheral blood smear 
• All subjects must have a chest radiograph during screening or have a previous chest radiograph within 48 hours prior to randomization showing the presence of new or progressive infiltrate(s) suggestive of bacterial pneumonia. A Computed Tomography scan in the same time window showing the same findings could also be acceptable • All subjects must have evidence of a Gram-negative bacterial infection involving the lower respiratory tract as documented by 1 or more of the following: 
a. Gram stain of lower respiratory secretions showing Gram-negative bacteria either alone or mixed with Gram-positive bacteria at or within 72 hours prior to randomization 
b. Microbiologic culture of respiratory tract secretions within 72 hours prior to randomization identifying Gram-negative aerobic bacteria 
c. Microbiologic culture (culture obtained to identify infection) from blood, urine, or skin identifying a Gram-negative aerobic bacterial pathogen within 72 hours prior to randomization 
d. Other diagnostic tests, including molecular tests, which provide evidence of Gram-negative bacterial infection of the lower respiratory tract 
e. Pneumonia highly suspected to be due to a Gram-negative bacteria based on prior antibiotic use or local epidemiologic evidence of Gram-negative infection outbreak
 
Key Exclusion Criteria:
• Subjects who have a known or suspected community-acquired bacterial pneumonia (CABP), atypical pneumonia, viral pneumonia, or chemical pneumonia (including aspiration of gastric contents, inhalation injury).
Other exclusions based on the prescribing information of meropenem or linezolid, the investigator’s brochure of S-649266, prior antibiotic usage, age, informed consent, and pregnancy are described in more detail in the protocol.
 

Interventional

S-649266 (INN: Cefiderocol)

S-649266, is a siderophore cephalosporin currently under development for the treatment of infections due to multi-drug resistant (MDR) and extensively drug resistant (XDR) Gram-negative bacteria, including Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia.
 
S-649266, 2 g, is to be administered intravenously q8h as a 3-hour infusion in subjects with normal renal function. Dose adjustment for renal function or dialysis is required, and the dosages established by clinical testing are presented in the protocol. The solution volume for infusion must be at least 100 mL.
 

Randomized

Double Blind

This is a randomized, double-blinded study. The investigator, site personnel, the sponsor, and the sponsor’s designees involved in blinded monitoring, data management, or other aspects of the study will be blinded to treatment assignment. The site pharmacist or qualified designee who will prepare the intravenous infusion solution will be unblinded so that he/she may obtain the assigned drug and prepare the intravenous dosing solutions. The drug supply itself will not be blinded.   Since this is a blinded study, S-649266 will be prepared and administered within the same timeframe after preparation as meropenem. The infusion bag containing a reconstituted study or comparator drug will be identified with the study number, subject’s identification number, and infusion rate but will not identify the specific drug product. For comparability of the study drug and the comparator drug meropenem, the dosing solutions will be normal saline and dosed within the time limits established for meropenem. Linezolid will not require blinding, and it will be labeled with the study number, subject’s identification number, and infusion rate and drug name.

Parallel

S-649266 is being developed to address the unmet medical need to treat carbapenem-resistant infections caused by Gram-negative bacteria, including Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia Independent of the underlying mechanism of carbapenem resistance. Although S-649266 was designed to have bacterial-killing ability for carbapenem-resistant species of Gram-negative bacteria, it also has improved bacterial-killing ability for common community-acquired Gram-negative infections as demonstrated by reduced minimum inhibitory concentration (MIC) values.

Phase III

33

Unspecified

Unspecified

07 Nov 2017

Utilization Utilization Info
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