Clinical Trials List
Protocol Number1424R2131
NCT Number(ClinicalTrials.gov Identfier)NCT02714595
2016-08-01 - 2018-12-31
Phase III
Terminated7
ICD-9041.89
Other specified bacterial infections of unspecified site
A Multicenter, Randomized, Open-label Clinical Study of S-649266 or Best Available Therapy for the Treatment of Severe Infections Caused by Carbapenem-resistant Gram-negative Pathogens
-
Trial Applicant
Pharmaceutical Research Associates Taiwan Inc.
-
Sponsor
Shionogi & Co., Ltd.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 湯宏仁 無
- 杜漢祥 無
- Wei-Ting Chang 未分科
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Yu-Chao Lin 無
- 梁信杰 無
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 趙文震 無
- Pin-Kuei Fu 無
- 王俊隆 無
- YEN-HSIANG HUANG 無
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- - - 無
- Jann-Tay Wang 無
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Condition/Disease
carbapenem-resistant Gram-negative bacterial infections
Objectives
Primary Objectives:
● To assess, at TOC, the clinical outcome of treatment with S-649266
or best available therapy (BAT) in adult patients with either HAP/ VAP /HCAP or bloodstream infections/sepsis (BSI/sepsis) caused by carbapenem-resistant Gram-negative pathogens
● To assess, at TOC, the microbiologic outcome of treatment with S-649266 or
BAT in adult patients with cUTI caused by carbapenem-resistant Gram-negative pathogens
Test Drug
S-649266
Active Ingredient
S-649266
Dosage Form
Injection vial
Dosage
1
Endpoints
Efficacy Assessment:
Both clinical and microbiological outcomes will be assessed by the investigator at EA,
EOT, TOC, and FUP. In case treatment duration is extended beyond 14 days, an
additional clinical outcome will be assessed on Day 14.
Safety Assessments:
Subject safety will be assessed daily while the subject is hospitalized and specifically at
EOT, TOC, and FUP evaluation by the identification of adverse events (AEs) defined as
new or worsening symptoms since the time of randomization. In case treatment duration
is extended beyond 14 days, additional safety assessments will be conducted on Day 14.
Safety surveillance will extend to up to 28 days after the last dose of the study drug.
Clinical laboratory tests of blood chemistry, hematology, and urinalysis will be
performed at Screening, EA, EOT, TOC, and FUP. In addition, an electrocardiogram
(ECG) will be performed at Screening/baseline and at EA. Vital signs including body
temperature and AEs will be recorded daily.
Pharmacokinetic Assessments:
All subjects treated with S-649266 will have blood drawn for sparse pharmacokinetic
(PK) sampling of plasma concentrations of study drug. The actual sampling date and
time will be recorded. PK blood sampling will occur on Day 3 (after at least 6 doses of
drug) at 4 timepoints: (1) just prior to the start of infusion, (2) 1 hour after start of
infusion, (3) at the end of infusion, and (4) 1 hour after the end of the infusion.
Patients with non-stable renal function resulting in a dosage adjustment (dose or interval)
at EA will undergo repeated blood PK sampling 24 to 72 hours after their dosing
adjustment. The timing for PK blood draws is same as above timing on Day 3.
If possible, a single blood sampling should be performed as soon as possible at EOT in
case of premature EOT.
Both clinical and microbiological outcomes will be assessed by the investigator at EA,
EOT, TOC, and FUP. In case treatment duration is extended beyond 14 days, an
additional clinical outcome will be assessed on Day 14.
Safety Assessments:
Subject safety will be assessed daily while the subject is hospitalized and specifically at
EOT, TOC, and FUP evaluation by the identification of adverse events (AEs) defined as
new or worsening symptoms since the time of randomization. In case treatment duration
is extended beyond 14 days, additional safety assessments will be conducted on Day 14.
Safety surveillance will extend to up to 28 days after the last dose of the study drug.
Clinical laboratory tests of blood chemistry, hematology, and urinalysis will be
performed at Screening, EA, EOT, TOC, and FUP. In addition, an electrocardiogram
(ECG) will be performed at Screening/baseline and at EA. Vital signs including body
temperature and AEs will be recorded daily.
Pharmacokinetic Assessments:
All subjects treated with S-649266 will have blood drawn for sparse pharmacokinetic
(PK) sampling of plasma concentrations of study drug. The actual sampling date and
time will be recorded. PK blood sampling will occur on Day 3 (after at least 6 doses of
drug) at 4 timepoints: (1) just prior to the start of infusion, (2) 1 hour after start of
infusion, (3) at the end of infusion, and (4) 1 hour after the end of the infusion.
Patients with non-stable renal function resulting in a dosage adjustment (dose or interval)
at EA will undergo repeated blood PK sampling 24 to 72 hours after their dosing
adjustment. The timing for PK blood draws is same as above timing on Day 3.
If possible, a single blood sampling should be performed as soon as possible at EOT in
case of premature EOT.
Inclution Criteria
General Inclusion Criteria:
Patients who fulfill the following criteria at Screening will be included in the study:
1. Hospitalized male and female patients, 18 years or older at the time of signing
informed consent
2. Patients 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 patient unable to comprehend or sign the informed consent is
allowed to be enrolled in the study)
3. Patients with clinically documented infection (HAP/VAP/HCAP, cUTI, or
BSI/sepsis) caused by a Gram-negative pathogen with evidence of carbapenem
resistance
4. Patients who have been treated previously with an empiric antibiotic other than
the study medications, but failed treatment, both clinically and microbiologically,
are eligible for the study if they have an identified pathogen which is nonsusceptible to the empiric treatment and is a carbapenem-resistant Gram-negative
pathogen before entering this study.
5. Male patients who are sterile or who agreed to use an appropriate method of
contraception (including use of a condom with spermicide) from Screening up to
28 days after EOT or according to country specific requirements, whichever is
longer or female patients who are surgically sterile by hysterectomy and/or
bilateral oophorectomy with appropriate documentation of such surgery, are
postmenopausal (defined as cessation of regular menstrual periods for 2 years or
more and confirmed by a follicle-stimulating hormone test), or females of
childbearing potential who agree to use barrier contraception (including condom,
diaphragm, or cervical cap) with spermicide or who agree to use a highlyeffective method of contraception (including contraceptive implant, injectable
contraceptive, combination oral contraceptive, intrauterine contraceptive device,
and vasectomized partner) from Screening up to 28 days after EOT or according
to country specific requirements, whichever is longer
6. Patients meeting specific criteria for each infection site (See Diagnosis Specific
Inclusion and Exclusion Criteria)
Patients who fulfill the following criteria at Screening will be included in the study:
1. Hospitalized male and female patients, 18 years or older at the time of signing
informed consent
2. Patients 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 patient unable to comprehend or sign the informed consent is
allowed to be enrolled in the study)
3. Patients with clinically documented infection (HAP/VAP/HCAP, cUTI, or
BSI/sepsis) caused by a Gram-negative pathogen with evidence of carbapenem
resistance
4. Patients who have been treated previously with an empiric antibiotic other than
the study medications, but failed treatment, both clinically and microbiologically,
are eligible for the study if they have an identified pathogen which is nonsusceptible to the empiric treatment and is a carbapenem-resistant Gram-negative
pathogen before entering this study.
5. Male patients who are sterile or who agreed to use an appropriate method of
contraception (including use of a condom with spermicide) from Screening up to
28 days after EOT or according to country specific requirements, whichever is
longer or female patients who are surgically sterile by hysterectomy and/or
bilateral oophorectomy with appropriate documentation of such surgery, are
postmenopausal (defined as cessation of regular menstrual periods for 2 years or
more and confirmed by a follicle-stimulating hormone test), or females of
childbearing potential who agree to use barrier contraception (including condom,
diaphragm, or cervical cap) with spermicide or who agree to use a highlyeffective method of contraception (including contraceptive implant, injectable
contraceptive, combination oral contraceptive, intrauterine contraceptive device,
and vasectomized partner) from Screening up to 28 days after EOT or according
to country specific requirements, whichever is longer
6. Patients meeting specific criteria for each infection site (See Diagnosis Specific
Inclusion and Exclusion Criteria)
Exclusion Criteria
General Exclusion Criteria:
Patients who meet any of the following criteria at Screening will be excluded from the
study:
1. Patients who have a documented history of any moderate or severe
hypersensitivity or allergic reaction to any β-lactam (Note: for β-lactams, a history
of a mild rash followed by uneventful re-exposure is not a contraindication to
enrollment)
2. Patients who need more than 3 systemic antibiotics as part of BAT for the
treatment of the Gram-negative infection (Patients with mixed Gram-positive or
anaerobic infections may receive appropriate concomitant narrow spectrum
antibiotics [eg, vancomycin, linezolid, metronidazole, clindamycin])
3. Patients with co-infection caused by invasive aspergillosis, mucormycosis or
other highly lethal mold
4. Patients who have CNS infection (eg, meningitis, brain abscess, shunt infection)
5. Patients with infection requiring > 3 weeks of antibiotic treatment (eg, bone and
joint infection, endocarditis)
6. Patients with cystic fibrosis or bronchiectasis
7. Patients in refractory septic shock defined as persistent hypotension despite
adequate fluid resuscitation or vasopressive therapy at the time of randomization
8. Patients with severe neutropenia, ie, white blood cell (WBC) < 100 cells/µL
9. Female patients who have a positive pregnancy test at screening or who are
lactating
10. Patients with APACHE II > 30
11. Patients who have received potentially effective antibiotic therapy for the
carbapenem-resistant Gram-negative infections for a continuous duration of more
than 24 hours in cUTI, 36 hours in HAP/VAP/HCAP or BSI/sepsis during the
previous 72 hours prior to randomization
12. Patients with any condition or circumstance that, in the opinion of the
investigator, would compromise the safety of the patient or the quality of the
study data
13. Patients requires continuing treatment with methotrexate, procainamide, or
probenecid
14. Patients who have received another investigational drug or device within 30 days
prior to study entry
15. Patients who have previously been randomized in this study or received S-649266
Patients who meet any of the following criteria at Screening will be excluded from the
study:
1. Patients who have a documented history of any moderate or severe
hypersensitivity or allergic reaction to any β-lactam (Note: for β-lactams, a history
of a mild rash followed by uneventful re-exposure is not a contraindication to
enrollment)
2. Patients who need more than 3 systemic antibiotics as part of BAT for the
treatment of the Gram-negative infection (Patients with mixed Gram-positive or
anaerobic infections may receive appropriate concomitant narrow spectrum
antibiotics [eg, vancomycin, linezolid, metronidazole, clindamycin])
3. Patients with co-infection caused by invasive aspergillosis, mucormycosis or
other highly lethal mold
4. Patients who have CNS infection (eg, meningitis, brain abscess, shunt infection)
5. Patients with infection requiring > 3 weeks of antibiotic treatment (eg, bone and
joint infection, endocarditis)
6. Patients with cystic fibrosis or bronchiectasis
7. Patients in refractory septic shock defined as persistent hypotension despite
adequate fluid resuscitation or vasopressive therapy at the time of randomization
8. Patients with severe neutropenia, ie, white blood cell (WBC) < 100 cells/µL
9. Female patients who have a positive pregnancy test at screening or who are
lactating
10. Patients with APACHE II > 30
11. Patients who have received potentially effective antibiotic therapy for the
carbapenem-resistant Gram-negative infections for a continuous duration of more
than 24 hours in cUTI, 36 hours in HAP/VAP/HCAP or BSI/sepsis during the
previous 72 hours prior to randomization
12. Patients with any condition or circumstance that, in the opinion of the
investigator, would compromise the safety of the patient or the quality of the
study data
13. Patients requires continuing treatment with methotrexate, procainamide, or
probenecid
14. Patients who have received another investigational drug or device within 30 days
prior to study entry
15. Patients who have previously been randomized in this study or received S-649266
The Estimated Number of Participants
-
Taiwan
20 participants
-
Global
150 participants
