Study of S-649266 or Best Available Therapy for the Treatment of Severe Infections Caused by Carbapenem-resistant Gram-negative Pathogens

Phase 1

Conditions: Hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP)/healthcare-associated pneumonia (HCAP) or bloodstream infections/sepsis (BSI/sepsis) caused by carbapenem-resistant Gram-negative pathogens. Complicated urinary tract infection (cUTI) caused by carbapenem-resistant Gram-negative pathogens.
MedDRA version: 20.0 Level: SOC Classification code 10021881 Term: Infections and infestations System Organ Class: 10021881 - Infections and infestations
MedDRA version: 20.0 Level: LLT Classification code 10076918 Term: Hospital acquired pneumonia System Organ Class: 10021881 - Infections and infestations
MedDRA version: 20.1 Level: LLT Classification code 10065153 Term: Ventilator associated pneumonia System Organ Class: 10021881 - Infections and infestations
MedDRA version: 20.0 Level: HLT Classification code 10046577 Term: Urinary tract infections System Organ Class: 10021881 - Infections and infestations
Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

Registration Number: EUCTR2015-004703-23-HR

Lead Sponsor: Shionogi B.V.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 150

Inclusion 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 was 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 regimen and failed treatment, both clinically and microbiologically, are eligible for the study, if they have an identified carbapenem-resistant, Gram-negative pathogen which has either been shown to be nonsusceptible in vitro to each of the antibiotic(s) of the empiric antibiotic regimen or been grown from a culture performed after at least two days of the empiric antibiotic regimen
5. Patient is male (no contraception required) or female and meets one of the following criteria:
•Surgically sterile by hysterectomy and/or bilateral oophorectomy or bilateral salpingectomy or tubal ligation for the purpose of contraception for at least 6 weeks with appropriate documentation of such surgery
•Postmenopausal (defined as older than 45 years of age with cessation of regular menstrual periods for 6 months and confirmed by a follicle-stimulating hormone level of > 40 mIU/ml, or amenorrhea for at least 12 months)
•Of childbearing potential and using combined (estrogen and progestogen) or progestogen-only hormonal contraception associated with inhibition of ovulation (including oral, intravaginal, injectable, implantable, and transdermal contraceptives), or an intrauterine device (IUD), or intrauterine hormone-releasing system (IUS) for the entire duration of the study
•Of childbearing potential and practice abstinence as a preferred and usual lifestyle, and agrees to continue practicing abstinence from screening and for the entire duration of the study
•Of childbearing potential, whose sole heterosexual partner has been successfully vasectomized and agrees to not have other heterosexual partners for the entire duration of the study
6. Patients meeting specific inclusion criteria for each infection site
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 75
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 75

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 history of any moderate or severe hypersensitivity or allergic reaction to any ß-lactam (Note: for ß-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 coinfection caused by invasive aspergillosis, mucormycosis or other highly lethal mold
4. Patients who have central nervous system 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 moderate to severe bronchiectasis
7. Patients in refractory septic shock defined as persistent hypotension despite adequate fluid resuscitation or despite vasopressive therapy at the time of randomization
8. Patients with severe neutropenia, ie, polymorphonuclear neutrophils (PMNs) < 100 cells/µL
9. Female patients who have a positive pregnancy test at Screening or who are lactating
10. Patients with Acute Physiology and Chronic Health Evaluation II (APACHE II) score > 30
11. Patients who have received a potentially effective antibiotic regimen for the carbapenem-resistant, Gram-negative infection for a continuous duration of more than 24 hours in cUTI, or 36 hours in HAP/VAP/HCAP or BSI/sepsis during the 72 hours leading 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 who have received another investigational drug or device within 30 days prior to study entry
14. Patients who have previously been randomized in this study or received S-649266
15. Patients receiving peritoneal dialysis
16. Patients meeting specific exclusion criteria for each infection site (See Diagnosis-Specific Exclusion Criteria)

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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