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 Gramnegative pathogens.Complicated urinary tract infection (cUTI) caused by carbapenemresistant Gram-negative pathogens.; MedDRA version: 20.0Level: LLTClassification code 10076918Term: Hospital acquired pneumoniaSystem Organ Class: 10021881 - Infections and infestations; MedDRA version: 20.0Level: SOCClassification code 10021881Term: Infections and infestationsSystem Organ Class: 10021881 - Infections and infestations; MedDRA version: 20.1Level: LLTClassification code 10065153Term: Ventilator associated pneumoniaSystem Organ Class: 10021881 - Infections and infestations; MedDRA version: 20.0Level: HLTClassification code 10046577Term: Urinary tract infectionsSystem Organ Class: 10021881 - Infections and infestations; Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

• Registration Number: EUCTR2015-004703-23-IT
• Lead Sponsor: SHIONOGI LIMITED

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-02-05
• Study Completion: 2019-04-22
• Last Update Posted: 12 March 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 152

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 folliclestimulating 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

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 Grampositive or anaerobic infections may receive appropriate concomitant narrowspectrum 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