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: 100000015664; MedDRA version: 20.0 Level: LLT Classification code 10065153 Term: Ventilator associated pneumonia System Organ Class: 100000015664; MedDRA version: 20.0 Level: HLT Classification code 10046577 Term: Urinary tract infections System Organ Class: 100000005053; Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

• Registration Number: EUCTR2015-004703-23-FR
• Lead Sponsor: Shionogi Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-09-21
• Last Update Posted: 30 June 2019

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 up to 14 days after the last dose of study drug
•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 documented 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 with severe neutropenia, ie, polymorphonuclear neutrophils (PMNs) < 100 cells/µL
3.Patients with Acute Physiology and Chronic Health Evaluation II (APACHE II) score > 30
4.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
5.Patients meeting specific exclusion criteria for each infection site

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified