serious urinary infections, bacterial pneumonia infections and/or blood infections known or suspected to be caused by carbapenem-resistant Enterobacteriaceae

Phase 1

• Conditions: serious infections, specifically complicated urinary tract infection (cUTI) or acute pyelonephritis (AP), hospital acquired bacterial pneumonia (HABP), ventilator associated bacterial pneumonia (VABP), and/or bacteremia, known or suspected to be caused by carbapenem-resistant Enterobacteriaceae (CRE); MedDRA version: 17.1Level: LLTClassification code 10003999Term: BacteremiaSystem Organ Class: 100000004862; MedDRA version: 17.1Level: LLTClassification code 10001032Term: Acute pyelonephritisSystem Organ Class: 100000004862; MedDRA version: 17.1Level: LLTClassification code 10004051Term: Bacterial pneumonia, unspecifiedSystem Organ Class: 100000004862; MedDRA version: 17.1Level: HLTClassification code 10046577Term: Urinary tract infectionsSystem Organ Class: 100000004862; Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

• Registration Number: EUCTR2014-000546-30-ES
• Lead Sponsor: Rempex Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-11-03
• Last Update Posted: 30 April 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

11.Willingness to comply with all study activities and procedures and to
provide signed, written informed consent prior to any study procedures.
If a subject is unable to provide informed consent due to their medical
condition, the subject's legal representative will be provided with study
information in order for consent to be obtained.
2.Hospitalized male or female, >18 years of age.
3.Weight >150 kg.
4.Have a confirmed diagnosis of a serious infection, specifically cUTI or AP, HABP, VABP, and/or bacteremia, requiring administration of IV antibacterial therapy (See inclusion number 7 for criteria for all
indications).
5.The following must be satisfied:
For known CRE infection:
-Have a known CRE infection based on evidence from CRE culture or
other phenotypic or molecular testing within 72 hours prior to Day 1,
alone or as a single isolate of a polymicrobial infection;
-Have received no more than 24 hours of a potentially effective (i.e.,
gram negative coverage) antimicrobial therapy prior to enrollment,
OR
-Have documented clinical evidence of failure (i.e., clinical deterioration
or failure to improve) while on a potentially effective regimen.
For suspected CRE infection:
-Have a suspected CRE infection based on evidence from CRE culture
(KPC producing) or other phenotypic or molecular testing, alone or as a
single isolate of a polymicrobial infection, from any source within 90
days prior to Day 1;
-Have received no more than 24 hours of a potentially effective (i.e.,
gram negative coverage) antimicrobial therapy prior to enrollment,
OR
-Have documented clinical evidence of failure (i.e., clinical deterioration
or failure to improve) while on a potentially effective regimen.
6.Expectation, in the opinion of the Investigator, that the subject's
infection will require treatment with IV antibiotics for a minimum of 7
days.
7.Diagnosis with either cUTI or AP, HABP, VABP, and/or bacteremia as
defined per protocol.
8.Female subjects of child-bearing potential, including those who are
less than 2 years post-menopausal, must agree to, and comply with,
using 2 highly effective methods of birth control (i.e., condom plus
spermicide, combined oral contraceptive, implant, injectable, indwelling
intrauterine device, sexual abstinence, or a vasectomized partner) while
participating in this study. In addition, all women of childbearing
potential must agree to continue to use 2 forms of birth control
throughout the study and for at least 30 days after administration of the
last dose of study drug.
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 60
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 90

Exclusion Criteria

1.History of any significant hypersensitivity or severe allergic reaction to any beta lactam antibiotics (e.g., cephalosporins, penicillins, carbapenems, or monobactams).
2.Known or suspected likely infection with New Delhi metallo- (NDM), Verona integron encoded metallo- (VIM), or IMP-metallo-beta-lactamases or oxacillinase- (OXA) beta lactamases (i.e., Class B or Class D beta lactamases).
3.For subjects to be enrolled with the primary indication of cUTI or AP, any of the following urologic conditions:
Likely to receive ongoing antibacterial drug prophylaxis after treatment of cUTI (e.g., subjects with vesico-ureteral reflux);
Suspected or confirmed prostatitis;
Requirement for bladder irrigation with antibiotics or for antibiotics to be administered directly via urinary catheter;
Previous or planned cystectomy or ileal loop surgery;
Uncomplicated urinary tract infection (for example, female subjects with urinary frequency, urgency or pain or discomfort without systemic symptoms or signs of infection);
Complete, permanent obstruction of the urinary tract;
Suspected or confirmed perinephric or renal corticomedullary abscess; or Polycystic kidney disease.
4.For subjects to be enrolled with the primary indication of HABP or VABP, any of the following conditions:
Diagnosis of ventilator-associated tracheobronchitis
Inability to obtain proper respiratory specimens for culture
5.For subjects to be enrolled with the indication of bacteremia unrelated to cUTI or AP, HABP, and VABP, any of the following:
Unverified CRE infection
Source of infection thought to be related to or involving a non removable or implantable device or line.
6.Impairment of renal function including a calculated creatinine clearance of <20 mL/min (Cockcroft-Gault), requirement for peritoneal dialysis, hemodialysis or hemofiltration, or oliguria (<20 mL urine output per hour over 24 hours).
7.Evidence of immediately life-threatening disease, including, but not limited to, acute heart failure, shock, acute coronary syndrome, unstable arrhythmias, hypertensive emergency, acute hepatic failure, active gastrointestinal bleeding, profound metabolic abnormalities (e.g., diabetic ketoacidosis), or acute cerebrovascular events, OR in the opinion of the Investigator, the subject is unlikely to survive the duration of the treatment.
8.Myasthenia gravis, Parkinsonism, or other neuromuscular disorder.
9.Acute Physiology and Chronic Health Evaluation (APACHE) II score >30. An APACHE II score is only required if calculated.
10.Known or suspected endocarditis, meningitis, intra-abdominal infection, or osteomyelitis.
11.Unremovable or implantable device or line thought to be the potential source of infection.
12.Evidence of significant hepatic, hematological, or immunologic disease or dysfunction determined by any of the following:
Known acute viral hepatitis;
Aspartate aminotransferase or alanine aminotransferase level >5 × upper limit of normal (ULN) or total bilirubin >3 × ULN;
Manifestations of end-stage liver disease, such as ascites or hepatic encephalopathy;
Current or anticipated neutropenia defined as <500 neutrophils/mm3;
Thrombocytopenia with platelet count <60,000 cells/mm3;
Human immunodeficiency virus with either a CD4 count <200 cells/mm3 at the last measurement, or current diagnosis of another Acquired Immune Deficiency Syndrome-defining illness;
Bone marrow-ablative chemotherapy or radiation therapy within the prior 3 months; or Requiring chronic treatmen

Study & Design

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