complicated urinary tract infection (cUTI). MedDRA version: 20.0 Level: HLT Classification code 10046577 Term: Urinary tract infections System Organ Class: 100000004862
Conditions
Interventions
Product Name: HY001
Product Code: HY001
Pharmaceutical Form: Powder and solution for solution for injection
INN or Proposed INN: ZIDOVUDINE
CAS Number: 30516-87-1
Concentration unit: mg milligram(s)
C
Sponsors
Helperby Therapeutics Ireland Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Hospitalised patients with cUTI (with or without pyelonephritis) or AP at risk for infection with MDR Gram-negative pathogens, and who have provided written informed consent and willing and able to comply with all study procedures and activities 2. Patients who could receive CMS treatment as part of their standard care 3. Age =18 years and 38.0 C) b. Flank pain (pyelonephritis) or pelvic pain c. Nausea or vomiting d. Dysuria, urinary frequency, or urinary urgency e. Costo-vertebral angle tenderness (pyelonephritis) on physical examination 7. Provide a pretreatment adequate urine sample (the urine sample must return a positive culture for the patient to remain eligible for the study) obtained before administration of study drug or administration of any potentially effective antibiotic therapy against Gram-negative pathogens. A positive urine culture is defined as =10^5 CFU/mL of a causative uropathogen a. If the patient’s pretreatment culture shows the presence of a colistin resistant or colistin intermediate susceptible pathogens after the patient has been enrolled, the Investigator must decide according to clinical signs and symptoms whether the patient can remain in the study b. In the event of a negative urine culture, the patient must be prematurely discontinued from study drug and switched to standard-of-care treatment. A negative urine culture is one in which a pathogen with <10^5 CFU/mL is present c. A urine culture is defined as contaminated if =1 causative pathogen with =10^5 CFU/mL is present AND =1 nonpathogen =10^5 CFU/mL are present 8. Have pyuria (ie, a dipstick analysis positive for leukocyte esterase or =10 white blood cells (WBCs) per cubic millimetre [1 µl]) in unspun urine, or =10 WBCs per high power field in spun urine 9. Be considered ill enough to be hospitalised for =5 days and require the initiation of parenteral therapy to manage cUTI by the standard of care 10. Contraception in women of childbearing potential must have been used for =2 months before starting the study; a documented negative highly sensitive serum pregnancy test must be provided and the patient must be nonlactating 11. If of non-childbearing potential, must be postmenopausal (ie, has had amenorrhea for =12 consecutive months) or surgically sterile for =6 months due to bilateral tubal ligation, bilateral oophorectomy, or hysterectomy 12. If of childbearing potential, agree to use a highly effective method of contraception, preferably with low use
Exclusion criteria
Exclusion criteria: 1.Patient has a confirmed or suspected fungal or anaerobic UTI, or UTI caused by a Gram-positive pathogen or UTI caused by a pathogen kown or suspected to be intrinsically resistant to colistin;2.Patients with asymptomatic bacteriuria, the presence of >10^5 CFU/mL of a causative pathogen, and pyuria, but without local or systemic symptoms;3.Patient is receiving haemodialysis or peritoneal dialysis or has impairment of renal function including an estimated glomerular filtration rate 14 days of study drug;12.Any patient receiving a long-acting antibiotic with potentially effective Gram-negative activity or >1 dose of any antibiotic with potentially effective Gram-negative activity, within 72 hours before the first dose of study drug; 13.Previous participation in a clinical trial or treatment with investigational medication within the last 4 weeks or =5 half-lives, whichever is shorter, before starting study drug or patients who have not recovered from side effects of such investigational therapy; 14.Significantly immunocompromised (defined as a WBC <1000/µL) and/or having a known infection with human immunodeficiency virus (HIV);15.Any haematological malignancy, bone marrow transplantation, or current immunosuppressive therapy (including but not limited to cancer chemotherapy, or medications for prevention of organ transplantation rejection) or current treatment with reverse transcriptase inhibitors with Gram-negative activity; 16.Any concomitant psychiatric, neurological, or behavioural disorder including epilepsy or other lesions of the central nervous system sufficient in the opinion of the Investigator to prevent or compromise the patient’s participation in the study; 17.Any known concomitant bacterial or fungal sexually transmitted disease, except for candidiasis; 18.Having, in the opinion of the Investigator, any clinically significant serious or unstable physical illness likely to impact on the patient’s wellbeing or the conduct and analysis of the study, including, but not limited to, acute hepatic failure, respiratory failure, severe, persistent diarrhoea and septic shock; 19.Any malignant disease or a history of malignant neoplasm requiring a treatment with immune suppressive properties in the past 6 months before baseline; 20.Known history of drug or alcohol abuse; 21.Clinically significant abno
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the composite outcome of clinical success and microbiologic success of intravenous (IV) HY-001 versus standard doses of colistin methanesulfonate (CMS; prodrug of colistin) monotherapy in patients with complicated urinary tract infection (cUTI) (with or without pyelonephritis) or acute uncomplicated pyelonephritis (AP) at risk for infection with multidrug resistant (MDR, according to Magiorakos 2012) Gram-negative pathogens in the microbiological Intent-to-Treat (microbiological-ITT) Population at Test-of-Cure (TOC) (approximately 7 days following the End-of-Treatment [EOT]).;Secondary Objective: Secondary: •To assess the safety and tolerability of IV HY-001 •To determine plasma and urine drug concentrations in a population of patients at various times. •To assess microbiological and clinical response for each pathogen isolated at baseline and for each patient based on culture data obtained during treatment at Early Assessment (EA), EOT, and at Late Follow-up (LFU). Exploratory: Exposure-response relationship with regards to the antimicrobial activity of HY-001 and CMS alone ;Primary end point(s): Primary endpoint is the combined outcome of clinical and microbiological response in the microbiological-ITT Population at TOC. To have an overall response, the patient must be both a clinical and microbiological success.;Timepoint(s) of evaluation of this end point: Test of cure (ToC) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Primary endpoint is the combined outcome of clinical and microbiological response in the microbiological-ITT Population at TOC. To have an overall response, the patient must be both a clinical and microbiological success.;Timepoint(s) of evaluation of this end point: Early Assessment (EA; Day 4 or 5), End of Therapy (EOT, 7-14 days after start of therapy), Late Follow-up (LFU, 14 days after EOT) | — |
Countries
Poland
Contacts
Public ContactHelperby Therapeutics Ireland Limit
Prof Anthony Coates, BSc, FRCP, MD, FRCPath -Helperby Therapeutics Ireland Limited
Outcome results
None listed