A randomized, double-blind double-dummy Phase 3 study performed at multiple study sites to evaluate the safety, efficacy and tolerability of the combinational product Carbavance (Meropenem/RPX7009) in comparison to Piperacillin/Tazobactam which is already approved in many countries to treat patients with complicated urinary tract infections, including acute pyelonephritis, in adults.
- Conditions
- complicated urinary tract infection (cUTI) or acute pyelonephritis (AP) with or without concurrent bacteremiaMedDRA version: 19.0Level: PTClassification code 10037597Term: Pyelonephritis acuteSystem Organ Class: 10021881 - Infections and infestationsMedDRA version: 19.0Level: HLTClassification code 10046577Term: Urinary tract infectionsSystem Organ Class: 10021881 - Infections and infestationsTherapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]
- Registration Number
- EUCTR2014-000545-78-PL
- Lead Sponsor
- Rempex Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 500
1. A signed informed consent form, the ability to understand the study conduct and tasks that are required for study participation, and a willingness to cooperate with all tasks, tests, and examinations as required by the protocol.
2. Male or female = 18 years of age.
3. Weight = 185 kg.
4. Expectation, in the judgment of the Investigator, that the subject's cUTI or AP requires initial treatment with at least 5 days of IV
antibiotics.
5. Documented or suspected cUTI or AP as defined in the protocol.
6. Expectation, in the judgment of the Investigator, that any indwelling urinary catheter or instrumentation (including nephrostomy tubes and/or indwelling stents) will be removed or replaced (if removal is not clinically acceptable) before or as soon as possible, but not longer than 12 hours, after randomization.
7. Expectation, in the judgment of the Investigator, that the subject will survive with effective antibiotic therapy and appropriate supportive care
for the anticipated duration of the study.
8. Women of childbearing potential must have a negative pregnancy test before randomization, and be willing to use a highly effective method of
contraception between randomization and for 7 days after the completion of the study. A highly effective method of contraception includes two of the following: hormonal implants/patch, injectable hormones, oral hormonal contraceptives, prior bilateral oophorectomy, prior hysterectomy, prior bilateral tubal ligation, intra-uterine device, approved cervical ring, condom, true abstinence (if approved by the Investigator), or a vasectomized partner.
9. Willingness to comply with all the study procedures, whether in the hospital or after discharge, for the duration of the study.
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 300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 200
1. Presence of any of the following conditions: a. Perinephric abscess; b. Renal corticomedullary abscess; c. Uncomplicated UTI; d. Polycystic kidney disease; e. Chronic vesicoureteral reflux; f. Previous or planned renal transplantation; g. Subjects receiving hemodialysis; h. Previous or planned cystectomy or ileal loop surgery; or i. Known candiduria.
2. Presence of suspected or confirmed acute bacterial prostatitis, orchitis, epididymitis, or chronic bacterial prostatitis as determined by history and/or physical examination.
3. Gross hematuria requiring intervention other than administration of study drug.
4. Urinary tract surgery within 7 days prior to randomization or urinary tract surgery planned during the study period (except surgery required to relieve an obstruction or place a stent or nephrostomy).
5. Renal function at screening as estimated by creatinine clearance <30 mL/min using the Cockcroft-Gault formula.
6. Known non-renal source of infection such as endocarditis, osteomyelitis, abscess, meningitis, or pneumonia diagnosed within 7 days prior to randomization.
7. Any of the following signs of severe sepsis: a. Shock or profound hypotension defined as systolic blood pressure <90 mmHg or a decrease of >40 mmHg from baseline (if known) that is not responsive to fluid challenge; b. Hypothermia (oral or tympanic temperature <35.6°C [<96.1°F] or rectal/core temperature <35.9°C [<96.6°F]); c. Disseminated intravascular coagulation as evidenced by prothrombin time or partial thromboplastin time ?2 × the upper limit of normal (ULN) or platelets <50% of the lower limit of normal.
8. Pregnant or breastfeeding women.
9. History of epilepsy or known seizure disorder requiring current treatment with anti-seizure medication.
10. Treatment within 30 days prior to enrollment with valproic acid.
11. Treatment within 30 days prior to enrollment with probenecid.
12. Treatment within 30 days prior to enrollment with any cancer chemotherapy, immunosuppressive medications for transplantation, or medications for rejection of transplantation.
13. Evidence of significant hepatic disease or dysfunction, including known acute viral hepatitis or hepatic encephalopathy.
14. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 × ULN, or total bilirubin > 1.5 × ULN.
15. Receipt of any investigational medication or investigational device during the last 30 days prior to randomization.
16. Prior exposure to RPX7009 alone or in combination with another product.
17. Receipt of any potentially therapeutic antibiotic agent within 48 hours before randomization. EXCEPTIONS: a) Subjects who received a single dose of a short-acting oral or IV antibiotic (dosed q4h, q6h or q8h with normal renal function). b) Subjects who received >48 hours of prior systemic antibiotic therapy for the current episode of cUTI with unequivocal clinical evidence of treatment failure (i.e., worsening signs and symptoms). c) Subjects who develop signs and symptoms of cUTI or AP while on antibiotics for another indication.
18. Requirement at time of enrollment for any reason for additional systemic antibiotic therapy (other than study drug) or antifungal therapy. Topical antifungal or a single oral dose of any antifungal treatment for vaginal candidiasis will be allowed.
19. Likely to require the use of an antibiotic for cUTI prophylaxis during the subject's participation in the study (from enrollment through the LFU visit).
20. Known history of human immunodefi
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the efficacy of Carbavance (meropenem/RPX7009) administered by IV infusion in subjects with cUTI or acute pyelonephritis (AP);<br><br>To assess the safety and tolerability of Carbavance (meropenem/RPX7009) administered by IV infusion in subjects with cUTI or AP; and<br><br>To assess the population PK of meropenem and RPX7009 in subjects with cUTI or AP.;Secondary Objective: Not applicable;Primary end point(s): Primary Endpoint for EMA<br>The primary efficacy endpoint for this study for the European Medicines Agency (EMA) will be the proportion of subjects in the co-primary m-<br>MITT and ME Populations who achieve a microbiologic outcome of Eradication at the TOC visit.<br>A microbiologic outcome of Eradication is defined as the demonstration that the bacterial pathogen(s) found at baseline is reduced to <103<br>CFU/mL of urine.<br>;Timepoint(s) of evaluation of this end point: LPLV
- Secondary Outcome Measures
Name Time Method