Clinical Trials List
Protocol NumberRempex-505
NCT Number(ClinicalTrials.gov Identfier)NCT02166476
2015-01-02 - 2016-06-30
Phase III
Terminated4
ICD-10N39.0
Urinary tract infection, site not specified
ICD-9599.0
Urinary tract infection, site not specified
A Phase 3, Multi-Center, Randomized, Double-Blind, Double-Dummy Study to Evaluate the Efficacy, Safety, and Tolerability of Carbavance (Meropenem/RPX7009) Compared to Piperacillin/Tazobactam in the Treatment of Complicated Urinary Tract Infections, Including Acute Pyelonephritis, in Adults
-
Trial Applicant
MEDPACE TAIWAN LIMITED
-
Sponsor
Rempex Pharmaceuticals, Inc.,
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 林蔚如 Division of Infectious Disease
- Chung-Hao Huang Division of Infectious Disease
- 謝旻翰 Division of Infectious Disease
- Po-Liang Lu Division of Infectious Disease
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Cheng-Kuang Yang Division of Urology
- Cheng-Che Chen Division of Urology
- Shian-Shiang Wang Division of Urology
- 蔡哲安 Division of Urology
- 洪啟峰 Division of Urology
- 歐宴泉 Division of Urology
- Jian-Ri Li Division of Urology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Un-in Wu Division of Infectious Disease
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Complicated Urinary Tract Infections, Including Acute Pyelonephritis, in Adults
Objectives
The objectives of the study are the following:
• To assess the efficacy of Carbavance (meropenem/RPX7009) administered
by intravenous (IV) infusion in subjects with cUTI or AP;
• To assess the safety and tolerability of Carbavance (meropenem/RPX7009)
administered by IV infusion in subjects with cUTI or AP; and
• To assess the population pharmacokinetics (PK) of meropenem and
RPX7009 in subjects with cUTI or AP.
Test Drug
Carbavance（meropenem/RPX7009）
Active Ingredient
meropenem/RPX7009
Dosage Form
Injection
Dosage
2g meropenem with 2g RPX7009
Endpoints
Primary Endpoint for FDA
The primary efficacy endpoint for this study for the Food and Drug
Administration (FDA) will be the proportion of subjects in the m-MITT
Population who achieve overall success at the EOIVT visit.
Overall success is achieved with a clinical outcome of Cure or Improvement and
microbiologic outcome of Eradication at EOIVT. A clinical outcome of Cure at
the EOIVT visit is defined as the complete resolution or significant improvement
of the baseline signs and symptoms of cUTI or AP. A clinical outcome of
Improvement at the EOIVT visit is defined as lessening, incomplete resolution, or
no worsening of the baseline signs and symptoms of cUTI or AP. A
microbiologic outcome of Eradication is defined as the demonstration that the
bacterial pathogen(s) found at baseline is reduced to <104
CFU/mL of urine.
Primary Endpoint for EMA
The primary efficacy endpoint for this study for the European Medicines Agency
(EMA) will be the proportion of subjects in the co-primary m-MITT and ME
Populations who achieve a microbiologic outcome of Eradication at the TOC
visit.
A microbiologic outcome of Eradication is defined as the demonstration that the
bacterial pathogen(s) found at baseline is reduced to <103
CFU/mL of urine.
Secondary Endpoints
The secondary endpoints for this study are the following:
• Proportion of subjects in the m-MITT Population with overall success at both
the EOIVT and TOC visits;
• Proportion of subjects in the m-MITT and ME Populations with a
microbiologic outcome of Eradication to <104
CFU/mL of urine for FDA and
<103
CFU/mL of urine for EMA at Day 3, EOIVT, EOT, TOC, and LFU;
• Proportion of subjects with a clinical outcome of Cure in the m-MITT, CE,
and ME Populations at Day 3, EOIVT, EOT, TOC, and LFU;
• Per-pathogen outcome in the m-MITT and ME Populations at Day 3, EOIVT,
EOT, TOC, and LFU;
• Pharmacokinetic characterization of plasma exposure of meropenem and
RPX7009; and
• Safety and tolerability profile of Carbavance (meropenem/RPX7009) by
incidence and severity of adverse events and serious adverse events, vital
signs, clinical laboratory tests, electrocardiograms (ECGs), and physical
examinations in the Safety Population.
The primary efficacy endpoint for this study for the Food and Drug
Administration (FDA) will be the proportion of subjects in the m-MITT
Population who achieve overall success at the EOIVT visit.
Overall success is achieved with a clinical outcome of Cure or Improvement and
microbiologic outcome of Eradication at EOIVT. A clinical outcome of Cure at
the EOIVT visit is defined as the complete resolution or significant improvement
of the baseline signs and symptoms of cUTI or AP. A clinical outcome of
Improvement at the EOIVT visit is defined as lessening, incomplete resolution, or
no worsening of the baseline signs and symptoms of cUTI or AP. A
microbiologic outcome of Eradication is defined as the demonstration that the
bacterial pathogen(s) found at baseline is reduced to <104
CFU/mL of urine.
Primary Endpoint for EMA
The primary efficacy endpoint for this study for the European Medicines Agency
(EMA) will be the proportion of subjects in the co-primary m-MITT and ME
Populations who achieve a microbiologic outcome of Eradication at the TOC
visit.
A microbiologic outcome of Eradication is defined as the demonstration that the
bacterial pathogen(s) found at baseline is reduced to <103
CFU/mL of urine.
Secondary Endpoints
The secondary endpoints for this study are the following:
• Proportion of subjects in the m-MITT Population with overall success at both
the EOIVT and TOC visits;
• Proportion of subjects in the m-MITT and ME Populations with a
microbiologic outcome of Eradication to <104
CFU/mL of urine for FDA and
<103
CFU/mL of urine for EMA at Day 3, EOIVT, EOT, TOC, and LFU;
• Proportion of subjects with a clinical outcome of Cure in the m-MITT, CE,
and ME Populations at Day 3, EOIVT, EOT, TOC, and LFU;
• Per-pathogen outcome in the m-MITT and ME Populations at Day 3, EOIVT,
EOT, TOC, and LFU;
• Pharmacokinetic characterization of plasma exposure of meropenem and
RPX7009; and
• Safety and tolerability profile of Carbavance (meropenem/RPX7009) by
incidence and severity of adverse events and serious adverse events, vital
signs, clinical laboratory tests, electrocardiograms (ECGs), and physical
examinations in the Safety Population.
Inclution Criteria
Subjects must meet all of the following criteria in order to be eligible for the
study:
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 ≤150 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
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.
study:
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 ≤150 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
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.
Exclusion Criteria
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.
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]); or
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 or alanine aminotransferase >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. HOWEVER, subjects who fail preceding
antimicrobial therapy and are documented to have a pathogen-causing cUTI
or AP that is resistant to the prior therapy may be enrolled in this study
(assuming the organism is known to be sensitive to piperacillin/tazobactam).
Subjects who develop signs and symptoms of cUTI or AP while on
antibiotics may also be enrolled.
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 immunodeficiency virus infection with a CD4
count <200/mm3
.
21. Presence of immunodeficiency or an immunocompromised condition
including hematologic malignancy, bone marrow transplant, or receiving
immunosuppressive therapy such as cancer chemotherapy, medications for
the rejection of transplantation, and long-term use of systemic
corticosteroids (equivalent to ≥20 mg a day of prednisone or systemic
equivalent for ≥2 weeks).
22. Presence of neutropenia (<1,000 polymorphonuclear leukocytes
[PMNs]/mm3
).
23. Presence of thrombocytopenia (<60,000 platelets/mm3
).
24. A corrected QT (Fridericia) (QTcF) >480 msec.
25. History of significant hypersensitivity or allergic reaction to Carbavance
(Meropenem/RPX7009), piperacillin/tazobactam, any of the excipients used
in the respective formulations, or any beta-lactam antibiotics (e.g.,
cephalosporins, penicillins, carbapenems, or monobactams).
26. Known hypersensitivity or inability to tolerate all of the
following: fluoroquinolones (including levofloxacin), trimethoprim/
sulfamethoxazole, cefdinir, or cefpodoxime, based on prescribing
information.
27. Unable or unwilling, in the judgment of the Investigator, to comply with the
protocol.
28. An employee of the Investigator or study center with direct involvement in
the proposed study or other studies under the direction of that Investigator
or study center, or a family member of the employee or the Investigator.
29. Acute Physiology and Chronic Health Evaluation (APACHE) II score >30.
An APACHE II score is only required if calculated.
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.
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]); or
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 or alanine aminotransferase >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. HOWEVER, subjects who fail preceding
antimicrobial therapy and are documented to have a pathogen-causing cUTI
or AP that is resistant to the prior therapy may be enrolled in this study
(assuming the organism is known to be sensitive to piperacillin/tazobactam).
Subjects who develop signs and symptoms of cUTI or AP while on
antibiotics may also be enrolled.
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 immunodeficiency virus infection with a CD4
count <200/mm3
.
21. Presence of immunodeficiency or an immunocompromised condition
including hematologic malignancy, bone marrow transplant, or receiving
immunosuppressive therapy such as cancer chemotherapy, medications for
the rejection of transplantation, and long-term use of systemic
corticosteroids (equivalent to ≥20 mg a day of prednisone or systemic
equivalent for ≥2 weeks).
22. Presence of neutropenia (<1,000 polymorphonuclear leukocytes
[PMNs]/mm3
).
23. Presence of thrombocytopenia (<60,000 platelets/mm3
).
24. A corrected QT (Fridericia) (QTcF) >480 msec.
25. History of significant hypersensitivity or allergic reaction to Carbavance
(Meropenem/RPX7009), piperacillin/tazobactam, any of the excipients used
in the respective formulations, or any beta-lactam antibiotics (e.g.,
cephalosporins, penicillins, carbapenems, or monobactams).
26. Known hypersensitivity or inability to tolerate all of the
following: fluoroquinolones (including levofloxacin), trimethoprim/
sulfamethoxazole, cefdinir, or cefpodoxime, based on prescribing
information.
27. Unable or unwilling, in the judgment of the Investigator, to comply with the
protocol.
28. An employee of the Investigator or study center with direct involvement in
the proposed study or other studies under the direction of that Investigator
or study center, or a family member of the employee or the Investigator.
29. Acute Physiology and Chronic Health Evaluation (APACHE) II score >30.
An APACHE II score is only required if calculated.
The Estimated Number of Participants
-
Taiwan
25 participants
-
Global
500 participants
