Complicated Urinary Tract Infection, Acute Pyelonephritis
Conditions
Brief summary
This study is a double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of IV ETX2514SUL in patients with complicated urinary tract infections (cUTIs) who are otherwise relatively healthy.
Detailed description
This study is a double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of IV ETX2514SUL in patients with cUTIs who are otherwise relatively healthy. Patients with Acute Pyelonephritis may also be enrolled. Approximately 80 patients will be randomized to receive either 1 g ETX2514/1 g sulbactam IV or matching placebo every 6 hours (q6h). All patients will receive background therapy with 500 mg IV imipenem/cilastatin q6h.
Interventions
DRUGSulbactam-ETX2514
The ETX2514SUL regimen of 1 g ETX2514/1 g sulbactam infused over 3 hours q6h.
DRUGPlacebo
Matching 1g IV solution.
All patients will receive background therapy with 500 mg IV imipenem/cilastatin q6h.
Sponsors
Entasis Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
This study is a double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of IV ETX2514SUL in patients with cUTIs.
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* A signed informed consent form (ICF). If a study patient is unable to provide informed consent due to their medical condition, the patient's legally authorized representative may consent on behalf of the study patient as permitted by local law and institutional Standard Operating Procedures. * Male or female, 18 to 90 years of age, inclusive. * Expectation, in the judgment of the Investigator, that the patient's cUTI would require initial hospitalization and treatment with IV antibiotics. * Documented or suspected cUTI or Acute pyelonephritis (AP).
Exclusion criteria
* Gross hematuria requiring intervention other than administration of study drug or removal or exchange of a urinary catheter. * Known non-renal source of infection such as endocarditis, osteomyelitis, abscess, meningitis, or pneumonia diagnosed within 7 days prior to randomization that would interfere with evaluation of response to the study antibiotics. * Patient requires continuing treatment with probenecid, methotrexate, ganciclovir, valproic acid, or divalproex sodium during the study. * Receipt of a single dose of a long-acting, potentially-effective systemic antibiotic with activity against Gram-negative uropathogens for more than 24 hours within the 72-hour window prior to randomization. * Requirement at time of randomization for any reason for additional systemic antimicrobial therapy (including antibacterial, antimycobacterial, or antifungal therapy) other than study drug, with the exception of a single oral dose of any antifungal treatment for vaginal candidiasis. * Likely to require the use of an antibiotic for cUTI or AP prophylaxis during the patient's participation in the study \[from randomization through the Late Follow-up (LFU) Visit\]. * Any patients previously randomized in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Overall Success | From baseline through day 21 | The primary efficacy endpoint for this study was the proportion of patients with an overall success (clinical cure and micro-biologic eradication) for the m-MITT (Micro-biologically Modified Intent-to-Treat) Population at the TOC Visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Cure | Baseline to day 21 | Proportion of patients with a response of clinical cure for the MITT(modified intent to treat), m-MITT (microbiologically modified intent to treat), CE(clinically evaluable), and ME(microbiologically evaluable) populations at the TOC(test of cure) visit. |
| Microbiologic Eradication | Baseline to day 21 | Proportion of patients with a response of microbiologic eradication for the m-MITT(microbiologically modified intent to treat) and ME(microbiologically evaluable) populations at the TOC visit |
Countries
Bulgaria
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sulbactam-ETX2514 (ETX2514SUL) + Imipenem/Cilastatin Sulbactam-ETX2514: The ETX2514SUL regimen of 1 g ETX2514/1 g sulbactam infused over 3 hours q6h.
Imipenem-cilastatin: All patients will receive background therapy with 500 mg IV imipenem/cilastatin q6h. | 53 |
| Placebo + Imipenem/Cilastatin Placebo: Matching 1g IV solution.
Imipenem-cilastatin: All patients will receive background therapy with 500 mg IV imipenem/cilastatin q6h. | 27 |
| Total | 80 |
Baseline characteristics
| Characteristic | Placebo + Imipenem/Cilastatin | Total | Sulbactam-ETX2514 (ETX2514SUL) + Imipenem/Cilastatin |
|---|---|---|---|
| Age, Continuous | 54.9 years STANDARD_DEVIATION 15.92 | 52.6 years STANDARD_DEVIATION 17 | 51.4 years STANDARD_DEVIATION 17.55 |
| BMI (Body Mass Index) | 28.63 Kg/m^2 STANDARD_DEVIATION 5.856 | 28.27 Kg/m^2 STANDARD_DEVIATION 6.368 | 28.09 Kg/m^2 STANDARD_DEVIATION 6.661 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants | 79 Participants | 52 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Height | 173.1 Centimeters STANDARD_DEVIATION 8.44 | 172.8 Centimeters STANDARD_DEVIATION 8.63 | 172.6 Centimeters STANDARD_DEVIATION 8.81 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 27 Participants | 80 Participants | 53 Participants |
| Screening Creatinine Clearance | 91.7 Milliliters per minute STANDARD_DEVIATION 18.19 | 93.4 Milliliters per minute STANDARD_DEVIATION 21.96 | 94.3 Milliliters per minute STANDARD_DEVIATION 23.76 |
| Sex: Female, Male Female | 11 Participants | 38 Participants | 27 Participants |
| Sex: Female, Male Male | 16 Participants | 42 Participants | 26 Participants |
| Weight | 85.76 Kilograms STANDARD_DEVIATION 17.929 | 84.45 Kilograms STANDARD_DEVIATION 19.677 | 83.79 Kilograms STANDARD_DEVIATION 20.644 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 53 | 0 / 27 |
| other Total, other adverse events | 8 / 53 | 3 / 27 |
| serious Total, serious adverse events | 0 / 53 | 0 / 27 |
Outcome results
Primary
Number of Participants With Overall Success
The primary efficacy endpoint for this study was the proportion of patients with an overall success (clinical cure and micro-biologic eradication) for the m-MITT (Micro-biologically Modified Intent-to-Treat) Population at the TOC Visit.
Time frame: From baseline through day 21
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sulbactam-ETX2514 (ETX2514SUL) + Imipenem/Cilastatin | Number of Participants With Overall Success | 36 Participants |
| Placebo + Imipenem/Cilastatin | Number of Participants With Overall Success | 17 Participants |
Secondary
Clinical Cure
Proportion of patients with a response of clinical cure for the MITT(modified intent to treat), m-MITT (microbiologically modified intent to treat), CE(clinically evaluable), and ME(microbiologically evaluable) populations at the TOC(test of cure) visit.
Time frame: Baseline to day 21
Population: The number analyzed for each population is different as the efficacy outcome is for the proportion of subjects with a clinical cure for each group.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sulbactam-ETX2514 (ETX2514SUL) + Imipenem/Cilastatin | Clinical Cure | MITT population | 52 Participants |
| Sulbactam-ETX2514 (ETX2514SUL) + Imipenem/Cilastatin | Clinical Cure | m-MITT population | 46 Participants |
| Sulbactam-ETX2514 (ETX2514SUL) + Imipenem/Cilastatin | Clinical Cure | CE population | 52 Participants |
| Sulbactam-ETX2514 (ETX2514SUL) + Imipenem/Cilastatin | Clinical Cure | ME population | 45 Participants |
| Placebo + Imipenem/Cilastatin | Clinical Cure | ME population | 21 Participants |
| Placebo + Imipenem/Cilastatin | Clinical Cure | MITT population | 27 Participants |
| Placebo + Imipenem/Cilastatin | Clinical Cure | CE population | 27 Participants |
| Placebo + Imipenem/Cilastatin | Clinical Cure | m-MITT population | 21 Participants |
Secondary
Microbiologic Eradication
Proportion of patients with a response of microbiologic eradication for the m-MITT(microbiologically modified intent to treat) and ME(microbiologically evaluable) populations at the TOC visit
Time frame: Baseline to day 21
Population: The analysis population differs for each group because the efficacy endpoint is for specific populations.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sulbactam-ETX2514 (ETX2514SUL) + Imipenem/Cilastatin | Microbiologic Eradication | m-MITT population | 37 Participants |
| Sulbactam-ETX2514 (ETX2514SUL) + Imipenem/Cilastatin | Microbiologic Eradication | ME population | 36 Participants |
| Placebo + Imipenem/Cilastatin | Microbiologic Eradication | m-MITT population | 17 Participants |
| Placebo + Imipenem/Cilastatin | Microbiologic Eradication | ME population | 17 Participants |