Trial Outcomes & Findings for Sulopenem Followed by Sulopenem-etzadroxil/Probenecid vs Ertapenem Followed by Cipro for Complicated UTI in Adults (NCT NCT03357614)

Last Updated: 2020-12-29

Results Overview

Clinical success is defined as complete resolution of cUTI symptoms present at study entry and no new cUTI symptoms; microbiologic success is defined as eradication of the bacterial pathogen found at study entry (reduced to \<1000 CFU/mL)

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1395 participants

Primary outcome timeframe

Day 21 +/- 1 day

Results posted on

2020-12-29

Participant Flow

Participant milestones

Participant milestones
Measure	Sulopenem Sulopenem 1000 mg IV once daily for a minimum of 5 days, followed by sulopenem-etzadroxil/probenecid 500 mg PO twice daily to complete 7-10 total days of treatment Sulopenem: Antibiotic therapy for complicated UTI Sulopenem-Etzadroxil/Probenecid: Antibiotic therapy for complicated UTI	Ertapenem Ertapenem 1000 mg IV once daily for a minimum of 5 days, followed by ciprofloxacin 500 mg PO twice daily or amoxicillin-clavulanate 500 mg PO twice daily to complete 7-10 total days of treatment Ertapenem: Antibiotic therapy for complicated UTI Ciprofloxacin: Antibiotic therapy for complicated UTI Amoxicillin-clavulanate: Antibiotic therapy for complicated UTI
Overall Study STARTED	697	698
Overall Study COMPLETED	672	670
Overall Study NOT COMPLETED	25	28

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Sulopenem Followed by Sulopenem-etzadroxil/Probenecid vs Ertapenem Followed by Cipro for Complicated UTI in Adults

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sulopenem n=697 Participants Sulopenem 1000 mg IV once daily for a minimum of 5 days, followed by sulopenem-etzadroxil/probenecid 500 mg PO twice daily to complete 7-10 total days of treatment Sulopenem: Antibiotic therapy for complicated UTI Sulopenem-Etzadroxil/Probenecid: Antibiotic therapy for complicated UTI	Ertapenem n=698 Participants Ertapenem 1000 mg IV once daily for a minimum of 5 days, followed by ciprofloxacin 500 mg PO twice daily or amoxicillin-clavulanate 500 mg PO twice daily to complete 7-10 total days of treatment Ertapenem: Antibiotic therapy for complicated UTI Ciprofloxacin: Antibiotic therapy for complicated UTI Amoxicillin-clavulanate: Antibiotic therapy for complicated UTI	Total n=1395 Participants Total of all reporting groups
Age, Continuous	57.8 years STANDARD_DEVIATION 18.2 • n=5 Participants	59.3 years STANDARD_DEVIATION 18.2 • n=7 Participants	58.5 years STANDARD_DEVIATION 18.2 • n=5 Participants
Sex: Female, Male Female	389 Participants n=5 Participants	380 Participants n=7 Participants	769 Participants n=5 Participants
Sex: Female, Male Male	308 Participants n=5 Participants	318 Participants n=7 Participants	626 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	22 Participants n=5 Participants	20 Participants n=7 Participants	42 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	672 Participants n=5 Participants	675 Participants n=7 Participants	1347 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment Latvia	31 participants n=5 Participants	42 participants n=7 Participants	73 participants n=5 Participants
Region of Enrollment Hungary	70 participants n=5 Participants	47 participants n=7 Participants	117 participants n=5 Participants
Region of Enrollment United States	30 participants n=5 Participants	31 participants n=7 Participants	61 participants n=5 Participants
Region of Enrollment Georgia	81 participants n=5 Participants	92 participants n=7 Participants	173 participants n=5 Participants
Region of Enrollment Estonia	16 participants n=5 Participants	18 participants n=7 Participants	34 participants n=5 Participants
Region of Enrollment Bulgaria	150 participants n=5 Participants	145 participants n=7 Participants	295 participants n=5 Participants
Region of Enrollment Czechia	8 participants n=5 Participants	10 participants n=7 Participants	18 participants n=5 Participants
Region of Enrollment Poland	3 participants n=5 Participants	3 participants n=7 Participants	6 participants n=5 Participants
Region of Enrollment Russia	180 participants n=5 Participants	194 participants n=7 Participants	374 participants n=5 Participants
Region of Enrollment Serbia	1 participants n=5 Participants	4 participants n=7 Participants	5 participants n=5 Participants
Region of Enrollment Slovakia	10 participants n=5 Participants	8 participants n=7 Participants	18 participants n=5 Participants
Region of Enrollment Ukraine	109 participants n=5 Participants	98 participants n=7 Participants	207 participants n=5 Participants
Region of Enrollment Croatia	8 participants n=5 Participants	6 participants n=7 Participants	14 participants n=5 Participants
Diabetes	114 Participants n=5 Participants	114 Participants n=7 Participants	228 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 21 +/- 1 day

Population: Analysis population is the microbiologic modified intent-to-treat population (all modified intent-to-treat patients with a positive study entry urine culture within 48 hours prior to first dose, defined as \>100,000 CFU/mL of a uropathogen and no more than 2 species of a uropathogen \>100,000 CFU/mL; if 1 of the uropathogens was also isolated from baseline blood culture, however, the patient was included in this population regardless of the baseline urine culture result).

Outcome measures

Outcome measures
Measure	Sulopenem n=444 Participants Sulopenem 1000 mg IV once daily for a minimum of 5 days, followed by sulopenem-etzadroxil/probenecid 500 mg PO twice daily to complete 7-10 total days of treatment Sulopenem: Antibiotic therapy for complicated UTI Sulopenem-Etzadroxil/Probenecid: Antibiotic therapy for complicated UTI	Ertapenem n=440 Participants Ertapenem 1000 mg IV once daily for a minimum of 5 days, followed by ciprofloxacin 500 mg PO twice daily or amoxicillin-clavulanate 500 mg PO twice daily to complete 7-10 total days of treatment Ertapenem: Antibiotic therapy for complicated UTI Ciprofloxacin: Antibiotic therapy for complicated UTI Amoxicillin-clavulanate: Antibiotic therapy for complicated UTI
Percentage of Participants With Overall Success	301 Participants	325 Participants

SECONDARY outcome

Timeframe: Day 21 +/- 1 day

Microbiologic success is defined as demonstrating \<1000 CFU/mL of the baseline urpathogen by quantitative urine culture

Outcome measures

Outcome measures
Measure	Sulopenem n=444 Participants Sulopenem 1000 mg IV once daily for a minimum of 5 days, followed by sulopenem-etzadroxil/probenecid 500 mg PO twice daily to complete 7-10 total days of treatment Sulopenem: Antibiotic therapy for complicated UTI Sulopenem-Etzadroxil/Probenecid: Antibiotic therapy for complicated UTI	Ertapenem n=440 Participants Ertapenem 1000 mg IV once daily for a minimum of 5 days, followed by ciprofloxacin 500 mg PO twice daily or amoxicillin-clavulanate 500 mg PO twice daily to complete 7-10 total days of treatment Ertapenem: Antibiotic therapy for complicated UTI Ciprofloxacin: Antibiotic therapy for complicated UTI Amoxicillin-clavulanate: Antibiotic therapy for complicated UTI
Percentage of Participants With Microbiologic Success	316 Participants	343 Participants

Adverse Events

Sulopenem

Serious events: 14 serious events

Other events: 0 other events

Deaths: 2 deaths

Ertapenem

Serious events: 6 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Adverse event data not reported

Additional Information

Senior Director, Clinical Development

Iterum Therapeutics

Phone: 18606614035

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The PIs will provide Iterum opportunity to review proposed publication/other type of disclosure before it's submitted/otherwise disclosed. PI will provide manuscripts, abstracts, or full text of intended disclosure (poster, invited speaker presentation, etc) to Iterum at least 30 days before submitted for publication/otherwise disclosed. If any patent action is required to protect intellectual property rights, PI agrees to delay disclosure for a period not to exceed an additional 60 days.
Publication restrictions are in place

Restriction type: OTHER

Measure	Sulopenem n=697 participants at risk Sulopenem 1000 mg IV once daily for a minimum of 5 days, followed by sulopenem-etzadroxil/probenecid 500 mg PO twice daily to complete 7-10 total days of treatment Sulopenem: Antibiotic therapy for complicated UTI Sulopenem-Etzadroxil/Probenecid: Antibiotic therapy for complicated UTI	Ertapenem n=698 participants at risk Ertapenem 1000 mg IV once daily for a minimum of 5 days, followed by ciprofloxacin 500 mg PO twice daily or amoxicillin-clavulanate 500 mg PO twice daily to complete 7-10 total days of treatment Ertapenem: Antibiotic therapy for complicated UTI Ciprofloxacin: Antibiotic therapy for complicated UTI Amoxicillin-clavulanate: Antibiotic therapy for complicated UTI
Cardiac disorders Cardiac failure	0.14% 1/697 • Number of events 1 • From the time of informed consent through the final visit, an average of 28 days.	0.00% 0/698 • From the time of informed consent through the final visit, an average of 28 days.
Cardiac disorders Cardiac failure congestive	0.14% 1/697 • Number of events 1 • From the time of informed consent through the final visit, an average of 28 days.	0.00% 0/698 • From the time of informed consent through the final visit, an average of 28 days.
Cardiac disorders Atrioventricular block complete	0.00% 0/697 • From the time of informed consent through the final visit, an average of 28 days.	0.14% 1/698 • Number of events 1 • From the time of informed consent through the final visit, an average of 28 days.
Infections and infestations Abscess neck	0.00% 0/697 • From the time of informed consent through the final visit, an average of 28 days.	0.14% 1/698 • Number of events 1 • From the time of informed consent through the final visit, an average of 28 days.
Infections and infestations Cystitis	0.00% 0/697 • From the time of informed consent through the final visit, an average of 28 days.	0.14% 1/698 • Number of events 1 • From the time of informed consent through the final visit, an average of 28 days.
Infections and infestations Pneumonia	0.14% 1/697 • Number of events 1 • From the time of informed consent through the final visit, an average of 28 days.	0.00% 0/698 • From the time of informed consent through the final visit, an average of 28 days.
Infections and infestations Pyelonephritis	0.00% 0/697 • From the time of informed consent through the final visit, an average of 28 days.	0.29% 2/698 • Number of events 2 • From the time of informed consent through the final visit, an average of 28 days.
Infections and infestations Pyelonephritis acute	0.29% 2/697 • Number of events 2 • From the time of informed consent through the final visit, an average of 28 days.	0.00% 0/698 • From the time of informed consent through the final visit, an average of 28 days.
Infections and infestations Pyelonephritis chronic	0.14% 1/697 • Number of events 1 • From the time of informed consent through the final visit, an average of 28 days.	0.14% 1/698 • Number of events 1 • From the time of informed consent through the final visit, an average of 28 days.
Infections and infestations Urinary tract infection	0.72% 5/697 • Number of events 5 • From the time of informed consent through the final visit, an average of 28 days.	0.00% 0/698 • From the time of informed consent through the final visit, an average of 28 days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	0.14% 1/697 • Number of events 1 • From the time of informed consent through the final visit, an average of 28 days.	0.00% 0/698 • From the time of informed consent through the final visit, an average of 28 days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Salivary gland neoplasm	0.14% 1/697 • Number of events 1 • From the time of informed consent through the final visit, an average of 28 days.	0.00% 0/698 • From the time of informed consent through the final visit, an average of 28 days.
Nervous system disorders Seizure	0.00% 0/697 • From the time of informed consent through the final visit, an average of 28 days.	0.14% 1/698 • Number of events 1 • From the time of informed consent through the final visit, an average of 28 days.
Nervous system disorders Syncope	0.00% 0/697 • From the time of informed consent through the final visit, an average of 28 days.	0.14% 1/698 • Number of events 1 • From the time of informed consent through the final visit, an average of 28 days.
Renal and urinary disorders Urinary retention	0.14% 1/697 • Number of events 1 • From the time of informed consent through the final visit, an average of 28 days.	0.14% 1/698 • Number of events 1 • From the time of informed consent through the final visit, an average of 28 days.
Respiratory, thoracic and mediastinal disorders Pulmonary artery thrombosis	0.00% 0/697 • From the time of informed consent through the final visit, an average of 28 days.	0.14% 1/698 • Number of events 1 • From the time of informed consent through the final visit, an average of 28 days.