Trial Outcomes & Findings for Oral Sulopenem-etzadroxil/Probenecid Versus Ciprofloxacin for Uncomplicated Urinary Tract Infection in Adult Women (NCT NCT03354598)

Last Updated: 2021-01-12

Results Overview

Overall Success: Clinical Success (resolution of uncomplicated urinary tract infection (uUTI) symptoms present at study entry and no new symptoms) AND Microbiologic success (eradication of the baseline pathogen)

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1671 participants

Primary outcome timeframe

Day 12+/-1 day

Results posted on

2021-01-12

Participant Flow

Participant milestones

Participant milestones
Measure	Sulopenem-etzadroxil/Probenecid Sulopenem-etzadroxil/probenecid 500 mg PO twice daily for 5 days Sulopenem-Etzadroxil/Probenecid: Treatment of uncomplicated urinary tract infection	Ciprofloxacin Ciprofloxacin 250 mg PO administered twice daily for 3 days Ciprofloxacin: Treatment of uncomplicated urinary tract infection
Overall Study STARTED	835	836
Overall Study Microbiologic Modified Intent to Treat Resistant (Micro-MITTR) Participants	147	139
Overall Study Microbiologic Modified Intent to Treat Susceptible (Micro-MITTS) Participants	370	415
Overall Study Microbiologic Modified Intent to Treat (Micro-MITT) Participants	517	554
Overall Study Modified Intent to Treat (MITT) Participants	785	794
Overall Study Intent to Treat (ITT) Participants	787	803
Overall Study Safety Participants	833	827
Overall Study COMPLETED	755	761
Overall Study NOT COMPLETED	80	75

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Oral Sulopenem-etzadroxil/Probenecid Versus Ciprofloxacin for Uncomplicated Urinary Tract Infection in Adult Women

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sulopenem-etzadroxil/Probenecid n=787 Participants Sulopenem-etzadroxil/probenecid 500 mg PO twice daily for 5 days Sulopenem-Etzadroxil/Probenecid: Treatment of uncomplicated urinary tract infection	Ciprofloxacin n=803 Participants Ciprofloxacin 250 mg PO administered twice daily for 3 days Ciprofloxacin: Treatment of uncomplicated urinary tract infection	Total n=1590 Participants Total of all reporting groups
Age, Continuous	49.8 years STANDARD_DEVIATION 18.8 • n=5 Participants	50.0 years STANDARD_DEVIATION 19.1 • n=7 Participants	49.9 years STANDARD_DEVIATION 19.0 • n=5 Participants
Sex: Female, Male Female	787 Participants n=5 Participants	803 Participants n=7 Participants	1590 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	253 Participants n=5 Participants	232 Participants n=7 Participants	485 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	529 Participants n=5 Participants	570 Participants n=7 Participants	1099 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment United States	448 participants n=5 Participants	441 participants n=7 Participants	889 participants n=5 Participants
Region of Enrollment Ukraine	144 participants n=5 Participants	137 participants n=7 Participants	281 participants n=5 Participants
Region of Enrollment Russia	195 participants n=5 Participants	225 participants n=7 Participants	420 participants n=5 Participants
Diabetes	93 Participants n=5 Participants	106 Participants n=7 Participants	199 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 12+/-1 day

Population: micro-MITTR population: patients with baseline uropathogen non-susceptible to the comparator ciprofloxacin.

Outcome measures

Outcome measures
Measure	Sulopenem-etzadroxil/Probenecid n=147 Participants Sulopenem-etzadroxil/probenecid 500 mg PO twice daily for 5 days Sulopenem-Etzadroxil/Probenecid: Treatment of uncomplicated urinary tract infection	Ciprofloxacin n=139 Participants Ciprofloxacin 250 mg PO administered twice daily for 3 days Ciprofloxacin: Treatment of uncomplicated urinary tract infection
Percentage of Microbiologic Modified Intent to Treat Resistant (Micro-MITTR) Participants With Overall Success	62.6 percentage of participants	36.0 percentage of participants

PRIMARY outcome

Timeframe: Day 12 +/- 1 day

Population: micro-MITTS population: patients with baseline uropathogen susceptible to the comparator ciprofloxacin.

Overall Success is Clinical Success (resolution of uUTI symptoms present at study entry and no new uUTI symptoms) AND Microbiologic success (eradication of the baseline pathogen)

Outcome measures

Outcome measures
Measure	Sulopenem-etzadroxil/Probenecid n=370 Participants Sulopenem-etzadroxil/probenecid 500 mg PO twice daily for 5 days Sulopenem-Etzadroxil/Probenecid: Treatment of uncomplicated urinary tract infection	Ciprofloxacin n=415 Participants Ciprofloxacin 250 mg PO administered twice daily for 3 days Ciprofloxacin: Treatment of uncomplicated urinary tract infection
Percentage of Microbiologic Modified Intent to Treat Susceptible (Micro-MITTS) Participants With Overall Success	66.8 percentage of participants	78.6 percentage of participants

SECONDARY outcome

Timeframe: Day 12+/-1 day

Population: micro-MITTR population: patients with baseline uropathogen non-susceptible to the comparator ciprofloxacin.

Microbiologic success is defined as eradication of the baseline pathogen (\<1000 Colony Forming Units (CFU)/mL) at the Test of Cure visit

Outcome measures

Outcome measures
Measure	Sulopenem-etzadroxil/Probenecid n=147 Participants Sulopenem-etzadroxil/probenecid 500 mg PO twice daily for 5 days Sulopenem-Etzadroxil/Probenecid: Treatment of uncomplicated urinary tract infection	Ciprofloxacin n=139 Participants Ciprofloxacin 250 mg PO administered twice daily for 3 days Ciprofloxacin: Treatment of uncomplicated urinary tract infection
Percentage of Microbiologic Modified Intent to Treat Resistant (Micro-MITTR) Patients With Microbiologic Success	74.1 percentage of participants	49.6 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 +/- 1 day

Population: micro-MITT population: micro-MITTR and micro-MITTS (ciprofloxacin nonsusceptible and ciprofloxacin susceptible) populations combined.

Overall Success is Clinical Success (resolution of uUTI symptoms present at study entry and no new uUTI symptoms) AND Microbiologic success (eradication of the baseline pathogen)

Outcome measures

Outcome measures
Measure	Sulopenem-etzadroxil/Probenecid n=517 Participants Sulopenem-etzadroxil/probenecid 500 mg PO twice daily for 5 days Sulopenem-Etzadroxil/Probenecid: Treatment of uncomplicated urinary tract infection	Ciprofloxacin n=554 Participants Ciprofloxacin 250 mg PO administered twice daily for 3 days Ciprofloxacin: Treatment of uncomplicated urinary tract infection
Percentage of Microbiologic Modified Intent to Treat (Micro-MITT) Participants With Overall Success	65.6 percentage of participants	67.9 percentage of participants

Adverse Events

Sulopenem-etzadroxil/Probenecid

Serious events: 6 serious events

Other events: 103 other events

Deaths: 1 deaths

Ciprofloxacin

Serious events: 2 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Sulopenem-etzadroxil/Probenecid n=833 participants at risk Sulopenem-etzadroxil/probenecid 500 mg PO twice daily for 5 days Sulopenem-Etzadroxil/Probenecid: Treatment of uncomplicated urinary tract infection	Ciprofloxacin n=827 participants at risk Ciprofloxacin 250 mg PO administered twice daily for 3 days Ciprofloxacin: Treatment of uncomplicated urinary tract infection
Gastrointestinal disorders Diarrhoea	0.00% 0/833 • From the time of informed consent through the final visit, an average of 28 days.	0.12% 1/827 • Number of events 1 • From the time of informed consent through the final visit, an average of 28 days.
Gastrointestinal disorders Abdominal pain upper	0.12% 1/833 • Number of events 1 • From the time of informed consent through the final visit, an average of 28 days.	0.00% 0/827 • From the time of informed consent through the final visit, an average of 28 days.
Gastrointestinal disorders small intestine obstruction	0.12% 1/833 • Number of events 1 • From the time of informed consent through the final visit, an average of 28 days.	0.00% 0/827 • From the time of informed consent through the final visit, an average of 28 days.
General disorders chest pain	0.12% 1/833 • Number of events 1 • From the time of informed consent through the final visit, an average of 28 days.	0.00% 0/827 • From the time of informed consent through the final visit, an average of 28 days.
Hepatobiliary disorders Bile duct stone	0.00% 0/833 • From the time of informed consent through the final visit, an average of 28 days.	0.12% 1/827 • Number of events 1 • From the time of informed consent through the final visit, an average of 28 days.
Infections and infestations Pneumonia	0.00% 0/833 • From the time of informed consent through the final visit, an average of 28 days.	0.12% 1/827 • Number of events 1 • From the time of informed consent through the final visit, an average of 28 days.
Infections and infestations pyelonephritis acute	0.12% 1/833 • Number of events 1 • From the time of informed consent through the final visit, an average of 28 days.	0.00% 0/827 • From the time of informed consent through the final visit, an average of 28 days.
Infections and infestations urosepsis	0.12% 1/833 • Number of events 1 • From the time of informed consent through the final visit, an average of 28 days.	0.00% 0/827 • From the time of informed consent through the final visit, an average of 28 days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) lung adenocarcinoma	0.12% 1/833 • Number of events 1 • From the time of informed consent through the final visit, an average of 28 days.	0.00% 0/827 • From the time of informed consent through the final visit, an average of 28 days.
Nervous system disorders presuncope	0.12% 1/833 • Number of events 1 • From the time of informed consent through the final visit, an average of 28 days.	0.00% 0/827 • From the time of informed consent through the final visit, an average of 28 days.
Skin and subcutaneous tissue disorders angioedema	0.12% 1/833 • Number of events 1 • From the time of informed consent through the final visit, an average of 28 days.	0.00% 0/827 • From the time of informed consent through the final visit, an average of 28 days.

Other adverse events

Other adverse events
Measure	Sulopenem-etzadroxil/Probenecid n=833 participants at risk Sulopenem-etzadroxil/probenecid 500 mg PO twice daily for 5 days Sulopenem-Etzadroxil/Probenecid: Treatment of uncomplicated urinary tract infection	Ciprofloxacin n=827 participants at risk Ciprofloxacin 250 mg PO administered twice daily for 3 days Ciprofloxacin: Treatment of uncomplicated urinary tract infection
Gastrointestinal disorders Diarrhea	12.4% 103/833 • Number of events 947 • From the time of informed consent through the final visit, an average of 28 days.	2.5% 21/827 • Number of events 91 • From the time of informed consent through the final visit, an average of 28 days.

Additional Information

Senior Director, Clinical Development

Iterum Therapeutics

Phone: 18606614035

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The PI will provide Iterum opportunity to review proposed publication/other type of disclosure before submitted/disclosed. PI will provide full text of intended disclosure to Iterum at least 30 days before submitted/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. PI will, on request, remove previously undisclosed Confidential Information before disclosure.
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