Trial Outcomes & Findings for Sulopenem Versus Ertapenem for Complicated Intra-abdominal Infection (cIAI) (NCT NCT03358576)

Last Updated: 2020-12-01

Results Overview

Clinical response is defined as resolution in signs and symptoms of the index infection and no new symptoms, without the need for additional antibiotics or interventions

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

674 participants

Primary outcome timeframe

Day 28 +/- 1 day

Results posted on

2020-12-01

Participant Flow

Participant milestones

Participant milestones
Measure	Sulopenem Sulopenem 1000 mg IV once daily for at least 5 days, followed by Sulopenem-Etzadroxil/Probenecid 500 mg PO twice daily to complete 7-10 days of treatment Sulopenem-Etzadroxil/Probenecid: Antibiotic for complicated intra-abdominal infection Sulopenem: Antibiotic for complicated intra-abdominal infection	Ertapenem Ertapenem 1000 mg IV once daily for at least 5 days, followed by ciprofloxacin 500 mg PO twice daily along with metronidazole 500 mg PO four times daily. If patient is found to have causative pathogens that are resistant to ciprofloxacin they will receive amoxicillin-clavulanate 875 mg PO twice daily instead Ertapenem: Antibiotic for complicated intra-abdominal infection Ciprofloxacin: Antibiotic for complicated intra-abdominal infection Metronidazole: Antibiotic for complicated intra-abdominal infection Amoxicillin-Clavulanate: Antibiotic for complicated intra-abdominal infection
Overall Study STARTED	338	336
Overall Study COMPLETED	312	311
Overall Study NOT COMPLETED	26	25

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Sulopenem Versus Ertapenem for Complicated Intra-abdominal Infection (cIAI)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sulopenem n=338 Participants Sulopenem 1000 mg IV once daily for at least 5 days, followed by Sulopenem-Etzadroxil/Probenecid 500 mg PO twice daily to complete 7-10 days of treatment Sulopenem-Etzadroxil/Probenecid: Antibiotic for complicated intra-abdominal infection Sulopenem: Antibiotic for complicated intra-abdominal infection	Ertapenem n=336 Participants Ertapenem 1000 mg IV once daily for at least 5 days, followed by ciprofloxacin 500 mg PO twice daily along with metronidazole 500 mg PO four times daily. If patient is found to have causative pathogens that are resistant to ciprofloxacin they will receive amoxicillin-clavulanate 875 mg PO twice daily instead Ertapenem: Antibiotic for complicated intra-abdominal infection Ciprofloxacin: Antibiotic for complicated intra-abdominal infection Metronidazole: Antibiotic for complicated intra-abdominal infection Amoxicillin-Clavulanate: Antibiotic for complicated intra-abdominal infection	Total n=674 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	226 Participants n=5 Participants	217 Participants n=7 Participants	443 Participants n=5 Participants
Age, Categorical >=65 years	112 Participants n=5 Participants	119 Participants n=7 Participants	231 Participants n=5 Participants
Age, Continuous	53.9 years STANDARD_DEVIATION 18.4 • n=5 Participants	54.8 years STANDARD_DEVIATION 18.0 • n=7 Participants	54.3 years STANDARD_DEVIATION 18.2 • n=5 Participants
Sex: Female, Male Female	160 Participants n=5 Participants	155 Participants n=7 Participants	315 Participants n=5 Participants
Sex: Female, Male Male	178 Participants n=5 Participants	181 Participants n=7 Participants	359 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	329 Participants n=5 Participants	328 Participants n=7 Participants	657 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Latvia	26 participants n=5 Participants	30 participants n=7 Participants	56 participants n=5 Participants
Region of Enrollment Hungary	25 participants n=5 Participants	21 participants n=7 Participants	46 participants n=5 Participants
Region of Enrollment United States	16 participants n=5 Participants	16 participants n=7 Participants	32 participants n=5 Participants
Region of Enrollment Georgia	38 participants n=5 Participants	45 participants n=7 Participants	83 participants n=5 Participants
Region of Enrollment Estonia	37 participants n=5 Participants	40 participants n=7 Participants	77 participants n=5 Participants
Region of Enrollment Czechia	10 participants n=5 Participants	7 participants n=7 Participants	17 participants n=5 Participants
Region of Enrollment Russia	19 participants n=5 Participants	21 participants n=7 Participants	40 participants n=5 Participants
Region of Enrollment Serbia	5 participants n=5 Participants	12 participants n=7 Participants	17 participants n=5 Participants
Region of Enrollment Ukraine	64 participants n=5 Participants	54 participants n=7 Participants	118 participants n=5 Participants
Region of Enrollment Bulgaria	98 participants n=5 Participants	90 participants n=7 Participants	188 participants n=5 Participants
creatinine clearance	92.7 mL/min STANDARD_DEVIATION 41.4 • n=5 Participants	87.9 mL/min STANDARD_DEVIATION 39.1 • n=7 Participants	90.3 mL/min STANDARD_DEVIATION 87.0 • n=5 Participants

PRIMARY outcome

Timeframe: Day 28 +/- 1 day

Population: micro-MITT population

Clinical response is defined as resolution in signs and symptoms of the index infection and no new symptoms, without the need for additional antibiotics or interventions

Outcome measures

Outcome measures
Measure	Sulopenem n=249 Participants Sulopenem 1000 mg IV once daily for at least 5 days, followed by Sulopenem-Etzadroxil/Probenecid 500 mg PO twice daily to complete 7-10 days of treatment Sulopenem-Etzadroxil/Probenecid: Antibiotic for complicated intra-abdominal infection Sulopenem: Antibiotic for complicated intra-abdominal infection	Ertapenem n=266 Participants Ertapenem 1000 mg IV once daily for at least 5 days, followed by ciprofloxacin 500 mg PO twice daily along with metronidazole 500 mg PO four times daily. If patient is found to have causative pathogens that are resistant to ciprofloxacin they will receive amoxicillin-clavulanate 875 mg PO twice daily instead Ertapenem: Antibiotic for complicated intra-abdominal infection Ciprofloxacin: Antibiotic for complicated intra-abdominal infection Metronidazole: Antibiotic for complicated intra-abdominal infection Amoxicillin-Clavulanate: Antibiotic for complicated intra-abdominal infection
Percentage of Participants With Clinical Success	85.5 percentage of participants	90.2 percentage of participants

SECONDARY outcome

Timeframe: Day 11-14 +/- 1 day

Population: micro-MITT population

Clinical response is defined as resolution in signs and symptoms of the index infection and no new symptoms, without the need for additional antibiotics or interventions

Outcome measures

Outcome measures
Measure	Sulopenem n=249 Participants Sulopenem 1000 mg IV once daily for at least 5 days, followed by Sulopenem-Etzadroxil/Probenecid 500 mg PO twice daily to complete 7-10 days of treatment Sulopenem-Etzadroxil/Probenecid: Antibiotic for complicated intra-abdominal infection Sulopenem: Antibiotic for complicated intra-abdominal infection	Ertapenem n=266 Participants Ertapenem 1000 mg IV once daily for at least 5 days, followed by ciprofloxacin 500 mg PO twice daily along with metronidazole 500 mg PO four times daily. If patient is found to have causative pathogens that are resistant to ciprofloxacin they will receive amoxicillin-clavulanate 875 mg PO twice daily instead Ertapenem: Antibiotic for complicated intra-abdominal infection Ciprofloxacin: Antibiotic for complicated intra-abdominal infection Metronidazole: Antibiotic for complicated intra-abdominal infection Amoxicillin-Clavulanate: Antibiotic for complicated intra-abdominal infection
Percentage of Participants With Clinical Success	208 Participants	227 Participants

Adverse Events

Sulopenem

Serious events: 25 serious events

Other events: 0 other events

Deaths: 4 deaths

Ertapenem

Serious events: 12 serious events

Other events: 0 other events

Deaths: 4 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 PI will provide manuscripts, abstracts, or full text of any other intended disclosure (poster, invited speaker or guest lecturer, etc) to Iterum at least 30 days before they are submitted for publication or otherwise disclosed. If any patent action is required to protect intellectual property rights, the PI agrees to delay disclosure for a period not to exceed an additional 60 days. The PI will, on request, remove any previously undisclosed Confidential Information before disclosure.
Publication restrictions are in place

Restriction type: OTHER

Measure	Sulopenem n=335 participants at risk；n=338 participants at risk Sulopenem 1000 mg IV once daily for at least 5 days, followed by Sulopenem-Etzadroxil/Probenecid 500 mg PO twice daily to complete 7-10 days of treatment Sulopenem-Etzadroxil/Probenecid: Antibiotic for complicated intra-abdominal infection Sulopenem: Antibiotic for complicated intra-abdominal infection	Ertapenem n=333 participants at risk；n=336 participants at risk Ertapenem 1000 mg IV once daily for at least 5 days, followed by ciprofloxacin 500 mg PO twice daily along with metronidazole 500 mg PO four times daily. If patient is found to have causative pathogens that are resistant to ciprofloxacin they will receive amoxicillin-clavulanate 875 mg PO twice daily instead Ertapenem: Antibiotic for complicated intra-abdominal infection Ciprofloxacin: Antibiotic for complicated intra-abdominal infection Metronidazole: Antibiotic for complicated intra-abdominal infection Amoxicillin-Clavulanate: Antibiotic for complicated intra-abdominal infection
Infections and infestations Abdominal abscess	1.8% 6/338 • Number of events 6 • From the time of informed consent through the test-of-cure visit, an average of 28 days	0.00% 0/336 • From the time of informed consent through the test-of-cure visit, an average of 28 days
Cardiac disorders cardiac arrest	0.30% 1/338 • Number of events 1 • From the time of informed consent through the test-of-cure visit, an average of 28 days	0.00% 0/336 • From the time of informed consent through the test-of-cure visit, an average of 28 days
Cardiac disorders ventricular fibrillation	0.30% 1/338 • Number of events 1 • From the time of informed consent through the test-of-cure visit, an average of 28 days	0.00% 0/336 • From the time of informed consent through the test-of-cure visit, an average of 28 days
Cardiac disorders Angina unstable	0.00% 0/338 • From the time of informed consent through the test-of-cure visit, an average of 28 days	0.30% 1/336 • Number of events 1 • From the time of informed consent through the test-of-cure visit, an average of 28 days
Cardiac disorders cardiac failure acute	0.00% 0/338 • From the time of informed consent through the test-of-cure visit, an average of 28 days	0.30% 1/336 • Number of events 1 • From the time of informed consent through the test-of-cure visit, an average of 28 days
Gastrointestinal disorders Diarrhoea	0.59% 2/338 • Number of events 2 • From the time of informed consent through the test-of-cure visit, an average of 28 days	0.00% 0/336 • From the time of informed consent through the test-of-cure visit, an average of 28 days
Gastrointestinal disorders Ileus paralytic	0.30% 1/338 • Number of events 1 • From the time of informed consent through the test-of-cure visit, an average of 28 days	0.00% 0/336 • From the time of informed consent through the test-of-cure visit, an average of 28 days
Gastrointestinal disorders intestinal perforation	0.30% 1/338 • Number of events 1 • From the time of informed consent through the test-of-cure visit, an average of 28 days	0.00% 0/336 • From the time of informed consent through the test-of-cure visit, an average of 28 days
Gastrointestinal disorders mesenteric artery thrombosis	0.30% 1/338 • Number of events 1 • From the time of informed consent through the test-of-cure visit, an average of 28 days	0.00% 0/336 • From the time of informed consent through the test-of-cure visit, an average of 28 days
Gastrointestinal disorders volvulus of small bowel	0.30% 1/338 • Number of events 1 • From the time of informed consent through the test-of-cure visit, an average of 28 days	0.00% 0/336 • From the time of informed consent through the test-of-cure visit, an average of 28 days
Gastrointestinal disorders ileus	0.00% 0/338 • From the time of informed consent through the test-of-cure visit, an average of 28 days	0.30% 1/336 • Number of events 1 • From the time of informed consent through the test-of-cure visit, an average of 28 days
Gastrointestinal disorders intra-abdominal haematoma	0.00% 0/338 • From the time of informed consent through the test-of-cure visit, an average of 28 days	0.30% 1/336 • Number of events 1 • From the time of informed consent through the test-of-cure visit, an average of 28 days
Gastrointestinal disorders intra-abdominal haemorrhage	0.00% 0/338 • From the time of informed consent through the test-of-cure visit, an average of 28 days	0.30% 1/336 • Number of events 1 • From the time of informed consent through the test-of-cure visit, an average of 28 days
Gastrointestinal disorders irritable bowel syndrome	0.00% 0/338 • From the time of informed consent through the test-of-cure visit, an average of 28 days	0.30% 1/336 • Number of events 1 • From the time of informed consent through the test-of-cure visit, an average of 28 days
Gastrointestinal disorders small intestine obstruction	0.00% 0/338 • From the time of informed consent through the test-of-cure visit, an average of 28 days	0.30% 1/336 • Number of events 1 • From the time of informed consent through the test-of-cure visit, an average of 28 days
General disorders multiple organ dysfunction syndrome	0.30% 1/338 • Number of events 1 • From the time of informed consent through the test-of-cure visit, an average of 28 days	0.30% 1/336 • Number of events 1 • From the time of informed consent through the test-of-cure visit, an average of 28 days
General disorders pyrexia	0.30% 1/338 • Number of events 1 • From the time of informed consent through the test-of-cure visit, an average of 28 days	0.00% 0/336 • From the time of informed consent through the test-of-cure visit, an average of 28 days
General disorders sudden death	0.30% 1/338 • Number of events 1 • From the time of informed consent through the test-of-cure visit, an average of 28 days	0.00% 0/336 • From the time of informed consent through the test-of-cure visit, an average of 28 days
General disorders systemic inflammatory response syndrome	0.00% 0/338 • From the time of informed consent through the test-of-cure visit, an average of 28 days	0.30% 1/336 • Number of events 1 • From the time of informed consent through the test-of-cure visit, an average of 28 days
Infections and infestations liver abscess	0.59% 2/338 • Number of events 2 • From the time of informed consent through the test-of-cure visit, an average of 28 days	0.30% 1/336 • Number of events 1 • From the time of informed consent through the test-of-cure visit, an average of 28 days
Infections and infestations appendiceal abscess	0.30% 1/338 • Number of events 1 • From the time of informed consent through the test-of-cure visit, an average of 28 days	0.00% 0/336 • From the time of informed consent through the test-of-cure visit, an average of 28 days
Infections and infestations colon gangrene	0.30% 1/338 • Number of events 1 • From the time of informed consent through the test-of-cure visit, an average of 28 days	0.00% 0/336 • From the time of informed consent through the test-of-cure visit, an average of 28 days
Infections and infestations peritonitis	0.30% 1/338 • Number of events 1 • From the time of informed consent through the test-of-cure visit, an average of 28 days	0.00% 0/336 • From the time of informed consent through the test-of-cure visit, an average of 28 days
Infections and infestations pneumonia	0.00% 0/338 • From the time of informed consent through the test-of-cure visit, an average of 28 days	0.30% 1/336 • Number of events 1 • From the time of informed consent through the test-of-cure visit, an average of 28 days
Injury, poisoning and procedural complications gastrointestinal anastomotic leak	0.30% 1/338 • Number of events 1 • From the time of informed consent through the test-of-cure visit, an average of 28 days	0.00% 0/336 • From the time of informed consent through the test-of-cure visit, an average of 28 days
Respiratory, thoracic and mediastinal disorders acute respiratory failure	0.30% 1/338 • Number of events 1 • From the time of informed consent through the test-of-cure visit, an average of 28 days	0.30% 1/336 • Number of events 1 • From the time of informed consent through the test-of-cure visit, an average of 28 days
Respiratory, thoracic and mediastinal disorders pulmonary embolism	0.30% 1/338 • Number of events 1 • From the time of informed consent through the test-of-cure visit, an average of 28 days	0.00% 0/336 • From the time of informed consent through the test-of-cure visit, an average of 28 days
Vascular disorders internal hemorrhage	0.30% 1/338 • Number of events 1 • From the time of informed consent through the test-of-cure visit, an average of 28 days	0.00% 0/336 • From the time of informed consent through the test-of-cure visit, an average of 28 days
Neoplasms benign, malignant and unspecified (incl cysts and polyps) colon cancer	0.00% 0/338 • From the time of informed consent through the test-of-cure visit, an average of 28 days	0.30% 1/336 • Number of events 1 • From the time of informed consent through the test-of-cure visit, an average of 28 days
Nervous system disorders cerebrovascular accident	0.30% 1/338 • Number of events 1 • From the time of informed consent through the test-of-cure visit, an average of 28 days	0.00% 0/336 • From the time of informed consent through the test-of-cure visit, an average of 28 days
Renal and urinary disorders renal impairment	0.30% 1/338 • Number of events 1 • From the time of informed consent through the test-of-cure visit, an average of 28 days	0.00% 0/336 • From the time of informed consent through the test-of-cure visit, an average of 28 days
Renal and urinary disorders renal failure	0.00% 0/338 • From the time of informed consent through the test-of-cure visit, an average of 28 days	0.30% 1/336 • Number of events 1 • From the time of informed consent through the test-of-cure visit, an average of 28 days