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

• Sponsor: Iterum Therapeutics, International Limited (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03358576
• Collaborator: (none)
• Enrollment: 674
• Locations: 42
• Arms: 2
• Actual Duration (Months): 12.5
• Patients Per Site: 16
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

This is a prospective, Phase 3, randomized, multi-center, double-blind study of the efficacy, tolerability and safety of sulopenem followed by sulopenem-etzadroxil/probenecid versus ertapenem followed by ciprofloxacin-metronidazole for treatment of complicated intra-abdominal infections in adults.

Condition or Disease	Intervention/Treatment	Phase
Intra Abdominal Infections	Drug: Ertapenem; Drug: Sulopenem-Etzadroxil/Probenecid; Drug: Ciprofloxacin; Drug: Metronidazole; Drug: Amoxicillin-Clavulanate; Drug: Sulopenem	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 674 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Prospective, Phase 3, Randomized, Multi-center, Double-blind Study of Efiicacy, Tolerability & Safety of Sulopenem & Sulopenem-etzadroxil/Probenecid vs Ertapenem Followed by Cipro-metronidazole for Treatment of cIAI in Adults
• Actual Study Start Date: Sep 18, 2018
• Actual Primary Completion Date: Oct 2, 2019
• Actual Study Completion Date: Oct 2, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Drug: Sulopenem-Etzadroxil/Probenecid; Antibiotic for complicated intra-abdominal infection; Drug: Sulopenem; Antibiotic for complicated intra-abdominal infection
Active Comparator: 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	Drug: Ertapenem; Antibiotic for complicated intra-abdominal infection; Other Names: Invanz ; Drug: Ciprofloxacin; Antibiotic for complicated intra-abdominal infection; Other Names: Cipro ; Drug: Metronidazole; Antibiotic for complicated intra-abdominal infection; Other Names: Flagyl ; Drug: Amoxicillin-Clavulanate; Antibiotic for complicated intra-abdominal infection; Other Names: Augmentin

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Clinical Success [Day 28 +/- 1 day]

   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

Secondary Outcome Measures

1. Percentage of Participants With Clinical Success [Day 11-14 +/- 1 day]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patient or the patient's legally acceptable representative able to provide a signed written informed consent prior to any study-specific procedures.

2. Adult patients ≥18 years of age

3. EITHER:

1. Intra-operative/post-operative enrollment with visual confirmation (presence of pus within the abdominal cavity) of an intra-abdominal infection associated with peritonitis including at least 1 of the following diagnosed during the surgical intervention: i. Cholecystitis with gangrenous rupture or perforation or progression of the infection beyond the gallbladder wall ii. Diverticular disease with perforation or abscess iii. Appendiceal perforation or peri-appendiceal abscess iv. Traumatic perforation of the intestines, only if operated on >12 hours after perforation occurs
2. Secondary peritonitis (but not spontaneous bacterial peritonitis associated with cirrhosis and chronic ascites) vi. Intra-abdominal abscess (including of liver or spleen provided that there was extension beyond the organ with evidence of intraperitoneal involvement).

OR:

1. Pre-operative enrollment where one of the following surgical procedures are planned within 24 hours prior to the first dose of study drug: i. Open laparotomy, percutaneous drainage of an intra-abdominal abscess, or laparoscopic surgery.

1. Evidence of systemic inflammatory indicators, with at least one of the following:

1. Fever (defined as body temperature >38°C) or hypothermia with a core body temperature <35°C ii. Elevated white blood cell count (>12,000 cells/mm3) iii. Drop in blood pressure (systolic BP must be <90 mmHg without pressor support) iv. Increased heart rate (>90 bpm) and respiratory rate (>20 breaths/min) v. Hypoxia (oxygen saturation ≤90 percent on room air)

1. Physical findings or symptoms consistent with intra-abdominal infection, with at least one of the following:

1. Abdominal pain and/or tenderness, with or without rebound ii. Localized or diffuse abdominal wall rigidity iii. Abdominal mass iv. Nausea/vomiting v. Altered Mental Status

1. Specimen/s from the surgical intervention were sent for culture.

Exclusion Criteria:

1. Patient diagnosed with traumatic bowel perforation undergoing surgery within 12 hours; perforation of gastroduodenal ulcers undergoing surgery within 24 hours. Other intra-abdominal processes in which the primary etiology was not likely to be infectious.

2. Patient has abdominal wall abscess or bowel obstruction without perforation or ischemic bowel without perforation.

3. Patient has simple cholecystitis or gangrenous cholecystitis without rupture, or simple appendicitis, or acute suppurative cholangitis; or infected necrotizing pancreatitis or pancreatic abscess.

4. Patient whose surgery included staged abdominal repair, or "open abdomen" technique, or marsupialization.

5. Patient known at study entry to have a complicated intra-abdominal infection caused by pathogens resistant to the study antimicrobial agents.

6. Patient needed effective concomitant systemic antibacterials (oral, IV, or intramuscular) or antifungals in addition to those designated in the 2 study groups, except vancomycin, linezolid, or daptomycin if started for known or suspected methicillin-resistant Staphylococcus aureus (MRSA) or Enterococcus spp. as per clinical study protocol (CSP).

7. Patient has perinephric infections or an indwelling peritoneal dialysis catheter.

8. Patient has suspected intra-abdominal infections due to fungus, parasites (e.g., amoebic liver abscess), virus, or tuberculosis.

9. Patient has a known history of serious allergy, hypersensitivity or any serious reaction to carbapenem antibiotics, or to other β-lactam antibiotics

10. Patient known to have any of the following laboratory values as defined below:

11. Hematocrit <25% or hemoglobin <8 g/dL

12. Absolute neutrophil count <1000/mm3

13. Platelet count <75,000/mm3

14. Bilirubin >3 x the upper limit of normal (ULN), unless isolated hyperbilirubinemia was directly related to the acute infection or known Gilbert's disease

15. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 x ULN values at Screening. Patients with elevations of AST and/or ALT up to 5 x ULN will be eligible if these elevations are acute and directly related to the infectious process being treated. This must be documented

16. Alkaline phosphatase (ALP) >3 x ULN. Patients with values >3.0 x ULN and <5.0 x ULN are eligible if this value is acute and directly related to the infectious process being treated. This must be documented.

17. Estimated creeatinine clearance <50 mL/min

18. Patient has a body mass index >45 kg/m2.

19. Patient has APACHE II score >30.

20. Patient considered unlikely to survive the 4-week study period or has a rapidly progressive or terminal illness, including septic shock that was associated with a high risk of mortality.

21. Patient unlikely to respond to 10-14 days of treatment with antibiotics.

22. Patient received systemic antibacterial agents within the 72-hour period prior to study entry, unless either of the following pertained:

1. Patient has a new infection (not considered a treatment failure) and both of the following were met: i. Patient received no more than 24 hours of total prior antibiotic therapy ii. Patient received ≤1 dose of a treatment regimen post-operatively and antibiotics were not received more than 6 hours post-procedure.

2. Patient considered to have failed the previous treatment regimen i.e., pre-operative treatment of any duration with non-study systemic antimicrobial therapy for peritonitis or abscess permitted provided that all of the following are met: i. The treatment regimen had been administered for at least 72 hours and was judged to have been inadequate ii. The patient had an operative intervention that was just completed or was intended no more than 24 hours after study entry iii. Findings of infection were documented at surgery iv. Specimens for bacterial cultures and susceptibility testing were taken at operative intervention v. No further non-study antibacterials were administered after randomization.

1. Patient has a concurrent infection that may interfere with the evaluation of response to the study antibiotic.

2. Patient receiving hemodialysis or peritoneal dialysis.

3. Patient has a history of acute hepatitis in the recent past (3 months prior to study entry), chronic hepatitis, cirrhosis, acute hepatic failure, or acute decompensation of chronic hepatic failure.

4. Patient has past or current history of epilepsy or seizure disorders excluding febrile seizures of childhood.

5. Patient immunocompromised as evidenced by any of the following:

6. Human immunodeficiency virus infection, with either a recent (in the past 6 months) acquired immune deficiency syndrome-defining condition or a CD4 + T lymphocyte count <200/mm3

7. Systemic or hematological malignancy requiring chemotherapeutic or radiologic/immunologic interventions within 6 weeks prior to randomization, or anticipated to begin prior to completion of study

8. Immunosuppressive therapy, including maintenance corticosteroid therapy (>40 mg/day equivalent prednisolone) for 5 days or more.

9. Patient participating in any other clinical study that involved the administration of an investigational medication at the time of presentation, during the course of the study, or who had received treatment with an investigational medication in the 30 days prior to study enrollment, or had previously been enrolled in this study or had been treated with sulopenem.

10. Patient is in a situation or has a condition that, in the investigator's opinion, may interfere with optimal participation in the study.

11. Patient unlikely to comply with protocol e.g., uncooperative attitude, inability to return for follow-up visits, and unlikely to complete the study.

12. Patient has known inflammatory bowel disease (ulcerative colitis or Crohn's disease) or Clostridium difficile-associated diarrhea.

13. Patients with a history of blood dyscrasias

14. Patients with a history of uric acid kidney stones

15. Patients with acute gouty attack

16. Patients on chronic methotrexate therapy

17. Females of child-bearing potential who are unable to take adequate contraceptive precautions, have a positive pregnancy test result within 24 hours of study entry, are otherwise known to be pregnant, or are currently breastfeeding an infant.

18. Male subjects who do not agree to use an effective barrier method of contraception during the study and for 14 days post treatment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical Facility	Chula Vista	California	United States	91911
2	Medical Facility	Torrance	California	United States	90509
3	Medical Facility	Idaho Falls	Idaho	United States	83404
4	Medical Facility	Boston	Massachusetts	United States	02111
5	Medical Facility	Royal Oak	Michigan	United States	48073
6	Medical Facility	Saint Louis	Missouri	United States	63110
7	Medical Facility	Butte	Montana	United States	59701
8	Medical Facility	Lincoln	Nebraska	United States	68510
9	Medical Facility	Omaha	Nebraska	United States	68114
10	Medical Facility	Somers Point	New Jersey	United States	08244
11	Medical Facility	Columbus	Ohio	United States	43210
12	Medical Facility	Columbus	Ohio	United States	43215
13	Medical Facility	Blagoevgrad		Bulgaria	2700
14	Medical Facility	Lom		Bulgaria	3600
15	Medical Facility	Pleven		Bulgaria	5809
16	Medical Facility	Plovdiv		Bulgaria	4003
17	Medical Facility	Plovdiv		Bulgaria	4004
18	Medical Facility	Ruse		Bulgaria	7002
19	Medical Facility	Sofia		Bulgaria	1606
20	Medical Facility	Varna		Bulgaria	9000
21	Medical Facility	Varna		Bulgaria	9002
22	Medical Facility	Kohtla-Järve		Estonia	31025
23	Medical Facility	Tallinn		Estonia	13419
24	Medical Facility	Tallin		Estonia	10138
25	Medical Facility	Tartu		Estonia	51014
26	Medical Facility	Viljandi		Estonia	71024
27	Medical Facility	Võru		Estonia	65526
28	Medical Facility	Gori		Georgia	1400
29	Medical Facility	Kutaisi		Georgia	4600
30	Medical Facility	Tbilisi		Georgia	0102
31	Medical Facility	Tbilisi		Georgia	0114
32	Medical Facility	Tbilisi		Georgia	0141
33	Medical Facility	Tbilisi		Georgia	0144
34	Medical Facility	Tbilisi		Georgia	0159
35	Medical Facility	Tbilisi		Georgia	0160
36	Medical Facility	Kaposvár		Hungary	7400
37	Medical Facility	Pécs		Hungary	7624
38	Medical Facility	Veszprém		Hungary	8200
39	Medical Facility	Daugavpils		Latvia	5417
40	Medical Facility	Riga		Latvia	1038
41	Medical Facility	Rēzekne		Latvia	4600
42	Medical Facility	Bielsk Podlaski		Poland	17-100

Sponsors and Collaborators

• Iterum Therapeutics, International Limited

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - May 29, 2018
• Statistical Analysis Plan - Dec 6, 2019

More Information

Publications

None provided.

• Responsible Party: Iterum Therapeutics, International Limited
• ClinicalTrials.gov Identifier: NCT03358576
• Other Study ID Numbers: IT001-303
• First Posted: Nov 30, 2017
• Last Update Posted: Dec 1, 2020
• Last Verified: Nov 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Infections; Intraabdominal Infections; Amoxicillin; Metronidazole; Ciprofloxacin; Clavulanic Acid; Clavulanic Acids; Amoxicillin-Potassium Clavulanate Combination; Ertapenem; Lactams; Probenecid

Study Results

Participant Flow

Arm/Group Title	Sulopenem	Ertapenem
Arm/Group Description	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 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
Period Title: Overall Study
STARTED	338	336
COMPLETED	312	311
NOT COMPLETED	26	25

Baseline Characteristics

Arm/Group Title	Sulopenem	Ertapenem	Total
Arm/Group Description	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 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 of all reporting groups
Overall Participants	338	336	674
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	226 66.9%	217 64.6%	443 65.7%
>=65 years	112 33.1%	119 35.4%	231 34.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.9 (18.4)	54.8 (18.0)	54.3 (18.2)
Sex: Female, Male (Count of Participants)
Female	160 47.3%	155 46.1%	315 46.7%
Male	178 52.7%	181 53.9%	359 53.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	9 2.7%	8 2.4%	17 2.5%
Not Hispanic or Latino	329 97.3%	328 97.6%	657 97.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Latvia	26 7.7%	30 8.9%	56 8.3%
Hungary	25 7.4%	21 6.3%	46 6.8%
United States	16 4.7%	16 4.8%	32 4.7%
Georgia	38 11.2%	45 13.4%	83 12.3%
Estonia	37 10.9%	40 11.9%	77 11.4%
Czechia	10 3%	7 2.1%	17 2.5%
Russia	19 5.6%	21 6.3%	40 5.9%
Serbia	5 1.5%	12 3.6%	17 2.5%
Ukraine	64 18.9%	54 16.1%	118 17.5%
Bulgaria	98 29%	90 26.8%	188 27.9%
creatinine clearance (mL/min) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mL/min]	92.7 (41.4)	87.9 (39.1)	90.3 (87.0)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Clinical Success
Description	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
Time Frame	Day 28 +/- 1 day

Outcome Measure Data

Analysis Population Description

micro-MITT population

Arm/Group Title	Sulopenem	Ertapenem
Arm/Group Description	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 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
Measure Participants	249	266
Number [percentage of participants]	85.5 25.3%	90.2 26.8%

2. Secondary Outcome

Title	Percentage of Participants With Clinical Success
Description	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
Time Frame	Day 11-14 +/- 1 day

Outcome Measure Data

Analysis Population Description

micro-MITT population

Arm/Group Title	Sulopenem	Ertapenem
Arm/Group Description	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 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
Measure Participants	249	266
Count of Participants [Participants]	208 61.5%	227 67.6%

Adverse Events

Time Frame	From the time of informed consent through the test-of-cure visit, an average of 28 days
Arm/Group Title	Sulopenem		Ertapenem
Arm/Group Description	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 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
All Cause Mortality
	Sulopenem		Ertapenem
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/338 (1.2%)		4/336 (1.2%)
Serious Adverse Events
	Sulopenem		Ertapenem
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/338 (7.4%)		12/336 (3.6%)
Cardiac disorders
cardiac arrest	1/338 (0.3%)	1	0/336 (0%)	0
ventricular fibrillation	1/338 (0.3%)	1	0/336 (0%)	0
Angina unstable	0/338 (0%)	0	1/336 (0.3%)	1
cardiac failure acute	0/338 (0%)	0	1/336 (0.3%)	1
Gastrointestinal disorders
Diarrhoea	2/338 (0.6%)	2	0/336 (0%)	0
Ileus paralytic	1/338 (0.3%)	1	0/336 (0%)	0
intestinal perforation	1/338 (0.3%)	1	0/336 (0%)	0
mesenteric artery thrombosis	1/338 (0.3%)	1	0/336 (0%)	0
volvulus of small bowel	1/338 (0.3%)	1	0/336 (0%)	0
ileus	0/338 (0%)	0	1/336 (0.3%)	1
intra-abdominal haematoma	0/338 (0%)	0	1/336 (0.3%)	1
intra-abdominal haemorrhage	0/338 (0%)	0	1/336 (0.3%)	1
irritable bowel syndrome	0/338 (0%)	0	1/336 (0.3%)	1
small intestine obstruction	0/338 (0%)	0	1/336 (0.3%)	1
General disorders
multiple organ dysfunction syndrome	1/338 (0.3%)	1	1/336 (0.3%)	1
pyrexia	1/338 (0.3%)	1	0/336 (0%)	0
sudden death	1/338 (0.3%)	1	0/336 (0%)	0
systemic inflammatory response syndrome	0/338 (0%)	0	1/336 (0.3%)	1
Infections and infestations
Abdominal abscess	6/338 (1.8%)	6	0/336 (0%)	0
liver abscess	2/338 (0.6%)	2	1/336 (0.3%)	1
appendiceal abscess	1/338 (0.3%)	1	0/336 (0%)	0
colon gangrene	1/338 (0.3%)	1	0/336 (0%)	0
peritonitis	1/338 (0.3%)	1	0/336 (0%)	0
pneumonia	0/338 (0%)	0	1/336 (0.3%)	1
Injury, poisoning and procedural complications
gastrointestinal anastomotic leak	1/338 (0.3%)	1	0/336 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
colon cancer	0/338 (0%)	0	1/336 (0.3%)	1
Nervous system disorders
cerebrovascular accident	1/338 (0.3%)	1	0/336 (0%)	0
Renal and urinary disorders
renal impairment	1/338 (0.3%)	1	0/336 (0%)	0
renal failure	0/338 (0%)	0	1/336 (0.3%)	1
Respiratory, thoracic and mediastinal disorders
acute respiratory failure	1/338 (0.3%)	1	1/336 (0.3%)	1
pulmonary embolism	1/338 (0.3%)	1	0/336 (0%)	0
Vascular disorders
internal hemorrhage	1/338 (0.3%)	1	0/336 (0%)	0
Other (Not Including Serious) Adverse Events
	Sulopenem		Ertapenem
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/335 (0%)		0/333 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.