A Safety and Tolerability Study of Doripenem Compared With Meropenem in Children Hospitalized With Complicated Intra-abdominal Infections

• Sponsor: Janssen Research & Development, LLC (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01110382
• Collaborator: (none)
• Enrollment: 41
• Locations: 19
• Arms: 2
• Duration (Months): 33
• Patients Per Site: 2.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of the study is to evaluate the safety and tolerability of doripenem compared with meropenem in children hospitalized with complicated intra-abdominal infections.

Condition or Disease	Intervention/Treatment	Phase
Abscess, Intra-Abdominal; Abdominal Abscess; Abdomen, Acute; Abdominal Pain; Appendicitis; Rupture; Infection; Intestinal Perforation; Peritonitis; Ileus	Drug: Doripenem; Drug: Meropenem placebo; Drug: Meropenem; Drug: Doripenem placebo; Drug: Amoxicillin/clavulanate potassium	Phase 3

Detailed Description

This is a randomized (study drug assigned by chance), double-blind (neither physician nor patient knows the name of the assigned study drugs), double-dummy (all patients are given both a placebo [salt solution] and study drug in alternating periods of time during the study), active comparator-controlled (compare the "test" treatment to standard-of-care therapy), multinational, multicenter study to evaluate the safety of the study drugs (doripenem and meropenem) administered by intravenous (iv) infusion (slow injection of drug solution into the vein over a period of time) in children aged 3 months to less than 18 years who are hospitalized with complicated intra abdominal infections (cIAI). Complicated intra abdominal infections include but are not limited to appendicitis with rupture and/or abscess (local collection of pus), acute (severe or intense) gastric, duodenal (beginning section of the small intestine), or gall bladder perforation (a hole in the wall of the stomach, small intestine, or gallbladder), and secondary peritonitis. The study will include 3 periods: a pretreatment (screening) period that will occur within 2 days prior to randomization (assignment of study drug), a treatment period of 5 to 14 days where patients will receive iv study drug treatment only or IV study therapy and a switch to oral antibiotic therapy, and a posttreatment period consisting of 2 study visits. The max duration of study drug therapy is 14 days. The total duration of the study is approximately 7 to 8 weeks. Safety and tolerability will be evaluated by examining the incidence, severity, and type of adverse events, changes in clinical laboratory tests, vital signs measurements, and findings from physical examinations observed during treatment and at each posttreatment visit. An independent monitoring committee (IDMC) will be established for this study to ensure that the safety of patients is not compromised. The IDMC will consist of individuals who are not associated with the conduct of the study, and will include but will not be limited to individuals with expertise relevant to the care of pediatric patients, and including at least one infectious disease physician and at least one statistician. Patients will receive IV Doripenem (20 mg/kg to 500 mg/dose) and meropenem placebo OR meropenem (20 mg/kg to 1 gram/dose) and doripenem placebo once every 8 hours for up to 14 days. If the patient's cIAI symptoms improve after 72 hours of treatment with iv study drug, the investigator may choose to stop iv study drug and switch the patient to an orally administered antibiotic (amoxicillin/clavulanate postassium) to complete the 5- to 14 day course of antibiotic therapy.

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Prospective, Randomized, Double-Blind, Multicenter Study to Establish the Safety and Tolerability of Doripenem Compared With Meropenem in Hospitalized Children With Complicated Intra-Abdominal Infections
• Study Start Date: Dec 1, 2010
• Actual Primary Completion Date: Sep 1, 2013
• Actual Study Completion Date: Sep 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Doripenem Doripenem 20 mg/kg per dose (up to 500 mg/dose)will be administered every 8 hours as 60-minutes IV (at least 3 days of IV doripenem only or IV doripenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.	Drug: Doripenem; Type=once every 8 hours infused over 60 minutes, Unit=mg, Number=20mg/kg up to 500mg/dose, Form=solution for infusion, Route-intravenous use. At least 3 days of iv doripenem administered every 8 hours immediately after meropenem placebo for up to 14 days; Drug: Meropenem placebo; Form=solution for infusion, Route=intravenous use, administered once every 8 hours infused over 30 minutes immediately before each iv infusion of doripenem for up to 14 days.; Drug: Amoxicillin/clavulanate potassium; Form=suspension or tablets, Route=oral (by mouth), may be administered at the discretion of the investigator once every 12 hours for up to 14 days following IV therapy with doripenem or meropenem.
Experimental: Meropenem Meropenem 20 mg/kg per dose (up to 1 g/dose) will be administered every 8 hours as 30-minutes IV (at least 3 days of IV meropenem only or IV meropenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.	Drug: Meropenem; Type=once every 8 hours infused over 30 minutes, Unit=mg, Number=20 mg/kg to 1 gram per dose, Form=solution for infusion, Route=intravenous use. At least 3 days of iv meropenem administered every 8 hours immediately before doripenem placebo for up to 14 days; Drug: Doripenem placebo; Form=solution for infusion, Route=intravenous use, administered once every 8 hours infused over 60 minutes immediately after each iv infusion of meropenem for up to 14 days; Drug: Amoxicillin/clavulanate potassium; Form=suspension or tablets, Route=oral (by mouth), may be administered at the discretion of the investigator once every 12 hours for up to 14 days following IV therapy with doripenem or meropenem.

Outcome Measures

Primary Outcome Measures

1. The Number of Participants With Clinical Cure Rate at Test Of Cure (TOC) Visit [TOC (7 to 14 days after the last dose of study medication therapy)]

   The participants were considered as clinical cure if they had clinical improvement in signs and symptoms of the intra-abdominal infection such that no additional antibacterial therapy or surgical or percutaneous intervention is/was required for the treatment of the index infection, no fever, and a favorable response at End of IV visit.

Secondary Outcome Measures

1. The Number of Participants With Clinical Improvement Rate at End of IV (EIV) Visit [EIV (within 24 hours after completion of the last dose of IV study medication therapy)]

   The participants were considered as clinical improved if they had clinical improvement in signs and symptoms of the intra-abdominal infection, no fever, decrease in WBC, and not received any nonstudy antibiotics for the treatment of intra-abdominal infection after IV study drug therapy had begun.

2. The Number of Participants With Clinical Cure Rate at Late Follow-Up (LFU) Visit [LFU (28 to 42 days after the last dose of study medication therapy)]

   The participants were considered as clinical cure if they had clinical improvement in signs and symptoms of the intra-abdominal infection such that no additional antibacterial therapy or surgical or percutaneous intervention is/was required for the treatment of the index infection, no fever, and a favorable response at End of IV visit.

3. The Number of Participants With Favorable Per-participant Microbiological Response [EIV (within 24 hours after completion of the last dose of IV study medication therapy), TOC (7 to 14 days after the last dose of study medication therapy), and LFU (28 to 42 days after the last dose of study medication therapy)]

   Favorable per-participant microbiological response rate was evaluated at the at End of IV (EIV) visit, Test Of Cure (TOC) visit, and Late Follow-Up (LFU) visit. The favorable per-participant microbiological response was considered when all baseline pathogens were eradicated (absence) or presumed eradicated (absence of material to culture in a participant who has a positive clinical response to treatment).

4. Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at End of IV (EIV) Visit [EIV (within 24 hours after completion of the last dose of IV study medication therapy)]

   A total of 24 pathogens in the doripenem group and 6 pathogens in the meropenem group were isolated at baseline from the intra-abdominal culture and were susceptible to the study drug received. The most common pathogens isolated from the intra-abdominal culture are listed in the table below; the numbers in parenthesis next to each pathogen represent the number of participants with the pathogen isolated at baseline in the doripenem and meropenem treatment groups, respectively. The favorable per-pathogen microbiological outcome was considered when all baseline pathogens were eradicated (absence) or presumed eradicated (absence of material to culture in a participant who has a positive clinical response to treatment).

5. Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at Test Of Cure (TOC) Visit [TOC (7 to 14 days after the last dose of study medication therapy)]

   A total of 24 pathogens in the doripenem group and 6 pathogens in the meropenem group were isolated at baseline from the intra-abdominal culture and were susceptible to the study drug received. The most common pathogens isolated from the intra-abdominal culture are listed in the table below; the numbers in parenthesis next to each pathogen represent the number of participants with the pathogen isolated at baseline in the doripenem and meropenem treatment groups, respectively. The favorable per-pathogen microbiological outcome was considered when all baseline pathogens were eradicated (absence) or presumed eradicated (absence of material to culture in a participant who has a positive clinical response to treatment).

6. Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at Late Follow-Up (LFU) Visit [LFU (28 to 42 days after the last dose of study medication therapy)]

   A total of 24 pathogens in the doripenem group and 6 pathogens in the meropenem group were isolated at baseline from the intra-abdominal culture and were susceptible to the study drug received. The most common pathogens isolated at baseline from the intra-abdominal culture are listed in the table below; the numbers in parenthesis next to each pathogen represent the number of participants with the pathogen isolated in the doripenem and meropenem treatment groups, respectively. The favorable per-pathogen microbiological outcome was considered when all baseline pathogens were eradicated (absence) or presumed eradicated (absence of material to culture in a participant who has a positive clinical response to treatment).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 3 Months to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients who are eligible for the study must have clinical evidence of cIAI

• Require surgical intervention (eg, laparotomy, laparoscopic surgery, or percutaneous drainage) to manage the cIAI

• Require antibacterial therapy for 5 to 14 days in addition to the surgical intervention

• Must, based on the judgment of the investigator, require hospitalization initially and antibacterial therapy for 5 to 14 days in addition to surgical intervention for the treatment of the current cIAI. (Note that the patient must require at least 3 days of IV antibiotic therapy initially)

• Have a signed informed consent form completed by the patient's parent or legal representative (and a signed assent form obtained from patients who are capable of providing assent, typically, children 7 years of age and older)

Exclusion Criteria:

• Have a history of hypersensitivity reactions to carbapenems, cephalosporins, penicillins, or other beta-lactam antibiotics

• concomitant infection including but not limited to suspected or confirmed meningitis or central nervous system infection requiring systemic antibiotic or antifungal therapy in addition to the iv study drug therapy at the time of randomization

• Receipt of nonstudy systemic antibiotic therapy for cIAI for more than 24 hours immediately preceding the start of the infusion of the first dose of iv study drug therapy

• Have a diagnosis of abdominal wall abscess confined to musculature of the abdominal wall, small bowel obstruction or ischemic bowel disease without perforation, traumatic bowel perforation requiring surgery within 12 hours of perforation, or perforation of gastroduodenal ulcers requiring surgery within 24 hours of perforation (these are considered situations of peritoneal soiling before the infection has become established)

• Have simple (noncomplicated), nonperforated appendicitis or gangrenous appendicitis without rupture into the peritoneal cavity identified during a surgical procedure OR presence of spontaneous bacterial peritonitis or peritonitis associated with cirrhosis or chronic ascites

• Known at the time of randomization to have a cIAI caused by at least one pathogen that is nonsusceptible to doripenem or meropenem

• Presence of any of the following clinically significant laboratory abnormalities: Hematocrit of less than 20%, absolute neutrophil count (ANC) <500 cells/µL, platelet count <40,000 cells/µL, serum alanine aminotransferase or aspartate aminotransferase (AST) or total bilirubin 5 times or greater the age-specific upper limit of normal (ULN) or acute/chronic renal insufficiency with a baseline creatinine clearance <50 mL per minute or requires dialysis therapy for any reason

• Have a history of uncontrolled epilepsy defined as at least 1 seizure within the 6 months before randomization

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		San Diego	California	United States
2		Washington	District of Columbia	United States
3		Cleveland	Ohio	United States
4		Toledo	Ohio	United States
5		Buenos Aires		Argentina
6		Córdoba		Argentina
7		Loma Hermosa N/A		Argentina
8		Paraná, Entre Ríos		Argentina
9		Santa Fe		Argentina
10		Passo Fundo		Brazil
11		São Paulo		Brazil
12		Santiago		Chile
13		Valdivia X Región		Chile
14		Bogota		Colombia
15		Floridablanca		Colombia
16		Riga		Latvia
17		Kaunas		Lithuania
18		Vilnius		Lithuania
19		Zona		Panama

Sponsors and Collaborators

• Janssen Research & Development, LLC

Investigators

• Study Director: Janssen Research & Development, LLC C. Clinical Trial, Janssen Research & Development, LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT01110382
• Other Study ID Numbers: CR016789; DORIPED3001; 2009-015864-32
• First Posted: Apr 26, 2010
• Last Update Posted: Jul 15, 2014
• Last Verified: Jul 1, 2014

• Keywords provided by Janssen Research & Development, LLC: Anti-Infective Agents; Doripenem; Meropenem; Child, Hospitalized; Complicated Intra-Abdominal Infections
• Additional relevant MeSH terms: Infections; Communicable Diseases; Appendicitis; Abscess; Peritonitis; Intraabdominal Infections; Abdominal Abscess; Intestinal Perforation; Abdominal Pain; Abdomen, Acute; Rupture; Amoxicillin; Meropenem; Clavulanic Acid; Clavulanic Acids; Doripenem; Amoxicillin-Potassium Clavulanate Combination

Study Results

Participant Flow

Arm/Group Title	Doripenem	Meropenem
Arm/Group Description	Doripenem 20 mg/kg per dose (up to 500 mg/dose) was administered every 8 hours as 60-minutes IV (at least 3 days of IV doripenem only or IV doripenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.	Meropenem 20 mg/kg per dose (up to 1 g/dose) was administered every 8 hours as 30-minutes IV (at least 3 days of IV meropenem only or IV meropenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.
Period Title: Overall Study
STARTED	31	10
COMPLETED	31	8
NOT COMPLETED	0	2

Baseline Characteristics

Arm/Group Title	Doripenem	Meropenem	Total
Arm/Group Description	Doripenem 20 mg/kg per dose (up to 500 mg/dose) was administered every 8 hours as 60-minutes IV (at least 3 days of IV doripenem only or IV doripenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.	Meropenem 20 mg/kg per dose (up to 1 g/dose) was administered every 8 hours as 30-minutes IV (at least 3 days of IV meropenem only or IV meropenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.	Total of all reporting groups
Overall Participants	31	10	41
Age (Count of Participants)
<=18 years	31 100%	10 100%	41 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	8.5 (3.40)	9.3 (4.52)	8.7 (3.66)
Age, Customized (participants) [Number]
3 months to <2 years	0 0%	0 0%	0 0%
2 to <6 years	5 16.1%	3 30%	8 19.5%
6 to <12 years	18 58.1%	4 40%	22 53.7%
12 to <18 years	8 25.8%	3 30%	11 26.8%
Sex: Female, Male (Count of Participants)
Female	15 48.4%	0 0%	15 36.6%
Male	16 51.6%	10 100%	26 63.4%

Outcome Measures

1. Primary Outcome

Title	The Number of Participants With Clinical Cure Rate at Test Of Cure (TOC) Visit
Description	The participants were considered as clinical cure if they had clinical improvement in signs and symptoms of the intra-abdominal infection such that no additional antibacterial therapy or surgical or percutaneous intervention is/was required for the treatment of the index infection, no fever, and a favorable response at End of IV visit.
Time Frame	TOC (7 to 14 days after the last dose of study medication therapy)

Outcome Measure Data

Analysis Population Description

Clinical Intent-to-Treat (CITT): All randomized participants who met the minimal disease definition of complicated intra-abdominal infection regardless if a baseline pathogen was isolated from the intra-abdominal cavity.

Arm/Group Title	Doripenem	Meropenem
Arm/Group Description	Doripenem 20 mg/kg per dose (up to 500 mg/dose) was administered every 8 hours as 60-minutes IV (at least 3 days of IV doripenem only or IV doripenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.	Meropenem 20 mg/kg per dose (up to 1 g/dose) was administered every 8 hours as 30-minutes IV (at least 3 days of IV meropenem only or IV meropenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.
Measure Participants	31	10
Number [participants]	23 74.2%	7 70%

2. Secondary Outcome

Title	The Number of Participants With Clinical Improvement Rate at End of IV (EIV) Visit
Description	The participants were considered as clinical improved if they had clinical improvement in signs and symptoms of the intra-abdominal infection, no fever, decrease in WBC, and not received any nonstudy antibiotics for the treatment of intra-abdominal infection after IV study drug therapy had begun.
Time Frame	EIV (within 24 hours after completion of the last dose of IV study medication therapy)

Outcome Measure Data

Analysis Population Description

Clinical Intent-to-Treat (CITT): All randomized participants who met the minimal disease definition of complicated intra-abdominal infection regardless if a baseline pathogen was isolated from the intra-abdominal cavity.

Arm/Group Title	Doripenem	Meropenem
Arm/Group Description	Doripenem 20 mg/kg per dose (up to 500 mg/dose) was administered every 8 hours as 60-minutes IV (at least 3 days of IV doripenem only or IV doripenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.	Meropenem 20 mg/kg per dose (up to 1 g/dose) was administered every 8 hours as 30-minutes IV (at least 3 days of IV meropenem only or IV meropenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.
Measure Participants	31	10
Number [participants]	29 93.5%	8 80%

3. Secondary Outcome

Title	The Number of Participants With Clinical Cure Rate at Late Follow-Up (LFU) Visit
Description	The participants were considered as clinical cure if they had clinical improvement in signs and symptoms of the intra-abdominal infection such that no additional antibacterial therapy or surgical or percutaneous intervention is/was required for the treatment of the index infection, no fever, and a favorable response at End of IV visit.
Time Frame	LFU (28 to 42 days after the last dose of study medication therapy)

Outcome Measure Data

Analysis Population Description

Clinical Intent-to-Treat (CITT): All randomized participants who met the minimal disease definition of complicated intra-abdominal infection regardless if a baseline pathogen was isolated from the intra-abdominal cavity.

Arm/Group Title	Doripenem	Meropenem
Arm/Group Description	Doripenem 20 mg/kg per dose (up to 500 mg/dose) was administered every 8 hours as 60-minutes IV (at least 3 days of IV doripenem only or IV doripenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.	Meropenem 20 mg/kg per dose (up to 1 g/dose) was administered every 8 hours as 30-minutes IV (at least 3 days of IV meropenem only or IV meropenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.
Measure Participants	31	10
Number [participants]	22 71%	6 60%

4. Secondary Outcome

Title	The Number of Participants With Favorable Per-participant Microbiological Response
Description	Favorable per-participant microbiological response rate was evaluated at the at End of IV (EIV) visit, Test Of Cure (TOC) visit, and Late Follow-Up (LFU) visit. The favorable per-participant microbiological response was considered when all baseline pathogens were eradicated (absence) or presumed eradicated (absence of material to culture in a participant who has a positive clinical response to treatment).
Time Frame	EIV (within 24 hours after completion of the last dose of IV study medication therapy), TOC (7 to 14 days after the last dose of study medication therapy), and LFU (28 to 42 days after the last dose of study medication therapy)

Outcome Measure Data

Analysis Population Description

Microbiological intent-to-treat - Participants of CITT with at least 1 baseline bacterial pathogen isolated from the intra-abdominal cavity that was susceptible to both doripenem and meropenem. 8 and 2 participants from doripenem and meropenem, respectively had no susceptible intra-abdominal pathogen at baseline and were excluded from this set.

Arm/Group Title	Doripenem	Meropenem
Arm/Group Description	Doripenem 20 mg/kg per dose (up to 500 mg/dose) was administered every 8 hours as 60-minutes IV (at least 3 days of IV doripenem only or IV doripenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.	Meropenem 20 mg/kg per dose (up to 1 g/dose) was administered every 8 hours as 30-minutes IV (at least 3 days of IV meropenem only or IV meropenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.
Measure Participants	23	8
EIV visit	21 67.7%	6 60%
TOC visit	17 54.8%	5 50%
LFU visit	17 54.8%	5 50%

5. Secondary Outcome

Title	Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at End of IV (EIV) Visit
Description	A total of 24 pathogens in the doripenem group and 6 pathogens in the meropenem group were isolated at baseline from the intra-abdominal culture and were susceptible to the study drug received. The most common pathogens isolated from the intra-abdominal culture are listed in the table below; the numbers in parenthesis next to each pathogen represent the number of participants with the pathogen isolated at baseline in the doripenem and meropenem treatment groups, respectively. The favorable per-pathogen microbiological outcome was considered when all baseline pathogens were eradicated (absence) or presumed eradicated (absence of material to culture in a participant who has a positive clinical response to treatment).
Time Frame	EIV (within 24 hours after completion of the last dose of IV study medication therapy)

Outcome Measure Data

Analysis Population Description

Microbiological intent-to-treat - Participants of CITT with at least 1 baseline bacterial pathogen isolated from the intra-abdominal cavity that was susceptible to both doripenem and meropenem. 8 and 2 participants from doripenem and meropenem, respectively had no susceptible intra-abdominal pathogen at baseline and were excluded from this set.

Arm/Group Title	Doripenem	Meropenem
Arm/Group Description	Doripenem 20 mg/kg per dose (up to 500 mg/dose) was administered every 8 hours as 60-minutes IV (at least 3 days of IV doripenem only or IV doripenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.	Meropenem 20 mg/kg per dose (up to 1 g/dose) was administered every 8 hours as 30-minutes IV (at least 3 days of IV meropenem only or IV meropenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.
Measure Participants	23	8
Streptococcus anginosus (13, 0)	12 38.7%	NA NaN
Escherichia coli (19, 8)	18 58.1%	6 60%
Bacteroides fragilis (11, 1)	10 32.3%	1 10%

6. Secondary Outcome

Title	Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at Test Of Cure (TOC) Visit
Description	A total of 24 pathogens in the doripenem group and 6 pathogens in the meropenem group were isolated at baseline from the intra-abdominal culture and were susceptible to the study drug received. The most common pathogens isolated from the intra-abdominal culture are listed in the table below; the numbers in parenthesis next to each pathogen represent the number of participants with the pathogen isolated at baseline in the doripenem and meropenem treatment groups, respectively. The favorable per-pathogen microbiological outcome was considered when all baseline pathogens were eradicated (absence) or presumed eradicated (absence of material to culture in a participant who has a positive clinical response to treatment).
Time Frame	TOC (7 to 14 days after the last dose of study medication therapy)

Outcome Measure Data

Analysis Population Description

Microbiological intent-to-treat - Participants of CITT with at least 1 baseline bacterial pathogen isolated from the intra-abdominal cavity that was susceptible to both doripenem and meropenem. 8 and 2 participants from doripenem and meropenem, respectively had no susceptible intra-abdominal pathogen at baseline and were excluded from this set.

Arm/Group Title	Doripenem	Meropenem
Arm/Group Description	Doripenem 20 mg/kg per dose (up to 500 mg/dose) was administered every 8 hours as 60-minutes IV (at least 3 days of IV doripenem only or IV doripenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.	Meropenem 20 mg/kg per dose (up to 1 g/dose) was administered every 8 hours as 30-minutes IV (at least 3 days of IV meropenem only or IV meropenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.
Measure Participants	23	8
Streptococcus anginosus (13, 0)	9 29%	NA NaN
Escherichia coli (19, 8)	15 48.4%	5 50%
Bacteroides fragilis (11, 1)	9 29%	1 10%

7. Secondary Outcome

Title	Number of Participants With Favorable Per-pathogen Microbiological Outcome Rate at Late Follow-Up (LFU) Visit
Description	A total of 24 pathogens in the doripenem group and 6 pathogens in the meropenem group were isolated at baseline from the intra-abdominal culture and were susceptible to the study drug received. The most common pathogens isolated at baseline from the intra-abdominal culture are listed in the table below; the numbers in parenthesis next to each pathogen represent the number of participants with the pathogen isolated in the doripenem and meropenem treatment groups, respectively. The favorable per-pathogen microbiological outcome was considered when all baseline pathogens were eradicated (absence) or presumed eradicated (absence of material to culture in a participant who has a positive clinical response to treatment).
Time Frame	LFU (28 to 42 days after the last dose of study medication therapy)

Outcome Measure Data

Analysis Population Description

Microbiological intent-to-treat - Participants of CITT with at least 1 baseline bacterial pathogen isolated from the intra-abdominal cavity that was susceptible to both doripenem and meropenem. 8 and 2 participants from doripenem and meropenem, respectively had no susceptible intra-abdominal pathogen at baseline and were excluded from this set.

Arm/Group Title	Doripenem	Meropenem
Arm/Group Description	Doripenem 20 mg/kg per dose (up to 500 mg/dose) was administered every 8 hours as 60-minutes IV (at least 3 days of IV doripenem only or IV doripenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.	Meropenem 20 mg/kg per dose (up to 1 g/dose) was administered every 8 hours as 30-minutes IV (at least 3 days of IV meropenem only or IV meropenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.
Measure Participants	23	8
Streptococcus anginosus (13, 0)	9 29%	NA NaN
Escherichia coli (19, 8)	15 48.4%	5 50%
Bacteroides fragilis (11, 1)	9 29%	1 10%

Adverse Events

Time Frame	Approximately 8 weeks
Arm/Group Title	Doripenem		Meropenem
Arm/Group Description	Doripenem 20 mg/kg per dose (up to 500 mg/dose) was administered every 8 hours as 60-minutes IV (at least 3 days of IV doripenem only or IV doripenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.		Meropenem 20 mg/kg per dose (up to 1 g/dose) was administered every 8 hours as 30-minutes IV (at least 3 days of IV meropenem only or IV meropenem followed by oral amoxicillin/clavulanate potassium). Total duration of treatment 5 to 14 days.
All Cause Mortality
	Doripenem		Meropenem
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Doripenem		Meropenem
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/31 (22.6%)		0/10 (0%)
Gastrointestinal disorders
Abdominal Pain	3/31 (9.7%)		0/10 (0%)
Functional Gastrointestinal Disorder	1/31 (3.2%)		0/10 (0%)
Infections and infestations
Abdominal Abscess	1/31 (3.2%)		0/10 (0%)
Injury, poisoning and procedural complications
Overdose	1/31 (3.2%)		0/10 (0%)
Seroma	1/31 (3.2%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Doripenem		Meropenem
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/31 (48.4%)		6/10 (60%)
Blood and lymphatic system disorders
Eosinophilia	2/31 (6.5%)		0/10 (0%)
Cardiac disorders
Ventricular Extrasystoles	0/31 (0%)		1/10 (10%)
Gastrointestinal disorders
Nausea	3/31 (9.7%)		0/10 (0%)
Abdominal Distension	2/31 (6.5%)		1/10 (10%)
Abdominal Pain	2/31 (6.5%)		0/10 (0%)
Constipation	2/31 (6.5%)		0/10 (0%)
Vomiting	2/31 (6.5%)		2/10 (20%)
Diarrhoea	1/31 (3.2%)		2/10 (20%)
Tongue Ulceration	0/31 (0%)		1/10 (10%)
Infections and infestations
Nasopharyngitis	0/31 (0%)		1/10 (10%)
Otitis Media	0/31 (0%)		1/10 (10%)
Investigations
Alanine Aminotransferase Increased	2/31 (6.5%)		0/10 (0%)
Gamma-Glutamyltransferase Increased	2/31 (6.5%)		0/10 (0%)
Electrocardiogram QT Prolonged	0/31 (0%)		1/10 (10%)
Skin and subcutaneous tissue disorders
Rash	0/31 (0%)		1/10 (10%)

Limitations/Caveats

This study was terminated early due to business reasons and not related to safety concerns or issues. As such, the limited enrollment precludes a meaningful conclusion about the efficacy and safety of doripenem compared with meropenem.

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Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.