Study to Compare TP-434 and Ertapenem in Community-acquired Complicated Intra-abdominal Infections

• Sponsor: Tetraphase Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01265784
• Collaborator: (none)
• Enrollment: 143
• Locations: 38
• Arms: 3
• Duration (Months): 16
• Patients Per Site: 3.8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a Phase 2, randomized, double-blind, double-dummy, multicenter, prospective study to assess the efficacy, safety, and pharmacokinetics of two dose regimens of TP-434 compared with ertapenem in the treatment of adult community-acquired complicated intra-abdominal infections (cIAIs).

Condition or Disease	Intervention/Treatment	Phase
Complicated Intra-abdominal Infection	Drug: TP-434; Drug: Ertapenem; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 143 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Randomized, Double-Blind, Double-Dummy, Multicenter, Prospective Study to Assess the Efficacy, Safety, and PK of 2 Dose Regimens of TP-434 Compared With Ertapenem in Adult Community-Acquired Complicated Intra-abdominal Infections
• Study Start Date: Jan 1, 2011
• Actual Primary Completion Date: May 1, 2012
• Actual Study Completion Date: May 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TP-434, 1.5 mg/kg q24h TP-434 was administered intravenously (IV) at a dose of 1.5 milligrams per kilogram of body weight (mg/kg) every 24 hours (q24h) for a minimum of 4 days and a maximum of 14 days (7 days for participants in India). TP-434 treatment was to be stopped when symptoms of complicated intra-abdominal infection (cIAI) resolved, there was treatment failure, or the maximum allowed number of infusion days was reached.	Drug: TP-434; Other Names: Eravacycline ; Drug: Placebo; Administered IV to maintain the blind.
Experimental: TP-434, 1.0 mg/kg q12h TP-434 was administered IV at a dose of 1.0 mg/kg every 12 hours (q12h) for a minimum of 4 days and a maximum of 14 days (7 days for participants in India). TP-434 treatment was to be stopped when symptoms of cIAI resolved, there was treatment failure, or the maximum allowed number of infusion days was reached.	Drug: TP-434; Other Names: Eravacycline ; Drug: Placebo; Administered IV to maintain the blind.
Active Comparator: Ertapenem, 1 g q24h Ertapenem was administered IV at a dose of 1 gram (g) q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India). Ertapenem treatment was to be stopped when symptoms of cIAI resolved, there was treatment failure, or the maximum allowed number of infusion days was reached.	Drug: Ertapenem; Other Names: Invanz ; Drug: Placebo; Administered IV to maintain the blind.

Outcome Measures

Primary Outcome Measures

1. Clinical Response to TP-434 and Ertapenem in the Microbiologically Evaluable (ME) Population at the Test-of-Cure Visit [TOC Visit (10-14 days after last dose of study drug)]

   Clinical response was classified as cure (complete resolution or significant improvement of signs and symptoms of the index infection), failure (death related to complicated intra-abdominal infection [cIAI], persisting or recurrent infection within the abdomen, postsurgical wound infection, or administration of effective concomitant antibacterial therapy), or indeterminate (Test-of-Cure [TOC] assessment was not available, death unrelated to cIAI, or some other reason).

Secondary Outcome Measures

1. Clinical Response to TP-434 and Ertapenem in the Modified Intent-to-treat (MITT) Population at the End-of-Treatment (EOT) Visit [EOT Visit (4-14 days after first dose of study drug)]

2. Clinical Response to TP-434 and Ertapenem in the Modified Intent-to-treat (MITT) Population at TOC Visit [TOC Visit (10-14 days after last dose of study drug)]

3. Clinical Response to TP-434 and Ertapenem in the Modified Intent-to-treat (MITT) Population at the Follow-up Visit [Follow-up Visit (28-42 days after last dose of study drug)]

4. Clinical Response to TP-434 and Ertapenem in the Clinically Modified Intent-to-treat (c-MITT) Population at the EOT Visit [EOT Visit (4-14 days after first dose of study drug)]

5. Clinical Response to TP-434 and Ertapenem in the Clinically Modified Intent-to-treat (c-MITT) Population at the TOC Visit [TOC Visit (10-14 days after last dose of study drug)]

6. Clinical Response to TP-434 and Ertapenem in the Clinically Modified Intent-to-treat (c-MITT) Population at the Follow-up Visit [Follow-up Visit (28-42 days after last dose of study drug)]

7. Clinical Response to TP-434 and Ertapenem in the Microbiologically Modified Intent-to-treat (m-MITT) Population at the EOT Visit [EOT Visit (4-14 days after first dose of study drug)]

8. Clinical Response to TP-434 and Ertapenem in the Microbiologically Modified Intent-to-treat (m-MITT) Population at the TOC Visit [TOC Visit (10-14 days after last dose of study drug)]

9. Clinical Response to TP-434 and Ertapenem in the Microbiologically Modified Intent-to-treat (m-MITT) Population at the Follow-up Visit [Follow-Up Visit (28-42 days after last dose of study drug)]

10. Clinical Response to TP-434 and Ertapenem in the Clinically Evaluable (CE) Population at the EOT Visit [EOT Visit (4-14 days after first dose of study drug)]

11. Clinical Response to TP-434 and Ertapenem in the Clinically Evaluable (CE) Population at the TOC Visit [TOC Visit (10-14 days after last dose of study drug)]

12. Clinical Response to TP-434 and Ertapenem in the Clinically Evaluable (CE) Population at the Follow-up Visit [Follow-up Visit (28-42 days after last dose of study drug)]

13. Clinical Response to TP-434 and Ertapenem in the Microbiologically Evaluable (ME) Population at the EOT Visit [EOT Visit (4-14 days after first dose of study drug)]

14. Clinical Response to TP-434 and Ertapenem in the Microbiologically Evaluable (ME) Population at the Follow-up Visit [Follow-up Visit (28-42 days after last dose of study drug)]

15. Microbiologic Response to TP-434 and Ertapenem in the m-MITT Population at the EOT Visit [EOT Visit (4-14 days after first dose of study drug)]

    Microbiological response was classified as favorable (eradication or presumed eradication), unfavorable (persistence, presumed persistence, superinfection, or new infection), or indeterminate (assessment not possible).

16. Microbiologic Response to TP-434 and Ertapenem in the m-MITT Population at the TOC Visit [TOC Visit (10-14 days after last dose of study drug)]

17. Microbiologic Response to TP-434 and Ertapenem in the ME Population at the EOT Visit [EOT Visit (4-14 days after first dose of study drug)]

18. Microbiologic Response to TP-434 and Ertapenem in the ME Population at the TOC Visit [TOC Visit (10-14 days after last dose of study drug)]

19. Pharmacokinetics: Maximum Concentration (Cmax) of TP-434 [Prior to first infusion and 1, 3, 7, 12, 48, and 108 hours after start of first infusion]

20. Pharmacokinetics: Area Under the Concentration Time Curve From Time 0 to 12 Hours (AUC[0-12]) of TP-434 [Prior to first infusion and 1, 3, 7, 12, 48, and 108 hours after start of first infusion]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Abdominal pain/discomfort with onset prior to hospitalization

• Evidence of a systemic inflammatory response

• Physical findings consistent with intra-abdominal infection (IAI)

• Clinical diagnosis of community-acquired IAI requiring urgent surgical or percutaneous intervention and not expected to require antibacterial therapy for longer than 14 days

• Body mass index (BMI) of ≤ 30 kilograms per square meter (kg/m^2)

• Able to provide informed consent. If the participant is unable to provide informed consent, the participant's legally acceptable representative may provide written consent in accordance with institutional guidelines

• If female, not pregnant or nursing or, if of child-bearing potential either: will commit to use at least two medically accepted, effective methods of birth control (for example, condom, oral contraceptive, indwelling intrauterine device, hormonal implant/patch, injections, approved cervical ring) during study drug dosing and for 90 days following last study drug dose or practicing sexual abstinence

Exclusion Criteria:

• Symptoms related to diagnosis of complicated appendicitis (if current diagnosis) for < 24 hours prior to current hospitalization

• Previously hospitalized or admitted to a healthcare facility within the last 6 months

• Managed by Staged Abdominal Repair or other open abdomen technique

• Known at study entry to have an IAI caused by a pathogen(s) resistant to both study drug antibiotics

• Acute Physiology and Chronic Health Evaluation (APACHE) II score > 25

• Unlikely to survive the 6-8 week study period

• Any rapidly-progressing disease or immediately life-threatening illness, including acute hepatic failure, respiratory failure and septic shock

• Requirement for vasopressors at therapeutic dosages

• Renal failure

• Presence or possible signs of hepatic disease

• Hematocrit < 25% or hemoglobin < 8 grams per deciliter (g/dL)

• Neutropenia with absolute neutrophil count < 1000 cells per cubic millimeter (mm^3)

• Platelet count < 50,000/mm3

• Abnormal coagulation tests or participant on anticoagulants

• Immunocompromised condition, including known human immunodeficiency virus (HIV) positivity or acquired immune deficiency syndrome (AIDS), organ (bone marrow) transplant recipients, and hematological malignancy. Immunosuppressive therapy, including use of high-dose corticosteroids (for example, > 40 milligrams [mg] prednisone or equivalent per day for greater than 2 weeks)

• History of hypersensitivity reactions to tetracyclines or carbapenems

• Participation in any investigational drug or device study within 30 days prior to study entry

• Known or suspected central nervous system (CNS) disorder that may predispose to seizures or lower seizure threshold

• Previously received TP-434 in a clinical trial

• More than 24 hours duration of systemic antibiotic coverage for current condition

• Received ertapenem or any other carbapenem, or tigecycline for the current infection

• Need for concomitant systemic antimicrobial agents other than study drug or received systemic (IV or oral) antibiotics in the last 3 months

• Refusal of mechanical ventilation, dialysis or hemofiltration, cardioversion or any other resuscitative measures and drug/fluid therapy at time of consent

• Known or suspected inflammatory bowel disease or associated visceral abscess

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Long Beach VA Medical Center	Long Beach	California	United States	90822
2	Denver Health Medical Center	Denver	Colorado	United States	80204
3	Henry Ford Hospital	Detroit	Michigan	United States	48202
4	Barnes Jewish Hospital	Saint Louis	Missouri	United States	63110
5	Mercury Street Medical Group	Butte	Montana	United States	59701
6	MHAT "Yulia Vrevska - Byala" EOOD, Byala	Byala		Bulgaria	7100
7	UMHAT "Dr. Georgi Stranski" EAD, Pleven	Pleven		Bulgaria	5800
8	UMHAT "Sveti Georgi" EAD, Plovdiv	Plovdiv		Bulgaria	4000
9	MHAT "Russe" AD, Russe	Russe		Bulgaria	7002
10	MHAT "Tokuda Hospital Sofia" AD, Sofia	Sofia		Bulgaria	1407
11	UMHAT "Tzaritza Yoanna" EAD, Sofia	Sofia		Bulgaria	1527
12	UMHATEM "N.I. Pirogov" EAD, Sofia	Sofia		Bulgaria	1606
13	UMHATEM "N.I.Pirogov" EAD, Sofia	Sofia		Bulgaria	1606
14	Bangalore Medical College and Research Institute, Victoria Hospital	Fort	Bangalore	India	560002
15	Amrita Institute of Medical Sciences and Research Centre	Kochi	Kerala	India	682041
16	Sahyadri Munot Hospital	Pune	Maharashtra	India	411042
17	S.R. Kalla Memorial Gastro & General Hospital	Jaipur	Rajasthan	India
18	HCG-Medisurge Hospitals Pvt. Ltd.	Ahmedabad		India	380006
19	Santosh Hospital	Bangalore		India	560005
20	K.R. Hospital	Bangalore		India	560050
21	M.S. Ramalah Medical College and Hospitals	Bangalore		India	560054
22	Sai Vani Hospitals, Ltd.	Hyderabad		India	500029
23	Daugavpils Regional Hospital	Daugavpils		Latvia	LV-5417
24	Jekabpils Regional Hospital	Jekabpils		Latvia	LV 5201
25	Rezeknes Hospital	Rezekne		Latvia	LV-4601
26	Vidzeme Hospital	Valmiera		Latvia	LV-4201
27	Kaunas Hospital	Kaunas		Lithuania	LT-45130
28	Kaunas Clinical Hospital	Kaunas		Lithuania	LT-47144
29	Hospital of Lithuanian University of Health Sciences Kaunas Clinics	Kaunas		Lithuania	LT-50009
30	Klaipeda University Hospital	Klaipeda		Lithuania	LT-92288
31	Vilnius University Hospital Santariskiu Clinics	Vilnius		Lithuania	LT-08661
32	Vilnius City Clinical Hospital	Vilnius		Lithuania	LT-10207
33	Emergency Clinical City Hospital	Timisoara	Timis	Romania	300079
34	"Dr. Carol Davila" Clinical Nephrology Hospital General Surgery Clinic	Bucharest		Romania	010701
35	Emergency Clinical Hospital Bucharest	Bucharest		Romania	014461
36	Coltea Clinical Hospital	Bucharest		Romania	030171
37	:Sfantul loan" Clinical Emergency Hospital	Bucharest		Romania	042122
38	University Emergency Hospital Bucharest	Bucharest		Romania	050098

Sponsors and Collaborators

• Tetraphase Pharmaceuticals, Inc.

Investigators

• Study Director: Patrick T Horn, MD, PhD, Tetraphase Pharmaceuticals, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Tetraphase Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT01265784
• Other Study ID Numbers: TP-434-P2-cIAI-1
• First Posted: Dec 23, 2010
• Last Update Posted: Jan 6, 2022
• Last Verified: Dec 1, 2021

• Additional relevant MeSH terms: Infections; Communicable Diseases; Intraabdominal Infections; Ertapenem

Study Results

Participant Flow

Pre-assignment Detail	Randomization was stratified by site of infection (complicated appendicitis versus all other diagnoses).

Arm/Group Title	TP-434, 1.5 mg/kg q24h	TP-434, 1.0 mg/kg q12h	Ertapenem, 1 g q24h
Arm/Group Description	TP-434 was administered intravenously (IV) at a dose of 1.5 milligrams per kilogram of body weight (mg/kg) every 24 hours (q24h) for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	TP-434 was administered IV at a dose of 1.0 mg/kg every 12 hours (q12h) for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	Ertapenem was administered IV at a dose of 1 gram (g) q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).
Period Title: Overall Study
STARTED	56	57	30
Received at Least 1 Dose of Study Drug	54	56	29
COMPLETED	44	49	26
NOT COMPLETED	12	8	4

Baseline Characteristics

Arm/Group Title	TP-434, 1.5 mg/kg q24h	TP-434, 1.0 mg/kg q12h	Ertapenem 1 g q24h	Total
Arm/Group Description	TP-434 was administered IV at a dose of 1.5 mg/kg q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	TP-434 was administered IV at a dose of 1.0 mg/kg q12h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	Ertapenem was administered IV at a dose of 1 g q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	Total of all reporting groups
Overall Participants	56	57	30	143
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43.6 (18.39)	42.1 (17.16)	41.8 (17.60)	42.6 (17.64)
Sex: Female, Male (Count of Participants)
Female	18 32.1%	14 24.6%	8 26.7%	40 28%
Male	38 67.9%	43 75.4%	22 73.3%	103 72%
Region of Enrollment (participants) [Number]
United States	0 0%	0 0%	1 3.3%	1 0.7%
Romania	6 10.7%	9 15.8%	6 20%	21 14.7%
Lithuania	17 30.4%	13 22.8%	7 23.3%	37 25.9%
Bulgaria	9 16.1%	6 10.5%	3 10%	18 12.6%
Latvia	8 14.3%	9 15.8%	4 13.3%	21 14.7%
India	16 28.6%	20 35.1%	9 30%	45 31.5%

Outcome Measures

1. Primary Outcome

Title	Clinical Response to TP-434 and Ertapenem in the Microbiologically Evaluable (ME) Population at the Test-of-Cure Visit
Description	Clinical response was classified as cure (complete resolution or significant improvement of signs and symptoms of the index infection), failure (death related to complicated intra-abdominal infection [cIAI], persisting or recurrent infection within the abdomen, postsurgical wound infection, or administration of effective concomitant antibacterial therapy), or indeterminate (Test-of-Cure [TOC] assessment was not available, death unrelated to cIAI, or some other reason).
Time Frame	TOC Visit (10-14 days after last dose of study drug)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug, met the minimal disease definition of cIAI, had a baseline pathogen identified, and had a microbiological response assessed.

Arm/Group Title	TP-434, 1.5 mg/kg q24h	TP-434, 1.0 mg/kg q12h	Ertapenem 1 g q24h
Arm/Group Description	TP-434 was administered IV at a dose of 1.5 mg/kg q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	TP-434 was administered IV at a dose of 1.0 mg/kg q12h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	Ertapenem was administered IV at a dose of 1 g q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).
Measure Participants	42	41	26
Cure	39 69.6%	41 71.9%	24 80%
Failure	3 5.4%	0 0%	2 6.7%
Indeterminate	0 0%	0 0%	0 0%

2. Secondary Outcome

Title	Clinical Response to TP-434 and Ertapenem in the Modified Intent-to-treat (MITT) Population at the End-of-Treatment (EOT) Visit
Time Frame	EOT Visit (4-14 days after first dose of study drug)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	TP-434, 1.5 mg/kg q24h	TP-434, 1.0 mg/kg q12h	Ertapenem 1 g q24h
Arm/Group Description	TP-434 was administered IV at a dose of 1.5 mg/kg q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	TP-434 was administered IV at a dose of 1.0 mg/kg q12h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	Ertapenem was administered IV at a dose of 1 g q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).
Measure Participants	54	56	29
Cure	49 87.5%	52 91.2%	28 93.3%
Failure	2 3.6%	1 1.8%	1 3.3%
Indeterminate	3 5.4%	3 5.3%	0 0%

3. Secondary Outcome

Title	Clinical Response to TP-434 and Ertapenem in the Modified Intent-to-treat (MITT) Population at TOC Visit
Time Frame	TOC Visit (10-14 days after last dose of study drug)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	TP-434, 1.5 mg/kg q24h	TP-434, 1.0 mg/kg q12h	Ertapenem 1 g q24h
Arm/Group Description	TP-434 was administered IV at a dose of 1.5 mg/kg q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	TP-434 was administered IV at a dose of 1.0 mg/kg q12h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	Ertapenem was administered IV at a dose of 1 g q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).
Measure Participants	54	56	29
Cure	46 82.1%	47 82.5%	26 86.7%
Failure	3 5.4%	1 1.8%	2 6.7%
Indeterminate	5 8.9%	8 14%	1 3.3%

4. Secondary Outcome

Title	Clinical Response to TP-434 and Ertapenem in the Modified Intent-to-treat (MITT) Population at the Follow-up Visit
Time Frame	Follow-up Visit (28-42 days after last dose of study drug)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	TP-434, 1.5 mg/kg q24h	TP-434, 1.0 mg/kg q12h	Ertapenem 1 g q24h
Arm/Group Description	TP-434 was administered IV at a dose of 1.5 mg/kg q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	TP-434 was administered IV at a dose of 1.0 mg/kg q12h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	Ertapenem was administered IV at a dose of 1 g q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).
Measure Participants	54	56	29
Cure	41 73.2%	45 78.9%	24 80%
Failure	4 7.1%	1 1.8%	2 6.7%
Indeterminate	9 16.1%	10 17.5%	3 10%

5. Secondary Outcome

Title	Clinical Response to TP-434 and Ertapenem in the Clinically Modified Intent-to-treat (c-MITT) Population at the EOT Visit
Time Frame	EOT Visit (4-14 days after first dose of study drug)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and met the minimal disease definition of intra-abdominal infection (IAI). The minimal disease definition included all IAI, whether complicated or not. Identification of a baseline pathogen was not required for this population.

Arm/Group Title	TP-434, 1.5 mg/kg q24h	TP-434, 1.0 mg/kg q12h	Ertapenem 1 g q24h
Arm/Group Description	TP-434 was administered IV at a dose of 1.5 mg/kg q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	TP-434 was administered IV at a dose of 1.0 mg/kg q12h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	Ertapenem was administered IV at a dose of 1 g q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).
Measure Participants	54	56	29
Cure	49 87.5%	52 91.2%	28 93.3%
Failure	2 3.6%	1 1.8%	1 3.3%
Indeterminate	3 5.4%	3 5.3%	0 0%

6. Secondary Outcome

Title	Clinical Response to TP-434 and Ertapenem in the Clinically Modified Intent-to-treat (c-MITT) Population at the TOC Visit
Time Frame	TOC Visit (10-14 days after last dose of study drug)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and met the minimal disease definition of IAI. The minimal disease definition included all IAI, whether complicated or not. Identification of a baseline pathogen was not required for this population.

Arm/Group Title	TP-434, 1.5 mg/kg q24h	TP-434, 1.0 mg/kg q12h	Ertapenem 1 g q24h
Arm/Group Description	TP-434 was administered IV at a dose of 1.5 mg/kg q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	TP-434 was administered IV at a dose of 1.0 mg/kg q12h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	Ertapenem was administered IV at a dose of 1 g q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).
Measure Participants	54	56	29
Cure	46 82.1%	47 82.5%	26 86.7%
Failure	3 5.4%	1 1.8%	2 6.7%
Indeterminate	5 8.9%	8 14%	1 3.3%

7. Secondary Outcome

Title	Clinical Response to TP-434 and Ertapenem in the Clinically Modified Intent-to-treat (c-MITT) Population at the Follow-up Visit
Time Frame	Follow-up Visit (28-42 days after last dose of study drug)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and met the minimal disease definition of IAI. The minimal disease definition included all IAI, whether complicated or not. Identification of a baseline pathogen was not required for this population.

Arm/Group Title	TP-434, 1.5 mg/kg q24h	TP-434, 1.0 mg/kg q12h	Ertapenem 1 g q24h
Arm/Group Description	TP-434 was administered IV at a dose of 1.5 mg/kg q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	TP-434 was administered IV at a dose of 1.0 mg/kg q12h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	Ertapenem was administered IV at a dose of 1 g q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).
Measure Participants	54	56	29
Cure	41 73.2%	45 78.9%	24 80%
Failure	4 7.1%	1 1.8%	2 6.7%
Indeterminate	9 16.1%	10 17.5%	3 10%

8. Secondary Outcome

Title	Clinical Response to TP-434 and Ertapenem in the Microbiologically Modified Intent-to-treat (m-MITT) Population at the EOT Visit
Time Frame	EOT Visit (4-14 days after first dose of study drug)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug, met the minimal disease definition of cIAI, and had a baseline pathogen identified. The minimal disease definition of cIAI included IAI that extended beyond the hollow viscus of origin into the peritoneal space and was associated with either abscess formation or peritonitis.

Arm/Group Title	TP-434, 1.5 mg/kg q24h	TP-434, 1.0 mg/kg q12h	Ertapenem 1 g q24h
Arm/Group Description	TP-434 was administered IV at a dose of 1.5 mg/kg q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	TP-434 was administered IV at a dose of 1.0 mg/kg q12h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	Ertapenem was administered IV at a dose of 1 g q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).
Measure Participants	45	47	27
Cure	41 73.2%	44 77.2%	26 86.7%
Failure	2 3.6%	0 0%	1 3.3%
Indeterminate	2 3.6%	3 5.3%	0 0%

9. Secondary Outcome

Title	Clinical Response to TP-434 and Ertapenem in the Microbiologically Modified Intent-to-treat (m-MITT) Population at the TOC Visit
Time Frame	TOC Visit (10-14 days after last dose of study drug)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug, met the minimal disease definition of cIAI, and had a baseline pathogen identified. The minimal disease definition of cIAI included IAI that extended beyond the hollow viscus of origin into the peritoneal space and was associated with either abscess formation or peritonitis.

Arm/Group Title	TP-434, 1.5 mg/kg q24h	TP-434, 1.0 mg/kg q12h	Ertapenem 1 g q24h
Arm/Group Description	TP-434 was administered IV at a dose of 1.5 mg/kg q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	TP-434 was administered IV at a dose of 1.0 mg/kg q12h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	Ertapenem was administered IV at a dose of 1 g q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).
Measure Participants	45	47	27
Cure	39 69.6%	41 71.9%	24 80%
Failure	3 5.4%	0 0%	2 6.7%
Indeterminate	3 5.4%	6 10.5%	1 3.3%

10. Secondary Outcome

Title	Clinical Response to TP-434 and Ertapenem in the Microbiologically Modified Intent-to-treat (m-MITT) Population at the Follow-up Visit
Time Frame	Follow-Up Visit (28-42 days after last dose of study drug)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug, met the minimal disease definition of cIAI, and had a baseline pathogen identified. The minimal disease definition of cIAI included IAI that extended beyond the hollow viscus of origin into the peritoneal space and was associated with either abscess formation or peritonitis.

Arm/Group Title	TP-434, 1.5 mg/kg q24h	TP-434, 1.0 mg/kg q12h	Ertapenem 1 g q24h
Arm/Group Description	TP-434 was administered IV at a dose of 1.5 mg/kg q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	TP-434 was administered IV at a dose of 1.0 mg/kg q12h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	Ertapenem was administered IV at a dose of 1 g q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).
Measure Participants	45	47	27
Cure	36 64.3%	39 68.4%	22 73.3%
Failure	4 7.1%	0 0%	2 6.7%
Indeterminate	5 8.9%	8 14%	3 10%

11. Secondary Outcome

Title	Clinical Response to TP-434 and Ertapenem in the Clinically Evaluable (CE) Population at the EOT Visit
Time Frame	EOT Visit (4-14 days after first dose of study drug)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug, met the minimal disease definition of cIAI, and for whom sufficient information was available to determine the participant's outcome with no confounding factors present that interfered with the assessment of that outcome.

Arm/Group Title	TP-434, 1.5 mg/kg q24h	TP-434, 1.0 mg/kg q12h	Ertapenem 1 g q24h
Arm/Group Description	TP-434 was administered IV at a dose of 1.5 mg/kg q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	TP-434 was administered IV at a dose of 1.0 mg/kg q12h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	Ertapenem was administered IV at a dose of 1 g q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).
Measure Participants	49	48	28
Cure	47 83.9%	47 82.5%	27 90%
Failure	2 3.6%	1 1.8%	1 3.3%
Indeterminate	0 0%	0 0%	0 0%

12. Secondary Outcome

Title	Clinical Response to TP-434 and Ertapenem in the Clinically Evaluable (CE) Population at the TOC Visit
Time Frame	TOC Visit (10-14 days after last dose of study drug)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug, met the minimal disease definition of cIAI, and for whom sufficient information was available to determine the participant's outcome with no confounding factors present that interfered with the assessment of that outcome.

Arm/Group Title	TP-434, 1.5 mg/kg q24h	TP-434, 1.0 mg/kg q12h	Ertapenem 1 g q24h
Arm/Group Description	TP-434 was administered IV at a dose of 1.5 mg/kg q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	TP-434 was administered IV at a dose of 1.0 mg/kg q12h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	Ertapenem was administered IV at a dose of 1 g q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).
Measure Participants	49	48	28
Cure	46 82.1%	47 82.5%	26 86.7%
Failure	3 5.4%	1 1.8%	2 6.7%
Indeterminate	0 0%	0 0%	0 0%

13. Secondary Outcome

Title	Clinical Response to TP-434 and Ertapenem in the Clinically Evaluable (CE) Population at the Follow-up Visit
Time Frame	Follow-up Visit (28-42 days after last dose of study drug)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug, met the minimal disease definition of cIAI, and for whom sufficient information was available to determine the participant's outcome with no confounding factors present that interfered with the assessment of that outcome.

Arm/Group Title	TP-434, 1.5 mg/kg q24h	TP-434, 1.0 mg/kg q12h	Ertapenem 1 g q24h
Arm/Group Description	TP-434 was administered IV at a dose of 1.5 mg/kg q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	TP-434 was administered IV at a dose of 1.0 mg/kg q12h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	Ertapenem was administered IV at a dose of 1 g q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).
Measure Participants	49	48	28
Cure	41 73.2%	45 78.9%	23 76.7%
Failure	4 7.1%	1 1.8%	2 6.7%
Indeterminate	4 7.1%	2 3.5%	3 10%

14. Secondary Outcome

Title	Clinical Response to TP-434 and Ertapenem in the Microbiologically Evaluable (ME) Population at the EOT Visit
Time Frame	EOT Visit (4-14 days after first dose of study drug)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug, met the minimal disease definition of cIAI, had a baseline pathogen identified, and had a microbiological response assessed.

Arm/Group Title	TP-434, 1.5 mg/kg q24h	TP-434, 1.0 mg/kg q12h	Ertapenem 1 g q24h
Arm/Group Description	TP-434 was administered IV at a dose of 1.5 mg/kg q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	TP-434 was administered IV at a dose of 1.0 mg/kg q12h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	Ertapenem was administered IV at a dose of 1 g q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).
Measure Participants	42	41	26
Cure	40 71.4%	41 71.9%	25 83.3%
Failure	2 3.6%	0 0%	1 3.3%
Indeterminate	0 0%	0 0%	0 0%

15. Secondary Outcome

Title	Clinical Response to TP-434 and Ertapenem in the Microbiologically Evaluable (ME) Population at the Follow-up Visit
Time Frame	Follow-up Visit (28-42 days after last dose of study drug)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug, met the minimal disease definition of cIAI, had a baseline pathogen identified, and had a microbiological response assessed.

Arm/Group Title	TP-434, 1.5 mg/kg q24h	TP-434, 1.0 mg/kg q12h	Ertapenem 1 g q24h
Arm/Group Description	TP-434 was administered IV at a dose of 1.5 mg/kg q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	TP-434 was administered IV at a dose of 1.0 mg/kg q12h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	Ertapenem was administered IV at a dose of 1 g q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).
Measure Participants	42	41	26
Cure	36 64.3%	39 68.4%	21 70%
Failure	4 7.1%	0 0%	2 6.7%
Indeterminate	2 3.6%	2 3.5%	3 10%

16. Secondary Outcome

Title	Microbiologic Response to TP-434 and Ertapenem in the m-MITT Population at the EOT Visit
Description	Microbiological response was classified as favorable (eradication or presumed eradication), unfavorable (persistence, presumed persistence, superinfection, or new infection), or indeterminate (assessment not possible).
Time Frame	EOT Visit (4-14 days after first dose of study drug)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug, met the minimal disease definition of cIAI, and had a baseline pathogen identified. The minimal disease definition of cIAI included IAI that extended beyond the hollow viscus of origin into the peritoneal space and was associated with either abscess formation or peritonitis.

Arm/Group Title	TP-434, 1.5 mg/kg q24h	TP-434, 1.0 mg/kg q12h	Ertapenem 1 g q24h
Arm/Group Description	TP-434 was administered IV at a dose of 1.5 mg/kg q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	TP-434 was administered IV at a dose of 1.0 mg/kg q12h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	Ertapenem was administered IV at a dose of 1 g q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).
Measure Participants	45	47	27
Favorable	41 73.2%	44 77.2%	26 86.7%
Unfavorable	2 3.6%	0 0%	1 3.3%
Indeterminate	2 3.6%	3 5.3%	0 0%

17. Secondary Outcome

Title	Microbiologic Response to TP-434 and Ertapenem in the m-MITT Population at the TOC Visit
Time Frame	TOC Visit (10-14 days after last dose of study drug)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug, met the minimal disease definition of cIAI, and had a baseline pathogen identified. The minimal disease definition of cIAI included IAI that extended beyond the hollow viscus of origin into the peritoneal space and was associated with either abscess formation or peritonitis.

Arm/Group Title	TP-434, 1.5 mg/kg q24h	TP-434, 1.0 mg/kg q12h	Ertapenem 1 g q24h
Arm/Group Description	TP-434 was administered IV at a dose of 1.5 mg/kg q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	TP-434 was administered IV at a dose of 1.0 mg/kg q12h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	Ertapenem was administered IV at a dose of 1 g q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).
Measure Participants	45	47	27
Favorable	39 69.6%	42 73.7%	24 80%
Unfavorable	3 5.4%	0 0%	2 6.7%
Indeterminate	3 5.4%	5 8.8%	1 3.3%

18. Secondary Outcome

Title	Microbiologic Response to TP-434 and Ertapenem in the ME Population at the EOT Visit
Time Frame	EOT Visit (4-14 days after first dose of study drug)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug, met the minimal disease definition of cIAI, had a baseline pathogen identified, and had a microbiological response assessed.

Arm/Group Title	TP-434, 1.5 mg/kg q24h	TP-434, 1.0 mg/kg q12h	Ertapenem 1 g q24h
Arm/Group Description	TP-434 was administered IV at a dose of 1.5 mg/kg q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	TP-434 was administered IV at a dose of 1.0 mg/kg q12h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	Ertapenem was administered IV at a dose of 1 g q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).
Measure Participants	42	41	26
Favorable	40 71.4%	41 71.9%	25 83.3%
Unfavorable	2 3.6%	0 0%	1 3.3%
Indeterminate	0 0%	0 0%	0 0%

19. Secondary Outcome

Title	Microbiologic Response to TP-434 and Ertapenem in the ME Population at the TOC Visit
Time Frame	TOC Visit (10-14 days after last dose of study drug)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug, met the minimal disease definition of cIAI, had a baseline pathogen identified, and had a microbiological response assessed.

Arm/Group Title	TP-434, 1.5 mg/kg q24h	TP-434, 1.0 mg/kg q12h	Ertapenem 1 g q24h
Arm/Group Description	TP-434 was administered IV at a dose of 1.5 mg/kg q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	TP-434 was administered IV at a dose of 1.0 mg/kg q12h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	Ertapenem was administered IV at a dose of 1 g q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).
Measure Participants	42	41	26
Favorable	39 69.6%	41 71.9%	24 80%
Unfavorable	3 5.4%	0 0%	2 6.7%
Indeterminate	0 0%	0 0%	0 0%

20. Secondary Outcome

Title	Pharmacokinetics: Maximum Concentration (Cmax) of TP-434
Time Frame	Prior to first infusion and 1, 3, 7, 12, 48, and 108 hours after start of first infusion

Outcome Measure Data

Analysis Population Description

All randomized participants without significant protocol deviations who received at least 1 dose of TP-434 and had evaluable Cmax data.

Arm/Group Title	TP-434, 1.5 mg/kg q24h	TP-434, 1.0 mg/kg q12h
Arm/Group Description	TP-434 was administered IV at a dose of 1.5 mg/kg q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	TP-434 was administered IV at a dose of 1.0 mg/kg q12h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).
Measure Participants	48	51
Mean (Standard Deviation) [nanograms per milliliter (ng/mL)]	1445.625 (1168.029)	952.608 (759.754)

21. Secondary Outcome

Title	Pharmacokinetics: Area Under the Concentration Time Curve From Time 0 to 12 Hours (AUC[0-12]) of TP-434
Time Frame	Prior to first infusion and 1, 3, 7, 12, 48, and 108 hours after start of first infusion

Outcome Measure Data

Analysis Population Description

All randomized participants without significant protocol deviations who received at least 1 dose of TP-434 and had evaluable AUC(0-12) data.

Arm/Group Title	TP-434, 1.5 mg/kg q24h	TP-434, 1.0 mg/kg q12h
Arm/Group Description	TP-434 was administered IV at a dose of 1.5 mg/kg q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).	TP-434 was administered IV at a dose of 1.0 mg/kg q12h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).
Measure Participants	48	47
Mean (Standard Deviation) [nanogram*hours per milliliter (ng*h/mL)]	4349.900 (2186.791)	3240.724 (1732.172)

Adverse Events

Arm/Group Title	TP-434, 1.5 mg/kg q24h		TP-434, 1.0 mg/kg q12h		Ertapenem 1 g q24h
Arm/Group Description	TP-434 was administered IV at a dose of 1.5 mg/kg q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).		TP-434 was administered IV at a dose of 1.0 mg/kg q12h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).		Ertapenem was administered IV at a dose of 1 g q24h for a minimum of 4 days and a maximum of 14 days (7 days for participants in India).
All Cause Mortality
	TP-434, 1.5 mg/kg q24h		TP-434, 1.0 mg/kg q12h		Ertapenem 1 g q24h
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	TP-434, 1.5 mg/kg q24h		TP-434, 1.0 mg/kg q12h		Ertapenem 1 g q24h
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/53 (11.3%)		1/56 (1.8%)		1/30 (3.3%)
Cardiac disorders
Atrial Fibrillation	1/53 (1.9%)		0/56 (0%)		0/30 (0%)
Gastrointestinal disorders
Duodenal Ulcer Haemorrhage	1/53 (1.9%)		0/56 (0%)		0/30 (0%)
Ileus	1/53 (1.9%)		0/56 (0%)		0/30 (0%)
Infections and infestations
Lobar Pneumonia	1/53 (1.9%)		0/56 (0%)		0/30 (0%)
Abdominal Wall Abscess	1/53 (1.9%)		0/56 (0%)		0/30 (0%)
Wound Infection	0/53 (0%)		1/56 (1.8%)		0/30 (0%)
Subdiaphragmatic Abscess	0/53 (0%)		0/56 (0%)		1/30 (3.3%)
Vascular disorders
Embolism	1/53 (1.9%)		0/56 (0%)		0/30 (0%)
Other (Not Including Serious) Adverse Events
	TP-434, 1.5 mg/kg q24h		TP-434, 1.0 mg/kg q12h		Ertapenem 1 g q24h
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/53 (20.8%)		10/56 (17.9%)		7/30 (23.3%)
Gastrointestinal disorders
Abdominal Pain	2/53 (3.8%)		0/56 (0%)		0/30 (0%)
Nausea	1/53 (1.9%)		6/56 (10.7%)		2/30 (6.7%)
Vomiting	3/53 (5.7%)		1/56 (1.8%)		0/30 (0%)
General disorders
Application Site Hypersensitivity	0/53 (0%)		0/56 (0%)		1/30 (3.3%)
Pyrexia	1/53 (1.9%)		1/56 (1.8%)		1/30 (3.3%)
Immune system disorders
Hypersensitivity	0/53 (0%)		0/56 (0%)		1/30 (3.3%)
Investigations
Blood Amylase Increased	3/53 (5.7%)		2/56 (3.6%)		1/30 (3.3%)
Lipase Increased	3/53 (5.7%)		4/56 (7.1%)		2/30 (6.7%)
Metabolism and nutrition disorders
Hypoalbuminaemia	1/53 (1.9%)		0/56 (0%)		1/30 (3.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/53 (0%)		0/56 (0%)		1/30 (3.3%)
Renal and urinary disorders
Haematuria	0/53 (0%)		0/56 (0%)		1/30 (3.3%)
Respiratory, thoracic and mediastinal disorders
Cough	0/53 (0%)		1/56 (1.8%)		1/30 (3.3%)
Vascular disorders
Thrombophlebitis	1/53 (1.9%)		2/56 (3.6%)		0/30 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

At least 60 days prior to submitting or presenting a manuscript, poster, presentation, abstract or other materials relating to the Trial, the PI shall provide to Sponsor all such manuscripts and materials, and Sponsor shall have 60 days to review and comment. If requested, the PI shall remove Confidential lnformation prior to submitting or presenting the materials, and shall delay publication or presentation for up to 90 days to allow Sponsor to protect its interests in any such materials.