Trial Outcomes & Findings for Study to Compare TP-434 and Ertapenem in Community-acquired Complicated Intra-abdominal Infections (NCT NCT01265784)
NCT ID: NCT01265784
Last Updated: 2022-01-06
Results Overview
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).
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
143 participants
Primary outcome timeframe
TOC Visit (10-14 days after last dose of study drug)
Results posted on
2022-01-06
Participant Flow
Randomization was stratified by site of infection (complicated appendicitis versus all other diagnoses).
Participant milestones
| Measure |
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, 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).
|
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).
|
|---|---|---|---|
|
Overall Study
STARTED
|
56
|
57
|
30
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
54
|
56
|
29
|
|
Overall Study
COMPLETED
|
44
|
49
|
26
|
|
Overall Study
NOT COMPLETED
|
12
|
8
|
4
|
Reasons for withdrawal
| Measure |
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, 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).
|
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).
|
|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
5
|
3
|
2
|
|
Overall Study
Withdrawal by Subject
|
0
|
5
|
0
|
|
Overall Study
Physician Decision
|
1
|
0
|
1
|
|
Overall Study
Adverse Event
|
1
|
0
|
0
|
|
Overall Study
Death
|
3
|
0
|
0
|
|
Overall Study
Protocol Violation
|
2
|
0
|
0
|
|
Overall Study
Incorrectly Randomized
|
0
|
0
|
1
|
Baseline Characteristics
Study to Compare TP-434 and Ertapenem in Community-acquired Complicated Intra-abdominal Infections
Baseline characteristics by cohort
| Measure |
TP-434, 1.5 mg/kg q24h
n=56 Participants
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, 1.0 mg/kg q12h
n=57 Participants
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 1 g q24h
n=30 Participants
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
n=143 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
43.6 years
STANDARD_DEVIATION 18.39 • n=5 Participants
|
42.1 years
STANDARD_DEVIATION 17.16 • n=7 Participants
|
41.8 years
STANDARD_DEVIATION 17.60 • n=5 Participants
|
42.6 years
STANDARD_DEVIATION 17.64 • n=4 Participants
|
|
Sex: Female, Male
Female
|
18 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
40 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
38 Participants
n=5 Participants
|
43 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
103 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
1 participants
n=4 Participants
|
|
Region of Enrollment
Romania
|
6 participants
n=5 Participants
|
9 participants
n=7 Participants
|
6 participants
n=5 Participants
|
21 participants
n=4 Participants
|
|
Region of Enrollment
Lithuania
|
17 participants
n=5 Participants
|
13 participants
n=7 Participants
|
7 participants
n=5 Participants
|
37 participants
n=4 Participants
|
|
Region of Enrollment
Bulgaria
|
9 participants
n=5 Participants
|
6 participants
n=7 Participants
|
3 participants
n=5 Participants
|
18 participants
n=4 Participants
|
|
Region of Enrollment
Latvia
|
8 participants
n=5 Participants
|
9 participants
n=7 Participants
|
4 participants
n=5 Participants
|
21 participants
n=4 Participants
|
|
Region of Enrollment
India
|
16 participants
n=5 Participants
|
20 participants
n=7 Participants
|
9 participants
n=5 Participants
|
45 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: TOC Visit (10-14 days after last dose of study drug)Population: 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.
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).
Outcome measures
| Measure |
TP-434, 1.5 mg/kg q24h
n=42 Participants
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, 1.0 mg/kg q12h
n=41 Participants
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 1 g q24h
n=26 Participants
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).
|
|---|---|---|---|
|
Clinical Response to TP-434 and Ertapenem in the Microbiologically Evaluable (ME) Population at the Test-of-Cure Visit
Indeterminate
|
0 participants
|
0 participants
|
0 participants
|
|
Clinical Response to TP-434 and Ertapenem in the Microbiologically Evaluable (ME) Population at the Test-of-Cure Visit
Cure
|
39 participants
|
41 participants
|
24 participants
|
|
Clinical Response to TP-434 and Ertapenem in the Microbiologically Evaluable (ME) Population at the Test-of-Cure Visit
Failure
|
3 participants
|
0 participants
|
2 participants
|
SECONDARY outcome
Timeframe: EOT Visit (4-14 days after first dose of study drug)Population: All randomized participants who received at least 1 dose of study drug.
Outcome measures
| Measure |
TP-434, 1.5 mg/kg q24h
n=54 Participants
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, 1.0 mg/kg q12h
n=56 Participants
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 1 g q24h
n=29 Participants
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).
|
|---|---|---|---|
|
Clinical Response to TP-434 and Ertapenem in the Modified Intent-to-treat (MITT) Population at the End-of-Treatment (EOT) Visit
Cure
|
49 participants
|
52 participants
|
28 participants
|
|
Clinical Response to TP-434 and Ertapenem in the Modified Intent-to-treat (MITT) Population at the End-of-Treatment (EOT) Visit
Failure
|
2 participants
|
1 participants
|
1 participants
|
|
Clinical Response to TP-434 and Ertapenem in the Modified Intent-to-treat (MITT) Population at the End-of-Treatment (EOT) Visit
Indeterminate
|
3 participants
|
3 participants
|
0 participants
|
SECONDARY outcome
Timeframe: TOC Visit (10-14 days after last dose of study drug)Population: All randomized participants who received at least 1 dose of study drug.
Outcome measures
| Measure |
TP-434, 1.5 mg/kg q24h
n=54 Participants
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, 1.0 mg/kg q12h
n=56 Participants
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 1 g q24h
n=29 Participants
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).
|
|---|---|---|---|
|
Clinical Response to TP-434 and Ertapenem in the Modified Intent-to-treat (MITT) Population at TOC Visit
Cure
|
46 participants
|
47 participants
|
26 participants
|
|
Clinical Response to TP-434 and Ertapenem in the Modified Intent-to-treat (MITT) Population at TOC Visit
Failure
|
3 participants
|
1 participants
|
2 participants
|
|
Clinical Response to TP-434 and Ertapenem in the Modified Intent-to-treat (MITT) Population at TOC Visit
Indeterminate
|
5 participants
|
8 participants
|
1 participants
|
SECONDARY outcome
Timeframe: Follow-up Visit (28-42 days after last dose of study drug)Population: All randomized participants who received at least 1 dose of study drug.
Outcome measures
| Measure |
TP-434, 1.5 mg/kg q24h
n=54 Participants
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, 1.0 mg/kg q12h
n=56 Participants
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 1 g q24h
n=29 Participants
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).
|
|---|---|---|---|
|
Clinical Response to TP-434 and Ertapenem in the Modified Intent-to-treat (MITT) Population at the Follow-up Visit
Cure
|
41 participants
|
45 participants
|
24 participants
|
|
Clinical Response to TP-434 and Ertapenem in the Modified Intent-to-treat (MITT) Population at the Follow-up Visit
Failure
|
4 participants
|
1 participants
|
2 participants
|
|
Clinical Response to TP-434 and Ertapenem in the Modified Intent-to-treat (MITT) Population at the Follow-up Visit
Indeterminate
|
9 participants
|
10 participants
|
3 participants
|
SECONDARY outcome
Timeframe: EOT Visit (4-14 days after first dose of study drug)Population: 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.
Outcome measures
| Measure |
TP-434, 1.5 mg/kg q24h
n=54 Participants
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, 1.0 mg/kg q12h
n=56 Participants
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 1 g q24h
n=29 Participants
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).
|
|---|---|---|---|
|
Clinical Response to TP-434 and Ertapenem in the Clinically Modified Intent-to-treat (c-MITT) Population at the EOT Visit
Cure
|
49 participants
|
52 participants
|
28 participants
|
|
Clinical Response to TP-434 and Ertapenem in the Clinically Modified Intent-to-treat (c-MITT) Population at the EOT Visit
Failure
|
2 participants
|
1 participants
|
1 participants
|
|
Clinical Response to TP-434 and Ertapenem in the Clinically Modified Intent-to-treat (c-MITT) Population at the EOT Visit
Indeterminate
|
3 participants
|
3 participants
|
0 participants
|
SECONDARY outcome
Timeframe: TOC Visit (10-14 days after last dose of study drug)Population: 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.
Outcome measures
| Measure |
TP-434, 1.5 mg/kg q24h
n=54 Participants
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, 1.0 mg/kg q12h
n=56 Participants
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 1 g q24h
n=29 Participants
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).
|
|---|---|---|---|
|
Clinical Response to TP-434 and Ertapenem in the Clinically Modified Intent-to-treat (c-MITT) Population at the TOC Visit
Cure
|
46 participants
|
47 participants
|
26 participants
|
|
Clinical Response to TP-434 and Ertapenem in the Clinically Modified Intent-to-treat (c-MITT) Population at the TOC Visit
Failure
|
3 participants
|
1 participants
|
2 participants
|
|
Clinical Response to TP-434 and Ertapenem in the Clinically Modified Intent-to-treat (c-MITT) Population at the TOC Visit
Indeterminate
|
5 participants
|
8 participants
|
1 participants
|
SECONDARY outcome
Timeframe: Follow-up Visit (28-42 days after last dose of study drug)Population: 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.
Outcome measures
| Measure |
TP-434, 1.5 mg/kg q24h
n=54 Participants
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, 1.0 mg/kg q12h
n=56 Participants
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 1 g q24h
n=29 Participants
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).
|
|---|---|---|---|
|
Clinical Response to TP-434 and Ertapenem in the Clinically Modified Intent-to-treat (c-MITT) Population at the Follow-up Visit
Cure
|
41 participants
|
45 participants
|
24 participants
|
|
Clinical Response to TP-434 and Ertapenem in the Clinically Modified Intent-to-treat (c-MITT) Population at the Follow-up Visit
Failure
|
4 participants
|
1 participants
|
2 participants
|
|
Clinical Response to TP-434 and Ertapenem in the Clinically Modified Intent-to-treat (c-MITT) Population at the Follow-up Visit
Indeterminate
|
9 participants
|
10 participants
|
3 participants
|
SECONDARY outcome
Timeframe: EOT Visit (4-14 days after first dose of study drug)Population: 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.
Outcome measures
| Measure |
TP-434, 1.5 mg/kg q24h
n=45 Participants
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, 1.0 mg/kg q12h
n=47 Participants
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 1 g q24h
n=27 Participants
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).
|
|---|---|---|---|
|
Clinical Response to TP-434 and Ertapenem in the Microbiologically Modified Intent-to-treat (m-MITT) Population at the EOT Visit
Cure
|
41 participants
|
44 participants
|
26 participants
|
|
Clinical Response to TP-434 and Ertapenem in the Microbiologically Modified Intent-to-treat (m-MITT) Population at the EOT Visit
Failure
|
2 participants
|
0 participants
|
1 participants
|
|
Clinical Response to TP-434 and Ertapenem in the Microbiologically Modified Intent-to-treat (m-MITT) Population at the EOT Visit
Indeterminate
|
2 participants
|
3 participants
|
0 participants
|
SECONDARY outcome
Timeframe: TOC Visit (10-14 days after last dose of study drug)Population: 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.
Outcome measures
| Measure |
TP-434, 1.5 mg/kg q24h
n=45 Participants
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, 1.0 mg/kg q12h
n=47 Participants
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 1 g q24h
n=27 Participants
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).
|
|---|---|---|---|
|
Clinical Response to TP-434 and Ertapenem in the Microbiologically Modified Intent-to-treat (m-MITT) Population at the TOC Visit
Cure
|
39 participants
|
41 participants
|
24 participants
|
|
Clinical Response to TP-434 and Ertapenem in the Microbiologically Modified Intent-to-treat (m-MITT) Population at the TOC Visit
Failure
|
3 participants
|
0 participants
|
2 participants
|
|
Clinical Response to TP-434 and Ertapenem in the Microbiologically Modified Intent-to-treat (m-MITT) Population at the TOC Visit
Indeterminate
|
3 participants
|
6 participants
|
1 participants
|
SECONDARY outcome
Timeframe: Follow-Up Visit (28-42 days after last dose of study drug)Population: 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.
Outcome measures
| Measure |
TP-434, 1.5 mg/kg q24h
n=45 Participants
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, 1.0 mg/kg q12h
n=47 Participants
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 1 g q24h
n=27 Participants
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).
|
|---|---|---|---|
|
Clinical Response to TP-434 and Ertapenem in the Microbiologically Modified Intent-to-treat (m-MITT) Population at the Follow-up Visit
Cure
|
36 participants
|
39 participants
|
22 participants
|
|
Clinical Response to TP-434 and Ertapenem in the Microbiologically Modified Intent-to-treat (m-MITT) Population at the Follow-up Visit
Failure
|
4 participants
|
0 participants
|
2 participants
|
|
Clinical Response to TP-434 and Ertapenem in the Microbiologically Modified Intent-to-treat (m-MITT) Population at the Follow-up Visit
Indeterminate
|
5 participants
|
8 participants
|
3 participants
|
SECONDARY outcome
Timeframe: EOT Visit (4-14 days after first dose of study drug)Population: 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.
Outcome measures
| Measure |
TP-434, 1.5 mg/kg q24h
n=49 Participants
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, 1.0 mg/kg q12h
n=48 Participants
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 1 g q24h
n=28 Participants
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).
|
|---|---|---|---|
|
Clinical Response to TP-434 and Ertapenem in the Clinically Evaluable (CE) Population at the EOT Visit
Cure
|
47 participants
|
47 participants
|
27 participants
|
|
Clinical Response to TP-434 and Ertapenem in the Clinically Evaluable (CE) Population at the EOT Visit
Failure
|
2 participants
|
1 participants
|
1 participants
|
|
Clinical Response to TP-434 and Ertapenem in the Clinically Evaluable (CE) Population at the EOT Visit
Indeterminate
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: TOC Visit (10-14 days after last dose of study drug)Population: 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.
Outcome measures
| Measure |
TP-434, 1.5 mg/kg q24h
n=49 Participants
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, 1.0 mg/kg q12h
n=48 Participants
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 1 g q24h
n=28 Participants
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).
|
|---|---|---|---|
|
Clinical Response to TP-434 and Ertapenem in the Clinically Evaluable (CE) Population at the TOC Visit
Cure
|
46 participants
|
47 participants
|
26 participants
|
|
Clinical Response to TP-434 and Ertapenem in the Clinically Evaluable (CE) Population at the TOC Visit
Failure
|
3 participants
|
1 participants
|
2 participants
|
|
Clinical Response to TP-434 and Ertapenem in the Clinically Evaluable (CE) Population at the TOC Visit
Indeterminate
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Follow-up Visit (28-42 days after last dose of study drug)Population: 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.
Outcome measures
| Measure |
TP-434, 1.5 mg/kg q24h
n=49 Participants
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, 1.0 mg/kg q12h
n=48 Participants
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 1 g q24h
n=28 Participants
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).
|
|---|---|---|---|
|
Clinical Response to TP-434 and Ertapenem in the Clinically Evaluable (CE) Population at the Follow-up Visit
Cure
|
41 participants
|
45 participants
|
23 participants
|
|
Clinical Response to TP-434 and Ertapenem in the Clinically Evaluable (CE) Population at the Follow-up Visit
Failure
|
4 participants
|
1 participants
|
2 participants
|
|
Clinical Response to TP-434 and Ertapenem in the Clinically Evaluable (CE) Population at the Follow-up Visit
Indeterminate
|
4 participants
|
2 participants
|
3 participants
|
SECONDARY outcome
Timeframe: EOT Visit (4-14 days after first dose of study drug)Population: 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.
Outcome measures
| Measure |
TP-434, 1.5 mg/kg q24h
n=42 Participants
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, 1.0 mg/kg q12h
n=41 Participants
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 1 g q24h
n=26 Participants
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).
|
|---|---|---|---|
|
Clinical Response to TP-434 and Ertapenem in the Microbiologically Evaluable (ME) Population at the EOT Visit
Cure
|
40 participants
|
41 participants
|
25 participants
|
|
Clinical Response to TP-434 and Ertapenem in the Microbiologically Evaluable (ME) Population at the EOT Visit
Failure
|
2 participants
|
0 participants
|
1 participants
|
|
Clinical Response to TP-434 and Ertapenem in the Microbiologically Evaluable (ME) Population at the EOT Visit
Indeterminate
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Follow-up Visit (28-42 days after last dose of study drug)Population: 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.
Outcome measures
| Measure |
TP-434, 1.5 mg/kg q24h
n=42 Participants
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, 1.0 mg/kg q12h
n=41 Participants
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 1 g q24h
n=26 Participants
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).
|
|---|---|---|---|
|
Clinical Response to TP-434 and Ertapenem in the Microbiologically Evaluable (ME) Population at the Follow-up Visit
Cure
|
36 participants
|
39 participants
|
21 participants
|
|
Clinical Response to TP-434 and Ertapenem in the Microbiologically Evaluable (ME) Population at the Follow-up Visit
Failure
|
4 participants
|
0 participants
|
2 participants
|
|
Clinical Response to TP-434 and Ertapenem in the Microbiologically Evaluable (ME) Population at the Follow-up Visit
Indeterminate
|
2 participants
|
2 participants
|
3 participants
|
SECONDARY outcome
Timeframe: EOT Visit (4-14 days after first dose of study drug)Population: 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.
Microbiological response was classified as favorable (eradication or presumed eradication), unfavorable (persistence, presumed persistence, superinfection, or new infection), or indeterminate (assessment not possible).
Outcome measures
| Measure |
TP-434, 1.5 mg/kg q24h
n=45 Participants
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, 1.0 mg/kg q12h
n=47 Participants
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 1 g q24h
n=27 Participants
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).
|
|---|---|---|---|
|
Microbiologic Response to TP-434 and Ertapenem in the m-MITT Population at the EOT Visit
Favorable
|
41 participants
|
44 participants
|
26 participants
|
|
Microbiologic Response to TP-434 and Ertapenem in the m-MITT Population at the EOT Visit
Unfavorable
|
2 participants
|
0 participants
|
1 participants
|
|
Microbiologic Response to TP-434 and Ertapenem in the m-MITT Population at the EOT Visit
Indeterminate
|
2 participants
|
3 participants
|
0 participants
|
SECONDARY outcome
Timeframe: TOC Visit (10-14 days after last dose of study drug)Population: 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.
Outcome measures
| Measure |
TP-434, 1.5 mg/kg q24h
n=45 Participants
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, 1.0 mg/kg q12h
n=47 Participants
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 1 g q24h
n=27 Participants
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).
|
|---|---|---|---|
|
Microbiologic Response to TP-434 and Ertapenem in the m-MITT Population at the TOC Visit
Favorable
|
39 participants
|
42 participants
|
24 participants
|
|
Microbiologic Response to TP-434 and Ertapenem in the m-MITT Population at the TOC Visit
Unfavorable
|
3 participants
|
0 participants
|
2 participants
|
|
Microbiologic Response to TP-434 and Ertapenem in the m-MITT Population at the TOC Visit
Indeterminate
|
3 participants
|
5 participants
|
1 participants
|
SECONDARY outcome
Timeframe: EOT Visit (4-14 days after first dose of study drug)Population: 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.
Outcome measures
| Measure |
TP-434, 1.5 mg/kg q24h
n=42 Participants
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, 1.0 mg/kg q12h
n=41 Participants
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 1 g q24h
n=26 Participants
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).
|
|---|---|---|---|
|
Microbiologic Response to TP-434 and Ertapenem in the ME Population at the EOT Visit
Favorable
|
40 participants
|
41 participants
|
25 participants
|
|
Microbiologic Response to TP-434 and Ertapenem in the ME Population at the EOT Visit
Unfavorable
|
2 participants
|
0 participants
|
1 participants
|
|
Microbiologic Response to TP-434 and Ertapenem in the ME Population at the EOT Visit
Indeterminate
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: TOC Visit (10-14 days after last dose of study drug)Population: 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.
Outcome measures
| Measure |
TP-434, 1.5 mg/kg q24h
n=42 Participants
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, 1.0 mg/kg q12h
n=41 Participants
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 1 g q24h
n=26 Participants
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).
|
|---|---|---|---|
|
Microbiologic Response to TP-434 and Ertapenem in the ME Population at the TOC Visit
Favorable
|
39 participants
|
41 participants
|
24 participants
|
|
Microbiologic Response to TP-434 and Ertapenem in the ME Population at the TOC Visit
Unfavorable
|
3 participants
|
0 participants
|
2 participants
|
|
Microbiologic Response to TP-434 and Ertapenem in the ME Population at the TOC Visit
Indeterminate
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Prior to first infusion and 1, 3, 7, 12, 48, and 108 hours after start of first infusionPopulation: All randomized participants without significant protocol deviations who received at least 1 dose of TP-434 and had evaluable Cmax data.
Outcome measures
| Measure |
TP-434, 1.5 mg/kg q24h
n=48 Participants
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, 1.0 mg/kg q12h
n=51 Participants
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 1 g q24h
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).
|
|---|---|---|---|
|
Pharmacokinetics: Maximum Concentration (Cmax) of TP-434
|
1445.625 nanograms per milliliter (ng/mL)
Standard Deviation 1168.029
|
952.608 nanograms per milliliter (ng/mL)
Standard Deviation 759.754
|
—
|
SECONDARY outcome
Timeframe: Prior to first infusion and 1, 3, 7, 12, 48, and 108 hours after start of first infusionPopulation: All randomized participants without significant protocol deviations who received at least 1 dose of TP-434 and had evaluable AUC(0-12) data.
Outcome measures
| Measure |
TP-434, 1.5 mg/kg q24h
n=48 Participants
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, 1.0 mg/kg q12h
n=47 Participants
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 1 g q24h
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).
|
|---|---|---|---|
|
Pharmacokinetics: Area Under the Concentration Time Curve From Time 0 to 12 Hours (AUC[0-12]) of TP-434
|
4349.900 nanogram*hours per milliliter (ng*h/mL)
Standard Deviation 2186.791
|
3240.724 nanogram*hours per milliliter (ng*h/mL)
Standard Deviation 1732.172
|
—
|
Adverse Events
TP-434, 1.5 mg/kg q24h
Serious events: 6 serious events
Other events: 11 other events
Deaths: 0 deaths
TP-434, 1.0 mg/kg q12h
Serious events: 1 serious events
Other events: 10 other events
Deaths: 0 deaths
Ertapenem 1 g q24h
Serious events: 1 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
TP-434, 1.5 mg/kg q24h
n=53 participants at risk
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, 1.0 mg/kg q12h
n=56 participants at risk
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 1 g q24h
n=30 participants at risk
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).
|
|---|---|---|---|
|
Infections and infestations
Lobar Pneumonia
|
1.9%
1/53
|
0.00%
0/56
|
0.00%
0/30
|
|
Gastrointestinal disorders
Duodenal Ulcer Haemorrhage
|
1.9%
1/53
|
0.00%
0/56
|
0.00%
0/30
|
|
Infections and infestations
Abdominal Wall Abscess
|
1.9%
1/53
|
0.00%
0/56
|
0.00%
0/30
|
|
Cardiac disorders
Atrial Fibrillation
|
1.9%
1/53
|
0.00%
0/56
|
0.00%
0/30
|
|
Vascular disorders
Embolism
|
1.9%
1/53
|
0.00%
0/56
|
0.00%
0/30
|
|
Gastrointestinal disorders
Ileus
|
1.9%
1/53
|
0.00%
0/56
|
0.00%
0/30
|
|
Infections and infestations
Wound Infection
|
0.00%
0/53
|
1.8%
1/56
|
0.00%
0/30
|
|
Infections and infestations
Subdiaphragmatic Abscess
|
0.00%
0/53
|
0.00%
0/56
|
3.3%
1/30
|
Other adverse events
| Measure |
TP-434, 1.5 mg/kg q24h
n=53 participants at risk
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, 1.0 mg/kg q12h
n=56 participants at risk
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 1 g q24h
n=30 participants at risk
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).
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal Pain
|
3.8%
2/53
|
0.00%
0/56
|
0.00%
0/30
|
|
Gastrointestinal disorders
Nausea
|
1.9%
1/53
|
10.7%
6/56
|
6.7%
2/30
|
|
Gastrointestinal disorders
Vomiting
|
5.7%
3/53
|
1.8%
1/56
|
0.00%
0/30
|
|
General disorders
Application Site Hypersensitivity
|
0.00%
0/53
|
0.00%
0/56
|
3.3%
1/30
|
|
General disorders
Pyrexia
|
1.9%
1/53
|
1.8%
1/56
|
3.3%
1/30
|
|
Immune system disorders
Hypersensitivity
|
0.00%
0/53
|
0.00%
0/56
|
3.3%
1/30
|
|
Investigations
Blood Amylase Increased
|
5.7%
3/53
|
3.6%
2/56
|
3.3%
1/30
|
|
Investigations
Lipase Increased
|
5.7%
3/53
|
7.1%
4/56
|
6.7%
2/30
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
1.9%
1/53
|
0.00%
0/56
|
3.3%
1/30
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/53
|
0.00%
0/56
|
3.3%
1/30
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/53
|
0.00%
0/56
|
3.3%
1/30
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/53
|
1.8%
1/56
|
3.3%
1/30
|
|
Vascular disorders
Thrombophlebitis
|
1.9%
1/53
|
3.6%
2/56
|
0.00%
0/30
|
Additional Information
Chief Development Officer
La Jolla Pharmaceutical Company
Phone: +1.617.715.3600
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER