Trial Outcomes & Findings for A Study Evaluating the Effect of Esomeprazole on SYN-004 Degradation of Ceftriaxone In Adults With an Ileostomy (NCT NCT02473640)
NCT ID: NCT02473640
Last Updated: 2018-11-27
Results Overview
Ceftriaxone concentration in the presence of SYN-004 and the absence of esomeprazole.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
15 participants
Primary outcome timeframe
0-8.5 hours
Results posted on
2018-11-27
Participant Flow
Participant milestones
| Measure |
150 mg SYN-004
There will be 2 in-house treatment periods: in Treatment Period 1, subjects will receive 2 oral doses of 150 mg SYN-004 (two 75 mg capsules) and 1g ceftriaxone, and in Treatment Period 2, subjects will receive 2 oral doses of 150mg SYN-004 (two 75 mg capsules) and 1g ceftriaxone in the presence of esomeprazole; Treatment Periods 1 and 2 will be separated by a 5- to 7-day run-in phase, during which subjects will self-administer 40 mg of esomeprazole once daily (QD) in the morning, at home.
SYN-004
Esomeprazole
Ceftriaxone
|
|---|---|
|
Treatment Period 1
STARTED
|
15
|
|
Treatment Period 1
COMPLETED
|
14
|
|
Treatment Period 1
NOT COMPLETED
|
1
|
|
Run-in Phase
STARTED
|
14
|
|
Run-in Phase
COMPLETED
|
14
|
|
Run-in Phase
NOT COMPLETED
|
0
|
|
Treatment Period 2
STARTED
|
14
|
|
Treatment Period 2
COMPLETED
|
14
|
|
Treatment Period 2
NOT COMPLETED
|
0
|
Reasons for withdrawal
| Measure |
150 mg SYN-004
There will be 2 in-house treatment periods: in Treatment Period 1, subjects will receive 2 oral doses of 150 mg SYN-004 (two 75 mg capsules) and 1g ceftriaxone, and in Treatment Period 2, subjects will receive 2 oral doses of 150mg SYN-004 (two 75 mg capsules) and 1g ceftriaxone in the presence of esomeprazole; Treatment Periods 1 and 2 will be separated by a 5- to 7-day run-in phase, during which subjects will self-administer 40 mg of esomeprazole once daily (QD) in the morning, at home.
SYN-004
Esomeprazole
Ceftriaxone
|
|---|---|
|
Treatment Period 1
Adverse Event
|
1
|
Baseline Characteristics
A Study Evaluating the Effect of Esomeprazole on SYN-004 Degradation of Ceftriaxone In Adults With an Ileostomy
Baseline characteristics by cohort
| Measure |
150 mg SYN-004
n=15 Participants
There will be 2 in-house treatment periods: in Treatment Period 1, subjects will receive 2 oral doses of 150 mg SYN-004 (two 75 mg capsules) and 1g ceftriaxone, and in Treatment Period 2, subjects will receive 2 oral doses of 150mg SYN-004 (two 75 mg capsules) and 1g ceftriaxone in the presence of steady-state esomeprazole; Treatment Periods 1 and 2 will be separated by a 5- to 7-day run-in phase, during which subjects will self-administer 40 mg of esomeprazole once daily (QD) in the morning, at home.
SYN-004
Esomeprazole
Ceftriaxone
|
|---|---|
|
Age, Continuous
|
45.1 years
STANDARD_DEVIATION 16.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
14 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 0-8.5 hoursPopulation: Subjects with functioning illeostomies who received a single IV infusion of 1 g ceftriaxone.
Ceftriaxone concentration in the presence of SYN-004 and the absence of esomeprazole.
Outcome measures
| Measure |
150 mg SYN-004
n=14 Participants
There will be 2 in-house treatment periods: in Treatment Period 1, subjects will receive 2 oral doses of 150 mg SYN-004 (two 75 mg capsules) and 1g ceftriaxone, and in Treatment Period 2, subjects will receive 2 oral doses of 150mg SYN-004 (two 75 mg capsules) and 1g ceftriaxone in the presence of esomeprazole; Treatment Periods 1 and 2 will be separated by a 5- to 7-day run-in phase, during which subjects will self-administer 40 mg of esomeprazole once daily (QD) in the morning, at home.
|
|---|---|
|
Ceftriaxone Concentration in Intestinal Chyme Period 1
Hour 0
|
0.00 ug/mL
Standard Error 0.00
|
|
Ceftriaxone Concentration in Intestinal Chyme Period 1
Hour 0.5
|
0.00 ug/mL
Standard Error 0.00
|
|
Ceftriaxone Concentration in Intestinal Chyme Period 1
Hour 1.5
|
5.60 ug/mL
Standard Error 4.39
|
|
Ceftriaxone Concentration in Intestinal Chyme Period 1
Hour 2.5
|
150.90 ug/mL
Standard Error 68.43
|
|
Ceftriaxone Concentration in Intestinal Chyme Period 1
Hour 3.5
|
231.40 ug/mL
Standard Error 144.06
|
|
Ceftriaxone Concentration in Intestinal Chyme Period 1
Hour 4.5
|
173.00 ug/mL
Standard Error 98.58
|
|
Ceftriaxone Concentration in Intestinal Chyme Period 1
Hour 5.5
|
29.00 ug/mL
Standard Error 25.40
|
|
Ceftriaxone Concentration in Intestinal Chyme Period 1
Hour 6.5
|
1.40 ug/mL
Standard Error 0.82
|
|
Ceftriaxone Concentration in Intestinal Chyme Period 1
Hour 7.5
|
0.10 ug/mL
Standard Error 0.10
|
|
Ceftriaxone Concentration in Intestinal Chyme Period 1
Hour 8.5
|
2.00 ug/mL
Standard Error 1.70
|
PRIMARY outcome
Timeframe: 0-8.5 hoursConcentrations of ribaximase (SYN-004) in intestinal chyme
Outcome measures
| Measure |
150 mg SYN-004
n=14 Participants
There will be 2 in-house treatment periods: in Treatment Period 1, subjects will receive 2 oral doses of 150 mg SYN-004 (two 75 mg capsules) and 1g ceftriaxone, and in Treatment Period 2, subjects will receive 2 oral doses of 150mg SYN-004 (two 75 mg capsules) and 1g ceftriaxone in the presence of esomeprazole; Treatment Periods 1 and 2 will be separated by a 5- to 7-day run-in phase, during which subjects will self-administer 40 mg of esomeprazole once daily (QD) in the morning, at home.
|
|---|---|
|
Ribaxamase Concentration in Intestinal Chyme Period 1
Hour 0
|
0.00 ng/mL
Standard Error 0.00
|
|
Ribaxamase Concentration in Intestinal Chyme Period 1
Hour 0.5
|
2 ng/mL
Standard Error 2.1
|
|
Ribaxamase Concentration in Intestinal Chyme Period 1
Hour 1.5
|
11 ng/mL
Standard Error 9.1
|
|
Ribaxamase Concentration in Intestinal Chyme Period 1
Hour 2.5
|
131 ng/mL
Standard Error 116.8
|
|
Ribaxamase Concentration in Intestinal Chyme Period 1
Hour 3.5
|
6727 ng/mL
Standard Error 3983.1
|
|
Ribaxamase Concentration in Intestinal Chyme Period 1
Hour 4.5
|
56795 ng/mL
Standard Error 25155.4
|
|
Ribaxamase Concentration in Intestinal Chyme Period 1
Hour 5.5
|
73090 ng/mL
Standard Error 29292.8
|
|
Ribaxamase Concentration in Intestinal Chyme Period 1
Hour 6.5
|
103171 ng/mL
Standard Error 52510.2
|
|
Ribaxamase Concentration in Intestinal Chyme Period 1
Hour 7.5
|
153274 ng/mL
Standard Error 87804.1
|
|
Ribaxamase Concentration in Intestinal Chyme Period 1
Hour 8.5
|
111946 ng/mL
Standard Error 71722.7
|
PRIMARY outcome
Timeframe: 0-8.5 hoursPopulation: Subjects with functioning illeostomies who received a single IV infusion of 1 g ceftriaxone.
Ceftriaxone concentration in the presence of SYN-004 and the absence of esomeprazole.
Outcome measures
| Measure |
150 mg SYN-004
n=14 Participants
There will be 2 in-house treatment periods: in Treatment Period 1, subjects will receive 2 oral doses of 150 mg SYN-004 (two 75 mg capsules) and 1g ceftriaxone, and in Treatment Period 2, subjects will receive 2 oral doses of 150mg SYN-004 (two 75 mg capsules) and 1g ceftriaxone in the presence of esomeprazole; Treatment Periods 1 and 2 will be separated by a 5- to 7-day run-in phase, during which subjects will self-administer 40 mg of esomeprazole once daily (QD) in the morning, at home.
|
|---|---|
|
Ceftriaxone Concentration in Intestinal Chyme Period 2
Hour 0
|
0.00 ug/mL
Standard Error 0.00
|
|
Ceftriaxone Concentration in Intestinal Chyme Period 2
Hour 0.5
|
0.00 ug/mL
Standard Error 0.00
|
|
Ceftriaxone Concentration in Intestinal Chyme Period 2
Hour 1.5
|
9.80 ug/mL
Standard Error 8.43
|
|
Ceftriaxone Concentration in Intestinal Chyme Period 2
Hour 2.5
|
31.70 ug/mL
Standard Error 22.57
|
|
Ceftriaxone Concentration in Intestinal Chyme Period 2
Hour 3.5
|
42.80 ug/mL
Standard Error 30.44
|
|
Ceftriaxone Concentration in Intestinal Chyme Period 2
Hour 4.5
|
80.50 ug/mL
Standard Error 56.28
|
|
Ceftriaxone Concentration in Intestinal Chyme Period 2
Hour 5.5
|
0.80 ug/mL
Standard Error 0.63
|
|
Ceftriaxone Concentration in Intestinal Chyme Period 2
Hour 6.5
|
0.10 ug/mL
Standard Error 0.10
|
|
Ceftriaxone Concentration in Intestinal Chyme Period 2
Hour 7.5
|
0.00 ug/mL
Standard Error 0.00
|
|
Ceftriaxone Concentration in Intestinal Chyme Period 2
Hour 8.5
|
0.20 ug/mL
Standard Error 0.14
|
PRIMARY outcome
Timeframe: 0-8.5 hoursConcentrations of ribaximase (SYN-004) in intestinal chyme
Outcome measures
| Measure |
150 mg SYN-004
n=14 Participants
There will be 2 in-house treatment periods: in Treatment Period 1, subjects will receive 2 oral doses of 150 mg SYN-004 (two 75 mg capsules) and 1g ceftriaxone, and in Treatment Period 2, subjects will receive 2 oral doses of 150mg SYN-004 (two 75 mg capsules) and 1g ceftriaxone in the presence of esomeprazole; Treatment Periods 1 and 2 will be separated by a 5- to 7-day run-in phase, during which subjects will self-administer 40 mg of esomeprazole once daily (QD) in the morning, at home.
|
|---|---|
|
Ribaxamase Concentration in Intestinal Chyme Period 2
Hour 0
|
0.00 ng/mL
Standard Error 0.00
|
|
Ribaxamase Concentration in Intestinal Chyme Period 2
Hour 0.5
|
436 ng/mL
Standard Error 435.6
|
|
Ribaxamase Concentration in Intestinal Chyme Period 2
Hour 1.5
|
281 ng/mL
Standard Error 206.6
|
|
Ribaxamase Concentration in Intestinal Chyme Period 2
Hour 2.5
|
97745 ng/mL
Standard Error 74180.
|
|
Ribaxamase Concentration in Intestinal Chyme Period 2
Hour 3.5
|
66936 ng/mL
Standard Error 46358.5
|
|
Ribaxamase Concentration in Intestinal Chyme Period 2
Hour 4.5
|
63696 ng/mL
Standard Error 26962.2
|
|
Ribaxamase Concentration in Intestinal Chyme Period 2
Hour 5.5
|
42316 ng/mL
Standard Error 15114.4
|
|
Ribaxamase Concentration in Intestinal Chyme Period 2
Hour 6.5
|
38874 ng/mL
Standard Error 21552.0
|
|
Ribaxamase Concentration in Intestinal Chyme Period 2
Hour 7.5
|
34756 ng/mL
Standard Error 19642.6
|
|
Ribaxamase Concentration in Intestinal Chyme Period 2
Hour 8.5
|
35092 ng/mL
Standard Error 20734.9
|
Adverse Events
Treatment Period 1
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Run-in Period
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Treatment Period 2
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment Period 1
n=15 participants at risk
In Treatment Period 1 (ceftriaxone + SYN-004), all 15 enrolled subjects received 1 g ceftriaxone and 14 received both 150 mg doses of SYN-004. One subject received only one 150 mg dose of SYN-004. In Treatment Period 1, one subject was discontinued from the study prior to receiving the second dose of SYN-004 due to a stoma site hemorrhage. The subject did not continue into the run-in phase or Treatment Period 2.
|
Run-in Period
n=14 participants at risk
Treatment Periods 1 and 2 were separated by a 5- to 7-day run-in phase, during which subjects self-administered 40 mg of esomeprazole once daily in the morning.
|
Treatment Period 2
n=14 participants at risk
In Treatment Period 2, subjects received 2 oral doses of 150mg SYN-004 and 1g ceftriaxone in the presence of esomeprazole. In Treatment Period 2 (ceftriaxone + SYN-004 + esomeprazole), 14 subjects were exposed to ceftriaxone, SYN-004, and esomeprazole. One subject did not receive study drug according to protocol.
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal Discomfort
|
0.00%
0/15
|
14.3%
2/14 • Number of events 2
|
0.00%
0/14
|
|
Gastrointestinal disorders
Nausea
|
6.7%
1/15 • Number of events 1
|
0.00%
0/14
|
0.00%
0/14
|
|
Nervous system disorders
Headache
|
6.7%
1/15 • Number of events 1
|
0.00%
0/14
|
7.1%
1/14 • Number of events 1
|
|
General disorders
Vessel puncture site bruise
|
0.00%
0/15
|
0.00%
0/14
|
7.1%
1/14 • Number of events 1
|
|
Injury, poisoning and procedural complications
Stoma site hemorrhage
|
6.7%
1/15 • Number of events 1
|
0.00%
0/14
|
0.00%
0/14
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/15
|
7.1%
1/14 • Number of events 1
|
0.00%
0/14
|
|
Reproductive system and breast disorders
Postmenopausal hemorrhage
|
6.7%
1/15 • Number of events 1
|
0.00%
0/14
|
0.00%
0/14
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.00%
0/15
|
7.1%
1/14 • Number of events 1
|
0.00%
0/14
|
|
Skin and subcutaneous tissue disorders
Erythema
|
6.7%
1/15 • Number of events 1
|
0.00%
0/14
|
0.00%
0/14
|
|
Vascular disorders
Hot flush
|
6.7%
1/15 • Number of events 1
|
0.00%
0/14
|
0.00%
0/14
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Investigators do not see trial results ahead of public disclosure unless it is under CDA. Investigators will not be allowed to publish or disclose any study results prior to sponsor communicating it to the public.
- Publication restrictions are in place
Restriction type: OTHER