Trial Outcomes & Findings for Phase 3 Study of Efficacy and Safety of the XaraColl® Bupivacaine Implant After Hernioplasty (NCT NCT02523599)
NCT ID: NCT02523599
Last Updated: 2021-01-08
Results Overview
Sum of Pain Intensity (SPI24). The time weighted sum of pain intensity from 0 to 24 hours (ie, the area under the NRS PI curve from 0 to 24 hours). Where 0 indicated "no pain" and 10 indicated "worst pain possible". This type of measurement scale is called "NRS" or Numerical Rating Scale For the purpose of (SPI) computation, PI at Time 0 (Baseline PI) is set to zero for all patients who have test article implantation. SPI will not be calculated for randomized but not treated patients. A lower score is a better outcome. Minimum value would be "0" and Maximum value would be 240. Time-weighted SPI is calculated as the sum of the pain intensities between successive time points (i.e., if SPI24 = ∑\[PI x (time t - time t-1)\], where "t" represents a given time point,"t-1" represents the previous time point, and time is expressed in hours). This represents the AUC (Area Under the Curve) of the pain intensities when calculated with the trapezoidal rule.
COMPLETED
PHASE3
305 participants
0 to 24 hours
2021-01-08
Participant Flow
Participant milestones
| Measure |
XaraColl
3 XaraColl Bupivacaine Implants each containing 100 mg of bupivacaine hydrochloride, for a 300 mg total dose
XaraColl: Surgical implantation of 3 bupivacaine collagen implants
|
Placebo
3 placebo implants
Placebo: Plain collagen implant (vehicle)
|
|---|---|---|
|
Overall Study
STARTED
|
204
|
101
|
|
Overall Study
Randomized But Not Treated
|
1
|
0
|
|
Overall Study
COMPLETED
|
196
|
100
|
|
Overall Study
NOT COMPLETED
|
8
|
1
|
Reasons for withdrawal
| Measure |
XaraColl
3 XaraColl Bupivacaine Implants each containing 100 mg of bupivacaine hydrochloride, for a 300 mg total dose
XaraColl: Surgical implantation of 3 bupivacaine collagen implants
|
Placebo
3 placebo implants
Placebo: Plain collagen implant (vehicle)
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
|
Overall Study
Physician Decision
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
4
|
1
|
|
Overall Study
Did not return for Day 30 visit
|
2
|
0
|
Baseline Characteristics
Phase 3 Study of Efficacy and Safety of the XaraColl® Bupivacaine Implant After Hernioplasty
Baseline characteristics by cohort
| Measure |
XaraColl
n=204 Participants
3 XaraColl Bupivacaine Implants each containing 100 mg of bupivacaine hydrochloride, for a 300 mg total dose
XaraColl: Surgical implantation of 3 bupivacaine collagen implants
|
Placebo
n=101 Participants
3 placebo implants
Placebo: Plain collagen implant (vehicle)
|
Total
n=305 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
53.1 years
STANDARD_DEVIATION 12.82 • n=99 Participants
|
53.3 years
STANDARD_DEVIATION 14.01 • n=107 Participants
|
53.1 years
STANDARD_DEVIATION 13.20 • n=206 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
12 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
196 Participants
n=99 Participants
|
97 Participants
n=107 Participants
|
293 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
204 participants
n=99 Participants
|
101 participants
n=107 Participants
|
305 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: 0 to 24 hoursPopulation: mITT Population
Sum of Pain Intensity (SPI24). The time weighted sum of pain intensity from 0 to 24 hours (ie, the area under the NRS PI curve from 0 to 24 hours). Where 0 indicated "no pain" and 10 indicated "worst pain possible". This type of measurement scale is called "NRS" or Numerical Rating Scale For the purpose of (SPI) computation, PI at Time 0 (Baseline PI) is set to zero for all patients who have test article implantation. SPI will not be calculated for randomized but not treated patients. A lower score is a better outcome. Minimum value would be "0" and Maximum value would be 240. Time-weighted SPI is calculated as the sum of the pain intensities between successive time points (i.e., if SPI24 = ∑\[PI x (time t - time t-1)\], where "t" represents a given time point,"t-1" represents the previous time point, and time is expressed in hours). This represents the AUC (Area Under the Curve) of the pain intensities when calculated with the trapezoidal rule.
Outcome measures
| Measure |
XaraColl
n=197 Participants
3 XaraColl Bupivacaine Implants each containing 100 mg of bupivacaine hydrochloride, for a 300 mg total dose
XaraColl: Surgical implantation of 3 bupivacaine collagen implants
|
Placebo
n=101 Participants
3 placebo implants
Placebo: Plain collagen implant (vehicle)
|
|---|---|---|
|
SPI24
|
85.0 units on a scale
Standard Deviation 47.18
|
106.8 units on a scale
Standard Deviation 48.20
|
SECONDARY outcome
Timeframe: Time 0 through 24 hoursPopulation: (mITT Population)
Total use of opioid analgesia (TOpA) from Time 0 through 24 hours (TOpA24). This is a basic measurement of counting in total the number of morphine tablets (15 mg) patients had use within a 24 hour period (typically called "rescue" to help manage pain. Zero (0) is the "lowest" score. The lower the number of tablets the better outcome.
Outcome measures
| Measure |
XaraColl
n=197 Participants
3 XaraColl Bupivacaine Implants each containing 100 mg of bupivacaine hydrochloride, for a 300 mg total dose
XaraColl: Surgical implantation of 3 bupivacaine collagen implants
|
Placebo
n=101 Participants
3 placebo implants
Placebo: Plain collagen implant (vehicle)
|
|---|---|---|
|
TOpA24
|
5 morphine mg equivalent
Interval 0.0 to 47.0
|
10 morphine mg equivalent
Interval 0.0 to 40.0
|
SECONDARY outcome
Timeframe: Time 0 through 48 hoursPopulation: mITT Population
Total use of Opioid Analgesia from Time 0 through 48 hours (TOpA48) This is a basic measurement of counting in total the number of morphine tablets (15 mg) patients had use within a 48-hour period (typically called "rescue" to help manage pain. Zero (0) is the "lowest" score. The lower the number of tablets the better outcome.
Outcome measures
| Measure |
XaraColl
n=197 Participants
3 XaraColl Bupivacaine Implants each containing 100 mg of bupivacaine hydrochloride, for a 300 mg total dose
XaraColl: Surgical implantation of 3 bupivacaine collagen implants
|
Placebo
n=101 Participants
3 placebo implants
Placebo: Plain collagen implant (vehicle)
|
|---|---|---|
|
TOpA48
|
5.0 morphine mg equivalent
Interval 0.0 to 82.0
|
14.0 morphine mg equivalent
Interval 0.0 to 65.0
|
SECONDARY outcome
Timeframe: Time 0 through 72 hoursTotal use of Opioid Analgesia (TOpA) from Time 0 through 72 hours. This is a basic measurement of counting in total the number of morphine tablets patients had use within a 72-hour period (typically called "rescue" to help manage pain. Zero (0) is the "lowest" score. The lower the number of tablets the better outcome.
Outcome measures
| Measure |
XaraColl
n=197 Participants
3 XaraColl Bupivacaine Implants each containing 100 mg of bupivacaine hydrochloride, for a 300 mg total dose
XaraColl: Surgical implantation of 3 bupivacaine collagen implants
|
Placebo
n=101 Participants
3 placebo implants
Placebo: Plain collagen implant (vehicle)
|
|---|---|---|
|
TOpA72
|
5.0 morphine mg equivalent
Interval 0.0 to 102.0
|
14.0 morphine mg equivalent
Interval 0.0 to 100.0
|
SECONDARY outcome
Timeframe: 0 to 48 hoursPopulation: mITT Population
Sum of pain intensity (SPI).The time weighted sum of pain intensity from 0 to 48 hours (ie, the area under the NRS PI curve from 0 to 48 hours). For the purpose of SPI computation, Pain Intensity at Time 0 (Baseline PI) is set to zero for all patients who have test article implantation. Minimum value would be "0" and Maximum value would be 480. Time-weighted SPI is calculated as the sum of the pain intensities between successive time points (i.e., if SPI24 = ∑\[PI x (time t - time t-1)\], where "t" represents a given time point,"t-1" represents the previous time point, and time is expressed in hours). This represents the AUC (Area Under the Curve) of the pain intensities when calculated with the trapezoidal rule.
Outcome measures
| Measure |
XaraColl
n=197 Participants
3 XaraColl Bupivacaine Implants each containing 100 mg of bupivacaine hydrochloride, for a 300 mg total dose
XaraColl: Surgical implantation of 3 bupivacaine collagen implants
|
Placebo
n=101 Participants
3 placebo implants
Placebo: Plain collagen implant (vehicle)
|
|---|---|---|
|
SPI48
|
165.7 units on a scale
Interval 0.0 to 408.9
|
190.1 units on a scale
Interval 6.6 to 470.7
|
SECONDARY outcome
Timeframe: 0 to 72 hoursPopulation: mITT Population
Sum of pain intensity (SPI). The time weighted sum of pain intensity from 0 to 72 hours (ie, the area under the NRS PI curve from 0 to 72 hours). For the purpose of SPI computation, PI at Time 0 (Baseline PI) is set to zero for all patients who have test article implantation. Where 0 indicates "no pain" and 10 indicated "worst pain possible". A lower score is a better outcome. Minimum value would be "0" and Maximum value would be 720. Time-weighted SPI is calculated as the sum of the pain intensities between successive time points (i.e., if SPI72 = ∑\[PI x (time t - time t-1)\], where "t" represents a given time point,"t-1" represents the previous time point, and time is expressed in hours). This represents the AUC (Area Under the Curve) of the pain intensities when calculated with the trapezoidal rule.
Outcome measures
| Measure |
XaraColl
n=197 Participants
3 XaraColl Bupivacaine Implants each containing 100 mg of bupivacaine hydrochloride, for a 300 mg total dose
XaraColl: Surgical implantation of 3 bupivacaine collagen implants
|
Placebo
n=101 Participants
3 placebo implants
Placebo: Plain collagen implant (vehicle)
|
|---|---|---|
|
SPI72
|
245.2 units on a scale
Interval 0.0 to 594.1
|
263.3 units on a scale
Interval 6.6 to 710.4
|
Adverse Events
XaraColl
Placebo
Serious adverse events
| Measure |
XaraColl
n=203 participants at risk
3 XaraColl Bupivacaine Implants each containing 100 mg of bupivacaine hydrochloride, for a 300 mg total dose
XaraColl: Surgical implantation of 3 bupivacaine collagen implants
|
Placebo
n=101 participants at risk
3 placebo implants
Placebo: Plain collagen implant (vehicle)
|
|---|---|---|
|
Gastrointestinal disorders
intestinal ischemia
|
0.49%
1/203 • Number of events 1 • 30 days
A total of 204 patients have been randomized to INL-001 active drug arm. However 1 patient was randomized and not treated. This means only 203 patients received the active compound. In the Placebo arm all patient randomized were treated.
|
0.00%
0/101 • 30 days
A total of 204 patients have been randomized to INL-001 active drug arm. However 1 patient was randomized and not treated. This means only 203 patients received the active compound. In the Placebo arm all patient randomized were treated.
|
|
Metabolism and nutrition disorders
hyponatremia
|
0.49%
1/203 • Number of events 1 • 30 days
A total of 204 patients have been randomized to INL-001 active drug arm. However 1 patient was randomized and not treated. This means only 203 patients received the active compound. In the Placebo arm all patient randomized were treated.
|
0.00%
0/101 • 30 days
A total of 204 patients have been randomized to INL-001 active drug arm. However 1 patient was randomized and not treated. This means only 203 patients received the active compound. In the Placebo arm all patient randomized were treated.
|
|
Gastrointestinal disorders
small intestinal obstruction
|
0.49%
1/203 • Number of events 1 • 30 days
A total of 204 patients have been randomized to INL-001 active drug arm. However 1 patient was randomized and not treated. This means only 203 patients received the active compound. In the Placebo arm all patient randomized were treated.
|
0.00%
0/101 • 30 days
A total of 204 patients have been randomized to INL-001 active drug arm. However 1 patient was randomized and not treated. This means only 203 patients received the active compound. In the Placebo arm all patient randomized were treated.
|
|
Gastrointestinal disorders
large intestine perforation
|
0.49%
1/203 • Number of events 1 • 30 days
A total of 204 patients have been randomized to INL-001 active drug arm. However 1 patient was randomized and not treated. This means only 203 patients received the active compound. In the Placebo arm all patient randomized were treated.
|
0.00%
0/101 • 30 days
A total of 204 patients have been randomized to INL-001 active drug arm. However 1 patient was randomized and not treated. This means only 203 patients received the active compound. In the Placebo arm all patient randomized were treated.
|
|
Infections and infestations
sepsis
|
0.49%
1/203 • Number of events 1 • 30 days
A total of 204 patients have been randomized to INL-001 active drug arm. However 1 patient was randomized and not treated. This means only 203 patients received the active compound. In the Placebo arm all patient randomized were treated.
|
0.00%
0/101 • 30 days
A total of 204 patients have been randomized to INL-001 active drug arm. However 1 patient was randomized and not treated. This means only 203 patients received the active compound. In the Placebo arm all patient randomized were treated.
|
|
Infections and infestations
peritonitis bacterial
|
0.49%
1/203 • Number of events 1 • 30 days
A total of 204 patients have been randomized to INL-001 active drug arm. However 1 patient was randomized and not treated. This means only 203 patients received the active compound. In the Placebo arm all patient randomized were treated.
|
0.00%
0/101 • 30 days
A total of 204 patients have been randomized to INL-001 active drug arm. However 1 patient was randomized and not treated. This means only 203 patients received the active compound. In the Placebo arm all patient randomized were treated.
|
|
Metabolism and nutrition disorders
malnutrition
|
0.49%
1/203 • Number of events 1 • 30 days
A total of 204 patients have been randomized to INL-001 active drug arm. However 1 patient was randomized and not treated. This means only 203 patients received the active compound. In the Placebo arm all patient randomized were treated.
|
0.00%
0/101 • 30 days
A total of 204 patients have been randomized to INL-001 active drug arm. However 1 patient was randomized and not treated. This means only 203 patients received the active compound. In the Placebo arm all patient randomized were treated.
|
|
Gastrointestinal disorders
colitis
|
0.49%
1/203 • Number of events 1 • 30 days
A total of 204 patients have been randomized to INL-001 active drug arm. However 1 patient was randomized and not treated. This means only 203 patients received the active compound. In the Placebo arm all patient randomized were treated.
|
0.00%
0/101 • 30 days
A total of 204 patients have been randomized to INL-001 active drug arm. However 1 patient was randomized and not treated. This means only 203 patients received the active compound. In the Placebo arm all patient randomized were treated.
|
|
Renal and urinary disorders
urinary retention
|
0.49%
1/203 • Number of events 1 • 30 days
A total of 204 patients have been randomized to INL-001 active drug arm. However 1 patient was randomized and not treated. This means only 203 patients received the active compound. In the Placebo arm all patient randomized were treated.
|
0.00%
0/101 • 30 days
A total of 204 patients have been randomized to INL-001 active drug arm. However 1 patient was randomized and not treated. This means only 203 patients received the active compound. In the Placebo arm all patient randomized were treated.
|
Other adverse events
| Measure |
XaraColl
n=203 participants at risk
3 XaraColl Bupivacaine Implants each containing 100 mg of bupivacaine hydrochloride, for a 300 mg total dose
XaraColl: Surgical implantation of 3 bupivacaine collagen implants
|
Placebo
n=101 participants at risk
3 placebo implants
Placebo: Plain collagen implant (vehicle)
|
|---|---|---|
|
Gastrointestinal disorders
constipation
|
8.4%
17/203 • Number of events 17 • 30 days
A total of 204 patients have been randomized to INL-001 active drug arm. However 1 patient was randomized and not treated. This means only 203 patients received the active compound. In the Placebo arm all patient randomized were treated.
|
11.9%
12/101 • Number of events 12 • 30 days
A total of 204 patients have been randomized to INL-001 active drug arm. However 1 patient was randomized and not treated. This means only 203 patients received the active compound. In the Placebo arm all patient randomized were treated.
|
|
Gastrointestinal disorders
nausea
|
11.3%
23/203 • Number of events 23 • 30 days
A total of 204 patients have been randomized to INL-001 active drug arm. However 1 patient was randomized and not treated. This means only 203 patients received the active compound. In the Placebo arm all patient randomized were treated.
|
14.9%
15/101 • Number of events 15 • 30 days
A total of 204 patients have been randomized to INL-001 active drug arm. However 1 patient was randomized and not treated. This means only 203 patients received the active compound. In the Placebo arm all patient randomized were treated.
|
|
Injury, poisoning and procedural complications
incision site pain
|
16.7%
34/203 • Number of events 34 • 30 days
A total of 204 patients have been randomized to INL-001 active drug arm. However 1 patient was randomized and not treated. This means only 203 patients received the active compound. In the Placebo arm all patient randomized were treated.
|
18.8%
19/101 • Number of events 19 • 30 days
A total of 204 patients have been randomized to INL-001 active drug arm. However 1 patient was randomized and not treated. This means only 203 patients received the active compound. In the Placebo arm all patient randomized were treated.
|
|
Injury, poisoning and procedural complications
incision site swelling
|
20.7%
42/203 • Number of events 42 • 30 days
A total of 204 patients have been randomized to INL-001 active drug arm. However 1 patient was randomized and not treated. This means only 203 patients received the active compound. In the Placebo arm all patient randomized were treated.
|
18.8%
19/101 • Number of events 19 • 30 days
A total of 204 patients have been randomized to INL-001 active drug arm. However 1 patient was randomized and not treated. This means only 203 patients received the active compound. In the Placebo arm all patient randomized were treated.
|
|
Injury, poisoning and procedural complications
post procedural discharge
|
7.4%
15/203 • Number of events 15 • 30 days
A total of 204 patients have been randomized to INL-001 active drug arm. However 1 patient was randomized and not treated. This means only 203 patients received the active compound. In the Placebo arm all patient randomized were treated.
|
5.9%
6/101 • Number of events 6 • 30 days
A total of 204 patients have been randomized to INL-001 active drug arm. However 1 patient was randomized and not treated. This means only 203 patients received the active compound. In the Placebo arm all patient randomized were treated.
|
|
Nervous system disorders
dizziness
|
15.3%
31/203 • Number of events 31 • 30 days
A total of 204 patients have been randomized to INL-001 active drug arm. However 1 patient was randomized and not treated. This means only 203 patients received the active compound. In the Placebo arm all patient randomized were treated.
|
11.9%
12/101 • Number of events 12 • 30 days
A total of 204 patients have been randomized to INL-001 active drug arm. However 1 patient was randomized and not treated. This means only 203 patients received the active compound. In the Placebo arm all patient randomized were treated.
|
|
Nervous system disorders
dysgeusia
|
6.9%
14/203 • Number of events 14 • 30 days
A total of 204 patients have been randomized to INL-001 active drug arm. However 1 patient was randomized and not treated. This means only 203 patients received the active compound. In the Placebo arm all patient randomized were treated.
|
3.0%
3/101 • Number of events 3 • 30 days
A total of 204 patients have been randomized to INL-001 active drug arm. However 1 patient was randomized and not treated. This means only 203 patients received the active compound. In the Placebo arm all patient randomized were treated.
|
|
Nervous system disorders
somnolence
|
17.7%
36/203 • Number of events 36 • 30 days
A total of 204 patients have been randomized to INL-001 active drug arm. However 1 patient was randomized and not treated. This means only 203 patients received the active compound. In the Placebo arm all patient randomized were treated.
|
19.8%
20/101 • Number of events 20 • 30 days
A total of 204 patients have been randomized to INL-001 active drug arm. However 1 patient was randomized and not treated. This means only 203 patients received the active compound. In the Placebo arm all patient randomized were treated.
|
|
Psychiatric disorders
restlessness
|
6.9%
14/203 • Number of events 14 • 30 days
A total of 204 patients have been randomized to INL-001 active drug arm. However 1 patient was randomized and not treated. This means only 203 patients received the active compound. In the Placebo arm all patient randomized were treated.
|
8.9%
9/101 • Number of events 9 • 30 days
A total of 204 patients have been randomized to INL-001 active drug arm. However 1 patient was randomized and not treated. This means only 203 patients received the active compound. In the Placebo arm all patient randomized were treated.
|
Additional Information
Charlene A. Tucker, MS Executive Director, Medical Writing and Document Management
Innocoll
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER