Trial Outcomes & Findings for Phase 3 Study of Efficacy and Safety of the XaraColl® Bupivacaine Implant After Hernioplasty (NCT NCT02525133)

NCT ID: NCT02525133

Last Updated: 2021-01-08

Results Overview

The primary efficacy variable (time-weighted sum of pain intensity from Time 0 through 24 hours \[SPI24\]) was compared once at a 2-sided 0.05 level. Therefore, no multiplicity adjustment was necessary for the primary efficacy analysis. Pain Intensity was assessed by the subject using the 11-point NRS, where 0 indicated "no pain" and 10 indicated "worst pain possible". 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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 319 participants
• Primary outcome timeframe: 0 to 24 hours
• Results posted on: 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	213	106
Overall Study Randomized But Not Treated	4	0
Overall Study COMPLETED	203	103
Overall Study NOT COMPLETED	10	3

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	0	1
Overall Study Death	0	1
Overall Study did not meet randomization criteria	1	0
Overall Study Lost to Follow-up	5	1
Overall Study randomized not enrolled	3	0
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

Phase 3 Study of Efficacy and Safety of the XaraColl® Bupivacaine Implant After Hernioplasty

Baseline characteristics by cohort

Measure	XaraColl n=207 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=105 Participants 3 placebo implants Placebo: Plain collagen implant (vehicle)	Total n=312 Participants Total of all reporting groups
Age, Continuous	50.7 years STANDARD_DEVIATION 13.69 • n=5 Participants	48.5 years STANDARD_DEVIATION 13.84 • n=7 Participants	50.0 years STANDARD_DEVIATION 13.79 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Sex: Female, Male Male	202 Participants n=5 Participants	102 Participants n=7 Participants	304 Participants n=5 Participants

PRIMARY outcome

Timeframe: 0 to 24 hours

Population: modified intent-to-treat - The mITT population consisted of randomized subjects who received any dose of INL-001 or placebo and who had at least 1 NRS PI score prior to hospital discharge, as needed, to compute SPI.

The primary efficacy variable (time-weighted sum of pain intensity from Time 0 through 24 hours [SPI24]) was compared once at a 2-sided 0.05 level. Therefore, no multiplicity adjustment was necessary for the primary efficacy analysis. Pain Intensity was assessed by the subject using the 11-point NRS, where 0 indicated "no pain" and 10 indicated "worst pain possible". 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=207 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=105 Participants 3 placebo implants Placebo: Plain collagen implant (vehicle)
SPI24	88.3 units on a scale Standard Deviation 47.01	116.2 units on a scale Standard Deviation 44.04

SECONDARY outcome

Timeframe: Time 0 through 24 hours

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 to 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=207 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=105 Participants 3 placebo implants Placebo: Plain collagen implant (vehicle)
TOpA24	5.0 morphine equivalents Interval 0.0 to 70.0	14 morphine equivalents Interval 0.0 to 53.0

SECONDARY outcome

Timeframe: Time 0 through 48 hours

Population: mITT Population)

Total use of opioid analgesia (TOpA) 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=207 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=105 Participants 3 placebo implants Placebo: Plain collagen implant (vehicle)
TOpA48	5 morphine equivalent Interval 0.0 to 70.0	14 morphine equivalent Interval 0.0 to 53.0

SECONDARY outcome

Timeframe: Time 0 through 72 hours

Total use of opioid analgesia (TOpA) from Time 0 through 72 hours (TOpA72) This is a basic measurement of counting in total the number of morphine tablets (15 mg) 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=207 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=105 Participants 3 placebo implants Placebo: Plain collagen implant (vehicle)
TOpA72	10 morphine tablets Interval 0.0 to 90.0	20 morphine tablets Interval 0.0 to 73.0

SECONDARY outcome

Timeframe: 0 to 48 hours

Population: (mITT Population)

Time-weighted sum of pain intensity from Time 0 through 48 hours (SPI48). Lower score has a better outcome. Pain Intensity was assessed by the subject using the 11-point NRS, where 0 indicated "no pain" and 10 indicated "worst pain possible". 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 SPI48 = ∑[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=207 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=105 Participants 3 placebo implants Placebo: Plain collagen implant (vehicle)
SPI48	188.1 units on a scale Interval 0.0 to 435.8	214.9 units on a scale Interval 0.0 to 429.3

SECONDARY outcome

Timeframe: 0 to 72 hours

Population: mITT Population

Time-weighted sum of pain intensity from Time 0 through 72 hours (SPI72) A lower score is a better outcome. Pain Intensity was assessed by the subject using the 11-point NRS, where 0 indicated "no pain" and 10 indicated "worst pain possible" 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=207 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=105 Participants 3 placebo implants Placebo: Plain collagen implant (vehicle)
SPI72	264.5 units on a scale Interval 0.0 to 651.7	299.7 units on a scale Interval 62.8 to 645.3

Adverse Events

XaraColl

Serious events: 3 serious events

Other events: 118 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 76 other events

Deaths: 1 deaths

Serious adverse events

Measure	XaraColl n=208 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=107 participants at risk 3 placebo implants Placebo: Plain collagen implant (vehicle)
Cardiac disorders Acute myocardial infarction	0.48% 1/208 • Number of events 1 • 30 days Subject 628-018 was randomized to the INL-001 group but received placebo; the subject was included in the INL-001 group for efficacy analyses (ie, ITT and mITT populations) and was included in the placebo group for safety analyses (ie, safety population). The ITT population consisted of all randomized subjects who may or may not have received any dose of INL-001 or placebo	0.93% 1/107 • Number of events 1 • 30 days Subject 628-018 was randomized to the INL-001 group but received placebo; the subject was included in the INL-001 group for efficacy analyses (ie, ITT and mITT populations) and was included in the placebo group for safety analyses (ie, safety population). The ITT population consisted of all randomized subjects who may or may not have received any dose of INL-001 or placebo
Cardiac disorders Atrial fibrillation	0.48% 1/208 • Number of events 1 • 30 days Subject 628-018 was randomized to the INL-001 group but received placebo; the subject was included in the INL-001 group for efficacy analyses (ie, ITT and mITT populations) and was included in the placebo group for safety analyses (ie, safety population). The ITT population consisted of all randomized subjects who may or may not have received any dose of INL-001 or placebo	0.00% 0/107 • 30 days Subject 628-018 was randomized to the INL-001 group but received placebo; the subject was included in the INL-001 group for efficacy analyses (ie, ITT and mITT populations) and was included in the placebo group for safety analyses (ie, safety population). The ITT population consisted of all randomized subjects who may or may not have received any dose of INL-001 or placebo
Gastrointestinal disorders Abdominal pain	0.00% 0/208 • 30 days Subject 628-018 was randomized to the INL-001 group but received placebo; the subject was included in the INL-001 group for efficacy analyses (ie, ITT and mITT populations) and was included in the placebo group for safety analyses (ie, safety population). The ITT population consisted of all randomized subjects who may or may not have received any dose of INL-001 or placebo	0.93% 1/107 • Number of events 1 • 30 days Subject 628-018 was randomized to the INL-001 group but received placebo; the subject was included in the INL-001 group for efficacy analyses (ie, ITT and mITT populations) and was included in the placebo group for safety analyses (ie, safety population). The ITT population consisted of all randomized subjects who may or may not have received any dose of INL-001 or placebo
Infections and infestations Appendicitis	0.48% 1/208 • Number of events 1 • 30 days Subject 628-018 was randomized to the INL-001 group but received placebo; the subject was included in the INL-001 group for efficacy analyses (ie, ITT and mITT populations) and was included in the placebo group for safety analyses (ie, safety population). The ITT population consisted of all randomized subjects who may or may not have received any dose of INL-001 or placebo	0.00% 0/107 • 30 days Subject 628-018 was randomized to the INL-001 group but received placebo; the subject was included in the INL-001 group for efficacy analyses (ie, ITT and mITT populations) and was included in the placebo group for safety analyses (ie, safety population). The ITT population consisted of all randomized subjects who may or may not have received any dose of INL-001 or placebo
Musculoskeletal and connective tissue disorders Groin pain	0.00% 0/208 • 30 days Subject 628-018 was randomized to the INL-001 group but received placebo; the subject was included in the INL-001 group for efficacy analyses (ie, ITT and mITT populations) and was included in the placebo group for safety analyses (ie, safety population). The ITT population consisted of all randomized subjects who may or may not have received any dose of INL-001 or placebo	0.93% 1/107 • Number of events 1 • 30 days Subject 628-018 was randomized to the INL-001 group but received placebo; the subject was included in the INL-001 group for efficacy analyses (ie, ITT and mITT populations) and was included in the placebo group for safety analyses (ie, safety population). The ITT population consisted of all randomized subjects who may or may not have received any dose of INL-001 or placebo

Other adverse events

Measure	XaraColl n=208 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=107 participants at risk 3 placebo implants Placebo: Plain collagen implant (vehicle)
Gastrointestinal disorders Constipation	8.7% 18/208 • Number of events 18 • 30 days Subject 628-018 was randomized to the INL-001 group but received placebo; the subject was included in the INL-001 group for efficacy analyses (ie, ITT and mITT populations) and was included in the placebo group for safety analyses (ie, safety population). The ITT population consisted of all randomized subjects who may or may not have received any dose of INL-001 or placebo	17.8% 19/107 • Number of events 19 • 30 days Subject 628-018 was randomized to the INL-001 group but received placebo; the subject was included in the INL-001 group for efficacy analyses (ie, ITT and mITT populations) and was included in the placebo group for safety analyses (ie, safety population). The ITT population consisted of all randomized subjects who may or may not have received any dose of INL-001 or placebo
Gastrointestinal disorders Nausea	7.7% 16/208 • Number of events 16 • 30 days Subject 628-018 was randomized to the INL-001 group but received placebo; the subject was included in the INL-001 group for efficacy analyses (ie, ITT and mITT populations) and was included in the placebo group for safety analyses (ie, safety population). The ITT population consisted of all randomized subjects who may or may not have received any dose of INL-001 or placebo	17.8% 19/107 • Number of events 19 • 30 days Subject 628-018 was randomized to the INL-001 group but received placebo; the subject was included in the INL-001 group for efficacy analyses (ie, ITT and mITT populations) and was included in the placebo group for safety analyses (ie, safety population). The ITT population consisted of all randomized subjects who may or may not have received any dose of INL-001 or placebo
Injury, poisoning and procedural complications Incision site complication	6.2% 13/208 • Number of events 13 • 30 days Subject 628-018 was randomized to the INL-001 group but received placebo; the subject was included in the INL-001 group for efficacy analyses (ie, ITT and mITT populations) and was included in the placebo group for safety analyses (ie, safety population). The ITT population consisted of all randomized subjects who may or may not have received any dose of INL-001 or placebo	5.6% 6/107 • Number of events 6 • 30 days Subject 628-018 was randomized to the INL-001 group but received placebo; the subject was included in the INL-001 group for efficacy analyses (ie, ITT and mITT populations) and was included in the placebo group for safety analyses (ie, safety population). The ITT population consisted of all randomized subjects who may or may not have received any dose of INL-001 or placebo
Injury, poisoning and procedural complications Incision site pain	9.1% 19/208 • Number of events 19 • 30 days Subject 628-018 was randomized to the INL-001 group but received placebo; the subject was included in the INL-001 group for efficacy analyses (ie, ITT and mITT populations) and was included in the placebo group for safety analyses (ie, safety population). The ITT population consisted of all randomized subjects who may or may not have received any dose of INL-001 or placebo	12.1% 13/107 • Number of events 13 • 30 days Subject 628-018 was randomized to the INL-001 group but received placebo; the subject was included in the INL-001 group for efficacy analyses (ie, ITT and mITT populations) and was included in the placebo group for safety analyses (ie, safety population). The ITT population consisted of all randomized subjects who may or may not have received any dose of INL-001 or placebo
Injury, poisoning and procedural complications Incision site swelling	8.7% 18/208 • Number of events 18 • 30 days Subject 628-018 was randomized to the INL-001 group but received placebo; the subject was included in the INL-001 group for efficacy analyses (ie, ITT and mITT populations) and was included in the placebo group for safety analyses (ie, safety population). The ITT population consisted of all randomized subjects who may or may not have received any dose of INL-001 or placebo	10.3% 11/107 • Number of events 11 • 30 days Subject 628-018 was randomized to the INL-001 group but received placebo; the subject was included in the INL-001 group for efficacy analyses (ie, ITT and mITT populations) and was included in the placebo group for safety analyses (ie, safety population). The ITT population consisted of all randomized subjects who may or may not have received any dose of INL-001 or placebo
Nervous system disorders Dizziness	16.3% 34/208 • Number of events 34 • 30 days Subject 628-018 was randomized to the INL-001 group but received placebo; the subject was included in the INL-001 group for efficacy analyses (ie, ITT and mITT populations) and was included in the placebo group for safety analyses (ie, safety population). The ITT population consisted of all randomized subjects who may or may not have received any dose of INL-001 or placebo	20.6% 22/107 • Number of events 22 • 30 days Subject 628-018 was randomized to the INL-001 group but received placebo; the subject was included in the INL-001 group for efficacy analyses (ie, ITT and mITT populations) and was included in the placebo group for safety analyses (ie, safety population). The ITT population consisted of all randomized subjects who may or may not have received any dose of INL-001 or placebo
Nervous system disorders Dysgeusia	8.2% 17/208 • Number of events 17 • 30 days Subject 628-018 was randomized to the INL-001 group but received placebo; the subject was included in the INL-001 group for efficacy analyses (ie, ITT and mITT populations) and was included in the placebo group for safety analyses (ie, safety population). The ITT population consisted of all randomized subjects who may or may not have received any dose of INL-001 or placebo	9.3% 10/107 • Number of events 10 • 30 days Subject 628-018 was randomized to the INL-001 group but received placebo; the subject was included in the INL-001 group for efficacy analyses (ie, ITT and mITT populations) and was included in the placebo group for safety analyses (ie, safety population). The ITT population consisted of all randomized subjects who may or may not have received any dose of INL-001 or placebo
Nervous system disorders Somnolence	15.9% 33/208 • Number of events 33 • 30 days Subject 628-018 was randomized to the INL-001 group but received placebo; the subject was included in the INL-001 group for efficacy analyses (ie, ITT and mITT populations) and was included in the placebo group for safety analyses (ie, safety population). The ITT population consisted of all randomized subjects who may or may not have received any dose of INL-001 or placebo	17.8% 19/107 • Number of events 19 • 30 days Subject 628-018 was randomized to the INL-001 group but received placebo; the subject was included in the INL-001 group for efficacy analyses (ie, ITT and mITT populations) and was included in the placebo group for safety analyses (ie, safety population). The ITT population consisted of all randomized subjects who may or may not have received any dose of INL-001 or placebo
Psychiatric disorders Anxiety	2.9% 6/208 • Number of events 6 • 30 days Subject 628-018 was randomized to the INL-001 group but received placebo; the subject was included in the INL-001 group for efficacy analyses (ie, ITT and mITT populations) and was included in the placebo group for safety analyses (ie, safety population). The ITT population consisted of all randomized subjects who may or may not have received any dose of INL-001 or placebo	7.5% 8/107 • Number of events 8 • 30 days Subject 628-018 was randomized to the INL-001 group but received placebo; the subject was included in the INL-001 group for efficacy analyses (ie, ITT and mITT populations) and was included in the placebo group for safety analyses (ie, safety population). The ITT population consisted of all randomized subjects who may or may not have received any dose of INL-001 or placebo
Psychiatric disorders Restlessness	7.7% 16/208 • Number of events 16 • 30 days Subject 628-018 was randomized to the INL-001 group but received placebo; the subject was included in the INL-001 group for efficacy analyses (ie, ITT and mITT populations) and was included in the placebo group for safety analyses (ie, safety population). The ITT population consisted of all randomized subjects who may or may not have received any dose of INL-001 or placebo	9.3% 10/107 • Number of events 10 • 30 days Subject 628-018 was randomized to the INL-001 group but received placebo; the subject was included in the INL-001 group for efficacy analyses (ie, ITT and mITT populations) and was included in the placebo group for safety analyses (ie, safety population). The ITT population consisted of all randomized subjects who may or may not have received any dose of INL-001 or placebo

Additional Information

Charlene A. Tucker, MS Executive Director, Medical Writing and Document Management

Innocoll

Phone: 484-406-5211

Email: ctucker@innocoll.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: OTHER