Trial Outcomes & Findings for Pharmacokinetics, Relative Bioavailability and Safety of INL-001 Compared to Marcaine After Open Hernioplasty (NCT NCT03234374)
NCT ID: NCT03234374
Last Updated: 2021-07-30
Results Overview
Maximum (peak) plasma concentration
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
52 participants
Primary outcome timeframe
0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48 and 72 hours.
Results posted on
2021-07-30
Participant Flow
Participant milestones
| Measure |
INL-001
3 x 100 mg INL-001 (bupivacaine HCl collagen implants). Total bupivacaine HCl dose 300 mg.
INL-001 (bupivacaine HCl collagen implant): 3 x 100 mg INL-001 bupivacaine HCl collagen-matrix implants (total bupivacaine HCl dose 300 mg)
|
Marcaine 0.25% Infiltration
Marcaine 0.25% infiltration (bupivacaine HCl 175 mg).
Marcaine 0.25% infiltration: Marcaine 0.25% (bupivacaine HCl) 175 mg infiltration
|
|---|---|---|
|
Overall Study
STARTED
|
35
|
17
|
|
Overall Study
COMPLETED
|
34
|
16
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Pharmacokinetics, Relative Bioavailability and Safety of INL-001 Compared to Marcaine After Open Hernioplasty
Baseline characteristics by cohort
| Measure |
INL-001
n=34 Participants
3 x 100 mg INL-001 (bupivacaine HCl collagen implants). Total bupivacaine HCl dose 300 mg.
INL-001 (bupivacaine HCl collagen implant): 3 x 100 mg INL-001 bupivacaine HCl collagen-matrix implants (total bupivacaine HCl dose 300 mg)
|
Marcaine 0.25% Infiltration
n=16 Participants
Marcaine 0.25% infiltration (bupivacaine HCl 175 mg).
Marcaine 0.25% infiltration: Marcaine 0.25% (bupivacaine HCl) 175 mg infiltration
|
Total
n=50 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
45.6 years
STANDARD_DEVIATION 14.84 • n=5 Participants
|
41.6 years
STANDARD_DEVIATION 12.18 • n=7 Participants
|
44.3 years
STANDARD_DEVIATION 14.04 • n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
33 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
49 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
31 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
46 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
34 participants
n=5 Participants
|
16 participants
n=7 Participants
|
50 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48 and 72 hours.Population: Per-Protocol PK Population
Maximum (peak) plasma concentration
Outcome measures
| Measure |
INL-001
n=34 Participants
3 x 100 mg INL-001 (bupivacaine HCl collagen implants). Total bupivacaine HCl dose 300 mg.
INL-001 (bupivacaine HCl collagen implant): 3 x 100 mg INL-001 bupivacaine HCl collagen-matrix implants (total bupivacaine HCl dose 300 mg)
|
Marcaine 0.25% Infiltration
n=16 Participants
Marcaine 0.25% infiltration (bupivacaine HCl 175 mg).
Marcaine 0.25% infiltration: Marcaine 0.25% (bupivacaine HCl) 175 mg infiltration
|
|---|---|---|
|
Cmax
|
663.412 ng/ml
Standard Deviation 263.826
|
641.000 ng/ml
Standard Deviation 262.684
|
PRIMARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48 and 72 hoursPopulation: Summary of Plasma Bupivacaine PK Parameters by Treatment - Per-Protocol PK Population
Time to maximum (peak) plasma concentration
Outcome measures
| Measure |
INL-001
n=34 Participants
3 x 100 mg INL-001 (bupivacaine HCl collagen implants). Total bupivacaine HCl dose 300 mg.
INL-001 (bupivacaine HCl collagen implant): 3 x 100 mg INL-001 bupivacaine HCl collagen-matrix implants (total bupivacaine HCl dose 300 mg)
|
Marcaine 0.25% Infiltration
n=16 Participants
Marcaine 0.25% infiltration (bupivacaine HCl 175 mg).
Marcaine 0.25% infiltration: Marcaine 0.25% (bupivacaine HCl) 175 mg infiltration
|
|---|---|---|
|
Tmax
|
3.03 hours
Interval 1.48 to 24.02
|
1.01 hours
Interval 0.53 to 3.97
|
PRIMARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48 and 72 hoursPopulation: Per-Protocol PK Population
Lag-time
Outcome measures
| Measure |
INL-001
n=34 Participants
3 x 100 mg INL-001 (bupivacaine HCl collagen implants). Total bupivacaine HCl dose 300 mg.
INL-001 (bupivacaine HCl collagen implant): 3 x 100 mg INL-001 bupivacaine HCl collagen-matrix implants (total bupivacaine HCl dose 300 mg)
|
Marcaine 0.25% Infiltration
n=16 Participants
Marcaine 0.25% infiltration (bupivacaine HCl 175 mg).
Marcaine 0.25% infiltration: Marcaine 0.25% (bupivacaine HCl) 175 mg infiltration
|
|---|---|---|
|
Tlag
|
0.51 hours
Standard Deviation 0.13
|
0.47 hours
Standard Deviation 0.13
|
PRIMARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48 and 72 hoursPopulation: Per-Protocol PK Population
Terminal half-life
Outcome measures
| Measure |
INL-001
n=34 Participants
3 x 100 mg INL-001 (bupivacaine HCl collagen implants). Total bupivacaine HCl dose 300 mg.
INL-001 (bupivacaine HCl collagen implant): 3 x 100 mg INL-001 bupivacaine HCl collagen-matrix implants (total bupivacaine HCl dose 300 mg)
|
Marcaine 0.25% Infiltration
n=16 Participants
Marcaine 0.25% infiltration (bupivacaine HCl 175 mg).
Marcaine 0.25% infiltration: Marcaine 0.25% (bupivacaine HCl) 175 mg infiltration
|
|---|---|---|
|
t½ Terminal Half Life
|
0.04 hours
Standard Deviation 0.01
|
0.09 hours
Standard Deviation 0.04
|
PRIMARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48 and 72 hoursPopulation: Per protocol population
Terminal phase rate constant
Outcome measures
| Measure |
INL-001
n=34 Participants
3 x 100 mg INL-001 (bupivacaine HCl collagen implants). Total bupivacaine HCl dose 300 mg.
INL-001 (bupivacaine HCl collagen implant): 3 x 100 mg INL-001 bupivacaine HCl collagen-matrix implants (total bupivacaine HCl dose 300 mg)
|
Marcaine 0.25% Infiltration
n=16 Participants
Marcaine 0.25% infiltration (bupivacaine HCl 175 mg).
Marcaine 0.25% infiltration: Marcaine 0.25% (bupivacaine HCl) 175 mg infiltration
|
|---|---|---|
|
λz
|
18.95 1/hour
Standard Deviation 5.95
|
9.08 1/hour
Standard Deviation 3.75
|
PRIMARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48 and 72 hoursPopulation: Per Protocol Population
Area under the plasma concentration-time curve from Time 0 to last time of last quantifiable plasma concentration (AUC0-last)
Outcome measures
| Measure |
INL-001
n=34 Participants
3 x 100 mg INL-001 (bupivacaine HCl collagen implants). Total bupivacaine HCl dose 300 mg.
INL-001 (bupivacaine HCl collagen implant): 3 x 100 mg INL-001 bupivacaine HCl collagen-matrix implants (total bupivacaine HCl dose 300 mg)
|
Marcaine 0.25% Infiltration
n=16 Participants
Marcaine 0.25% infiltration (bupivacaine HCl 175 mg).
Marcaine 0.25% infiltration: Marcaine 0.25% (bupivacaine HCl) 175 mg infiltration
|
|---|---|---|
|
AUC
|
18,186.9 h*ng/[mL*mg]
Geometric Coefficient of Variation 39.0
|
8836.9 h*ng/[mL*mg]
Geometric Coefficient of Variation 46.3
|
PRIMARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48 and 72 hoursPopulation: Per protocol population
AUC from Time 0 to infinity
Outcome measures
| Measure |
INL-001
n=34 Participants
3 x 100 mg INL-001 (bupivacaine HCl collagen implants). Total bupivacaine HCl dose 300 mg.
INL-001 (bupivacaine HCl collagen implant): 3 x 100 mg INL-001 bupivacaine HCl collagen-matrix implants (total bupivacaine HCl dose 300 mg)
|
Marcaine 0.25% Infiltration
n=16 Participants
Marcaine 0.25% infiltration (bupivacaine HCl 175 mg).
Marcaine 0.25% infiltration: Marcaine 0.25% (bupivacaine HCl) 175 mg infiltration
|
|---|---|---|
|
AUC0-∞
|
19,012.5 h*ng/[mL*mg]
Geometric Coefficient of Variation 38.7
|
8920.1 h*ng/[mL*mg]
Geometric Coefficient of Variation 0.65
|
PRIMARY outcome
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48 and 72 hoursAUC = area under the plasma concentration-time curve;
Outcome measures
| Measure |
INL-001
n=34 Participants
3 x 100 mg INL-001 (bupivacaine HCl collagen implants). Total bupivacaine HCl dose 300 mg.
INL-001 (bupivacaine HCl collagen implant): 3 x 100 mg INL-001 bupivacaine HCl collagen-matrix implants (total bupivacaine HCl dose 300 mg)
|
Marcaine 0.25% Infiltration
n=16 Participants
Marcaine 0.25% infiltration (bupivacaine HCl 175 mg).
Marcaine 0.25% infiltration: Marcaine 0.25% (bupivacaine HCl) 175 mg infiltration
|
|---|---|---|
|
AUC Extrapolated
|
2.96 (h*ng/mL)
Standard Deviation 120.9
|
0.65 (h*ng/mL)
Standard Deviation 122.5
|
Adverse Events
INL-001
Serious events: 0 serious events
Other events: 33 other events
Deaths: 0 deaths
Marcaine 0.25% Infiltration
Serious events: 0 serious events
Other events: 15 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
INL-001
n=34 participants at risk
3 x 100 mg INL-001 (bupivacaine HCl collagen implants). Total bupivacaine HCl dose 300 mg.
INL-001 (bupivacaine HCl collagen implant): 3 x 100 mg INL-001 bupivacaine HCl collagen-matrix implants (total bupivacaine HCl dose 300 mg)
|
Marcaine 0.25% Infiltration
n=16 participants at risk
Marcaine 0.25% infiltration (bupivacaine HCl 175 mg).
Marcaine 0.25% infiltration: Marcaine 0.25% (bupivacaine HCl) 175 mg infiltration
|
|---|---|---|
|
Nervous system disorders
Somnolence
|
55.9%
19/34 • Number of events 19 • 30 days
Safety Population
|
62.5%
10/16 • Number of events 10 • 30 days
Safety Population
|
|
Nervous system disorders
Dizziness
|
35.3%
12/34 • Number of events 12 • 30 days
Safety Population
|
43.8%
7/16 • Number of events 7 • 30 days
Safety Population
|
|
Nervous system disorders
Tremor
|
17.6%
6/34 • Number of events 6 • 30 days
Safety Population
|
18.8%
3/16 • Number of events 3 • 30 days
Safety Population
|
|
Nervous system disorders
Dysgeusia
|
11.8%
4/34 • Number of events 4 • 30 days
Safety Population
|
25.0%
4/16 • Number of events 4 • 30 days
Safety Population
|
|
Nervous system disorders
Headache
|
11.8%
4/34 • Number of events 4 • 30 days
Safety Population
|
6.2%
1/16 • Number of events 1 • 30 days
Safety Population
|
|
Gastrointestinal disorders
Constipation
|
23.5%
8/34 • Number of events 8 • 30 days
Safety Population
|
6.2%
1/16 • Number of events 1 • 30 days
Safety Population
|
|
Gastrointestinal disorders
Hypoaesthesia oral
|
8.8%
3/34 • Number of events 3 • 30 days
Safety Population
|
12.5%
2/16 • Number of events 2 • 30 days
Safety Population
|
|
Gastrointestinal disorders
Nausea
|
8.8%
3/34 • Number of events 3 • 30 days
Safety Population
|
12.5%
2/16 • Number of events 2 • 30 days
Safety Population
|
|
Gastrointestinal disorders
Paraesthesia oral
|
8.8%
3/34 • Number of events 3 • 30 days
Safety Population
|
12.5%
2/16 • Number of events 2 • 30 days
Safety Population
|
|
Eye disorders
Vision blurred
|
23.5%
8/34 • Number of events 8 • 30 days
Safety Population
|
18.8%
3/16 • Number of events 3 • 30 days
Safety Population
|
|
Psychiatric disorders
Restlessness
|
17.6%
6/34 • Number of events 6 • 30 days
Safety Population
|
12.5%
2/16 • Number of events 2 • 30 days
Safety Population
|
|
Psychiatric disorders
Anxiety
|
5.9%
2/34 • Number of events 2 • 30 days
Safety Population
|
6.2%
1/16 • Number of events 1 • 30 days
Safety Population
|
|
Injury, poisoning and procedural complications
Incision site complication
|
8.8%
3/34 • Number of events 3 • 30 days
Safety Population
|
0.00%
0/16 • 30 days
Safety Population
|
|
Ear and labyrinth disorders
Tinnitus
|
8.8%
3/34 • Number of events 3 • 30 days
Safety Population
|
6.2%
1/16 • Number of events 1 • 30 days
Safety Population
|
|
Cardiac disorders
Bradycardia
|
5.9%
2/34 • Number of events 2 • 30 days
Safety Population
|
6.2%
1/16 • Number of events 1 • 30 days
Safety Population
|
Additional Information
Charlene A. Tucker, MS Executive Director, Medical Writing and Document Management
Innocoll
Phone: 484-406-5211
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place