Pharmacokinetics, Relative Bioavailability and Safety of INL-001 Compared to Marcaine After Open Hernioplasty

A Randomized, Single Blind Study to Investigate the PK, Relative Bioavailability and Safety of INL-001 Bupivacaine HCl Collagen-Matrix Implant 300 mg Compared to Marcaine™ 0.25% (Bupivacaine HCl) 175 mg Infiltration After Open Hernioplasty

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03234374

Enrollment

Registered

2017-07-31

Start date

2017-06-02

Completion date

2017-08-15

Last updated

2021-07-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hernioplasty

Keywords

Pharmacokinetics, Bioavailability, Safety, Bupivacaine, Collagen, Implant, Marcaine, Hernioplasty

Brief summary

This is a multicenter randomized, single-blind, controlled study. The primary objectives of this study are to obtain the pharmacokinetic profile and the relative bioavailability of the INL-001 matrix during and after open hernioplasty compared to Marcaine™ 0.25% infiltration.

Detailed description

This is a multicenter randomized, single-blind, controlled study. Prior to surgery on Day 1, 48 subjects who continue to meet study entry criteria will be randomized just prior to surgery in a 2:1 ratio to receive either 3 x 100 mg INL-001 bupivacaine HCl collagen-matrix implants (total bupivacaine HCl dose 300 mg) or Marcaine 0.25% (bupivacaine HCl) 175 mg infiltration. Subjects will then undergo open hernioplasty according to standard procedure. Subjects will remain in the clinic at least until after the 72 hour blood sample has been collected for PK analysis on Day 4. Subjects discharged after the 72 hour blood draw will be instructed to return to the clinic to complete the 96 hour PK blood draw on Day 5. Follow-up safety assessments will include clinic visits on Day 7, Day 15 and Day 30. Pharmacokinetic blood samples will be collected from subjects before surgery and at predetermined time points up to 96 hours after administration of study drug. Safety assessments will include frequent assessment of vital signs through 72 hours, continuous electrocardiogram (ECG) monitoring for at least 24 hours, oxygen saturation levels, and adverse events (AEs) reporting with particular emphasis on the signs and symptoms of CNS and cardiovascular bupivacaine toxicity. The surgical wound will be assessed frequently for adverse events associated with altered wound healing.

Interventions

COMBINATION_PRODUCTINL-001 (bupivacaine HCl collagen implant)

3 x 100 mg INL-001 bupivacaine HCl collagen-matrix implants (total bupivacaine HCl dose 300 mg)

DRUGMarcaine 0.25% infiltration

Marcaine 0.25% (bupivacaine HCl) 175 mg infiltration

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

OTHER

Masking

SINGLE (Subject)

Masking description

This is a single-blind study in which the study subject is blinded to treatment group. All precautions will be taken to ensure that the blinding of the treatment group is maintained throughout the study period. Unblinding to the subject will not be permitted unless it is deemed necessary for appropriate treatment of a medical emergency.

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

To be eligible for inclusion into the study, subjects must: * Be a man or woman ≥18 years of age. * Be eligible for unilateral inguinal hernioplasty with mesh (open laparotomy, tension-free technique) performed according to standard surgical technique under general anesthesia. Repair of multiple hernias through a single incision is permitted. If female of childbearing potential, have a negative pregnancy test at screening and before randomization on Day 1 AND be using an effective contraception method (ie, abstinence, intrauterine device \[IUD\], hormonal \[estrogen/progestin\] contraceptives, or barrier control) for at least one menstrual cycle prior to study enrollment and for the duration of the study, OR be surgically sterile, OR be a postmenopausal female (no menses for at least 1 year or hysterectomy). * Has the ability and willingness to comply with the study procedures. * Be willing to use only permitted medications throughout the study. * Be willing to use opioid analgesia. * Be able to fluently speak and understand either English or Spanish and be able to provide meaningful written informed consent for the study.

Exclusion criteria

A subject will be excluded from study participation if prior to surgery he/she: * Has a known hypersensitivity to amide local anesthetics, morphine, acetaminophen, or bovine products. * Is scheduled for bilateral inguinal hernioplasty or other significant concomitant surgical procedure. * Has undergone major surgery within 3 months of the scheduled hernioplasty or plans to undergo another laparotomy procedure within the 30 day postoperative period. * Has known or suspected history of alcohol or drug abuse or misuse within 3 years of screening or evidence of tolerance or physical dependency on opioid analgesics or sedative-hypnotic medications. * Has any clinically significant unstable cardiac, neurological, immunological, renal, hepatic or hematological disease or any other condition that, in the opinion of the investigator, could compromise the subject's welfare, ability to communicate with the study staff or otherwise contraindicate study participation. * Has venous access difficulties that may preclude the frequent pharmacokinetic sampling requirements of the study. * Has participated in a clinical trial (investigational or marketed product) within 30 days of surgery.

Design outcomes

Primary

Measure	Time frame	Description
Cmax	0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48 and 72 hours.	Maximum (peak) plasma concentration
Tmax	0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48 and 72 hours	Time to maximum (peak) plasma concentration
Tlag	0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48 and 72 hours	Lag-time
t½ Terminal Half Life	0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48 and 72 hours	Terminal half-life
λz	0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48 and 72 hours	Terminal phase rate constant
AUC	0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48 and 72 hours	Area under the plasma concentration-time curve from Time 0 to last time of last quantifiable plasma concentration (AUC0-last)
AUC0-∞	0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48 and 72 hours	AUC from Time 0 to infinity
AUC Extrapolated	0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48 and 72 hours	AUC = area under the plasma concentration-time curve;

Countries

United States

Participant flow

Participants by arm

Arm	Count
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)	34
Marcaine 0.25% Infiltration Marcaine 0.25% infiltration (bupivacaine HCl 175 mg). Marcaine 0.25% infiltration: Marcaine 0.25% (bupivacaine HCl) 175 mg infiltration	16
Total	50

Baseline characteristics

Characteristic	Marcaine 0.25% Infiltration	Total	INL-001
Age, Continuous	41.6 years STANDARD_DEVIATION 12.18	44.3 years STANDARD_DEVIATION 14.04	45.6 years STANDARD_DEVIATION 14.84
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants	3 Participants	3 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants	1 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	15 Participants	46 Participants	31 Participants
Region of Enrollment United States	16 participants	50 participants	34 participants
Sex: Female, Male Female	0 Participants	1 Participants	1 Participants
Sex: Female, Male Male	16 Participants	49 Participants	33 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 34	0 / 16
other Total, other adverse events	33 / 34	15 / 16
serious Total, serious adverse events	0 / 34	0 / 16

Outcome results

Primary

AUC

Area under the plasma concentration-time curve from Time 0 to last time of last quantifiable plasma concentration (AUC0-last)

Time frame: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48 and 72 hours

Population: Per Protocol Population

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
INL-001	AUC	18,186.9 hng/[mLmg]	Geometric Coefficient of Variation 39
Marcaine 0.25% Infiltration	AUC	8836.9 hng/[mLmg]	Geometric Coefficient of Variation 46.3

Primary

AUC0-∞

AUC from Time 0 to infinity

Time frame: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48 and 72 hours

Population: Per protocol population

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
INL-001	AUC0-∞	19,012.5 hng/[mLmg]	Geometric Coefficient of Variation 38.7
Marcaine 0.25% Infiltration	AUC0-∞	8920.1 hng/[mLmg]	Geometric Coefficient of Variation 0.65

Primary

AUC Extrapolated

AUC = area under the plasma concentration-time curve;

Time frame: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48 and 72 hours

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
INL-001	AUC Extrapolated	2.96 (h*ng/mL)	Standard Deviation 120.9
Marcaine 0.25% Infiltration	AUC Extrapolated	0.65 (h*ng/mL)	Standard Deviation 122.5

Primary

Cmax

Maximum (peak) plasma concentration

Time frame: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48 and 72 hours.

Population: Per-Protocol PK Population

Arm	Measure	Value (MEAN)	Dispersion
INL-001	Cmax	663.412 ng/ml	Standard Deviation 263.826
Marcaine 0.25% Infiltration	Cmax	641.000 ng/ml	Standard Deviation 262.684

Primary

t½ Terminal Half Life

Terminal half-life

Time frame: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48 and 72 hours

Population: Per-Protocol PK Population

Arm	Measure	Value (MEAN)	Dispersion
INL-001	t½ Terminal Half Life	0.04 hours	Standard Deviation 0.01
Marcaine 0.25% Infiltration	t½ Terminal Half Life	0.09 hours	Standard Deviation 0.04

Primary

Tlag

Lag-time

Time frame: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48 and 72 hours

Population: Per-Protocol PK Population

Arm	Measure	Value (MEAN)	Dispersion
INL-001	Tlag	0.51 hours	Standard Deviation 0.13
Marcaine 0.25% Infiltration	Tlag	0.47 hours	Standard Deviation 0.13

Primary

Tmax

Time to maximum (peak) plasma concentration

Time frame: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48 and 72 hours

Population: Summary of Plasma Bupivacaine PK Parameters by Treatment - Per-Protocol PK Population

Arm	Measure	Value (MEDIAN)
INL-001	Tmax	3.03 hours
Marcaine 0.25% Infiltration	Tmax	1.01 hours

Primary

λz

Terminal phase rate constant

Time frame: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48 and 72 hours

Population: Per protocol population

Arm	Measure	Value (MEAN)	Dispersion
INL-001	λz	18.95 1/hour	Standard Deviation 5.95
Marcaine 0.25% Infiltration	λz	9.08 1/hour	Standard Deviation 3.75

Source: ClinicalTrials.gov · Data processed: Feb 25, 2026

Pharmacokinetics, Relative Bioavailability and Safety of INL-001 Compared to Marcaine After Open Hernioplasty

Conditions

Keywords

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Masking description

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Countries

Participant flow

Participants by arm

Baseline characteristics

Adverse events

Outcome results

AUC

AUC0-∞

AUC Extrapolated

Cmax

t½ Terminal Half Life

Tlag

Tmax

λz