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

NCT03234374 | Completed Phase 1 Results FDA Drug

• 1 other identifier: INN-CB-022
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 5

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.

Conditions

Hernioplasty

Keywords

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

Outcome Measures

Primary Outcomes (8)

• Cmax

  Maximum (peak) plasma concentration

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

• Tmax

  Time to maximum (peak) plasma concentration

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

• Tlag

  Lag-time

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

• t½ Terminal Half Life

  Terminal half-life

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

• λz

  Terminal phase rate constant

  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 from Time 0 to last time of last quantifiable plasma concentration (AUC0-last)

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

• AUC0-∞

  AUC from Time 0 to infinity

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

• AUC Extrapolated

  AUC = area under the plasma concentration-time curve;

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

Study Arms (2)

INL-001

EXPERIMENTAL

3 x 100 mg INL-001 (bupivacaine HCl collagen implants). Total bupivacaine HCl dose 300 mg.

Combination Product: INL-001 (bupivacaine HCl collagen implant)

Marcaine 0.25% infiltration

ACTIVE COMPARATOR

Marcaine 0.25% infiltration (bupivacaine HCl 175 mg).

Drug: Marcaine 0.25% infiltration

Interventions

INL-001 (bupivacaine HCl collagen implant) COMBINATION_PRODUCT

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

Also known as: INL-001

INL-001

Marcaine 0.25% infiltration DRUG

Marcaine 0.25% (bupivacaine HCl) 175 mg infiltration

Also known as: Marcaine

Marcaine 0.25% infiltration

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Innocoll: lead
• Medpace, Inc.: collaborator

Study Sites (5)

Pinnacle Research Group

Anniston, Alabama, 36207, United States

Location

Park Place Surgery Center

Longwood, Florida, 32750, United States

Location

Research Concepts

Houston, Texas, 77004, United States

Location

Research Concepts GP, LLC - Houston

Houston, Texas, 77027, United States

Location

Jean Brown Research

Salt Lake City, Utah, 84124, United States

Location

Related Publications (1)

• Leiman D, Niebler G, Minkowitz HS. Pharmacokinetics and Safety of INL-001 (Bupivacaine HCl) Implants Compared with Bupivacaine HCl Infiltration After Open Unilateral Inguinal Hernioplasty. Adv Ther. 2021 Jan;38(1):691-706. doi: 10.1007/s12325-020-01565-x. Epub 2020 Nov 25.

  PMID: 33237534 DERIVED

MeSH Terms

Interventions

Bupivacaine

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Results Point of Contact

• Title: Charlene A. Tucker, MS Executive Director, Medical Writing and Document Management
• Organization: Innocoll

ctucker@innocoll.com

484-406-5211

Study Officials

• Gwendolyn Niebler, D.O.

  Innocoll

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: 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.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2017
• First Posted: July 31, 2017
• Study Start: June 2, 2017
• Primary Completion: August 15, 2017
• Study Completion: August 15, 2017
• Last Updated: July 30, 2021
• Results First Posted: December 31, 2020

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)