HernioplastyPhase 1NCT03234374
Pharmacokinetics, Relative Bioavailability and Safety of INL-001 Compared to Marcaine After Open Hernioplasty
A Phase 1 study testing INL-001 (bupivacaine HCl collagen implant) and Marcaine 0.25% infiltration in people with Hernioplasty, run by Innocoll at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hernioplasty
- What is being tested?
- INL-001 (bupivacaine HCl collagen implant) and Marcaine 0.25% infiltration
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 5 sitesUnited States
- Study dates
- 2 Jun 2017to 15 Aug 2017
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Pinnacle Research Group
Anniston, Alabama, 36207
Research Concepts
Houston, Texas, 77004
Research Concepts GP, LLC - Houston
Houston, Texas, 77027
Park Place Surgery Center
Longwood, Florida, 32750
Jean Brown Research
Salt Lake City, Utah, 84124
About this study
Official title: 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
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.
Read the 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.
- Conditions
- Hernioplasty
- Being tested
- INL-001 (bupivacaine HCl collagen implant), Marcaine 0.25% infiltration
- Keywords
- Pharmacokinetics, Bioavailability, Safety, Bupivacaine, Collagen, Implant, Marcaine, Hernioplasty
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
INL-001 (bupivacaine HCl collagen implant)Combination product
Also called INL-001
3 x 100 mg INL-001 bupivacaine HCl collagen-matrix implants (total bupivacaine HCl dose 300 mg)
Marcaine 0.25% infiltrationDrug
Also called Marcaine
Marcaine 0.25% (bupivacaine HCl) 175 mg infiltration
| Study group | Role | What they receive |
|---|---|---|
| INL-001 | Experimental | 3 x 100 mg INL-001 (bupivacaine HCl collagen implants). Total bupivacaine HCl dose 300 mg. Receives: Combination Product: INL-001 (bupivacaine HCl collagen implant) |
| Marcaine 0.25% infiltration | Active comparator | Marcaine 0.25% infiltration (bupivacaine HCl 175 mg). Receives: Drug: Marcaine 0.25% infiltration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cmax
Maximum (peak) plasma concentration
Measured: 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
Measured: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48 and 72 hours
Tlag
Lag-time
Measured: 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
Measured: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48 and 72 hours
λz
Terminal phase rate constant
Measured: 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)
Measured: 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
Measured: 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;
Measured: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48 and 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2017
- Study start2 Jun 2017
- Primary completion15 Aug 2017
- Study completion15 Aug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HernioplastyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- Innocoll
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Medpace, Inc.
- Responsible party
- Sponsor
- Investigators
- Gwendolyn Niebler, D.O., Study director, Innocoll
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03234374
- Sponsor's protocol ID
- INN-CB-022
- Status last verified
- Jul 2021
- First submitted
- 28 Jun 2017
- Last updated
- 30 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 33237534
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03234374
- Acronym / sponsor ID
- INN-CB-022
- Conditions
- Hernioplasty
- Keywords
- Pharmacokinetics, Bioavailability, Safety, Bupivacaine, Collagen, Implant, Marcaine, Hernioplasty
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- InnocollIndustry (pharma, biotech, devices)
- Collaborators
- Medpace, Inc.
- Study start
- 2 Jun 2017 (actual)
- Primary completion
- 15 Aug 2017 (actual)
- Study completion
- 15 Aug 2017 (actual)
- First posted
- 31 Jul 2017 (actual)
- Results
- Posted 31 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| INL-001 | Experimental | Combination Product: INL-001 (bupivacaine HCl collagen implant)3 x 100 mg INL-001 (bupivacaine HCl collagen implants). Total bupivacaine HCl dose 300 mg. |
| Marcaine 0.25% infiltration | Active comparator | Drug: Marcaine 0.25% infiltrationMarcaine 0.25% infiltration (bupivacaine HCl 175 mg). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| INL-001 (bupivacaine HCl collagen implant)Also: INL-0013 x 100 mg INL-001 bupivacaine HCl collagen-matrix implants (total bupivacaine HCl dose 300 mg) | Combination product | INL-001 |
| Marcaine 0.25% infiltrationAlso: MarcaineMarcaine 0.25% (bupivacaine HCl) 175 mg infiltration | Drug | Marcaine 0.25% infiltration |
Primary outcome
Cmax
Time frame: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48 and 72 hours.
Maximum (peak) plasma concentration
Tmax
Time frame: 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
Time frame: 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
Time frame: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48 and 72 hours
Terminal half-life
λz
Time frame: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48 and 72 hours
Terminal phase rate constant
AUC
Time frame: 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-∞
Time frame: 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
Time frame: 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;
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33237534Leiman 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gwendolyn Niebler, D.O. study director
Innocoll
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing INL-001 (bupivacaine HCl collagen implant) and Marcaine 0.25% infiltration in people with Hernioplasty, run by Innocoll at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cmax (time frame: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48 and 72 hours.). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03234374, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2021.