Hernioplasty
Conditions
Keywords
unilateral inguinal hernioplasty
Brief summary
Assess the pharmacokinetic profile of 2 doses of the XaraColl® implant after open laparotomy hernioplasty and assess the relative bioavailability of Xaracoll compared to a local bupivacaine infiltration.
Detailed description
Inguinal hernioplasty is a common surgery. Common surgical methods used include laparoscopic and open placement of synthetic mesh. Managing postoperative pain and preventing morbidity after open mesh hernioplasty remain considerable medical challenges. Bupivacaine is a local anesthetic (pain medicine) that has an established safety profile. Collagen is a protein that is found in all mammals. The Xaracoll implant is a thin flat sponge made out of collagen that comes from cow tendons and contains bupivacaine. When inserted into a surgical site, the collagen breaks down and bupivacaine is released at the surgical site to provide postoperative pain control. This study will assess the pharmacokinetic profile of 2 doses of the XaraColl implant after open laparotomy hernioplasty and assess the relative bioavailability of the Xaracoll implant compared to a local bupivacaine infiltration.
Interventions
DRUG2 100mg Xaracoll implants
DRUG3 100mg Xaracoll implants
DRUG150mg Bupivacaine HCl injection
Sponsors
Premier Research
Innocoll
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Man or woman who is ≥ 18 years of age 2. Has a planned unilateral inguinal hernioplasty (open laparotomy, tension free technique) 3. If female, is nonpregnant
Exclusion criteria
1. Scheduled for bilateral inguinal hernioplasty or other significant concomitant surgical procedures 2. Has undergone major surgery within 3 months of the scheduled hernioplasty or plans to undergo another laparotomy procedure within 30 days postoperatively 3. 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 patient's welfare, ability to communicate with the study staff or otherwise contraindicate study participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax | 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 72, and 96 hours after surgery. | Maximum drug plasma concentration |
| AUC0-last | 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 72, and 96 hours after surgery. | Area under the plasma concentration-time curve from Time 0 to time of last quantifiable plasma concentration. |
| Tmax | 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 72, and 96 hours after surgery. | Time to maximum plasma concentration. |
| t1/2 (Hour) | 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 72, and 96 hours after surgery. | Terminal half-life. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 2 100mg Xaracoll Implants Bupivacaine HCl implant
2 100mg Xaracoll implants | 26 |
| 3 100mg Xaracoll Implants Bupivacaine HCl implant
3 100mg Xaracoll implants | 25 |
| 150mg Bupivacaine HCl Injection Bupivacaine HCl
150mg Bupivacaine HCl injection | 13 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | ineligibility | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 |
| Overall Study | surgical complication | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | 2 100mg Xaracoll Implants | 3 100mg Xaracoll Implants | 150mg Bupivacaine HCl Injection | Total |
|---|---|---|---|---|
| Age, Continuous | 42.7 years STANDARD_DEVIATION 11.93 | 46.1 years STANDARD_DEVIATION 11.4 | 48.2 years STANDARD_DEVIATION 12.76 | 45.2 years STANDARD_DEVIATION 11.9 |
| Region of Enrollment United States | 26 participants | 25 participants | 13 participants | 64 participants |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 24 Participants | 25 Participants | 12 Participants | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 21 / 26 | 15 / 24 | 8 / 12 |
| serious Total, serious adverse events | 0 / 26 | 0 / 24 | 0 / 12 |
Outcome results
Primary
AUC0-last
Area under the plasma concentration-time curve from Time 0 to time of last quantifiable plasma concentration.
Time frame: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 72, and 96 hours after surgery.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2 100mg Xaracoll Implants | AUC0-last | 10793.449 ng/mL∙hr | Standard Deviation 5523.4326 |
| 3 100mg Xaracoll Implants | AUC0-last | 18589.907 ng/mL∙hr | Standard Deviation 7841.1973 |
| 150mg Bupivacaine HCl Injection | AUC0-last | 8323.188 ng/mL∙hr | Standard Deviation 4312.194 |
Primary
Cmax
Maximum drug plasma concentration
Time frame: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 72, and 96 hours after surgery.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2 100mg Xaracoll Implants | Cmax | 340.4 ng/mL | Standard Deviation 111.05 |
| 3 100mg Xaracoll Implants | Cmax | 524.8 ng/mL | Standard Deviation 146.45 |
| 150mg Bupivacaine HCl Injection | Cmax | 348.4 ng/mL | Standard Deviation 184.02 |
Primary
t1/2 (Hour)
Terminal half-life.
Time frame: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 72, and 96 hours after surgery.
Population: Per protocol PK population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2 100mg Xaracoll Implants | t1/2 (Hour) | 16.922 hours | Standard Deviation 7.626 |
| 3 100mg Xaracoll Implants | t1/2 (Hour) | 18.058 hours | Standard Deviation 7.6699 |
| 150mg Bupivacaine HCl Injection | t1/2 (Hour) | 8.819 hours | Standard Deviation 4.5292 |
Primary
Tmax
Time to maximum plasma concentration.
Time frame: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 72, and 96 hours after surgery.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2 100mg Xaracoll Implants | Tmax | 7.271 hours | Standard Deviation 10.8603 |
| 3 100mg Xaracoll Implants | Tmax | 8.567 hours | Standard Deviation 10.2484 |
| 150mg Bupivacaine HCl Injection | Tmax | 8.783 hours | Standard Deviation 1.8761 |