An Open-label Safety and Pharmacokinetic Study of INL-001 in Adults Following Various Open Soft-Tissue Surgeries

Phase 3

Completed

• Conditions: Hysterectomy; Reduction Mammoplasty; Hernia, Ventral; Abdominoplasty; Pain, Postoperative; Colectomy
• Interventions: Combination Product: INL-001 (bupivacaine hydrochloride) implant

• Registration Number: NCT04785638
• Lead Sponsor: Innocoll

Brief Summary

This is a multicenter, Phase 3, open-label, safety, tolerability, and characterization of pharmacokinetics study of the INL 001 (bupivacaine HCl) implant, at 300 mg, in patients following various soft-tissue surgeries: open ventral hernia repair, abdominoplasty, open abdominal hysterectomy, laparoscopic-assisted colectomy, and reduction mammoplasty.

Detailed Description

This is a multicenter, Phase 3, open-label, safety, tolerability, and characterization of pharmacokinetics study of the INL-001 (bupivacaine HCl) implant, at 300 mg, in patients following various soft-tissue surgeries: open ventral hernia repair, abdominoplasty, open abdominal hysterectomy, laparoscopic-assisted colectomy, and reduction mammoplasty. After a screening period, eligible patients will undergo study surgery under general anesthesia and have INL-001 implanted intraoperatively. Efficacy is also an exploratory measure in this study.

The study includes a screening period, an inpatient period (preoperative, intraoperative, postoperative) of approximately 5 days, and an outpatient follow-up period (up to 30 days after treatment). Posttreatment safety and/or efficacy assessments will be made throughout the study and as specifically scheduled through 96 hours posttreatment, on day 7 (telephone), on day 15 (clinic visit), and on day 30 (clinic visit). Unless the investigator determines further hospitalization is necessary, patients will be discharged approximately 96 hours posttreatment (inpatient day 5).

During the screening period, all patients will undergo eligibility and other screening and safety assessments. In addition, the investigator will administer the Pain Catastrophizing Scale (screening only) as an exploratory measure and the 15-item Quality of Recovery (QoR-15) questionnaire (baseline).

Adverse event and concomitant medication information, including use of rescue pain medication, will be collected throughout the study (inpatient and outpatient). Surgical wound healing/grading assessments and assessment for signs and symptoms potentially indicative of systemic bupivacaine toxicity will be made.

Blood samples for pharmacokinetic assessments will be collected from patients at multiple time points for the measurement of concentrations of bupivacaine in plasma.

After surgery, patient reports of pain intensity using an 11-point numeric pain rating scale (NPRS) will be recorded at multiple time points through 96 hours posttreatment. Patients will be permitted rescue medication (oral and/or intravenous) to manage breakthrough pain when it occurs. The QoR-15 questionnaire and Patient Global Assessment (for pain control) will be administered on an inpatient basis and on day 7. The Opioid Related Symptom Distress Scale will be administered on an inpatient basis.

Study Timeline

• Study First Submitted: 2021-03-01
• Study First Submitted QC: 2021-03-04
• Study First Posted: 2021-03-08
• Study Start: 2021-04-14
• Primary Completion: 2023-01-10
• Study Completion: 2023-01-10
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-10
• Last Update Posted: 2023-02-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Has a body mass index of 18-35 kg/m2.
• Has a planned (nonemergency) open ventral hernia repair, abdominoplasty (with rectus sheath plication, in the opinion of the surgeon), open abdominal hysterectomy, laparoscopic-assisted colectomy, or reduction mammoplasty to be conducted using standard surgical technique under general anesthesia.
• Has the ability and willingness to comply with all study procedures including being domiciled for at least 96 hours after surgery.
• Is willing to use opioid analgesia, if needed.

Exclusion Criteria

• Has a known hypersensitivity to amide-type local anesthetics, fentanyl, morphine, oxycodone, acetaminophen, NSAIDs, or bovine products.
• Is scheduled for other significant concurrent surgical procedures (eg, cholecystectomy or additional cosmetic procedures concurrent with abdominoplasty).
• Has used an opioid analgesic on an extended daily basis (≥5 mg oral morphine equivalents per day for 3 or more days a week) within 4 weeks before surgery and/or chronically uses pain medication.
• Has any chronic painful condition (eg, fibromyalgia), as determined by the investigator, that may confound the assessment of pain associated with the study surgery.
• For open hernia repair, has open ventral hernia with primary suture repair and mesh placement requiring an incisional length greater than 12 cm.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
INL-001 (bupivacaine hydrochloride) implant	INL-001 (bupivacaine hydrochloride) implant	INL-001 (bupivacaine hydrochloride) implant

Primary Outcome Measures

Name	Time	Method
Evaluate the safety and tolerability	Day 1 through Day 30	The primary objective of the study is to evaluate the safety and tolerability of the INL-001 implant in patients. Measured by frequency and incidents of adverse events.

Secondary Outcome Measures

Name	Time	Method
λz	0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48, 72 and 96 hours	Terminal phase rate constant
Tlag	0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48, 72 and 96 hours	Lag-time
AUC	0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48, 72 and 96 hours	Area under the plasma concentration-time curve from Time 0 to last time of last quantifiable plasma concentration (AUC0-last)
t½ Terminal Half life	0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48, 72 and 96 hours	Terminal Half life
AUC0-∞	0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48, 72 and 96 hours	AUC from Time 0 to infinity
Cmax	0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48, 72 and 96 hours	Maximum (peak) plasma concentration
Tmax	0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48, 72 and 96 hours	Time to maximum (peak) plasma concentration

Trial Locations

Locations (8)

Daneshvari Solanki; 🇺🇸 Houston, Texas, United States

Baylor College of Medicine; 🇺🇸 Houston, Texas, United States

Memorial Hermann; 🇺🇸 Houston, Texas, United States

North Alabama Medical Center; 🇺🇸 Florence, Alabama, United States

Helen Keller Hospital; 🇺🇸 Sheffield, Alabama, United States

Lotus Clinical Research; 🇺🇸 Pasadena, California, United States

Midwest Clinical Research; 🇺🇸 Dayton, Ohio, United States

Endeavor Clinical Trials; 🇺🇸 San Antonio, Texas, United States