Clinical trial NCT04785638: An Open-label Safety and Pharmacokinetic Study of INL-001 in Adults Following Various Open Soft-Tissue Surgeries
Official title: An Open-label Safety and Pharmacokinetic Study of INL-001 in Adults Following Open Ventral Hernia Repair, Abdominoplasty, Open Abdominal Hysterectomy, Laparoscopic-assisted Colectomy, and Reduction Mammoplasty
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pain, Postoperative
Hernia, Ventral
Abdominoplasty
Hysterectomy
Colectomy
Reduction Mammoplasty
Keywords: Pain
Analgesia
Postoperative
Hernia
Abdominoplasty
Tummy tuck
Hysterectomy
Colectomy
Bupivacaine
Postsurgical
Implant
Safety
Efficacy
Pharmacokinetic
Opioid
Nonopioid
Post-operative
Post-surgical
Surgery
Soft tissue
Open-label
Phase 3
Local anesthetic
Lead sponsor: Innocoll
Sponsor class: INDUSTRY
First posted: 2021-03-08
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Evaluate the safety and tolerability
timeFrame: Day 1 through Day 30
Secondary outcomes:
measure: Cmax
timeFrame: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48, 72 and 96 hours
measure: Tmax
timeFrame: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48, 72 and 96 hours
measure: Tlag
timeFrame: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48, 72 and 96 hours
measure: t½ Terminal Half life
timeFrame: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48, 72 and 96 hours
measure: λz
timeFrame: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48, 72 and 96 hours
measure: AUC
timeFrame: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48, 72 and 96 hours
measure: AUC0-∞
timeFrame: 0.5, 1, 1.5, 2, 3, 4, 5, 6, 9, 12, 18, 24, 36, 48, 72 and 96 hours
Other outcomes:
measure: SPI24
timeFrame: 0 to 24 hours
measure: SPI48
timeFrame: 0 to 48 hours
measure: SPI72
timeFrame: 0 to 72 Hours
measure: Total use of opioid rescue analgesia
timeFrame: 0 to 24 hours postoperatively
measure: Total use of opioid rescue analgesia
timeFrame: 0 to 72 hours postoperatively
measure: Total use of opioid rescue analgesia
timeFrame: 0 to 48 hours postoperatively
measure: Time to discharge from the postanesthesia care unit (PACU)
timeFrame: Immediately after the intervention/procedure/surgery
measure: Opioid-related Symptom Distress Scale (OR-SDS)
timeFrame: 24, 48, 72, and 96 hours posttreatment
measure: 15-item Quality of Recovery (QoR-15) Questionnaire
timeFrame: 24, 48, 72, and 96 hours, and day 7 posttreatment
measure: Patient Global Assessment (PGA) as Related to Postoperative Pain
timeFrame: 24, 48, 72, and 96 hours, and day 7 posttreatment
Locations:
city: Florence
country: United States
facility: North Alabama Medical Center
state: Alabama
city: Sheffield
country: United States
facility: Helen Keller Hospital
state: Alabama
city: Pasadena
country: United States
facility: Lotus Clinical Research
state: California
city: Dayton
country: United States
facility: Midwest Clinical Research
state: Ohio
city: Houston
country: United States
facility: Daneshvari Solanki
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Memorial Hermann
state: Texas
city: San Antonio
country: United States
facility: Endeavor Clinical Trials
state: Texas
Study officials:
affiliation: Lotus Clinical Research
name: Anne Arriaga
role: STUDY_DIRECTOR
References: