Phase 1, Dose Escalation Study to Evaluate of Safety, Pharmacokinetics and Pharmacodynamics of Liposomal Bupivacaine 13.3 Administered Via a Single Intrathecal Injection to Healthy Volunteers

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Pacira

Status and phase

Enrolling
Phase 1

Conditions

Healthy

Treatments

Drug: Liposomal Bupivacaine 13.3
Drug: Bupivacaine
Other: Placebo

Study type

Interventional

Funder types

Industry

Identifiers

NCT05456490
402-C-124

Details and patient eligibility

About

Primary Objective: To assess the safety and tolerability of Liposomal Bupivacaine 13.3 administered as a single intrathecal injection in healthy volunteers. Secondary Objective: To characterize the pharmacokinetic (PK) and pharmacodynamic (PD) profile of Liposomal Bupivacaine 13.3 administered as a single intrathecal injection in healthy volunteers.

Full description

This is a Phase-1, single center, randomized, double-blind, active and placebo-controlled study in approximately 54 adult healthy subjects (Cohort 1, Cohort 2, and Cohort 3). Eighteen subjects will be enrolled in each of the 3 cohorts. Subjects in Cohort 1, Cohort 2, and Cohort 3 will be randomized 1:1:1 with 6 subjects receiving Liposomal Bupivacaine 13.3 intrathecal (IT), 6 subjects receiving bupivacaine IT, and 6 subjects receiving placebo IT in each cohort. The dose of Liposomal Bupivacaine 13.3 (and volume of injectate across all three treatment arms) will be determined by the cohort. Cohort 1 subjects randomized to the Liposomal Bupivacaine 13.3 arm will be dosed 2 mL (26.6 mg) of Liposomal Bupivacaine 13.3, Cohort 2 subjects randomized to the Liposomal Bupivacaine 13.3 arm will be dosed 3 mL (39.9 mg) of Liposomal Bupivacaine 13.3, and Cohort 3 subjects randomized to the Liposomal Bupivacaine 13.3 arm will be dosed 4 mL (53.2 mg) of Liposomal Bupivacaine 13.3. The dose of bupivacaine IT administered in all cohorts will be 15 mg. Cohort 1 subjects randomized to the bupivacaine arm will be dosed 2 mL (7.5 mg/ 1 mL) of 0.75% bupivacaine. Cohort 2 subjects randomized to the bupivacaine arm will be dosed 2 mL (7.5 mg/ 1 mL) of 0.75% bupivacaine mixed with 1 mL of preservative free normal saline to create a total volume of solution administered of 3 mL. Cohort 3 subjects randomized to the bupivacaine arm will be dosed 2 mL (7.5 mg / 1 mL) of 0.75% bupivacaine mixed with 2 mL of preservative free normal saline to create a total volume of solution administered of 4 mL. Cohort 1 subjects randomized to the placebo arm will be dosed 2 mL of preservative free normal saline. Cohort 2 subjects randomized to the placebo arm will be dosed 3 mL of preservative free normal saline. Cohort 3 subjects randomized to the placebo arm will be dosed 4 mL of preservative free normal saline. The decision to proceed to the next cohort will be made following a full review of the safety, PK, sensory, motor, neurological history and assessment questionnaires, comprehensive neurological exam and Adverse Event data from the current completed cohort(s). All subjects will remain in the Early Phase Research Unit (EPRU) for 5 days after drug administration and will be discharged on Day 6. Subjects will be instructed to return to the research facility for a Day 9 follow-up visit. Subjects will also receive a phone call on Day 30 (±3 days) to assess safety.

Enrollment

54 estimated patients

Sex

All

Ages

18 to 50 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

  • Healthy adult male or female volunteers ages ≥18 and ≤50 years old.
  • American Society of Anesthesiologists physical status 1
  • Able to provide informed consent, adhere to the study schedule, and complete all study assessments.

Exclusion criteria

  • Allergy, hypersensitivity, intolerance, or contraindication to any of the study medications for which an alternative is not named in the protocol (e.g., amide-type local anesthetics, opioids, bupivacaine, NSAIDs, spinal anesthesia).
  • Impaired renal or hepatic function (e.g., serum creatinine level >2 mg/dL [176.8 µmol/L], blood urea nitrogen level >50 mg/dL [17.9 mmol/L], serum aspartate aminotransferase level >1.5 times the upper limit of normal [ULN], or serum alanine aminotransferase level >1.5 times the ULN).
  • Subjects at an increased risk for bleeding or who have a coagulation disorder (defined as platelet count less than 80,000 × 103/mm3).
  • Subjects with a history of a difficult airway or a potential difficult airway based on exam by an anesthesiologist.
  • Subjects with a history of migraine, cluster, or tension headache (diagnosed by a healthcare provider) at any time over the life-course.
  • Subjects without a formal headache diagnosis, but currently experiencing frequent headaches (of any severity), defined as headache occurring > or = 1 time per week for the last 3 months.
  • Subjects with a history of a lower back condition (e.g., ankylosing spondylitis, scoliosis, dysraphism, prior back surgery) or a history of chronic low back pain.
  • Subjects with BMIs less than 25 kg/m2.
  • Comorbidity impacting current physical function that, in the opinion of the investigator, may confound the post dosing assessments
  • Concurrent painful physical condition that may require analgesic treatment (such as long-term, consistent use of opioids) in the post dosing period for pain and which may confound the post dosing assessments.
  • Women of childbearing potential must have a documented negative pregnancy test at screening and must be confirmed on the day of drug administration. If postmenopausal, must have a documented follicle stimulating hormone test confirming menopause at screening.
  • Currently pregnant, nursing, or planning to become pregnant during the study.
  • Clinically significant abnormal ECG that in the opinion of the investigator would preclude the subject from participation in the study.
  • Previous participation in a Pacira sponsored study.
  • Use of systemic corticosteroids and neuromodulating agents (e.g., gabapentin, pregabalin [Lyrica], duloxetine [Cymbalta] etc.) up to 3 days prior to study drug administration.
  • Opioid medications and NSAIDs are not permitted up to 3 days prior to study drug administration.
  • History of, suspected, or known addiction to or abuse of illicit drug(s), prescription medicine(s), or alcohol within the past 2 years.
  • Administration of an investigational drug within 30 days or 5 elimination half-lives of such investigational drug, whichever is longer, prior to study drug administration, or planned administration of another investigational product or procedure during the subject's participation in this study.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Sequential Assignment

Masking

Quadruple Blind

54 participants in 3 patient groups, including a placebo group

Liposomal Bupivacaine 13.3
Experimental group
Description:
Cohort 1 subjects will be dosed 2 mL (26.6 mg) of Liposomal Bupivacaine 13.3. Cohort 2 subjects randomized to the Liposomal Bupivacaine 13.3 arm will be dosed 3 mL (39.9 mg) of Liposomal Bupivacaine 13.3. Cohort 3 subjects randomized to the Liposomal Bupivacaine 13.3 arm will be dosed 4 mL (53.2 mg) of Liposomal Bupivacaine 13.3.
Treatment:
Drug: Liposomal Bupivacaine 13.3
Bupivacaine IT
Active Comparator group
Description:
Cohort 1 subjects randomized to the bupivacaine arm will be dosed 2 mL (7.5 mg/ 1 mL) of 0.75% bupivacaine. Cohort 2 subjects randomized to the bupivacaine arm will be dosed 2 mL (7.5 mg/ 1 mL) of 0.75% bupivacaine mixed with 1 mL of preservative free normal saline to create a total volume of solution administered of 3 mL. Cohort 3 subjects randomized to the bupivacaine arm will be dosed 2 mL (7.5 mg / 1 mL) of 0.75% bupivacaine mixed with 2 mL of preservative free normal saline to create a total volume of solution administered of 4 mL.
Treatment:
Drug: Bupivacaine
Placebo
Placebo Comparator group
Description:
Cohort 1 subjects randomized to the placebo arm will be dosed 2 mL of preservative free normal saline. Cohort 2 subjects randomized to the placebo arm will be dosed 3 mL of preservative free normal saline. Cohort 3 subjects randomized to the placebo arm will be dosed 4 mL of preservative free normal saline.
Treatment:
Other: Placebo

Trial contacts and locations

1

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Central trial contact

Christine Brozyniak

Data sourced from clinicaltrials.gov

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