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

NCT05456490 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 402-C-124
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Keywords

Pharmacodynamics; Pharmacokinetics; Safety; Efficiency

Outcome Measures

Primary Outcomes (6)

• Area under the plasma concentration-versus-time curve (AUC0-last and AUC0- ∞)

  Pharmacokinetic Endpoint

  7-8 weeks

• Maximum plasma concentration (Cmax)

  Pharmacokinetic Endpoint

  7-8 weeks

• Time of Cmax (Tmax)

  Pharmacokinetic Endpoint

  7-8 weeks

• The apparent terminal elimination half-life (t1/2el)

  Pharmacokinetic Endpoint

  7-8 weeks

• Apparent clearance (CL/F)

  Pharmacokinetic Endpoint

  7-8 weeks

• Apparent volume of distribution (Vd)

  Pharmacokinetic Endpoint

  7-8 weeks

Secondary Outcomes (2)

• Average time to onset of sensory block and motor block

  7-8 weeks

• Average duration of sensory block and motor block

  7-8 weeks

Other Outcomes (2)

• Incidence of treatment-emergent AEs (TEAEs) through Day 9

  7-8 weeks

• Proportion of subjects who have any of the neurological events.

  7-8 weeks

Study Arms (3)

Liposomal Bupivacaine 13.3

EXPERIMENTAL

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.

Drug: Liposomal Bupivacaine 13.3

Bupivacaine IT

ACTIVE COMPARATOR

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.

Drug: Bupivacaine

Placebo

PLACEBO COMPARATOR

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.

Other: Placebo

Interventions

Liposomal Bupivacaine 13.3 DRUG

Injection into the Intrathecal space

Liposomal Bupivacaine 13.3

Bupivacaine DRUG

Injection into the Intrathecal space

Bupivacaine IT

Placebo OTHER

Injection into the Intrathecal space

Also known as: Normal Saline

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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 who report hormonal headaches occurring during their monthly menstrual cycle that are not diagnosed by a healthcare provider (e.g., pure menstrual migraine without aura, menstrually-related migraine without aura, pure menstrual migraine with aura, menstrually-related migraine with aura) will be excluded if there is a reported pattern of headaches that occur consistently or most of the time during or before their monthly menstrual period. Note: if a subject reports hormonal headaches that are not diagnosed by a healthcare provider, the subject may be included in the study if the headache episodes are infrequent (e.g., one episode in the past 3 months), at the discretion of the Principal Investigator.
• 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 20 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 up to 3 days prior to study drug administration.

Sponsors & Collaborators

• Pacira Pharmaceuticals, Inc: lead

Study Sites (1)

Duke University

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Interventions

Bupivacaine; Saline Solution

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Sergey Zaets

  Pacira Pharmaceuticals, Inc

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Each of the cohorts will be masked as to proceed to subsequent next dose escalation cohort.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: June 22, 2022
• First Posted: July 13, 2022
• Study Start: April 18, 2023
• Primary Completion: February 27, 2025
• Study Completion: February 27, 2025
• Last Updated: March 17, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)