Evaluation of Safety, Pharmacokinetics and Pharmacodynamics of EXPAREL® Administered Via a Single Intrathecal Injection to Healthy Volunteers

Healthy Clinical Trial

Official title:

Phase 1, Randomized, Double-Blind, Active and Placebo Controlled, Dose Escalation Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of EXPAREL® Administered Via a Single Intrathecal Injection to Healthy Volunteers.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04173611
• Other study ID #: 402-C-121
• Status: Terminated
• Phase: Phase 1
• Start date: June 8, 2020
• Est. completion date: December 7, 2020

Study information

• Verified date: April 2021
• Source: Pacira Pharmaceuticals, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary objective: To assess the safety and tolerability of EXPAREL® administered as a single intrathecal injection in healthy volunteers

Secondary objective: To characterize the pharmacokinetic (PK) and pharmacodynamic (PD) profile of EXPAREL® administered as a single intrathecal injection in healthy volunteers

Description:

This is a Phase-1, single center, randomized, double-blind, active and placebo-controlled study in approximately 40 healthy adult subjects.

On Day 1, eligible subjects will be randomized in blocks of 5, in a ratio of 3:1:1 to receive EXPAREL® or bupivacaine or placebo (saline) injection, respectively. Starting with treatment Cohort 1, healthy volunteers will be randomized to the 3 treatment arms within cohorts. Each cohort will consist of 10 subjects (6 EXPAREL®, 2 bupivacaine and 2 placebo). In each cohort, all 10 subjects in each cohort will receive cerebrospinal fluid (CSF) taps. Within the EXPAREL® arm, subjects will be randomized 2:1 with 4 subjects undergoing CSF tap and 2 subjects not undergoing CSF tap in each cohort. Subjects who are not undergoing CSF tap, will still be injected with needles without draw of CSF to prevent subject bias. Such a randomization will allow for characterization of the complete pharmacodynamics profile of the drug without risk of drug removal in the CSF. For those subjects randomized to the EXPAREL® arm - the dose of EXPAREL® will be determined by the cohort. Starting at 1 mL (13.3 mg) for Cohort 1, the volume of EXPAREL® will be increased by 1 mL in each subsequent cohort for a maximum of 4 mL (53.2 mg). The decision to proceed to the next cohort will be made following a full review of the safety, PK, and PD (sensory and motor) data from current completed cohort(s). All subjects will remain in the EPRU for 5 days after drug administration and will be discharged on Day 6. Subjects will be instructed to return for a follow up visit on Day 9. Adverse events (AEs) and serious adverse events (SAEs) will be recorded from the time of consent through 30 days after drug administration.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 20
• Est. completion date: December 7, 2020
• Est. primary completion date: December 7, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

1. Healthy adult male or female volunteers ages =18 and =50 years old.

2. American Society of Anesthesiologists (ASA) physical status 1.

3. Able to provide informed consent, adhere to the study schedule, and complete all study assessments.

Exclusion Criteria:

1. Allergy, hypersensitivity, intolerance, or contraindication to any of the study medications for which an alternative is not named in the protocol (eg, amide-type local anesthetics, opioids, bupivacaine, non-steroidal anti-inflammatory drugs [NSAIDs], spinal anesthesia).

2. Impaired renal or hepatic function (eg, serum creatinine level >2 mg/dL [176.8 µmol/L], blood urea nitrogen level >50 mg/dL [17.9 mmol/L], serum aspartate aminotransferase [AST] level >1.5 times the upper limit of normal [ULN], or serum alanine aminotransferase [ALT] level >1.5 times the ULN).

3. Subjects at an increased risk for bleeding or who have a coagulation disorder (defined as platelet count less than 80,000 × 103/mm3).

4. 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.

5. 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 (FSH) test confirming menopause at screening.

6. Currently pregnant, nursing, or planning to become pregnant during the study or within 30 days after completion of the study.

7. Positive serology test result for Human Immunodeficiency Virus (HIV), Hepatitis B virus, or Hepatitis C virus.

8. Clinically significant abnormal ECG that in the opinion of the investigator would preclude the subject from participation in the study.

9. Previous participation in a Pacira study.

10. History of, suspected, or known addiction to or abuse of illicit drug(s), prescription medicine(s), or alcohol within the past 2 years.

11. 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

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• EXPAREL
Injection into the Intrathecal space.
• Bupivacaine Hydrochloride
Injection into the Intrathecal space.

Other:
• Placebo
Injection into the Intrathecal space.

Locations

Country	Name	City	State
United States	Duke University	Durham	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Pacira Pharmaceuticals, Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Average time to onset of sensory block and motor block	Pharmacodynamic Endpoint	6-8 weeks
Other	Average duration of sensory block and motor block	Pharmacodynamic Endpoint	6-8 weeks
Primary	Area under the plasma concentration-versus-time curve	Pharmacokinetic endpoint	6-8 weeks
Primary	Maximum plasma concentration (Cmax) and time of Cmax (Tmax).	Pharmacokinetic endpoint	6-8 weeks
Primary	The apparent terminal elimination half-life (t1/2el)	Pharmacokinetic endpoint	6-8 weeks
Primary	Apparent clearance (CL/F)	Pharmacokinetic endpoint	6-8 weeks
Primary	Apparent volume of distribution (Vd)	Pharmacokinetic endpoint	6-8 weeks
Secondary	Incidence of treatment-emergent AEs (TEAEs) through Day 9	Safety endpoint	6-8 weeks
Secondary	Proportion of subjects who have any of neurological events	Safety endpoint	6-8 weeks