HealthyPhase 1NCT04173611
Evaluation of Safety, Pharmacokinetics and Pharmacodynamics of EXPAREL® Administered Via a Single Intrathecal Injection to Healthy Volunteers
A Phase 1 study testing EXPAREL and Bupivacaine Hydrochloride in people with Healthy, run by Pacira Pharmaceuticals, Inc at 1 site in United States.
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 Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- EXPAREL and Bupivacaine Hydrochloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Jun 2020to 7 Dec 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy adult male or female volunteers ages ≥18 and ≤50 years old.
- American Society of Anesthesiologists (ASA) physical status 1.
- Able to provide informed consent, adhere to the study schedule, and complete all study assessments.
Who cannot join
- 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).
- 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).
- Subjects at an increased risk for bleeding or who have a coagulation disorder (defined as platelet count less than 80,000 × 103/mm3).
- 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 (FSH) test confirming menopause at screening.
- Currently pregnant, nursing, or planning to become pregnant during the study or within 30 days after completion of the study.
Show all 11Show fewer
- Positive serology test result for Human Immunodeficiency Virus (HIV), Hepatitis B virus, or Hepatitis C virus.
- 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 study.
- 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 locations and contacts
1 site in 1 country.
About this study
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.
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
Read the detailed 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.
- Conditions
- Healthy
- Being tested
- EXPAREL, Bupivacaine Hydrochloride, Placebo
- Keywords
- Pharmacodynamics, Pharmacokinetics, Safety, Efficacy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EXPARELDrug
Injection into the Intrathecal space.
Bupivacaine HydrochlorideDrug
Also called 0.5% Bupivacaine HCl
Injection into the Intrathecal space.
PlaceboOther
Also called Saline
Injection into the Intrathecal space.
| Study group | Role | What they receive |
|---|---|---|
| EXPAREL® | Experimental | For those subjects randomized to EXPAREL® arm - the dose of EXPAREL® will be determined by the cohort. Starting at 1mL (13.3mg) for cohort 1, the volume of EXPAREL® will be increased by 1 mL in each subsequent cohort for a maximum of 4mL (53.2mg). Receives: Drug: EXPAREL |
| Bupivacaine | Active comparator | In each cohort, subjects randomized to the bupivacaine arm will receive 15mg of plain bupivacaine HCL (the equivalent of 13.3mg bupivacaine base) providing a 1:1 reference to the starting dose level chosen for EXPAREL®. Receives: Drug: Bupivacaine Hydrochloride |
| Placebo | Active comparator | Subjects in the placebo arm will receive normal saline intrathecal injection Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the plasma concentration-versus-time curve
Pharmacokinetic endpoint
Measured: 6-8 weeks
Maximum plasma concentration (Cmax) and time of Cmax (Tmax).
Pharmacokinetic endpoint
Measured: 6-8 weeks
The apparent terminal elimination half-life (t1/2el)
Pharmacokinetic endpoint
Measured: 6-8 weeks
Apparent clearance (CL/F)
Pharmacokinetic endpoint
Measured: 6-8 weeks
Apparent volume of distribution (Vd)
Pharmacokinetic endpoint
Measured: 6-8 weeks
Secondary outcomes (2)
Incidence of treatment-emergent AEs (TEAEs) through Day 9
Safety endpoint
Measured: 6-8 weeks
Proportion of subjects who have any of neurological events
Safety endpoint
Measured: 6-8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2019
- Study start8 Jun 2020
- Primary completion7 Dec 2020
- Study completion7 Dec 2020
Why it stopped: Terminated for strategic and administrative reasons
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- The decision to proceed to each next cohort will be made following a full review of the safety, PK, and PD data from the previous completed cohort(s).
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pacira Pharmaceuticals, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Donald C Manning, MD, PhD, Study director, Pacira Pharmaceuticals, Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04173611
- Sponsor's protocol ID
- 402-C-121
- Status last verified
- Apr 2021
- First submitted
- 18 Nov 2019
- Last updated
- 6 May 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT04173611
- Acronym / sponsor ID
- 402-C-121
- Conditions
- Healthy
- Keywords
- Pharmacodynamics, Pharmacokinetics, Safety, Efficacy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated for strategic and administrative reasons
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Pacira Pharmaceuticals, IncIndustry (pharma, biotech, devices)
- Study start
- 8 Jun 2020 (actual)
- Primary completion
- 7 Dec 2020 (actual)
- Study completion
- 7 Dec 2020 (actual)
- First posted
- 22 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- The decision to proceed to each next cohort will be made following a full review of the safety, PK, and PD data from the previous completed cohort(s).
| Arm | Type | Receives |
|---|---|---|
| EXPAREL® | Experimental | Drug: EXPARELFor those subjects randomized to EXPAREL® arm - the dose of EXPAREL® will be determined by the cohort. Starting at 1mL (13.3mg) for cohort 1, the volume of EXPAREL® will be increased by 1 mL in each subsequent cohort for a maximum of 4mL (53.2mg). |
| Bupivacaine | Active comparator | Drug: Bupivacaine HydrochlorideIn each cohort, subjects randomized to the bupivacaine arm will receive 15mg of plain bupivacaine HCL (the equivalent of 13.3mg bupivacaine base) providing a 1:1 reference to the starting dose level chosen for EXPAREL®. |
| Placebo | Active comparator | Other: PlaceboSubjects in the placebo arm will receive normal saline intrathecal injection |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Healthy adult male or female volunteers ages ≥18 and ≤50 years old.
- American Society of Anesthesiologists (ASA) physical status 1.
- Able to provide informed consent, adhere to the study schedule, and complete all study assessments.
Key exclusion criteria (11 listed)
- 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).
- 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).
- Subjects at an increased risk for bleeding or who have a coagulation disorder (defined as platelet count less than 80,000 × 103/mm3).
- 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 (FSH) test confirming menopause at screening.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EXPARELInjection into the Intrathecal space. | Drug | EXPAREL® |
| Bupivacaine HydrochlorideAlso: 0.5% Bupivacaine HClInjection into the Intrathecal space. | Drug | Bupivacaine |
| PlaceboAlso: SalineInjection into the Intrathecal space. | Other | Placebo |
Primary outcome
Area under the plasma concentration-versus-time curve
Time frame: 6-8 weeks
Pharmacokinetic endpoint
Maximum plasma concentration (Cmax) and time of Cmax (Tmax).
Time frame: 6-8 weeks
Pharmacokinetic endpoint
The apparent terminal elimination half-life (t1/2el)
Time frame: 6-8 weeks
Pharmacokinetic endpoint
Apparent clearance (CL/F)
Time frame: 6-8 weeks
Pharmacokinetic endpoint
Apparent volume of distribution (Vd)
Time frame: 6-8 weeks
Pharmacokinetic endpoint
2 secondary outcomes
Incidence of treatment-emergent AEs (TEAEs) through Day 9
Time frame: 6-8 weeks
Proportion of subjects who have any of neurological events
Time frame: 6-8 weeks
Results and safety
The study was stopped early (reason given: Terminated for strategic and administrative reasons). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Donald C Manning, MD, PhD study director
Pacira Pharmaceuticals, Inc
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing EXPAREL and Bupivacaine Hydrochloride in people with Healthy, run by Pacira Pharmaceuticals, Inc at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 6 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Terminated for strategic and administrative reasons). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area under the plasma concentration-versus-time curve (time frame: 6-8 weeks). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2021.