Single Ascending Dose Study of Two Liquidia Bupivacaine Formulations

August 23, 2017 updated by: Liquidia Technologies, Inc.

A Phase 1 Randomized, Controlled, Double-Blind, Single Ascending Dose Safety and Pharmacokinetic/Pharmacodynamic Study in Healthy Adult Males After LIQ865 Injection

This study is designed to assess and characterize the safety and tolerability profile of LIQ865A and LIQ865B formulations compared to diluent or aqueous bupivacaine hydrochloride when infiltrated into a defined area of the medial calf, and to characterize bupivacaine plasma pharmacokinetic (PK) and pharmacodynamic (PD) profiles after a single dose of LIQ865A or LIQ865B, and to determine the individual plasma concentration/time curves and mean PK parameters of each product.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Infiltration of an aqueous local anesthetic, for example, bupivacaine, into surgical sites at closure provides temporary analgesia, typically lasting up to 6 hours, and is one aspect of the multimodal approach to postsurgical analgesia or fast-track surgery. However, the limited duration of action of local anesthetics, even longer acting agents such as bupivacaine, result in patients who are likely to experience end of duration breakthrough pain before they are able to take or tolerate oral analgesics, thus necessitating the use of strong parenteral analgesics in the immediate postsurgical period. LIQ865A and LIQ865B are two distinct formulations of bupivacaine manufactured via Liquidia Technologies PRINT (Particle Replication In Non-wetting Templates), which Liquidia intends to pursue for product approval. Both formulations being tested have the potential for producing long-lasting control of post-surgical incisional pain.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
29

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Copenhagen, Denmark, 2400
        • DanTrial Aps

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • provide written informed consent prior to enrollment
  • be a non-smoking male, American Society of Anesthesiologist (ASA) physical class 1 or 2
  • have a BMI between 18.5 and 25 kg. inclusive, and a weight of at least 60 kg
  • be willing and able to participate for the duration of the study
  • be healthy on the basis of pre-study physical examination (PE), medical history review, vital signs, lab test results as specified in the protocol
  • negative urine drug test results
  • negative alcohol screening test
  • negative antibody test results for hepatitis B, hepatitis C, and HIV

Exclusion Criteria:

  • allergic to bupivacaine, or other amide local anesthetics, or the excipients in the LIQ865 formulations or the diluent
  • has taken any concomitant medications or supplements for the 3 days prior to Day 0
  • has been on blood thinner or medication affecting platelet formation for the 7 days prior to Day 0
  • in the opinion of the investigator, is either a hyper or hypo-responder to screening sensitivity testing
  • has a history of moderate or severe renal or hepatic impairment, moderate or severe active hepatic disease, or any other clinically significant medical condition that may preclude safe study participation
  • has a clinically significant test result for any screening lab parameter
  • has a history or ECG screening documentation of a clinically meaningful conduction abnormality
  • has scarring, tattoos, infections, or other skin changes in the area of planned study medication injection
  • has known neurological disease or dysfunction (central or peripheral) that may interfere with assessments
  • is unable to adequately communicate with study staff, properly give informed consent, or otherwise comply with study procedures, particularly the ability to return for outpatient follow up visits
  • has participated in another interventional clinical study (investigational or marketed product) within the 30 days prior to Day 0.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: LIQ865A bupivacaine formulation
Liquidia's PRINT bupivacaine free base/PLGA (poly D,L-lactic-co-glycolic acid) suspension for subcutaneous injection at doses ranging from 150mg to 600mg
Drug: LIQ865A bupivacaine formulation
single subcutaneous injection in medial calf
Other Names:
  • Marcaine
  • Exparel
  • Sensorcaine
  • Marcaine Spinal
  • Sensorcaine-MPF
  • Sensorcaine-MPF Spinal
  • Marcaine HCl
Drug: Diluent for LIQ865
Sterile diluent composed of 12.5mg/g sodium hyaluronate, 5.8mg/g sodium chloride, 1mg/g polysorbate 80, 6.1mg/g Tris base, in sterile water for injection - single subcutaneous injection
Other Names:
  • Hyaluronic Acid
Experimental: LIQ865B bupivacaine formulation
Liquidia's PRINT bupivacaine free base suspension for subcutaneous injection at doses ranging from 150mg to 600mg
Drug: Diluent for LIQ865
Sterile diluent composed of 12.5mg/g sodium hyaluronate, 5.8mg/g sodium chloride, 1mg/g polysorbate 80, 6.1mg/g Tris base, in sterile water for injection - single subcutaneous injection
Other Names:
  • Hyaluronic Acid
Drug: LIQ865B bupivacaine formulation
single subcutaneous injection in medial calf
Other Names:
  • Marcaine
  • Exparel
  • Sensorcaine
  • Marcaine Spinal
  • Sensorcaine-MPF
  • Sensorcaine-MPF Spinal
  • Marcaine HCl
Placebo Comparator: Diluent for LIQ865
Negative control for subcutaneous injection. Each subject will act as his own control, receiving a LIQ865 formulation subcutaneous injection in one calf, and a diluent subcutaneous injection in his other calf
Drug: LIQ865A bupivacaine formulation
single subcutaneous injection in medial calf
Other Names:
  • Marcaine
  • Exparel
  • Sensorcaine
  • Marcaine Spinal
  • Sensorcaine-MPF
  • Sensorcaine-MPF Spinal
  • Marcaine HCl
Drug: Diluent for LIQ865
Sterile diluent composed of 12.5mg/g sodium hyaluronate, 5.8mg/g sodium chloride, 1mg/g polysorbate 80, 6.1mg/g Tris base, in sterile water for injection - single subcutaneous injection
Other Names:
  • Hyaluronic Acid
Drug: LIQ865B bupivacaine formulation
single subcutaneous injection in medial calf
Other Names:
  • Marcaine
  • Exparel
  • Sensorcaine
  • Marcaine Spinal
  • Sensorcaine-MPF
  • Sensorcaine-MPF Spinal
  • Marcaine HCl
Active Comparator: 0.5% bupivacaine hydrochoride
Positive control arm to be used with one of the LIQ865 cohorts, with each subject acting as his own positive control (i.e., one leg will receive subcutaneous injection of LIQ865A or LIQ865B, and the other leg will receive subcutaneous injection of 0.5% bupivacaine hydrochloride).
Drug: LIQ865A bupivacaine formulation
single subcutaneous injection in medial calf
Other Names:
  • Marcaine
  • Exparel
  • Sensorcaine
  • Marcaine Spinal
  • Sensorcaine-MPF
  • Sensorcaine-MPF Spinal
  • Marcaine HCl
Drug: LIQ865B bupivacaine formulation
single subcutaneous injection in medial calf
Other Names:
  • Marcaine
  • Exparel
  • Sensorcaine
  • Marcaine Spinal
  • Sensorcaine-MPF
  • Sensorcaine-MPF Spinal
  • Marcaine HCl
Drug: 0.5% bupivacaine hydrochoride
single subcutaneous injection
Other Names:
  • Marcaine
  • Exparel
  • Sensorcaine
  • Marcaine Spinal
  • Sensorcaine-MPF
  • Sensorcaine-MPF Spinal
  • Marcaine HCl

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Incidence of Treatment Emergent Adverse Events (AEs)
Time Frame: 30 days
Safety assessments will include the incidence and severity of AEs during treatment and the follow-up period of the study
30 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Pharmacokinetic - Area under the plasma concentration curve from time zero to Day 5
Time Frame: Timepoints (draws) at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24 hours and 2, 3, 4, 5 days after treatment
Timepoints (draws) at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24 hours and 2, 3, 4, 5 days after treatment
Pharmacokinetic - Cmax (ng/mL)
Time Frame: Timepoints (draws) at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24 hours and 2, 3, 4, 5 days after treatment
Maximum plasma concentration over the entire sampling period, directly obtained from the experimental data of plasma concentration versus time curves, without interpolation.
Timepoints (draws) at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24 hours and 2, 3, 4, 5 days after treatment
Pharmacokinetic - Tmax (h)
Time Frame: Timepoints (draws) at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24 hours and 2, 3, 4, 5 days after treatment
Time to reach maximum plasma concentration
Timepoints (draws) at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24 hours and 2, 3, 4, 5 days after treatment
Pharmacokinetic - t1/2 (h)
Time Frame: Timepoints (draws) at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24 hours and 2, 3, 4, 5 days after treatment
Apparent terminal elimination half-life
Timepoints (draws) at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24 hours and 2, 3, 4, 5 days after treatment
Pharmacokinetic - CST1/2 (h)
Time Frame: Timepoints (draws) at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24 hours and 2, 3, 4, 5 days after treatment
Context-sensitive half-time measured from Tmax to time for plasma concentration to reach half of Cmax following study medication injection.
Timepoints (draws) at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24 hours and 2, 3, 4, 5 days after treatment
Pharmacodynamic Response - Pain intensity (Numeric Rating Scale) with Short Tonic Heat Stimulus (STHS) testing at various time points
Time Frame: 1, 2, 12, 24, 48, 72, 96, and 120 hours
Testing done to calculate time-weighted Sum of Pain Intensity Differences (SPID) at the time points noted, compared to Baseline, and time specific SPID results
1, 2, 12, 24, 48, 72, 96, and 120 hours
Pharmacodynamic Response - Change in Mechanical Pain Threshold (MPT) compared to Baseline using various time points
Time Frame: 12, 24, 48, 72, 96, and 120 hours
Calculate the time-weighted sum of threshold differences (calculated as area-under-the-curve (AUC): AUC12, AUC24, AUC48, AUC72, AUC96, AUC120
12, 24, 48, 72, 96, and 120 hours
Pharmacodynamic Response - Change in Heat Pain Threshold (HPT) compared to Baseline using various time points
Time Frame: 12, 24, 48, 72, 96, and 120 hours
Calculate the time-weighted sum of threshold differences (calculated as area-under-the-curve (AUC): AUC12, AUC24, AUC48, AUC72, AUC96, AUC120
12, 24, 48, 72, 96, and 120 hours
Pharmacodynamic Response - Change Mechanical Detection Threshold (MDT) compared to Baseline using various time points
Time Frame: 12, 24, 48, 72, 96, and 120 hours
Calculate the time-weighted sum of threshold differences (calculated as area-under-the-curve (AUC): AUC12, AUC24, AUC48, AUC72, AUC96, AUC120
12, 24, 48, 72, 96, and 120 hours
Pharmacodynamic Response - Change in Warmth Detection Threshold (WDT) compared to Baseline using various time points
Time Frame: 12, 24, 48, 72, 96, and 120 hours
Calculate the time-weighted sum of threshold differences (calculated as area-under-the-curve (AUC): AUC12, AUC24, AUC48, AUC72, AUC96, AUC120
12, 24, 48, 72, 96, and 120 hours
Pharmacodynamic Response - Change in Cold Detection Threshold (CDT) compared to Baseline using various time points
Time Frame: 12, 24, 48, 72, 96, and 120 hours
Calculate the time-weighted sum of threshold differences (calculated as area-under-the-curve (AUC): AUC12, AUC24, AUC48, AUC72, AUC96, AUC120
12, 24, 48, 72, 96, and 120 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Liquidia Technologies, Inc.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Premier Research Group plc

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Mads U Werner, MD, Multidisciplinary Pain Center, Rigshospitalet

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 5, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 23, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 26, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 22, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 1, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 6, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 24, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 23, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • LTI-111
  • 2016-002420-88 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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