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Trial record 1 of 1 for:    NCT02982889
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Single Ascending Dose Study of Two Liquidia Bupivacaine Formulations

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02982889
First Posted: December 6, 2016
Last Update Posted: August 24, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Premier Research Group plc
Information provided by (Responsible Party):
Liquidia Technologies, Inc.
  Purpose
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.

Condition Intervention Phase
Acute Pain Drug: LIQ865A bupivacaine formulation Drug: LIQ865B bupivacaine formulation Drug: Diluent for LIQ865 Drug: 0.5% bupivacaine hydrochoride Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: A Phase 1 Randomized, Controlled, Double-Blind, Single Ascending Dose Safety and Pharmacokinetic/Pharmacodynamic Study in Healthy Adult Males After LIQ865 Injection

Resource links provided by NLM:


Further study details as provided by Liquidia Technologies, Inc.:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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 ]
  • 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.

  • 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

  • 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

  • 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.

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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


Enrollment: 29
Actual Study Start Date: December 5, 2016
Study Completion Date: April 26, 2017
Primary Completion Date: March 23, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
  • Marcaine Spinal
  • Sensorcaine
  • Sensorcaine-MPF
  • Sensorcaine-MPF Spinal
  • Marcaine HCl
  • Exparel
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 Name: Hyaluronic Acid
Experimental: LIQ865B bupivacaine formulation
Liquidia's PRINT bupivacaine free base suspension for subcutaneous injection at doses ranging from 150mg to 600mg
Drug: LIQ865B bupivacaine formulation
single subcutaneous injection in medial calf
Other Names:
  • Marcaine
  • Marcaine Spinal
  • Sensorcaine
  • Sensorcaine-MPF
  • Sensorcaine-MPF Spinal
  • Marcaine HCl
  • Exparel
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 Name: Hyaluronic Acid
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
  • Marcaine Spinal
  • Sensorcaine
  • Sensorcaine-MPF
  • Sensorcaine-MPF Spinal
  • Marcaine HCl
  • Exparel
Drug: LIQ865B bupivacaine formulation
single subcutaneous injection in medial calf
Other Names:
  • Marcaine
  • Marcaine Spinal
  • Sensorcaine
  • Sensorcaine-MPF
  • Sensorcaine-MPF Spinal
  • Marcaine HCl
  • Exparel
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 Name: Hyaluronic Acid
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
  • Marcaine Spinal
  • Sensorcaine
  • Sensorcaine-MPF
  • Sensorcaine-MPF Spinal
  • Marcaine HCl
  • Exparel
Drug: LIQ865B bupivacaine formulation
single subcutaneous injection in medial calf
Other Names:
  • Marcaine
  • Marcaine Spinal
  • Sensorcaine
  • Sensorcaine-MPF
  • Sensorcaine-MPF Spinal
  • Marcaine HCl
  • Exparel
Drug: 0.5% bupivacaine hydrochoride
single subcutaneous injection
Other Names:
  • Marcaine
  • Marcaine Spinal
  • Sensorcaine
  • Sensorcaine-MPF
  • Sensorcaine-MPF Spinal
  • Marcaine HCl
  • Exparel

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.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02982889


Locations
Denmark
DanTrial Aps
Copenhagen, Denmark, 2400
Sponsors and Collaborators
Liquidia Technologies, Inc.
Premier Research Group plc
Investigators
Principal Investigator: Mads U Werner, MD Multidisciplinary Pain Center, Rigshospitalet
  More Information

Responsible Party: Liquidia Technologies, Inc.
ClinicalTrials.gov Identifier: NCT02982889     History of Changes
Other Study ID Numbers: LTI-111
2016-002420-88 ( EudraCT Number )
First Submitted: November 22, 2016
First Posted: December 6, 2016
Last Update Posted: August 24, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Liquidia Technologies, Inc.:
Analytical, Diagnostic,Therapeutic Technique and Equipment
Anesthesia and Analgesia

Additional relevant MeSH terms:
Acute Pain
Pain
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Bupivacaine
Hyaluronic Acid
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Adjuvants, Immunologic
Immunologic Factors
Viscosupplements
Protective Agents