Single Ascending Dose Study of Two Liquidia Bupivacaine Formulations

NCT ID: NCT02982889

Last Updated: 2017-08-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-05
• Study Completion Date: 2017-04-26

Brief Summary

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.

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.

Conditions

Acute Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: EXPERIMENTAL

LIQ865A bupivacaine formulation

Intervention Type: DRUG

single subcutaneous injection in medial calf

Diluent for LIQ865

Intervention Type: DRUG

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

LIQ865B bupivacaine formulation

Liquidia's PRINT bupivacaine free base suspension for subcutaneous injection at doses ranging from 150mg to 600mg

Group Type: EXPERIMENTAL

LIQ865B bupivacaine formulation

Intervention Type: DRUG

single subcutaneous injection in medial calf

Diluent for LIQ865

Intervention Type: DRUG

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

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

Group Type: PLACEBO_COMPARATOR

LIQ865A bupivacaine formulation

Intervention Type: DRUG

single subcutaneous injection in medial calf

LIQ865B bupivacaine formulation

Intervention Type: DRUG

single subcutaneous injection in medial calf

Diluent for LIQ865

Intervention Type: DRUG

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

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).

Group Type: ACTIVE_COMPARATOR

LIQ865A bupivacaine formulation

Intervention Type: DRUG

single subcutaneous injection in medial calf

LIQ865B bupivacaine formulation

Intervention Type: DRUG

single subcutaneous injection in medial calf

0.5% bupivacaine hydrochoride

Intervention Type: DRUG

single subcutaneous injection

Interventions

LIQ865A bupivacaine formulation

single subcutaneous injection in medial calf

Intervention Type: DRUG

LIQ865B bupivacaine formulation

single subcutaneous injection in medial calf

Intervention Type: 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

Intervention Type: DRUG

0.5% bupivacaine hydrochoride

single subcutaneous injection

Intervention Type: DRUG

Other Intervention Names

Marcaine; Marcaine Spinal; Sensorcaine; Sensorcaine-MPF; Sensorcaine-MPF Spinal; Marcaine HCl; Exparel; Marcaine; Marcaine Spinal; Sensorcaine; Sensorcaine-MPF; Sensorcaine-MPF Spinal; Marcaine HCl; Exparel; Hyaluronic Acid; Marcaine; Marcaine Spinal; Sensorcaine; Sensorcaine-MPF; Sensorcaine-MPF Spinal; Marcaine HCl; Exparel

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Premier Research Group plc

UNKNOWN

Sponsor Role: collaborator

Liquidia Technologies, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mads U Werner, MD

Role: PRINCIPAL_INVESTIGATOR

Multidisciplinary Pain Center, Rigshospitalet

Locations

DanTrial Aps

Copenhagen, , Denmark

Countries

Denmark

Other Identifiers

2016-002420-88

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

LTI-111

Identifier Type: -

Identifier Source: org_study_id