Single Ascending Dose Study of Two Liquidia Bupivacaine Formulations

NCT02982889 | Completed Phase 1

• 2 other identifiers: LTI-1112016-002420-88
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Pain

Keywords

Analytical, Diagnostic,Therapeutic Technique and Equipment; Anesthesia and Analgesia

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment Emergent Adverse Events (AEs)

  Safety assessments will include the incidence and severity of AEs during treatment and the follow-up period of the study

  30 days

Secondary Outcomes (11)

• Pharmacokinetic - Area under the plasma concentration curve from time zero to Day 5

  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)

  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)

  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)

  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)

  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

Study Arms (4)

LIQ865A bupivacaine formulation

EXPERIMENTAL

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; Drug: Diluent for LIQ865

LIQ865B bupivacaine formulation

EXPERIMENTAL

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

Drug: LIQ865B bupivacaine formulation; Drug: Diluent for LIQ865

Diluent for LIQ865

PLACEBO COMPARATOR

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; Drug: LIQ865B bupivacaine formulation; Drug: Diluent for LIQ865

0.5% bupivacaine hydrochoride

ACTIVE COMPARATOR

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; Drug: LIQ865B bupivacaine formulation; Drug: 0.5% bupivacaine hydrochoride

Interventions

LIQ865A bupivacaine formulation DRUG

single subcutaneous injection in medial calf

Also known as: Marcaine, Marcaine Spinal, Sensorcaine, Sensorcaine-MPF, Sensorcaine-MPF Spinal, Marcaine HCl, Exparel

0.5% bupivacaine hydrochoride; Diluent for LIQ865; LIQ865A bupivacaine formulation

LIQ865B bupivacaine formulation DRUG

single subcutaneous injection in medial calf

Also known as: Marcaine, Marcaine Spinal, Sensorcaine, Sensorcaine-MPF, Sensorcaine-MPF Spinal, Marcaine HCl, Exparel

0.5% bupivacaine hydrochoride; Diluent for LIQ865; LIQ865B bupivacaine formulation

Diluent for LIQ865 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

Also known as: Hyaluronic Acid

Diluent for LIQ865; LIQ865A bupivacaine formulation; LIQ865B bupivacaine formulation

0.5% bupivacaine hydrochoride DRUG

single subcutaneous injection

Also known as: Marcaine, Marcaine Spinal, Sensorcaine, Sensorcaine-MPF, Sensorcaine-MPF Spinal, Marcaine HCl, Exparel

0.5% bupivacaine hydrochoride

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Liquidia Technologies, Inc.: lead
• Premier Research: collaborator

Study Sites (1)

DanTrial Aps

Copenhagen, 2400, Denmark

Location

MeSH Terms

Conditions

Acute Pain; Disease; Agnosia

Interventions

Bupivacaine; Hyaluronic Acid

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pathologic Processes; Perceptual Disorders; Neurobehavioral Manifestations; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Mads U Werner, MD

  Multidisciplinary Pain Center, Rigshospitalet

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2016
• First Posted: December 6, 2016
• Study Start: December 5, 2016
• Primary Completion: March 23, 2017
• Study Completion: April 26, 2017
• Last Updated: August 24, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)