A Phase 1 Randomized, Controlled, Double-Blind, Single Ascending Dose Safety and Pharmacokinetic/Pharmacodynamic Study in Healthy Adult Males After LIQ865 Injection
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 29
- 试验地点
- 1
- 主要终点
- Incidence of Treatment Emergent Adverse Events (AEs)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
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
干预措施: LIQ865A bupivacaine formulation (Drug)
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
干预措施: Diluent for LIQ865 (Drug)
LIQ865B bupivacaine formulation
Liquidia's PRINT bupivacaine free base suspension for subcutaneous injection at doses ranging from 150mg to 600mg
干预措施: LIQ865B bupivacaine formulation (Drug)
LIQ865B bupivacaine formulation
Liquidia's PRINT bupivacaine free base suspension for subcutaneous injection at doses ranging from 150mg to 600mg
干预措施: Diluent for LIQ865 (Drug)
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
干预措施: LIQ865A bupivacaine formulation (Drug)
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
干预措施: LIQ865B bupivacaine formulation (Drug)
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
干预措施: Diluent for LIQ865 (Drug)
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).
干预措施: LIQ865A bupivacaine formulation (Drug)
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).
干预措施: LIQ865B bupivacaine formulation (Drug)
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).
干预措施: 0.5% bupivacaine hydrochoride (Drug)
结局指标
主要结局
Incidence of Treatment Emergent Adverse Events (AEs)
时间窗: 30 days
Safety assessments will include the incidence and severity of AEs during treatment and the follow-up period of the study
次要结局
- 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)
- Pharmacodynamic Response - Pain intensity (Numeric Rating Scale) with Short Tonic Heat Stimulus (STHS) testing at various time points(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(12, 24, 48, 72, 96, and 120 hours)
- Pharmacodynamic Response - Change in Heat Pain Threshold (HPT) compared to Baseline using various time points(12, 24, 48, 72, 96, and 120 hours)
- Pharmacodynamic Response - Change Mechanical Detection Threshold (MDT) compared to Baseline using various time points(12, 24, 48, 72, 96, and 120 hours)
- Pharmacodynamic Response - Change in Warmth Detection Threshold (WDT) compared to Baseline using various time points(12, 24, 48, 72, 96, and 120 hours)
- Pharmacodynamic Response - Change in Cold Detection Threshold (CDT) compared to Baseline using various time points(12, 24, 48, 72, 96, and 120 hours)