A Phase I Dose-escalation Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of a Single Administration of Extended-Release Injectable Suspension (ND-340) as Post-operative Analgesia in Patients With Total Knee Arthroplasty (TKA)

Nang Kuang Pharmaceutical Co., Ltd.1 个研究点分布在 1 个国家目标入组 36 人开始时间: 2020年10月15日最近更新: 2023年11月9日

适应症

干预措施

试验速览

阶段: 1 期
状态: 暂停
发起方: Nang Kuang Pharmaceutical Co., Ltd.
入组人数: 36
试验地点: 1
主要终点: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This study focused on ND-340 extended release injection suspension for patients undergoing total knee arthroplasty with a one-time nerve blockade to assess drug side effects, pharmacokinetics and the effect of pain relief after surgery.

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Parallel
主要目的: Treatment
盲法: None

入排标准

年龄范围: 20 Years 至 80 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•Subject with age between 20 and 80 (inclusive) years old at the screening visit
•With physician's order to undergo scheduled primary unilateral TKA
•Female subject with childbearing potential must have a negative serum pregnancy test at the screening visit
•Both male and female subjects with childbearing potential must agree to use 2 medically accepted methods of contraception (e.g., barrier contraceptives [male condom, female condom, or diaphragm with a spermicidal gel], hormonal contraceptives [implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings], and intrauterine devices) during the course of the study with their partners (excluding women who are not of childbearing potential and men who have been sterilized).
•Able and willing to comply with all study visits and procedures
•Able to speak, read, and understand the language of the informed consent form (ICF), study questionnaires, and other instruments used for collecting subject-reported outcomes, in order to enable accurate and appropriate responses to pain scales and other required study assessments
•Willing and capable of providing written informed consent

排除标准

•Body weight < 50 kilograms or a morbidly obese (body mass index ≥ 35kg/m2)
•Subject with American Society of Anesthesiologists (ASA) physical status > 3 at the screening visit
•Undergoing or is plan to undergo bilateral or revision total knee replacement
•Previous contralateral TKA or open knee surgery on the knee being considered for TKA in this study within 1 year prior to screening. Prior arthroscopy at least 1 week prior to TKA is permitted.
•Use of any of the following medications within the time specified before TKA
•Use of any opioid within 24 hours or long-acting opioid within 3 days
•Use of any NSAID including selective COX-2 inhibitor within 3 days
•Use of any selective serotonin reuptake inhibitors (SSRIs), gabapentin, pregabalin (LYRICA®), or duloxetine (CYMBALTA®) within 3 days
•Use of monoamine oxidase inhibitors (MAOIs) within 14 days
•Concurrent painful physical condition, diseases or concurrent surgery that may require analgesic treatment (such as NSAIDs or opioids) in the post-operative period for pain that is not strictly related to the surgery, and which may confound the post-operative assessments (e.g., significant pain from other joints including the non-index knee joint, chronic neuropathic pain, concurrent or prior contralateral TKA, concurrent foot surgery)
•Pre-operative liver insufficiency as defined by liver function tests [i.e. alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), or total bilirubin] ≥ 1.5 times the upper limit of normal (ULN) at the screening visit
•Pre-operative renal insufficiency (creatinine clearance < 60 mL/min) at the screening visit
•Known of active infection with HIV, HBV, or HCV at the screening visit
•With abnormal ECG at screening and admission, which is not suitable to participate into this study as judged by the investigator before TKA
•With abnormal results of sensory examination as judged by the investigator before TKA
•Administration of an investigational drug within 30 days or 5 elimination half- lives of such investigational drug, whichever is longer, prior to study drug administration; or planned administration of another investigational product or procedure during the study period
•Receiving other surgeries within 30 days prior to screening
•Receiving blood transfusion within 30 days prior to screening
•With a history of allergy or hypersensitivity to local anesthetics
•Previous hypersensitivity to or contraindication to any of the pain-control agents planned for surgical or post-operative use in this study (i.e., morphine, bupivacaine, tramadol, and acetaminophen)
•History of, suspected, or known addiction to or abuse of illicit drug(s), prescription medicine(s), or alcohol within the past 2 years prior to screening
•Uncontrolled anxiety, schizophrenia, or other psychiatric disorder that could interfere with study assessments or compliance in the opinion of the investigator
•Current or historical evidence of any clinically significant disease or condition, especially terminal stage cancer, poorly controlled diabetic mellitus (i.e., HbA1c > 8%), or neurological disease that, in the opinion of the investigator, may increase the risk of study treatment and TKA, or complicate the subject's post-operative course or interfere with the determination of pain intensity related solely to the TKA
•Subject with severe heart diseases (NYHA class-III and IV), with ischemic heart diseases (angina pectoris and myocardial infarction) and subject who underwent percutaneous transluminal coronary angioplasty (PTCA) or had treatments for coronary artery bypass graft within 6 months prior to screening
•With pre-existed psychiatric or neurological deficits, which may compromise the neurological toxicity evaluations in this study by the investigator's judgment
•With stroke within 1 year prior to screening
•With bone cancer within 5 years prior to screening
•Inability to understand or operate the PCA machine
•Female subject who is breast-feeding, pregnant, or planning to become pregnant

研究组 & 干预措施

Control

Active Comparator

Standard practice of pain management for post-TKA

干预措施: IV-PCA (Drug)

ND-340

Experimental

ND-340 90mg~320mg at dose escalations

干预措施: ND-340 (Drug)

结局指标

主要结局

Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

时间窗: up to 3 months

The AEs of special interest, including any symptom of local anesthetic systemic toxicity (LAST), cardiac events, neurologic events, and falls, will be analyzed by cohort.

AUC 0-t