A Randomized, Double-Blind, Parallel Group, Placebo-Controlled Study to Evaluate the Analgesic Efficacy and Safety of VVZ-149 Injection for Post-operative Pain Following Total Hip Arthroplasty
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Change of Pain Intensity
研究概览
简要总结
The purpose of this phase 2 study is to evaluate the efficacy and safety of an analgesic drug candidate, VVZ-149 Injections. The study is designed as randomized, double-blind, parallel, and placebo-controlled study.
详细描述
VVZ-149 is a dual antagonist of GlyT2 and 5HT2A. GlyT2 blockage increases inhibitory synaptic transmission by glycine in the spinal cord, resulting in a reduction of pain transmissions to the brain. 5HT2A blockage decreases descending serotonergic facilitatory modulation on pain transmission by the brain and reduces nociceptor activation in peripheral nerves, which are primary sources of pain in post-surgical pain. VVZ-149 has been shown to have comparable efficacy to morphine in well controlled (blind, complete randomization with a positive control) animal studies using rat models of post-operative pain and formalin-induced pain. The PK/PD study in animals indicates that therapeutic plasma concentration in human subjects will be 600-1,900 ng/ml. A clinical Phase 1 study performed in healthy subjects has shown no clinically significant adverse events up to a plasma concentration level of 3,261 ng/ml other than brief symptoms of mild nausea or dizziness, and mild somnolence when the plasma exposure level is more than 2,000 ng/ml.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 25 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient between the ages of 25 and 65 years old
- •Male patient, in the case of female patient, postmenopausal women, or women physically incapable of childbearing
- •Subject who underwent surgery specially for the clinical study
- •Ability to provide written informed consent prior to any study procedures.
- •Ability to understand study procedures and communicate clearly with the investigator and staff.
- •Subjects with body weight under 100kg and body mass index (BMI) level lower than 35 kg/m2, inclusive
- •Single-side surgery patient
排除标准
- •< Surgical Factors >
- •Emergency or unplanned surgery.
- •Repeat operation
- •< Subject Characteristics >
- •Women with childbearing potential, Women who are pregnant or breastfeeding.
- •Unstable or poorly controlled psychiatric condition (e.g., untreated PTSD, anxiety, or depression). Subjects who take stable doses of antidepressants and anti-anxiety drugs may be included.
- •Unstable or acute medical condition (e.g., unstable angina, congestive heart failure, renal failure, hepatic failure, AIDS).
- •Subjects who have long QPR (>200msec) or prolonged QTc (> 450msec in male, >470msec in female) at Screening
- •< Drug, Alcohol, and Pharmacological Considerations >
- •History of alcohol, opiate or other drug abuse or dependence within 12 months prior to Screening .
- •Ongoing or recent (within 6 hour prior to surgery) use of steroids, opioids, or antipsychotics.
- •Alcohol consumption within 24 hours of surgery.
- •Use of nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen within 6 hours of surgery.
- •Use of herbal agents or nutraceuticals (i.e., chaparral, comfrey, germander, jin bu huan, kava, pennyroyal, skullcap, St. John's wort, or valerian) within 7 days prior to surgery.
- •< Anesthetic and Other Exclusion Considerations >
- •Use of neuraxial or regional anesthesia related to the surgery.
- •Use of ketamine, gabapentin, pregabalin, or lidocaine (>1 mg/kg) intra or peri-operatively, or within 24 hours of surgery.
- •Subject with known allergies to hydromorphone.
- •Subjects who received another investigational drug within 30 days of scheduled surgery
研究组 & 干预措施
VVZ-149 injections
VVZ-149 injections will be mixed with saline, then intravenous infusion for 10hr. The drug product will be administrated with a 1000mg for 10 hours.
干预措施: VVZ-149 injections (Drug)
Placebo
Placebo group will receive an water for injection the same volume and period of experimental group.
干预措施: Placebo (Drug)
结局指标
主要结局
Change of Pain Intensity
时间窗: prior to PCA, at 0,1, 2, 4, 6, 8, 10, 24 hours post-PCA
Change of Pain Intensity assessed using the Numerical Rating Scale (NRS, 0-10)
次要结局
- Fentanyl Consumption(0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-14, 14-16, 16-18, 18-20, 20-22, 22-24 hours post-PCA)
- the number of Fentanyl request(0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-14, 14-16, 16-18, 18-20, 20-22, 22-24 hours post-PCA)
- the amount of rescue dose(0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-14, 14-16, 16-18, 18-20, 20-22, 22-24 hours post-dose)
- the number of requested rescue dose(0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-14, 14-16, 16-18, 18-20, 20-22, 22-24 hours post-dose)
- Area under a curve (AUC) of Pain intensity and sum of AUC of pain intensity (SPI)(0-1, 1-2, 2-4, 4-6, 6-8, 8-10, 10-24 hours post-PCA)
- Global measurement of patient satisfaction assessed on the questionnaire (0-5 points scale)(8, 24 hours post-PCA)
- the correlation between Pharmacokinetic (PK) and Pharmacodynamic (PD)(0, 2, 6 hours post-PCA)
- Number of Vomiting(8, 24 hours post-PCA)