A Phase 2, Randomized, Double-blind, Placebo-Controlled Efficacy, Pharmacokinetics and Safety Study of CA-008 (Vocacapsaicin) in Subjects Undergoing Total Knee Arthroplasty
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 55
- 试验地点
- 1
- 主要终点
- CA-008 Dose vs. Placebo Comparison: Area Under the Curve (AUC) 0 to 96 Hours
研究概览
简要总结
This is a two-part, Phase 2, multi-center, randomized, double-blind, placebo-controlled, parallel design study of CA-008 (vocacapsaicin) vs. placebo injected/instilled during an elective TKA.
详细描述
This is a Phase 2, multi-center, randomized, double-blind, placebo-controlled, parallel design study evaluating, in a pilot stage of the study, up to 3 ascending dose level cohorts each evaluating a single dose of CA-008 vs. placebo injected/instilled during an elective TKA. Up to 54 subjects will be randomized in the pilot stage. During the optional second stage of the study, subjects will be randomized to one of either 2 or 3 CA-008 dose levels (to be determined) or placebo. The Sponsor made the decision not to proceed with the second stage.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Plan to undergo an elective primary unilateral total knee arthroplasty (TKA or knee replacement), without collateral procedure or additional surgeries.
- •Be a reasonably healthy adult aged 18 - 80 years old, inclusive, with a BMI ≤ 36 kg/m2 and American Society of Anesthesiology (ASA) physical Class 1, 2 or 3 at the time of randomization.
- •Males and females must abstain from intercourse, use acceptable birth control methods or be sterile or otherwise incapable of having children.
- •Be willing and able to sign the informed consent form (ICF)
- •Be willing and able to complete study procedures and pain scales and to communicate meaningfully in English. Be able and willing to return for outpatient follow up visits as required.
排除标准
- •In the opinion of the Investigator,
- •have a concurrent painful condition, other than pain in the knee to be replaced, that may require pain treatment during the study period.
- •have active skin disease or other clinically significant abnormality at the anticipated site of surgery that could interfere with the planned surgery.
- •Have a known allergy to chili peppers, capsaicin or the components of CA-008, ropivacaine, ketorolac, acetaminophen, fentanyl, hydromorphone, morphine or oxycodone.
- •Have significant medical, neuropsychiatric or other condition.
- •The following are considered disallowed medications:
- •tolerant to opioids as defined
- •capsaicin-containing products or foods.
- •central nervous system active agent as an analgesic adjunct medication
- •antiarrhythmics except beta-blockers, digoxin, warfarin, lithium, or aminoglycosides or other antibiotics for an infection
- •parenteral or oral corticosteroids.
- •antianginal, antihypertensive agent or diabetic regimen at a dose that has not been stable for at least 30 days or which is not expected to remain stable while participating in the study.
- •Have positive results on the alcohol breath/saliva test indicative of alcohol abuse or urine drug screen indicative of illicit drug use at screening, and/or prior to surgery.
研究组 & 干预措施
CA-008 5 mg (0.05 mg/mL) Cohort 1
Cohort 1 (5 mg), was prepared at 0.05 mg/mL CA-008 (vocacapsaicin)
干预措施: CA-008 (Drug)
Placebo - Cohort 1
Placebo for Cohort 1
Placebo comparator identical in appearance to the investigational product, containing the same excipients as the active
干预措施: Placebo (Drug)
CA-008 10 mg (0.1 mg/mL) Cohort 2
Cohort 2 (10 mg), was prepared at 0.1 mg/mL CA-008 (vocacapsaicin)
干预措施: CA-008 (Drug)
CA-008 15 mg (0.15 mg/mL) Cohort 3
Cohort 3 (15 mg), was prepared at 0.15 mg/mL CA-008 (vocacapsaicin)
干预措施: CA-008 (Drug)
Placebo - Cohorts 2 and 3
Placebo - Cohorts 2 and 3
Placebo comparator identical in appearance to the investigational product, containing the same excipients as the active
干预措施: Placebo (Drug)
结局指标
主要结局
CA-008 Dose vs. Placebo Comparison: Area Under the Curve (AUC) 0 to 96 Hours
时间窗: From 0 hours to 96 hours
Primary Efficacy Endpoint for Stage 2. Area Under the Curve (AUC) of the NRS current pain intensity scores from Time 0 hours to 96 hours at rest (AUC0 to 96h) where 0 is no pain and 10 is the worst pain imaginable for CA-008 compared to placebo. • During the inpatient stay, NRS at rest beginning with the PACU admission may be assessed once the subject is awake. The maximum is an NRS score of 10 x all 96 hours = 960 NRS units\*hrs; the minimum is 0 x 96h = 0 NRS units\*hrs
Time-specific Mean Pain Intensity Scores (NRS) at Time 96 Hours for CA-008 vs. Placebo
时间窗: At 96 hours
Primary Efficacy Endpoint for the Pilot Stage. Time-specific mean pain intensity scores at Time 96 hours for CA-008 vs. placebo based on a 10-point numerical rating scale (NRS) from 0-10 where 0 is no pain and 10 is the worst pain imaginable).
次要结局
- Total Opioid Consumption (in Daily Oral Morphine Equivalents)(OC from Time 0 hours to Time 96 hours: OC 0 hours to 96 hours)
- Percentage of Subjects Who do Not Require Opioids(Time 0 hours to Time 96 hours: Opioid Free 0 hours to 96 hours)