A Randomized, Single-Blind, Active-Controlled, Dose-Ranging Study to Evaluate the Pharmacokinetics, Safety, and Efficacy of Local Administration of DepoTXA for Reduced Postsurgical Bleeding in Subjects Undergoing Total Knee Arthroplasty
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 16
- 试验地点
- 5
- 主要终点
- Area Under the Plasma Concentration-versus-time Curve From Time 0 Extrapolated to Infinity After Drug Administration
研究概览
简要总结
This is a Phase 2, randomized, single-blind, active-controlled dose-ranging study in subjects scheduled to undergo total knee arthroplasty (TKA).
详细描述
Approximately 60 subjects (15 per arm) are planned for enrollment. Subjects will be randomized in a 1:1:1:1 ratio to receive either DepoTXA 400 mg, DepoTXA 800 mg, DepoTXA 1200 mg, or IV TXA (Cyklokapron® 1 gram).
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
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, ≥18 years of age at screening.
- •Scheduled to undergo elective unilateral open TKA under general, spinal, or regional anesthesia.
- •American Society of Anesthesiology (ASA) physical status 1, 2, or
- •Female subject must be surgically sterile; or at least 2 years postmenopausal; or have a monogamous partner who is surgically sterile; or practicing double-barrier contraception; or practicing abstinence (must agree to use double-barrier contraception in the event of sexual activity); or using an insertable, injectable, or transdermal, contraceptive approved by the FDA for greater than 2 months prior to screening and commit to the use of an acceptable form of birth control for the duration of the study and for 30 days after completion of the study.
- •Able to provide informed consent, adhere to the study visit schedule, and complete all study assessments.
排除标准
- •Currently pregnant, nursing, or planning to become pregnant during the study or within 1 month after study drug administration.
- •Planned concurrent surgical procedure (e.g., bilateral TKA).
- •Prior open knee surgery on ipsilateral knee. Prior arthroscopy is permitted.
- •Subjects taking a medication with a known procoagulant effect (e.g., combination hormonal contraceptives, Factor IX complex concentrates or anti-inhibitor coagulant concentrates, or all-trans retinoic acid).
- •Contraindication or hypersensitivity to TXA.
- •History of thrombosis or prior Venous thromboembolism (VTE).
- •Known coagulopathy or active intravascular clotting.
- •Prior myocardial infarction.
- •Prior cardiovascular accident (stroke) or subarachnoid hemorrhage.
- •History of epilepsy.
- •Presence of an intravascular stent.
- •History of impaired kidney function, chronic respiratory disease, rheumatoid arthritis, coagulopathy, or loss of sensation in extremities.
- •Renal insufficiency (serum creatinine level >2 mg/dL).
- •Anemia (Hb level <10 g/dL).
- •Uncontrolled anxiety, psychiatric, or neurological disorder that might interfere with study assessments.
- •Acquired defective color vision.
- •Malignancy in the last 2 years, with the exception of non-metastatic basal cell or squamous cell carcinoma of the skin or localized carcinoma in situ of the cervix.
- •Suspected or known history of drug or alcohol abuse within the previous year.
- •Body weight <50 kg (110 pounds) or a body mass index >44 kg/m
- •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 subject's participation in this study.
研究组 & 干预措施
DepoTXA 400mg
400mg Intracapsular at the end of surgery one time
干预措施: DepoTXA (Drug)
DepoTXA 800mg
800mg Intracapsular at the end of surgery one time
干预措施: DepoTXA (Drug)
DepoTXA 1200mg
1200mg Intracapsular at the end of surgery one time
干预措施: DepoTXA (Drug)
IV Tranexamic acid (TXA)
1 g of IV TXA at the end of surgery
干预措施: Tranexamic Acid (Drug)
结局指标
主要结局
Area Under the Plasma Concentration-versus-time Curve From Time 0 Extrapolated to Infinity After Drug Administration
时间窗: Baseline; 5, 15, and 30 min; at 1, 2, 4, 6, 8, 12, 16, and 24 hours after study drug administration for all treatment groups. Additional blood samples were collected at 36, 48, 60, 72, and 96 hours for DepoTXA-treated subjects.
Area Under the Plasma Concentration-versus-time Curve From Time 0 to the Last Collection Time After Drug Administration
时间窗: Baseline; 5, 15, and 30 min; at 1, 2, 4, 6, 8, 12, 16, and 24 hours after study drug administration for all treatment groups. Additional blood samples were collected at 36, 48, 60, 72, and 96 hours for DepoTXA-treated subjects.
The Apparent Terminal Elimination Rate Constant
时间窗: Baseline; 5, 15, and 30 min; at 1, 2, 4, 6, 8, 12, 16, and 24 hours after study drug administration for all treatment groups. Additional blood samples were collected at 36, 48, 60, 72, and 96 hours for DepoTXA-treated subjects.
Maximum Plasma Concentration (Cmax)
时间窗: Baseline; 5, 15, and 30 min; at 1, 2, 4, 6, 8, 12, 16, and 24 hours after study drug administration for all treatment groups. Additional blood samples were collected at 36, 48, 60, 72, and 96 hours for DepoTXA-treated subjects.
Time to Maximum Plasma Concentration (Tmax)
时间窗: Baseline; 5, 15, and 30 min; at 1, 2, 4, 6, 8, 12, 16, and 24 hours after study drug administration for all treatment groups. Additional blood samples were collected at 36, 48, 60, 72, and 96 hours for DepoTXA-treated subjects.
The Apparent Terminal Elimination Half-life
时间窗: Baseline; 5, 15, and 30 min; at 1, 2, 4, 6, 8, 12, 16, and 24 hours after study drug administration for all treatment groups. Additional blood samples were collected at 36, 48, 60, 72, and 96 hours for DepoTXA-treated subjects.
次要结局
- Incidence of Reoperation Due to Hematoma or Wound Dehiscence(Through day 60)
- Summary of Neurological Assessments (Proportion of Subjects Who Were Oriented and Proportion of Subjects Who Had Any of the Neurologic Events) at Each Assessed Timepoint(12, 24, 36, 48, 60, 72, and 96 hours after study drug administration)
- Incidence of Transfusion (Number of Units, Number of Units/Subject, Number of Subjects Transfused)(Day 60)
- Number of Participants With 90˚ Passive and Active Knee Flexion(24, 48, and 72 hours)
- Time to Complete Timed Up-and-Go (TUG) Test(Day 1; at approximately 8:00 am and 8:00 pm (±2 hours) daily from Day 2 through hospital discharge; and on Day 7)
- Change in Knee and Thigh Measurements(48 hours and Day 7)
- Area Under the Curve (AUC) of NRS From 0-24 Hours, 0-48 Hours, and 24-48 Hours(Preoperative; arrival in Post-Anesthesia Care Unit (PACU); 2, 4, 6, 8, 12, 16, 24, 36, 48 hours, Day 7)