A Multicenter, Randomized, Double-blind, Placebo-controlled, Dose-finding Phase II Clinical Trial to Evaluate the Efficacy and Safety of TRD205 Tablets in the Treatment of Chronic Postoperative Neuralgia
试验速览
- 阶段
- 2 期
- 状态
- Enrolling By Invitation
- 入组人数
- 184
- 试验地点
- 1
- 主要终点
- The change in the weekly average NRS (numeric pain rating scale,0~10:0 equated to no pain, and 10 equated to the worst pain imaginable )pain score from baseline after 6 weeks of treatment
研究概览
简要总结
This is a phase II, multicenter ,randomized, double-blind, placebo-controlled, dose-finding study designed to evaluate the efficacy and safety of TRD205 tablets in the treatment of chronic postoperative neuralgia
详细描述
This study used a placebo as a control to explore the efficacy, safety and pharmacokinetic characteristics of multiple administration of TRD205 tablets at different doses forchronic postoperative neuralgia .
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
- •18 Years ≤ Age ≤ 80 years (calculated as time of signing ICF), both male and female.
- •Subject experienced pain following surgical procedures including Thyroid gland and Breast surgery, orthopedic surgery , thoracotomy Etc. (except neurosurgery, amputation, cesarean section).
- •Chronic pain ≥ 3 months post-op with pain localized to the operative site, Or The area of innervation that projects to the nerve at this site (Including radicular pain radiating to one side or limb after spinal surgery) Or involving the dermatome.
- •DN4 scale ≥ 4, AND The subject's pain was judged by the investigator to be neuropathic in nature.
- •Subjects had moderate to severe pain intensity (ie, averaged over the single-blind run-in period NRS Score ≥ 4 Points, see requirements for single-blind run-in period and randomization criteria for details).
- •The subject is able to communicate well with the investigators, fully understand the purpose and requirements of this trial, voluntarily participate in the clinical trial and sign the informed consent form .
- •Subject is willing to voluntarily use the contraception specified in the protocol from signing the ICF to 1 month after the last dose of investigational drug (For details see Fig. 附录 4) . Both male and female subjects had no plans to donate sperm or ova during the study and for 1 month after investigational product administration.
排除标准
- •Investigator Judge the pain of subjects in whole or in part Pathological pain or pain in the central nervous system Caused by other postoperative complications (e.g., infection, disease recurrence, etc.).
- •Present Other Causally induced pain, such as the presence of skin disease in the affected skin area, cervical and lumbar spine disease, trauma, etc., thus affecting the investigator's evaluation of CPSNP or confusing the subject's self-assessment of CPSNP.
- •Presence of other neurological or psychiatric disorders that, in the judgment of the investigator, could confound the subject's self-assessment of CPSNP or affect the subject's ability to complete diary card completion.
- •Known history of hypersensitivity to investigational products or components or excipients of rescue medication during the study period, or history of hypersensitivity to two or more drugs.
- •Previously Received Any prohibited medication or non-drug therapy, and in Fig. Single-Blind Run-in Period Pre Did not undergo the protocol-required washout period (excluded medications Elution Phase: Single-Blind Run-in Period ≥ 5 half-lives or 7 days prior, whichever is longer; non-drug therapy is prohibited Elution Phase: Single-Blind Run-in Period ≥ 30 days prior) that may interfere with the evaluation of the test drug during the study.
- •Have an electrical stimulation instrument or intrathecal drug infusion system implanted to treat pain.
- •History of alcoholism (> 14 units/week of alcohol, 1 unit is equivalent to 360 mL of beer, or 45 mL of spirits with 40% alcohol, or 150 mL of wine) or drug abuse or drug abuse within 1 year prior to signing the ICF.
- •Patients with clinically significant acute or chronic diseases or unstable diseases, such as but not limited to acute cardiovascular disease, cerebrovascular disease, liver, kidney, respiratory system, blood system, immune system and other diseases, inflammatory or rheumatic diseases, uncontrolled infection, untreated endocrine diseases, etc., and affecting the subjects at the investigator's discretion.
- •Present Dysphagia Or any gastrointestinal disorder affecting drug absorption.
- •Malignancy diagnosed within 2 years prior to signing the ICF (with the exception of non-metastatic cutaneous basal cell or squamous cell carcinoma or carcinoma in situ of the cervix that has been appropriately treated or excised).
- •Patients with previous suicidal behavior or a positive response to Item 4 or 5 on the C-SSRS scale (for the 12 months prior to signing the ICF) .
- •Systolic BP ≥ 160 mmHg and/or diastolic BP ≥ 100 mmHg; Systolic pressure ≤ 90 mmHg and/or diastolic pressure ≤ 60 mmHg; Heart rate < 50 or > 110 beats per minute.
- •Neutrophil count < 1.5 × 10 9 /L; platelet count < 100 × 10 9 /L; Aspartate aminotransferase (AST) > 2.0 × upper limit of normal (ULN); alanine aminotransferase (ALT) > 2.0 × ULN; Urea or urea nitrogen (Urea or BUN) > 1.5 × ULN; Creatine kinase > 2.0 × ULN; Estimated serum creatinine clearance < 60 mL/min by Cockcroft-Gault formula.
- •Treponema pallidum antibody or human immunodeficiency virus antibody positive in any test at screening and judged by the investigator as not suitable for the subject .
- •Subjects who are expected to require reoperation from signing the ICF to the end of the study.
- •Females who are lactating or pregnant, or intend to become pregnant (female subjects or partners of male subjects) during the study period and within 1 month after dosing.
- •Those who have participated in or are participating in other clinical trials within 1 month prior to signing the ICF.
- •Other conditions not suitable for inclusion as judged by the investigator.
研究组 & 干预措施
200mg treatment group
Take TRD205 tables or placebo orally once a day every morning for 6 consecutive weeks
干预措施: TRD205 tablets (Drug)
400mg treatment group
Take TRD205 tables or placebo orally once a day every morning for 6 consecutive weeks
干预措施: TRD205 tablets (Drug)
600mg treatment group
Take TRD205 tables or placebo orally once a day every morning for 6 consecutive weeks
干预措施: TRD205 tablets (Drug)
Placebo
Take placebo orally once a day every morning for 6 consecutive weeks
干预措施: Placebo (Drug)
结局指标
主要结局
The change in the weekly average NRS (numeric pain rating scale,0~10:0 equated to no pain, and 10 equated to the worst pain imaginable )pain score from baseline after 6 weeks of treatment
时间窗: 8 weeks
The Digital Assessment Scale (NRS) is used to evaluate the degree of pain in patients using the 11-point numeric pain rating scale (0-10; 0 equated to no pain, and 10 equated to the worst pain imaginable).The NRS pain score will be was assessed during the single-blind introduction period, the double-blind treatment period, and at the early end of the visit.The baseline of the NRS pain score is defined as the weekly average of the NRS pain score collected during the single-blind introduction period. Before taking the medicine every morning, the subjects retrospectively evaluated the average pain level in the past 24 hours. In addition, 1 hour before each remedial analgesia, the average pain intensity from the previous use of the investigational drug to the use of the remedial medication should be retrospectively assessed.NRS scores were collected at Visit 3, Visit 4, Visit 5, Visit 6, Visit 7, and at the early end of the visit for the calculation of the weekly average score.
次要结局
- Treatment-Related Adverse Events(7 weeks)
- Peak Plasma Concentration（Cmax）(Within 4 hours after the last administration)
- Area under the plasma concentration versus time curve （AUC）(Within 4 hours after the last administration)