Clinical Pharmacology of LT5001 Drug Product in Hemodialysis Patients With Uremic Pruritus to Assess the Safety, Local Tolerance and Pharmacokinetics
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Number of Events With AE by Severity
研究概览
简要总结
A Randomized, Double Blind, Placebo-Controlled study to assess the Safety, Local Tolerance, and Pharmacokinetics of LT5001 drug product in Hemodialysis Patients with Uremic Pruritus
详细描述
In Part A, patient participation is expected to last up to 63 days, including a 28-day screening period(consisting of a 7-day diary run-in to build baseline itch NRS) and a 36-day on study period (consisting of 56 total doses from Day 1 to Day 29, and a 7 day follow-up/EOS visit at Day 36).
In Part B, patient participation is expected to last up to 85 days, including a 28-day screening period (consisting of a 7-day diary run-in to build baseline itch NRS) and a 57-day on study treatment period.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 20 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female 20 to 75 years of age, inclusive, at the time of signing informed consent.
- •Patient must have been receiving in-center hemodialysis for ≥ 3 months and currently on a schedule of 3 times per week.
- •Patient must have had at least 2 urea reduction ratio (URR) measurements ≥ 65%, at least 2 single-pool Kt/V measurements ≥ 1.2, or 1 single-pool Kt/V measurement ≥ 1.2 and 1 URR measurement ≥ 65% on different dialysis days within the last 3 month period prior to the Screening Visit.
- •Body weight ≥ 40 kg (not to exceed 115 kg) and BMI ≥ 18.0 and ≤ 31.0 kg/m2 at screening and Day 1 (after hemodialysis).
- •History of pruritus > 4 weeks of duration
- •Females with childbearing potential (defined as women ≤50 years of age with a history of amenorrhea for <12 months prior to study entry) must agree to use effective methods of contraception from screening through the last dose of study drug.
- •Males who are sexually active and whose partners are females of childbearing potential must agree to use condoms from screening through 90 days, whichever is longer, after administration of the last dose of study drug, and their partners must be willing to use a highly effective method of contraception from screening through 90 days after administration of the last dose of study drug.
- •Males must agree to not donate sperm from screening through 90 days, whichever is longer, after administration of the last dose of study drug.
- •Patient must have completed at least 6 days of Worst Itching Intensity NRS worksheets in the 7-day Diary run-in period and have a mean Worst Itching Intensity NRS score > 4 prior to randomization.
- •Patients must be able to complete questionnaires, understand the study procedures, and communicate effectively with the study personnel.
排除标准
- •History of alcohol abuse, illicit drug use, physical dependence to any opioid or narcotic, or any history of drug abuse or addiction within 6 months of screening.
- •History of major surgery or trauma within 12 weeks of screening in the judgement of the investigator, or surgery planned during the study.
- •Has received ultraviolet B treatment, opioid antagonists (eg, naloxone, naltrexone), or opioid mixed agonist-antagonist (eg, nalbuphine) within 30 days prior to the Screening Visit or anticipated to receive such treatment during the study.
- •Has had a significant alteration in dialysis regimen within 2 weeks of the Screening Visit or anticipated to be receiving nocturnal dialysis, home hemodialysis treatment, or kidney transplant during the study.
- •Has any known history of allergic reaction to opioids.
- •History of latest positive serology test for HBV (HBsAg) or HCV (anti-HCV) within 1 year prior randomization consistent with current infection. Confirmatory tests will be allowed at the discretion of the investigator to rule out false positives.
- •Has any known history of HIV.
- •Positive pregnancy test or is lactating.
- •Has required peritoneal dialysis.
- •Alanine aminotransferase and/or aspartate aminotransferase concentration > 2 x the ULN, or total bilirubin > 1.8 x ULN, or hemoglobin concentration < 9 g/dL at the Screening Visit.
- •Has taken other investigational drugs or participated in any clinical study within 30 days or 5 half-lives (if known) of the investigational drug's PK, PD, or biological activity (if known), whichever is longer, prior to first dose of study drug in this study or is currently participating in another clinical study.
- •Has received a vaccination within 3 days prior to administration of the first dose of study drug.
- •Has pruritus probably or definitely attributed to a cause other than renal disease or its complications such as atopic dermatitis, chronic urticarial, or hepatic pruritus caused by chronic liver disease.
- •Presence of skin infection (as defined by the investigator) on the area to be treated.
- •Any other condition or prior therapy that, in the investigator's opinion, would make the patient unsuitable for the study, or unable or unwilling to comply with the study procedures
- •Involved in the planning or conduct of this study.
- •Unwilling or unlikely to comply with the requirements of the study.
研究组 & 干预措施
LT5001
Administered twice daily (maximum 6 g per time, morning and evening respectively)
干预措施: LT5001 (Drug)
Placebo
Administered twice daily (maximum 6 g per time, morning and evening respectively)
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Events With AE by Severity
时间窗: Week 4
The number of reported AE events by severity
Number of Patients With AE by Severity
时间窗: Week 4
Adverse events (AEs) were collected and categorized by severity (mild, moderate, or severe) according to standard clinical criteria. The outcome measure is defined as the number of patients who experienced at least one adverse event of each severity level during the study period.
The Number of Patients With AE by Causality
时间窗: 4 weeks
Adverse events were assessed for their causal relationship to the study treatment by the investigator and categorized as related or not related. The outcome measure is defined as the number of patients who experienced at least one adverse event in each causality category during the study period.
Number of AE Event by Causality
时间窗: week 4
The number of reported events by causality
次要结局
- Systemic Ctrough Exposure of LT5001 in Hemodialysis Patients.(Week 4)
- Change in Mean Worst Itching Intensity From Baseline to the End of Week 4 Using NRS.(Week 4)
- Proportion of Patients With Changes in Numerical Rating Scale (>=2 Points, >=3 Points, >=4 Points) From Baseline(Week 4)
- Improvement in Itch-related Quality of Life as Assessed by the Change From Baseline in 5-D Pruritus Scale at the End of Week 4.(Week 4)
- Improvement in Itch-related Quality of Life as Assessed by the Change From Baseline in Total Skindex-10 Scale Score at the End of Week 4.(Week 4)