A Two-Part, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Intravenous CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 226
- 试验地点
- 4
- 主要终点
- Change From Baseline in the Weekly Mean of the Daily 24-hour Worst Itching Intensity NRS Score During Week 8
研究概览
简要总结
2 Part Study: Part A will assess 3 different dosing levels of IV CR845 versus placebo in patient on hemodialysis who have moderate-to-severe itching due to uremic pruritus. Patients will receive either CR845 or placebo after each dialysis session for eight weeks. The safety and efficacy of CR845 will be monitored throughout the study. A sub-group of patients will also have pharmacokinetic assessments completed. Part B of the study will assess one dose of IVCR845 versus placebo for 12 weeks in patients on hemodialysis who have moderate-to-severe itching. The dose of CR845 used in Part B will be based on safety and efficacy found in Part A.
详细描述
This is a two-part study. Patients participating in Part A will be consented and trained on the completion of questionnaires about the severity of itching and overall health. Patients will be required to complete questionnaires during their visits to the dialysis center and also while at home on other days. Results of the screening questionnaires will assess eligibility for the study. Additional laboratory tests and measurements for safety will also be completed during the screening period. Patients meeting all criteria for entry into Part A of the study will be randomized to receive either one of three different doses of CR845 or a placebo. Patients will receive the study drug for eight weeks IV after each hemodialysis treatment (i.e. 3 times per week). Assessments for intensity of itch and safety will also be completed during the 8 week treatment period. When patients have completed treatment, a Follow-up visit will be completed 7 days later.
Patients participating in Part B will be consented and trained on the completion of questionnaires about itching and overall health. Patients will be required to complete questionnaires during their visits to the dialysis center and also while at home on other days. Laboratory tests and measurements for safety will also be completed during the screening period to determine study eligibility. Patients meeting all criteria for entry into Part B of the study will be randomized to receive either CR845 or a placebo. The dose of CR845 used will have been determined based on the safety and efficacy from Part A. Patients will be dosed with either CR845 or placebo for twelve weeks after each hemodialysis treatment (i.e. 3 times per week). Assessments for intensity of itch and safety will be completed during the treatment period also. When patients have completed treatment, a Follow-up visit will be completed 7 days later.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Willing and able to provide written informed consent prior to participating in this study;
- •Able to communicate clearly with the Investigator and staff, able to read, complete questionnaires, and understand the study procedures;
- •Males or females 18 years of age or older;
- •ESRD patients who have been on hemodialysis 3 times per week for at least 3 months prior to the start of Screening;
- •Women of child-bearing potential must have a negative serum pregnancy test and agree to practice an acceptable form of birth control for the duration of the study
- •Male patients that are not biologically or surgically sterile must agree to practice an acceptable from of birth control for the duration of the study
- •Weigh between 88.2 lb (40.0 kg) and 297.6 lb (135.0 kg).
- •Patient must self-report pruritus in the month prior to screening.
- •If patient is receiving treatment for itch, this treatment must be stable prior to screening and during treatment period.
- •At least 2 single-pool Kt/V measurements ≥ 1.2, or at least 2 urea reduction ratio measurements ≥ 65%, or 1 single-pool Kt/V measurement ≥ 1.2 and 1 urea reduction ratio measurement ≥ 65% on different dialysis days during the 3 months period prior to Screening;
- •Patient who self-categorize as moderate-to-severe itch.
排除标准
- •Known to be non-compliant with dialysis treatment (i.e., has missed more than 2 dialysis sessions in the past 2 months because of non-compliance);
- •Anticipated to receive a kidney transplant during the study;
- •Known history of allergic reaction to opiates, such as hives
- •Known or suspected history of alcohol, narcotic, or other drug abuse or dependence within 12 months prior to Screening;
- •Patient has any clinically relevant acute or chronic medical or neuropsychiatric condition which, in the opinion of the Investigator, would pose undue risk to the patient, would impede completion of the study procedures, or would compromise the validity of the study measurements;
- •Serum alanine aminotransferase or aspartate aminotransferase greater than 2.5 times the reference upper limit of normal (ULN), or total bilirubin greater than 2 times ULN at Screening;
- •Received another investigational drug within 30 days prior to the start of Screening or has planned to participate in another clinical trial while enrolled in this study;
- •Has pruritus probably or definitely attributed to a cause other than ESRD or its complications (e.g., patients with concomitant pruritic dermatological disease or cholestatic liver disease would be excluded). (Note: Patients whose pruritus is attributed to ESRD complications such as hyperparathyroidism, hyperphosphatemia, anemia, or the dialysis procedure or prescription may be enrolled);
- •Has localized itch restricted to the palms of the hands;
- •Has pruritus only during the dialysis session (by patient report);
- •Anticipated to receive opioid antagonists (e.g., naloxone, naltrexone), or opioid mixed agonist-antagonist (e.g., buprenorphine, nalbuphine) from the start of Screening through the end of the Treatment Period;
- •Used Salvia divinorum or Salvinorin A within 30 days prior to the start of Screening or is anticipated to use it during the study;
- •Received ultraviolet B treatment within 30 days prior to the start of Screening or anticipated to receive such treatment during the study;
- •Participated in a previous clinical trial with CR845.
研究组 & 干预措施
CR845 0.5mcg/kg
Part A of study: IV CR845 0.5 mcg/kg administered after each dialysis session (3 times/week)
干预措施: CR845 0.5 mcg/kg (Drug)
CR845 1 mcg/kg
Part A of study: IV CR845 1 mcg/kg administered after each dialysis session (3 times/week)
干预措施: CR845 1 mcg/kg (Drug)
CR845 1.5mcg/kg
Part A of study: IV CR845 1.5 mcg/kg administered after each dialysis session (3 times/week)
干预措施: CR845 1.5mcg/kg (Drug)
Placebo
Part A of study: IV Placebo administered after each dialysis session (3 times/week)
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in the Weekly Mean of the Daily 24-hour Worst Itching Intensity NRS Score During Week 8
时间窗: Baseline, Week 8
Intensity of itch was measured using a numerical rating scale (NRS) used to indicate the intensity of the worst itching over the past 24 hours using a 0 to 10 numeric rating scale, where "0" represents "no itching" and "10" represents "worst itching imaginable". Higher scores meant worse itch intensity.
次要结局
- 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 8(Baseline, Week 8)