Study to Investigate the Safety of LT5001 Drug Product for Uremic Pruritus in Hemodialysis Patients

Study Overview
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Brief Summary
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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

Detailed Description
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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.

Official Title
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Clinical Pharmacology of LT5001 Drug Product in Hemodialysis Patients With Uremic Pruritus to Assess the Safety, Local Tolerance and Pharmacokinetics

Conditions
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Uremic Pruritus

Intervention / Treatment
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* Drug: LT5001
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: LT5001<br>Administered twice daily (maximum 6 g per time, morning and evening respectively) | Drug: LT5001<br>* Administered twice daily<br>* Other names: DNS;|
| Placebo Comparator: Placebo<br>Administered twice daily (maximum 6 g per time, morning and evening respectively) | Drug: Placebo<br>* Administered twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nature and severity of adverse events (AEs) and number of patients with AEs | To evaluate the safety of LT5001 | Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systemic Ctrough exposure of LT5001 in hemodialysis patients. | To evaluate the systemic exposure of LT5001 | Week 4 | 
| Change in mean Worst Itching Intensity from baseline to the end of Week 4 using NRS. | Intensity of itch will be measured using an 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. | Week 4 | 
| Reduction of itch intensity as assessed by the proportion of patients achieving an improvement from baseline with respect to the weekly mean of the daily 24-hour Worst Itching Intensity NRS score | Intensity of itch will be measured using an 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. | Week 4 | 
| Improvement in itch-related quality of life as assessed by the change from baseline in 5-D Itch Scale score at the end of Week 4. | The 5-D Itch Scale is a multidimensional questionnaire which assesses itch-related quality of life over the past 2 weeks. The questions cover five dimensions of itch including the degree, duration of itch/day, direction (improvement/worsening), disability (impact on activities such as work), and body distribution of itch. A lower total score represents better quality of life. | 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. | The Skindex-10 Scale is a multidimensional questionnaire which assesses itch-related quality of life over the past week. The questions cover 3 domains: disease, mood/emotional distress, and social functioning domain. A lower total score represents better quality of life. | Week 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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uremic pruritus, Hemodialysis