A Study to Evaluate the Safety and Efficacy of CR845 in Chronic Kidney Disease Patients With Moderate-to-Severe Pruritus

Phase 2

Completed

Interventions: Drug: Placebo Oral Tablet
Drug: CR845 0.25 mg Oral Tablet
Drug: CR845 0.5 mg Oral Tablet
Drug: CR845 1 mg Oral Tablet

Brief Summary: This is a multicenter, double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of 3 dose levels of oral CR845 compared to placebo in reducing the intensity of itch in chronic kidney disease (CKD) patients with moderate-to-severe pruritus. This study will consist of a Screening Period, a 7-day Run-in Period, a 12 week Treatment Period, and a Follow-up Visit (approximately 7 days after the last dose of study drug).

Detailed Description: This study will consist of a Screening Period, a 7-day Run-in Period, a 12 week Treatment Period, and a Follow-up Visit (approximately 7 to 10 days after the last dose of study drug). Informed consent will be obtained prior to performing any study-specific procedures. Screening will occur within 7 to 28 days prior to randomization to assess eligibility.

If patients continue to meet all inclusion and no exclusion criteria at the end of the 7-day Run-in Period, they will be randomized in a 1:1:1:1 ratio to receive orally once daily either placebo or CR845 tablets at doses of 0.25, 0.5 or 1 mg. Randomization will be stratified according to the patient's renal disease status: moderate CKD; severe CKD non-dialysis; severe CKD on dialysis (ie, 3 categories). A final safety Follow-up Visit will be conducted 7 to 10 days after the last dose of study drug.

Recruitment & Eligibility

Inclusion Criteria

To be eligible for inclusion into the study, a patient must meet the following criteria:

CKD patients with stage III, IV, or V (ie, moderate renal impairment with estimated glomerular filtration rate (GFR) ≥30 and <60 mL/min/1.73 m2 or severe renal impairment with estimated GFR <30 mL/min/1.73 m2).
For severe CKD patients on hemodialysis, they must be receiving hemodialysis 3 times per week for at least 3 months prior to the start of screening;
Prior to randomization:
1. Has completed at least 4 Worst Itching Intensity NRS worksheets from the start of the 7-day Run-in Period;
2. Has a mean baseline Worst Itching Intensity NRS score ≥5, defined as the average of all non-missing scores reported from the start of the 7-day Run-in Period.

Exclusion Criteria

A patient will be excluded from the study if any of the following criteria are met:

Patients not currently on dialysis who are likely to initiate routine dialysis during study participation;
Scheduled to receive a kidney transplant during the study;
New or change of treatment received for itch including antihistamines and corticosteroids (oral, intravenous [IV], or topical) within 14 days prior to screening;
Received another investigational drug within 30 days prior to the start of screening or is planning to participate in another clinical study while enrolled in this study;
Received ultraviolet B treatment within 30 days prior to the start of screening or anticipates receiving such treatment during the study;
Participated in a previous clinical study with CR845.

Arm && Interventions

Group	Intervention	Description
Placebo Oral Tablet	Placebo Oral Tablet	Oral Placebo to be taken orally once daily
CR845 0.25 mg Oral Tablet	CR845 0.25 mg Oral Tablet	Oral CR845 0.25 mg to be taken orally once daily for 12 weeks
CR845 0.5 mg Oral Tablet	CR845 0.5 mg Oral Tablet	Oral CR845 0.5 mg to be taken orally once daily for 12 weeks
CR845 1 mg Oral Tablet	CR845 1 mg Oral Tablet	Oral CR845 1 mg to be taken orally once daily for 12 weeks

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Weekly Mean of the Daily 24-hour Worst Itching Intensity Numerical Rating Scale (NRS) Score During Week 12	Baseline, Week 12	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". Higher scores meant worse itch intensity.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Total Skindex-10 Scale Score at the End of Week 12	Baseline, Week 12	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. The Skindex-10 has 10 questions; the total Skindex-10 score ranges from 0 to 60. A lower total score represents better quality of life.
Change From Baseline in 5-D Itch Scale Score at the End of Week 12	Baseline, Week 12	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. The 5-D Itch Scale has 5 questions; the total 5-D Itch Scale score ranges from 5 to 25, with higher scores indicating worse responses.
Reduction of Itch Intensity as Assessed by the Proportion of Patients Achieving an Improvement From Baseline ≥3 Points With Respect to the Weekly Mean of the Daily 24-hour Worst Itching Intensity NRS Score at Week 12	Week 12

Locations (3): Cara Therapeutics Study Site 1
🇺🇸
Miami, Florida, United States
Cara Therapeutics Study Site 2
🇺🇸
Flint, Michigan, United States
Cara Therapeutics Study Site
🇺🇸
Alexandria, Virginia, United States