A Study to Evaluate the Safety and Efficacy of CR845 in Chronic Kidney Disease 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 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.

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:

• Has completed at least 4 Worst Itching Intensity NRS worksheets from the start of the 7-day Run-in Period;
• 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.