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:

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.