Safety and Pharmacokinetics of IV CR845 in Hemodialysis Patients, and Its Efficacy in Patients With Uremic Pruritus

Placebo-controlled

Inclusion criteria:

- Able to provide written informed consent prior to any study procedures;

- Able to communicate clearly with the Investigator and staff, able to read and
understand the study procedures;

- Males or females 18 years of age or older;

- End stage renal disease (ESRD) patients who have been on hemodialysis for at least
three months and are currently on hemodialysis:

- At least three times per week (Part A)

- Three times per week (Part B)

- Has a body weight ≤ 135 kg

- Part B: Patient who self-reports daily or near daily pruritus during the 6 weeks
prior to Screening;

- Part B: Patient who reports a Patient B or Patient C profile on the Patient
Self-categorization of Pruritus Disease Severity questionnaire at Screening;

- Part B: At the end of the Run-in Period:

- Patient who completed ratings of worst itching intensity [visual analog scale
(VAS)] at least 8 times out of 14 VAS assessments;

- Patient who has a mean value of >40 mm on the worst itching VAS over the one
week Run-in Period.

Exclusion criteria:

- Known to be non-compliant with dialysis treatment (i.e., has a history of missed
dialysis sessions due to non-compliance in the past 2 months);

- Anticipated to receive a kidney transplant during the study;

- Known history of allergic reaction to opiates such as hives (Note: side effects
related to the use of opioids such as constipation or nausea would not exclude the
patients from the study);

- Known or suspected history of Diagnostic and Statistical Manual of Mental Disorders,
Fifth Edition (DSM-5)-diagnosed alcohol, narcotic, or other drug abuse or dependence
within 12 months prior to Screening;

- Acute or unstable medical condition(s) such as congestive heart failure [New York
Heart Association (NYHA) class IV], which in the opinion of the Investigator would
pose undue risk to the patient or would impede complete collection of the data or its
evaluability;

- Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) greater than
2.5X the reference upper limit of normal (ULN), or bilirubin greater than 4X the ULN
at Screening;

- Received another investigational drug within 30 days prior to the start of the Run-in
Period or has planned to participate in another clinical trial while enrolled in this
study

- Part B: 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);

- Part B: Has localized itch restricted to the palms of the hands as determined from
the Brief Itch Inventory diagram, completed during the Screening Period;

- Part B: Has pruritus only during the dialysis session (by patient report);

- Part B: Has used gabapentin, calcineurin inhibitors, opioids; antipsychotics;
systemic or topical corticosteroids (other than otic or ophthalmic preparations);
sedatives; hypnotics; anti-anxiety agents selective serotonin reuptake inhibitors
(SSRIs); or tricyclic antidepressants for < 4 weeks prior to the start of the Run-In
Period or had a dose change within the previous 30 days;

- Part B: Is not willing to abstain from use of antihistamines (oral, IV, or topical)
for 3 weeks (from the start of the Run-In Period through the end of Week 2);

- Part B: Not willing to abstain from making changes to topical non-drug treatments
(e.g., emollients, creams, oils) for pruritus for 3 weeks (from the start of the
Run-In Period through the end of Week 2);

- Part B: Received ultraviolet B treatment within 30 days prior to the start of the
Run-in Period.