Study to Evaluate IV CR845 in Hemodialysis Patients With Moderate-to-Severe Pruritus

This is a two-part study. Patients participating in Part A will be consented and trained on
the completion of questionnaires about the severity of itching and overall health. Patients
will be required to complete questionnaires during their visits to the dialysis center and
also while at home on other days. Results of the screening questionnaires will assess
eligibility for the study. Additional laboratory tests and measurements for safety will also
be completed during the screening period. Patients meeting all criteria for entry into Part A
of the study will be randomized to receive either one of three different doses of CR845 or a
placebo. Patients will receive the study drug for eight weeks IV after each hemodialysis
treatment (i.e. 3 times per week). Assessments for intensity of itch and safety will also be
completed during the 8 week treatment period. When patients have completed treatment, a
Follow-up visit will be completed 7 days later.

Patients participating in Part B will be consented and trained on the completion of
questionnaires about itching and overall health. Patients will be required to complete
questionnaires during their visits to the dialysis center and also while at home on other
days. Laboratory tests and measurements for safety will also be completed during the
screening period to determine study eligibility. Patients meeting all criteria for entry into
Part B of the study will be randomized to receive either CR845 or a placebo. The dose of
CR845 used will have been determined based on the safety and efficacy from Part A. Patients
will be dosed with either CR845 or placebo for twelve weeks after each hemodialysis treatment
(i.e. 3 times per week). Assessments for intensity of itch and safety will be completed
during the treatment period also. When patients have completed treatment, a Follow-up visit
will be completed 7 days later.

Inclusion Criteria:

1. Willing and able to provide written informed consent prior to participating in this
study;

2. Able to communicate clearly with the Investigator and staff, able to read, complete
questionnaires, and understand the study procedures;

3. Males or females 18 years of age or older;

4. ESRD patients who have been on hemodialysis 3 times per week for at least 3 months
prior to the start of Screening;

5. Women of child-bearing potential must have a negative serum pregnancy test and agree
to practice an acceptable form of birth control for the duration of the study

6. Male patients that are not biologically or surgically sterile must agree to practice
an acceptable from of birth control for the duration of the study

7. Weigh between 88.2 lb (40.0 kg) and 297.6 lb (135.0 kg).

8. Patient must self-report pruritus in the month prior to screening.

9. If patient is receiving treatment for itch, this treatment must be stable prior to
screening and during treatment period.

10. At least 2 single-pool Kt/V measurements ≥ 1.2, or at least 2 urea reduction ratio
measurements ≥ 65%, or 1 single-pool Kt/V measurement ≥ 1.2 and 1 urea reduction ratio
measurement ≥ 65% on different dialysis days during the 3 months period prior to
Screening;

11. Patient who self-categorize as moderate-to-severe itch.

Exclusion Criteria:

1. Known to be non-compliant with dialysis treatment (i.e., has missed more than 2
dialysis sessions in the past 2 months because of non-compliance);

2. Anticipated to receive a kidney transplant during the study;

3. Known history of allergic reaction to opiates, such as hives

4. Known or suspected history of alcohol, narcotic, or other drug abuse or dependence
within 12 months prior to Screening;

5. Patient has any clinically relevant acute or chronic medical or neuropsychiatric
condition which, in the opinion of the Investigator, would pose undue risk to the
patient, would impede completion of the study procedures, or would compromise the
validity of the study measurements;

6. Serum alanine aminotransferase or aspartate aminotransferase greater than 2.5 times
the reference upper limit of normal (ULN), or total bilirubin greater than 2 times ULN
at Screening;

7. Received another investigational drug within 30 days prior to the start of Screening
or has planned to participate in another clinical trial while enrolled in this study;

8. 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);

9. Has localized itch restricted to the palms of the hands;

10. Has pruritus only during the dialysis session (by patient report);

11. Anticipated to receive opioid antagonists (e.g., naloxone, naltrexone), or opioid
mixed agonist-antagonist (e.g., buprenorphine, nalbuphine) from the start of Screening
through the end of the Treatment Period;

12. Used Salvia divinorum or Salvinorin A within 30 days prior to the start of Screening
or is anticipated to use it during the study;

13. Received ultraviolet B treatment within 30 days prior to the start of Screening or
anticipated to receive such treatment during the study;

14. Participated in a previous clinical trial with CR845.