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.