Evaluate the Safety, Tolerability, and PK of EP547 in Healthy Subjects and Subjects With Cholestatic or Uremic Pruritus
Condition: Pruritus; Cholestasis; Kidney Failure
MeSH terms: Cholestasis; Renal Insufficiency; Pruritus
Intervention: EP547; Placebo
Intervention description: EP547; Placebo
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 89.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This first in human, Phase 1/1b trial will evaluate the safety, tolerability, and
      pharmacokinetics of single and multiple ascending doses of EP547 in healthy subjects and
      subjects with cholestatic or uremic pruritus.
    

Eligibility criteria:

        Inclusion Criteria:

        Healthy Subjects:

          -  Age 18 to 60 years, inclusive

          -  Body mass index greater than or equal to 19 to less than or equal to 35 kg/m2

          -  Medically healthy with no clinically significant medical history, physical
             examination, vital sign, standard 12- lead ECG, chemistry, hematology, urinalysis, or
             coagulation results at Screening as deemed by the Investigator

          -  Male and female subjects must use adequate birth control and agree not to donate sperm
             or eggs for the time periods specified in the protocol

        Subjects with Cholestatic Pruritus:

          -  Age 18 to 80 years, inclusive

          -  Has a cholestatic disorder

          -  Has experienced daily or near-daily moderate to severe pruritus for greater than 4
             weeks before Screening and at study entry has itch scores indicative of moderate to
             severe pruritus

          -  If currently taking medications to treat the cholestatic disorder, must be on a stable
             dose for greater than 12 weeks before Screening and plans to maintain the regimen
             throughout the study

          -  If currently taking medications known to impact pruritus, must be on a stable dose for
             greater than 4 weeks before Screening and plans to maintain the regimen throughout the
             study

          -  Male and female subjects must use adequate birth control and agree not to donate sperm
             or eggs for the time periods specified in the protocol

        Subjects with Uremic Pruritus

          -  Age 18 to 80 years, inclusive

          -  Has ESRD and is receiving hemodialysis 3× per week

          -  Has experienced daily or near-daily moderate to severe pruritus for greater than 4
             weeks before Screening and at study entry has itch scores indicative of moderate to
             severe pruritus

          -  If currently taking medications known to impact pruritus, must be on a stable dose for
             greater than 4 weeks before Screening and plans to maintain the regimen throughout the
             study

          -  Male and female subjects must use adequate birth control and agree not to donate sperm
             or eggs for the time periods specified in the protocol

        Exclusion Criteria:

        Healthy Subjects:

          -  Any prescription medications within 14 days of Screening

          -  Positive result for HIV HBV, or HCV at Screening

          -  History of malignancy within the past 5 years

          -  Tobacco product or electronic cigarette use within 90 days of Day -1

          -  Positive drug, alcohol, or cotinine screen results at Screening or Day -1

          -  Significant history of abuse of drugs, solvents, or alcohol in the past 2 years

        Subjects with Cholestatic Pruritus:

          -  Scheduled to receive a liver transplant during the study (placement on a transplant
             waiting list is not exclusionary)

          -  Is receiving ongoing UVB treatment or anticipates receiving such treatment during the
             study

          -  Pruritus is secondary to biliary obstruction

          -  History or presence of hepatocellular carcinoma, hepatic abscess, or acute portal vein
             Thrombosis

        Subjects with Uremic Pruritus:

          -  Scheduled to receive a kidney transplant during the study (placement on a transplant
             waiting list is not exclusionary)

          -  Is receiving ongoing UVB treatment or anticipates receiving such treatment during the
             study

          -  Known noncompliance with hemodialysis treatment that, in the opinion of the
             Investigator, would impede completion or validity of the study

          -  Pruritus is attributed mainly to any disease unrelated to kidney disease, is only
             present during the hemodialysis sessions, or is attributed to a skin disorder that
             occurs in this population with associated itch (eg, acquired perforating dermatosis)