Clinical trial NCT04510090: Evaluate the Safety, Tolerability, and PK of EP547 in Healthy Subjects and Subjects With Cholestatic or Uremic Pruritus
Official title: Randomized, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of EP547 in Healthy Subjects and Subjects With Cholestatic or Uremic Pruritus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pruritus
Cholestasis
Kidney Failure
Lead sponsor: Escient Pharmaceuticals, Inc
Sponsor class: INDUSTRY
Collaborators: name: Novotech (Australia) Pty Limited
First posted: 2020-08-12
Enrollment: 89
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: This study consists of both single and multiple ascending doses in healthy subjects and in subjects with cholestatic or uremic pruritus.

Up to 48 healthy subjects will receive a single dose of EP547 or placebo. There will be a screening period of up to 28 days prior to the first dose, and a follow up visit 7 days after dosing is completed.

24 healthy subjects will receive multiple doses of EP547 or placebo for 7 days. There will be a screening period of up to 28 days prior to the first dose, and a follow up visit 7 days and then 14 days after dosing is completed.

6 subjects with cholestatic disease will receive a single dose of EP547. There will be a screening period of up to 28 days prior to the first dose, and a follow up visit 7 days after dosing is completed.

Up to 16 subjects with cholestatic pruritus will receive multiple doses of EP547 or placebo for 7 days. There will be a screening period of up to 28 days prior to the first dose, and a follow up visit 7 days and then 14 days after dosing is completed.

6 subjects with uremic disease will receive a single dose of EP547. There will be a screening period of up to 28 days prior to the first dose, and a follow up visit 7 days after dosing is completed.

Up to 16 subjects with uremic pruritus will receive multiple doses of EP547 or placebo for 7 days. There will be a screening period of up to 28 days prior to the first dose, and a follow up visit 7 days and then 14 days after dosing is completed.

12 healthy subjects will receive two doses of EP547 under fasted or fed condition.

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)

Primary outcomes:
measure: Incidence of Adverse Events
timeFrame: Measured from Day 1 to End of Study or Early Termination (up to 3 weeks)
Secondary outcomes:
measure: Maximum Plasma Concentration [Cmax] After Single Dose of EP547
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, and 12 hours post-dose on Day 1
measure: Maximum Plasma Concentration [Cmax] After Multiple Doses of EP547
timeFrame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12, and 24 hours post-dose on Day 7
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: CMAX Clinical Research
state: South Australia
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Grafton
country: New Zealand
facility: Auckland Clinical Studies (ACS)
state: Auckland
Study officials:
References: