Evaluate the Safety, Tolerability, and PK of EP547 in Healthy Subjects and Subjects With Cholestatic or Uremic Pruritus

Kidney Failure Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04510090
• Other study ID #: EP-547-101
• Status: Completed
• Phase: Phase 1
• Start date: September 7, 2020
• Est. completion date: July 8, 2021

Study information

• Verified date: July 2022
• Source: Escient Pharmaceuticals, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 89
• Est. completion date: July 8, 2021
• Est. primary completion date: July 8, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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)

Related Conditions & MeSH terms

• Cholestasis
• Kidney Failure
• Pruritus
• Renal Insufficiency

Intervention

Drug:
• EP547
EP547
• Placebo
Placebo

Locations

Country	Name	City	State
Australia	CMAX Clinical Research	Adelaide	South Australia
Australia	Monash Medical Centre	Clayton	Victoria
Australia	The Alfred Hospital	Melbourne	Victoria
New Zealand	Auckland Clinical Studies (ACS)	Grafton	Auckland

Sponsors (2)

Lead Sponsor	Collaborator
Escient Pharmaceuticals, Inc	Novotech (Australia) Pty Limited

Countries where clinical trial is conducted

Australia,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Adverse Events	To assess safety and tolerability of EP547 following single and multiple oral administration	Measured from Day 1 to End of Study or Early Termination (up to 3 weeks)
Secondary	Maximum Plasma Concentration [Cmax] After Single Dose of EP547	To evaluate the pharmacokinetics of single dose of EP547	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, and 12 hours post-dose on Day 1
Secondary	Maximum Plasma Concentration [Cmax] After Multiple Doses of EP547	To evaluate the pharmacokinetics of multiple doses of EP547	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