Evaluate the Safety, Tolerability, and PK of EP547 in Healthy Subjects and Subjects With Cholestatic or Uremic Pruritus
Primary Purpose
Pruritus, Cholestasis, Kidney Failure
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
EP547
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for 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)
Sites / Locations
- CMAX Clinical Research
- Monash Medical Centre
- The Alfred Hospital
- Auckland Clinical Studies (ACS)
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Placebo Comparator
Placebo Comparator
Arm Label
EP547 Single Dose
EP547 Multiple Doses
Placebo Single Dose
Placebo Multiple Doses
Arm Description
Single doses of EP547
Multiple doses of EP547
Single doses of placebo
Multiple doses of placebo
Outcomes
Primary Outcome Measures
Incidence of Adverse Events
To assess safety and tolerability of EP547 following single and multiple oral administration
Secondary Outcome Measures
Maximum Plasma Concentration [Cmax] After Single Dose of EP547
To evaluate the pharmacokinetics of single dose of EP547
Maximum Plasma Concentration [Cmax] After Multiple Doses of EP547
To evaluate the pharmacokinetics of multiple doses of EP547
Full Information
NCT ID
NCT04510090
First Posted
August 7, 2020
Last Updated
July 8, 2022
Sponsor
Escient Pharmaceuticals, Inc
Collaborators
Novotech (Australia) Pty Limited
1. Study Identification
Unique Protocol Identification Number
NCT04510090
Brief Title
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
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Completed
Study Start Date
September 7, 2020 (Actual)
Primary Completion Date
July 8, 2021 (Actual)
Study Completion Date
July 8, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Escient Pharmaceuticals, Inc
Collaborators
Novotech (Australia) Pty Limited
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pruritus, Cholestasis, Kidney Failure
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
89 (Actual)
8. Arms, Groups, and Interventions
Arm Title
EP547 Single Dose
Arm Type
Experimental
Arm Description
Single doses of EP547
Arm Title
EP547 Multiple Doses
Arm Type
Experimental
Arm Description
Multiple doses of EP547
Arm Title
Placebo Single Dose
Arm Type
Placebo Comparator
Arm Description
Single doses of placebo
Arm Title
Placebo Multiple Doses
Arm Type
Placebo Comparator
Arm Description
Multiple doses of placebo
Intervention Type
Drug
Intervention Name(s)
EP547
Intervention Description
EP547
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Incidence of Adverse Events
Description
To assess safety and tolerability of EP547 following single and multiple oral administration
Time Frame
Measured from Day 1 to End of Study or Early Termination (up to 3 weeks)
Secondary Outcome Measure Information:
Title
Maximum Plasma Concentration [Cmax] After Single Dose of EP547
Description
To evaluate the pharmacokinetics of single dose of EP547
Time Frame
Pre-dose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, and 12 hours post-dose on Day 1
Title
Maximum Plasma Concentration [Cmax] After Multiple Doses of EP547
Description
To evaluate the pharmacokinetics of multiple doses of EP547
Time Frame
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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)
Facility Information:
Facility Name
CMAX Clinical Research
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Facility Name
Monash Medical Centre
City
Clayton
State/Province
Victoria
ZIP/Postal Code
3168
Country
Australia
Facility Name
The Alfred Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Facility Name
Auckland Clinical Studies (ACS)
City
Grafton
State/Province
Auckland
ZIP/Postal Code
1010
Country
New Zealand
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Evaluate the Safety, Tolerability, and PK of EP547 in Healthy Subjects and Subjects With Cholestatic or Uremic Pruritus
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