Evaluate the Safety, Tolerability, and PK of EP547 in Healthy Subjects and Subjects With Cholestatic or Uremic Pruritus
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: EP547 Single Dose Single doses of EP547 |
Drug: EP547
EP547
|
| Experimental: EP547 Multiple Doses Multiple doses of EP547 |
Drug: EP547
EP547
|
| Placebo Comparator: Placebo Single Dose Single doses of placebo |
Drug: Placebo
Placebo
|
| Placebo Comparator: Placebo Multiple Doses Multiple doses of placebo |
Drug: Placebo
Placebo
|
Outcome Measures
Primary Outcome Measures
- Incidence of Adverse Events [Safety and Tolerability] [Measured from Day 1 to End of Study or Early Termination (up to 3 weeks)]
Safety and tolerability of single and multiple ascending doses of EP547 in healthy subjects and subjects with cholestatic or uremic pruritus measured through adverse events.
Secondary Outcome Measures
- Maximum Plasma Concentration [Cmax] [Measured from Day 1 to End of Study (up to 3 weeks)]
To evaluate the pharmacokinetics of single and multiple ascending doses of EP547 in healthy subjects and subjects with cholestatic or uremic pruritus.
Eligibility Criteria
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)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | CMAX Clinical Research | Adelaide | South Australia | Australia | 5000 |
| 2 | Monash Medical Centre | Clayton | Victoria | Australia | 3168 |
| 3 | The Alfred Hospital | Melbourne | Victoria | Australia | 3004 |
| 4 | Auckland Clinical Studies (ACS) | Grafton | Auckland | New Zealand | 1010 |
Sponsors and Collaborators
- Escient Pharmaceuticals, Inc
- Novotech (Australia) Pty Limited
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- EP-547-101