Cholestasis, Kidney Failure, Pruritus
Conditions
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.
Interventions
DRUGEP547
EP547
DRUGPlacebo
Placebo
Sponsors
Novotech (Australia) Pty Limited
Escient Pharmaceuticals, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events | Measured from Day 1 to End of Study or Early Termination (up to 3 weeks) | To assess safety and tolerability of EP547 following single and multiple oral administration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration [Cmax] After 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 | To evaluate the pharmacokinetics of single dose of EP547 |
| Maximum Plasma Concentration [Cmax] After 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 | To evaluate the pharmacokinetics of multiple doses of EP547 |
Countries
Australia, New Zealand
Participant flow
Recruitment details
This study was conducted on 85 subjects at 4 sites in Australia and New Zealand. This study consisted of 7 segments: single ascending dose in healthy subjects (SAD-HS), multiple ascending dose in healthy subjects (MAD-HS), food effect in healthy subjects (FE-HS), single dose in subjects with cholestatic pruritus (SD-CP), multiple dose in subjects with cholestatic pruritus (MD-CP), single dose in subjects with uremic pruritus (SD-UP), and multiple dose in subjects with uremic pruritus (MD-UP).
Pre-assignment details
A total of 89 subjects (85 unique subjects) participated in the study. SAD-HS n=40 MAD-HS n=24 FE-HS n=5 SD-CP n=5 SD-UP n=6 MD-CP n=3 MD-UP N=6 (4 subjects participated in both SD-UP and MD-UP)
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants in all segments received placebo matched to EP547. | 19 |
| EP547 20 mg Participants in MD-UP segment received 20 mg of EP547 QD for 7 days. | 4 |
| EP547 25 mg Participants in SAD-HS segment received a single 25 mg dose of EP547. Participants in MAD-HS segment received 25 mg of EP547 QD for 7 days. | 12 |
| EP547 30 mg Participants in MD-CP segment received 30 mg of EP547 QD for 7 days. | 2 |
| EP547 75 mg Participants in SAD-HS segment received a single 75 mg dose of EP547. Participants in MAD-HS segment received 75 mg of EP547 QD for 7 days. Participants in FE-HS segment received a single 75 mg dose of EP547 under fed or fasted condition, separated by a washout period.
Participants in SD-CP and SD-UP segments received a single 75 mg dose of EP547. | 28 |
| EP547 225 mg Participants in SAD-HS segment received a single 225 mg dose of EP547. Participants in MAD-HS segment received 225 mg of EP547 QD for 7 days. | 12 |
| EP547 450 mg Participants in SAD-HS segment received a single 450 mg dose of EP547. | 6 |
| EP547 675 mg Participants in SAD-HS segment received a single 675 mg dose of EP547. | 6 |
| Total | 89 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| FE-HS | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | EP547 75 mg | EP547 225 mg | EP547 25 mg | Placebo | EP547 30 mg | EP547 20 mg | EP547 450 mg | EP547 675 mg |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous FE-HS | 40.4 Years STANDARD_DEVIATION 13.39 | 40.4 Years STANDARD_DEVIATION 13.4 | — | — | — | — | — | — | — |
| Age, Continuous MAD-HS | 35.3 Years STANDARD_DEVIATION 13.94 | 42.0 Years STANDARD_DEVIATION 14.1 | 36.3 Years STANDARD_DEVIATION 16.3 | 30.0 Years STANDARD_DEVIATION 13.5 | 32.8 Years STANDARD_DEVIATION 12.2 | — | — | — | — |
| Age, Continuous MD-CP | 51.7 Years STANDARD_DEVIATION 10.02 | — | — | — | 63.0 Years | 46.0 Years STANDARD_DEVIATION 2.8 | — | — | — |
| Age, Continuous MD-UP | 52.7 Years STANDARD_DEVIATION 17.88 | — | — | — | 74.5 Years STANDARD_DEVIATION 4.9 | — | 41.8 Years STANDARD_DEVIATION 6.9 | — | — |
| Age, Continuous SAD-HS | 31.2 Years STANDARD_DEVIATION 9.36 | 32.5 Years STANDARD_DEVIATION 9.1 | 32.7 Years STANDARD_DEVIATION 11.1 | 30.7 Years STANDARD_DEVIATION 12.3 | 27.3 Years STANDARD_DEVIATION 9.9 | — | — | 30.2 Years STANDARD_DEVIATION 4.2 | 36.2 Years STANDARD_DEVIATION 4.2 |
| Age, Continuous SD-CP | 58.8 Years STANDARD_DEVIATION 15.69 | 58.8 Years STANDARD_DEVIATION 15.7 | — | — | — | — | — | — | — |
| Age, Continuous SD-UP | 39.8 Years STANDARD_DEVIATION 10.26 | 39.8 Years STANDARD_DEVIATION 10.3 | — | — | — | — | — | — | — |
| Ethnicity (NIH/OMB) FE-HS Hispanic or Latino | 0 Participants | 0 Participants | — | — | — | — | — | — | — |
| Ethnicity (NIH/OMB) FE-HS Not Hispanic or Latino | 5 Participants | 5 Participants | — | — | — | — | — | — | — |
| Ethnicity (NIH/OMB) FE-HS Unknown or Not Reported | 0 Participants | 0 Participants | — | — | — | — | — | — | — |
| Ethnicity (NIH/OMB) MAD-HS Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | — | — | — | — |
| Ethnicity (NIH/OMB) MAD-HS Not Hispanic or Latino | 22 Participants | 5 Participants | 5 Participants | 6 Participants | 6 Participants | — | — | — | — |
| Ethnicity (NIH/OMB) MAD-HS Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | — | — | — | — |
| Ethnicity (NIH/OMB) MD-CP Hispanic or Latino | 0 Participants | — | — | — | 0 Participants | 0 Participants | — | — | — |
| Ethnicity (NIH/OMB) MD-CP Not Hispanic or Latino | 2 Participants | — | — | — | 1 Participants | 1 Participants | — | — | — |
| Ethnicity (NIH/OMB) MD-CP Unknown or Not Reported | 1 Participants | — | — | — | 0 Participants | 1 Participants | — | — | — |
| Ethnicity (NIH/OMB) MD-UP Hispanic or Latino | 0 Participants | — | — | — | 0 Participants | — | 0 Participants | — | — |
| Ethnicity (NIH/OMB) MD-UP Not Hispanic or Latino | 6 Participants | — | — | — | 2 Participants | — | 4 Participants | — | — |
| Ethnicity (NIH/OMB) MD-UP Unknown or Not Reported | 0 Participants | — | — | — | 0 Participants | — | 0 Participants | — | — |
| Ethnicity (NIH/OMB) SAD-HS Hispanic or Latino | 9 Participants | 0 Participants | 3 Participants | 0 Participants | 3 Participants | — | — | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) SAD-HS Not Hispanic or Latino | 29 Participants | 6 Participants | 3 Participants | 6 Participants | 7 Participants | — | — | 3 Participants | 4 Participants |
| Ethnicity (NIH/OMB) SAD-HS Unknown or Not Reported | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | — | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) SD-CP Hispanic or Latino | 0 Participants | 0 Participants | — | — | — | — | — | — | — |
| Ethnicity (NIH/OMB) SD-CP Not Hispanic or Latino | 5 Participants | 5 Participants | — | — | — | — | — | — | — |
| Ethnicity (NIH/OMB) SD-CP Unknown or Not Reported | 0 Participants | 0 Participants | — | — | — | — | — | — | — |
| Ethnicity (NIH/OMB) SD-UP Hispanic or Latino | 0 Participants | 0 Participants | — | — | — | — | — | — | — |
| Ethnicity (NIH/OMB) SD-UP Not Hispanic or Latino | 6 Participants | 6 Participants | — | — | — | — | — | — | — |
| Ethnicity (NIH/OMB) SD-UP Unknown or Not Reported | 0 Participants | 0 Participants | — | — | — | — | — | — | — |
| Race/Ethnicity, Customized FE-HS American Indian or Native American | 0 Participants | 0 Participants | — | — | — | — | — | — | — |
| Race/Ethnicity, Customized FE-HS Asian | 0 Participants | 0 Participants | — | — | — | — | — | — | — |
| Race/Ethnicity, Customized FE-HS Black or African American | 0 Participants | 0 Participants | — | — | — | — | — | — | — |
| Race/Ethnicity, Customized FE-HS Native Hawaiian or Pacific Islander | 0 Participants | 0 Participants | — | — | — | — | — | — | — |
| Race/Ethnicity, Customized FE-HS Other | 0 Participants | 0 Participants | — | — | — | — | — | — | — |
| Race/Ethnicity, Customized FE-HS White | 5 Participants | 5 Participants | — | — | — | — | — | — | — |
| Race/Ethnicity, Customized MAD-HS American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | — | — | — |
| Race/Ethnicity, Customized MAD-HS Asian | 5 Participants | 1 Participants | 2 Participants | 0 Participants | 2 Participants | — | — | — | — |
| Race/Ethnicity, Customized MAD-HS Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | — | — | — |
| Race/Ethnicity, Customized MAD-HS Native Hawaiian or Pacific Islander | 4 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | — | — | — | — |
| Race/Ethnicity, Customized MAD-HS Other | 4 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | — | — | — | — |
| Race/Ethnicity, Customized MAD-HS White | 12 Participants | 3 Participants | 2 Participants | 4 Participants | 3 Participants | — | — | — | — |
| Race/Ethnicity, Customized SAD-HS American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | — | — | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized SAD-HS Asian | 6 Participants | 2 Participants | 1 Participants | 0 Participants | 2 Participants | — | — | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized SAD-HS Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | — | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized SAD-HS Native Hawaiian or Pacific Islander | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | — | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized SAD-HS Other | 8 Participants | 1 Participants | 2 Participants | 0 Participants | 2 Participants | — | — | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized SAD-HS White | 25 Participants | 5 Participants | 3 Participants | 6 Participants | 5 Participants | — | — | 2 Participants | 4 Participants |
| Sex: Female, Male FE-HS Female | 3 Participants | 3 Participants | — | — | — | — | — | — | — |
| Sex: Female, Male FE-HS Male | 2 Participants | 2 Participants | — | — | — | — | — | — | — |
| Sex: Female, Male MAD-HS Female | 7 Participants | 2 Participants | 1 Participants | 3 Participants | 1 Participants | — | — | — | — |
| Sex: Female, Male MAD-HS Male | 17 Participants | 4 Participants | 5 Participants | 3 Participants | 5 Participants | — | — | — | — |
| Sex: Female, Male MD-CP Female | 2 Participants | — | — | — | 1 Participants | 1 Participants | — | — | — |
| Sex: Female, Male MD-CP Male | 1 Participants | — | — | — | 0 Participants | 1 Participants | — | — | — |
| Sex: Female, Male MD-UP Female | 2 Participants | — | — | — | 1 Participants | — | 1 Participants | — | — |
| Sex: Female, Male MD-UP Male | 4 Participants | — | — | — | 1 Participants | — | 3 Participants | — | — |
| Sex: Female, Male SAD-HS Female | 25 Participants | 5 Participants | 4 Participants | 4 Participants | 8 Participants | — | — | 3 Participants | 1 Participants |
| Sex: Female, Male SAD-HS Male | 15 Participants | 1 Participants | 2 Participants | 2 Participants | 2 Participants | — | — | 3 Participants | 5 Participants |
| Sex: Female, Male SD-CP Female | 3 Participants | 3 Participants | — | — | — | — | — | — | — |
| Sex: Female, Male SD-CP Male | 2 Participants | 2 Participants | — | — | — | — | — | — | — |
| Sex: Female, Male SD-UP Female | 2 Participants | 2 Participants | — | — | — | — | — | — | — |
| Sex: Female, Male SD-UP Male | 4 Participants | 4 Participants | — | — | — | — | — | — | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 6 | 0 / 1 | 0 / 2 | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 2 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 5 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 5 / 10 | 3 / 6 | 1 / 1 | 1 / 2 | 2 / 4 | 4 / 6 | 6 / 6 | 1 / 2 | 5 / 6 | 4 / 6 | 3 / 5 | 4 / 5 | 1 / 6 | 3 / 6 | 4 / 6 | 3 / 6 | 4 / 6 |
| serious Total, serious adverse events | 0 / 10 | 0 / 6 | 0 / 1 | 0 / 2 | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 2 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 5 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Incidence of Adverse Events
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)
Population: All safety analyses were based on the Safety Population, which included all subjects who received at least one dose of study drug (EP547 or placebo).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Incidence of Adverse Events | MAD-HS : Any drug-related TEAE | 2 participants |
| Placebo | Incidence of Adverse Events | MD-UP : Any TEAE leading to discontinuation of study drug | 0 participants |
| Placebo | Incidence of Adverse Events | MAD-HS : Any TEAE | 3 participants |
| Placebo | Incidence of Adverse Events | SAD-HS : Any TEAE leading to discontinuation of study drug | 0 participants |
| Placebo | Incidence of Adverse Events | MD-UP : Any drug-related TEAE | 0 participants |
| Placebo | Incidence of Adverse Events | MAD-HS : Any Serious TEAE | 0 participants |
| Placebo | Incidence of Adverse Events | SAD-HS : Any TEAE | 5 participants |
| Placebo | Incidence of Adverse Events | MD-CP : Any TEAE | 1 participants |
| Placebo | Incidence of Adverse Events | MAD-HS : Any TEAE leading to discontinuation of study drug | 0 participants |
| Placebo | Incidence of Adverse Events | SAD-HS : Any drug-related TEAE | 0 participants |
| Placebo | Incidence of Adverse Events | MD-UP : Any Serious TEAE | 0 participants |
| Placebo | Incidence of Adverse Events | MD-UP : Any TEAE | 1 participants |
| Placebo | Incidence of Adverse Events | MD-CP : Any TEAE leading to discontinuation of study drug | 0 participants |
| Placebo | Incidence of Adverse Events | MD-CP : Any drug-related TEAE | 0 participants |
| Placebo | Incidence of Adverse Events | MD-CP : Any Serious TEAE | 0 participants |
| Placebo | Incidence of Adverse Events | SAD-HS : Any Serious TEAE | 0 participants |
| EP547 20 mg | Incidence of Adverse Events | MD-UP : Any TEAE leading to discontinuation of study drug | 0 participants |
| EP547 20 mg | Incidence of Adverse Events | MD-UP : Any Serious TEAE | 0 participants |
| EP547 20 mg | Incidence of Adverse Events | MD-UP : Any drug-related TEAE | 0 participants |
| EP547 20 mg | Incidence of Adverse Events | MD-UP : Any TEAE | 2 participants |
| EP547 25 mg | Incidence of Adverse Events | SAD-HS : Any Serious TEAE | 0 participants |
| EP547 25 mg | Incidence of Adverse Events | SAD-HS : Any TEAE | 5 participants |
| EP547 25 mg | Incidence of Adverse Events | MAD-HS : Any Serious TEAE | 0 participants |
| EP547 25 mg | Incidence of Adverse Events | SAD-HS : Any drug-related TEAE | 2 participants |
| EP547 25 mg | Incidence of Adverse Events | SAD-HS : Any TEAE leading to discontinuation of study drug | 0 participants |
| EP547 25 mg | Incidence of Adverse Events | MAD-HS : Any TEAE | 6 participants |
| EP547 25 mg | Incidence of Adverse Events | MAD-HS : Any drug-related TEAE | 5 participants |
| EP547 25 mg | Incidence of Adverse Events | MAD-HS : Any TEAE leading to discontinuation of study drug | 0 participants |
| EP547 30 mg | Incidence of Adverse Events | MD-CP : Any TEAE leading to discontinuation of study drug | 0 participants |
| EP547 30 mg | Incidence of Adverse Events | MD-CP : Any TEAE | 1 participants |
| EP547 30 mg | Incidence of Adverse Events | MD-CP : Any drug-related TEAE | 1 participants |
| EP547 30 mg | Incidence of Adverse Events | MD-CP : Any Serious TEAE | 0 participants |
| EP547 75 mg | Incidence of Adverse Events | MAD-HS : Any Serious TEAE | 0 participants |
| EP547 75 mg | Incidence of Adverse Events | SAD-HS : Any drug-related TEAE | 1 participants |
| EP547 75 mg | Incidence of Adverse Events | MAD-HS : Any TEAE | 4 participants |
| EP547 75 mg | Incidence of Adverse Events | SAD-HS : Any TEAE | 5 participants |
| EP547 75 mg | Incidence of Adverse Events | MAD-HS : Any TEAE leading to discontinuation of study drug | 0 participants |
| EP547 75 mg | Incidence of Adverse Events | FE-HS : Any TEAE | 3 participants |
| EP547 75 mg | Incidence of Adverse Events | FE-HS : Any Serious TEAE | 0 participants |
| EP547 75 mg | Incidence of Adverse Events | SD-CP : Any Serious TEAE | 0 participants |
| EP547 75 mg | Incidence of Adverse Events | SD-CP : Any drug-related TEAE | 0 participants |
| EP547 75 mg | Incidence of Adverse Events | SD-CP : Any TEAE leading to discontinuation of study drug | 0 participants |
| EP547 75 mg | Incidence of Adverse Events | SD-UP : Any TEAE | 1 participants |
| EP547 75 mg | Incidence of Adverse Events | SD-UP : Any Serious TEAE | 0 participants |
| EP547 75 mg | Incidence of Adverse Events | SD-UP : Any drug-related TEAE | 0 participants |
| EP547 75 mg | Incidence of Adverse Events | SD-UP : Any TEAE leading to discontinuation of study drug | 0 participants |
| EP547 75 mg | Incidence of Adverse Events | SAD-HS : Any Serious TEAE | 0 participants |
| EP547 75 mg | Incidence of Adverse Events | SD-CP : Any TEAE | 4 participants |
| EP547 75 mg | Incidence of Adverse Events | FE-HS : Any TEAE leading to discontinuation of study drug | 0 participants |
| EP547 75 mg | Incidence of Adverse Events | FE-HS : Any drug-related TEAE | 1 participants |
| EP547 75 mg | Incidence of Adverse Events | SAD-HS : Any TEAE leading to discontinuation of study drug | 0 participants |
| EP547 75 mg | Incidence of Adverse Events | MAD-HS : Any drug-related TEAE | 3 participants |
| EP547 225 mg | Incidence of Adverse Events | SAD-HS : Any TEAE leading to discontinuation of study drug | 0 participants |
| EP547 225 mg | Incidence of Adverse Events | SAD-HS : Any TEAE | 3 participants |
| EP547 225 mg | Incidence of Adverse Events | MAD-HS : Any drug-related TEAE | 2 participants |
| EP547 225 mg | Incidence of Adverse Events | SAD-HS : Any drug-related TEAE | 0 participants |
| EP547 225 mg | Incidence of Adverse Events | MAD-HS : Any Serious TEAE | 0 participants |
| EP547 225 mg | Incidence of Adverse Events | MAD-HS : Any TEAE leading to discontinuation of study drug | 0 participants |
| EP547 225 mg | Incidence of Adverse Events | SAD-HS : Any Serious TEAE | 0 participants |
| EP547 225 mg | Incidence of Adverse Events | MAD-HS : Any TEAE | 4 participants |
| EP547 450 mg | Incidence of Adverse Events | SAD-HS : Any TEAE leading to discontinuation of study drug | 0 participants |
| EP547 450 mg | Incidence of Adverse Events | SAD-HS : Any TEAE | 3 participants |
| EP547 450 mg | Incidence of Adverse Events | SAD-HS : Any Serious TEAE | 0 participants |
| EP547 450 mg | Incidence of Adverse Events | SAD-HS : Any drug-related TEAE | 1 participants |
| EP547 675 mg | Incidence of Adverse Events | SAD-HS : Any TEAE | 4 participants |
| EP547 675 mg | Incidence of Adverse Events | SAD-HS : Any Serious TEAE | 0 participants |
| EP547 675 mg | Incidence of Adverse Events | SAD-HS : Any TEAE leading to discontinuation of study drug | 0 participants |
| EP547 675 mg | Incidence of Adverse Events | SAD-HS : Any drug-related TEAE | 2 participants |
Secondary
Maximum Plasma Concentration [Cmax] After Multiple Doses of EP547
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
Population: All PK analyses were based on the PK Population. For non-FE segments, the PK Population included all subjects who received ≥1 dose of EP547 and for whom a sufficient number of samples were available to determine at least 1 PK parameter.~For FE segment, the PK Population included all randomized subjects who received ≥1 dose of EP547, had no protocol deviations affecting the PK variables of EP547, and for whom a sufficient number of samples were available to determine at least 1 PK parameter.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| EP547 20 mg | Maximum Plasma Concentration [Cmax] After Multiple Doses of EP547 | MD-UP | 3192.7 ng/mL | Geometric Coefficient of Variation 49.5 |
| EP547 25 mg | Maximum Plasma Concentration [Cmax] After Multiple Doses of EP547 | MAD-HS | 2834.7 ng/mL | Geometric Coefficient of Variation 16.4 |
| EP547 30 mg | Maximum Plasma Concentration [Cmax] After Multiple Doses of EP547 | MD-CP | 3421.0 ng/mL | Geometric Coefficient of Variation 27.8 |
| EP547 75 mg | Maximum Plasma Concentration [Cmax] After Multiple Doses of EP547 | MAD-HS | 8760.7 ng/mL | Geometric Coefficient of Variation 27.4 |
| EP547 225 mg | Maximum Plasma Concentration [Cmax] After Multiple Doses of EP547 | MAD-HS | 29613.1 ng/mL | Geometric Coefficient of Variation 21 |
| Unknown | Maximum Plasma Concentration [Cmax] After Multiple Doses of EP547 | FE-HS | — ng/mL | — |
| Unknown | Maximum Plasma Concentration [Cmax] After Multiple Doses of EP547 | SAD-HS | — ng/mL | — |
| Unknown | Maximum Plasma Concentration [Cmax] After Multiple Doses of EP547 | SD-CP | — ng/mL | — |
| Unknown | Maximum Plasma Concentration [Cmax] After Multiple Doses of EP547 | SD-UP | — ng/mL | — |
Secondary
Maximum Plasma Concentration [Cmax] After Single Dose of EP547
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
Population: All PK analyses were based on the PK Population. For non-FE segments, the PK Population included all subjects who received ≥1 dose of EP547 and for whom a sufficient number of samples were available to determine at least 1 PK parameter.~For FE segment, the PK Population included all randomized subjects who received ≥1 dose of EP547, had no protocol deviations affecting the PK variables of EP547, and for whom a sufficient number of samples were available to determine at least 1 PK parameter.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| EP547 20 mg | Maximum Plasma Concentration [Cmax] After Single Dose of EP547 | MD-UP | 781.0 ng/mL | Geometric Coefficient of Variation 54.6 |
| EP547 25 mg | Maximum Plasma Concentration [Cmax] After Single Dose of EP547 | MAD-HS | 1506.6 ng/mL | Geometric Coefficient of Variation 38.4 |
| EP547 25 mg | Maximum Plasma Concentration [Cmax] After Single Dose of EP547 | SAD-HS | 1421.0 ng/mL | Geometric Coefficient of Variation 29.4 |
| EP547 30 mg | Maximum Plasma Concentration [Cmax] After Single Dose of EP547 | MD-CP | 1728.5 ng/mL | Geometric Coefficient of Variation 93.7 |
| EP547 75 mg | Maximum Plasma Concentration [Cmax] After Single Dose of EP547 | SD-UP | 3483.3 ng/mL | Geometric Coefficient of Variation 75 |
| EP547 75 mg | Maximum Plasma Concentration [Cmax] After Single Dose of EP547 | SAD-HS | 6309.6 ng/mL | Geometric Coefficient of Variation 19.3 |
| EP547 75 mg | Maximum Plasma Concentration [Cmax] After Single Dose of EP547 | MAD-HS | 3973.4 ng/mL | Geometric Coefficient of Variation 35.5 |
| EP547 75 mg | Maximum Plasma Concentration [Cmax] After Single Dose of EP547 | FE-HS (Fasted) | 5780.3 ng/mL | Geometric Coefficient of Variation 22.9 |
| EP547 75 mg | Maximum Plasma Concentration [Cmax] After Single Dose of EP547 | FE-HS (Fed) | 3504.0 ng/mL | Geometric Coefficient of Variation 30 |
| EP547 75 mg | Maximum Plasma Concentration [Cmax] After Single Dose of EP547 | SD-CP | 5019.5 ng/mL | Geometric Coefficient of Variation 31.7 |
| EP547 225 mg | Maximum Plasma Concentration [Cmax] After Single Dose of EP547 | SAD-HS | 17232.6 ng/mL | Geometric Coefficient of Variation 17.6 |
| EP547 225 mg | Maximum Plasma Concentration [Cmax] After Single Dose of EP547 | MAD-HS | 16954.8 ng/mL | Geometric Coefficient of Variation 35 |
| EP547 450 mg | Maximum Plasma Concentration [Cmax] After Single Dose of EP547 | SAD-HS | 27799.2 ng/mL | Geometric Coefficient of Variation 29.8 |
| EP547 675 mg | Maximum Plasma Concentration [Cmax] After Single Dose of EP547 | SAD-HS | 36352.2 ng/mL | Geometric Coefficient of Variation 38.3 |