Study to Evaluate EP547 in Subjects With Cholestatic Pruritus Due to Primary Biliary Cholangitis or Primary Sclerosing Cholangitis

Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Effects of EP547 in Subjects With Cholestatic Pruritus Due to Primary Biliary Cholangitis or Primary Sclerosing Cholangitis

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05525520

Acronym

PACIFIC

Enrollment

Registered

2022-09-01

Start date

2022-10-06

Completion date

2024-09-05

Last updated

2025-07-31

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pruritus

Keywords

Pruritus, Itch, Primary Biliary Cholangitis, Primary Sclerosing Cholangitis, PACIFIC, EP547

Brief summary

This phase 2 trial will evaluate the effects of EP547 in subjects with cholestatic pruritus due to Primary Biliary Cholangitis (PBC) or Primary Sclerosing Cholangitis (PSC)

Interventions

DRUGEP547

Once daily

DRUGPlacebo

Once daily

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

Inclusion criteria

* Age 18 to 80 years * Documented primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC) * Presence of consistent moderate to severe pruritus * Use of anti-pruritic and anti-cholestatic (including UDCA and obeticholic acid) medication allowed if meeting additional criteria * Individuals with concomitant inflammatory bowel disease must meet additional relevant criteria

Exclusion criteria

* Pruritus associated with an etiology other than PBC or PSC * Prior or planned liver transplantation * Evidence of compensated or decompensated cirrhosis * Alternative causes of liver disease * Presence of documented secondary sclerosing cholangitis * Current evidence of clinically significant high-grade strictures or presence of biliary stent * History of significant small bowel resection or short bowel syndrome * Has exclusionary laboratory or biochemical results at Screening

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in the Worst Itch Numeric Rating Scale (WI-NRS) Score up to Week 6	Baseline; up to Week 6	Participants were asked to rate the severity of their worst level of itching in the past 24 hours using the daily WI-NRS, an 11-point scale ranging from 0 (no itching) to 10 (worst itching imaginable). Itching severity scores collected via the WI-NRS have been categorized in the as mild (\<4), moderate (≥4 to \<7), or severe (≥7). The average WI-NRS score using the daily values from the week before the first dose of study drug (including the WI-NRS score captured on Study Day 1 of dosing) served as the Baseline score. A weekly score was determined based on the average of all available daily scores of the week. Change from Baseline was calculated as the post-Baseline score minus the Baseline score.

Secondary

Measure	Time frame	Description
Change From Baseline in the 5-D Itch Scale Total Score at Week 6	Baseline; Week 6	The 5-D Itch Scale is a multidimensional (degree, duration, direction, disability, and distribution) questionnaire measuring changes in pruritis. The duration, degree, and direction domain scores range from 1 (no pruritus) to 5 (most severe pruritus). The disability domain includes 4 items assessing itching impact on daily activities: sleep, leisure/social activities, housework/errands, and work/school. Disability domain score=highest score on any of the 4 categories (1 \[no pruritis\] to 5 \[most severe pruritis\]). For the distribution domain, 16 body parts are listed to determine the distribution of itching over the last 2 weeks; the number of affected body parts is tallied (potential sum=0-16); the sum is sorted into 5 thresholds: 0-2 is assigned a score of 1; 3-5, a score of 2; 6-10, a score of 3; 11-13, a score of 4; 14-16, a score of 5. Higher scores indicate more severe pruritis. The 5 domain scores are summed to get a total 5-D score: 5 (no pruritus) to 25 (most severe pruritus).
Percentage of Participants With Improvement in Pruritus as Defined by Patient Global Impression of Change (PGI-C) at Week 6	Baseline; Week 6	Participants were asked to rate their impression of overall change in pruritus in the past 7 days compared to before they started taking study drug using the PGI-C, a 7-point scale ranging from much improved to much worse, with higher scores indicating less improvement in pruritus. Participants that reported a change in their itch of minimally improved or better were considered to be responders in terms of improvement in pruritus.
Percentage of Participants With Improvement in Pruritus Severity From Baseline as Defined by Change in Patient Global Impress of Severity (PGI-S) at Week 6	Baseline; Week 6	Participants were asked to rate the severity of their pruritus in the past 7 days using the PGI-S, a 4-point scale ranging from none to severe. Participants that reported a positive shift in their categorical assessment of itch compared to their Baseline level (e.g., severe at Visit 2 \[Day 1\] with a shift to moderate at Visit 6 \[Week 6\]) were considered to be responders in terms of improvement in pruritus.
Percentage of Participants With a Reduction in WI-NRS Score ≥3 From Baseline at Week 6	Baseline; Week 6	Participants were asked to rate the severity of their worst level of itching in the past 24 hours using the daily WI-NRS, an 11-point scale ranging from 0 (no itching) to 10 (worst itching imaginable). Itching severity scores collected via the WI-NRS have been categorized in the as mild (\<4), moderate (≥4 to \<7), or severe (≥7). The average WI-NRS score using the daily values from the week before the first dose of study drug (including the WI-NRS score captured on Study Day 1 of dosing) served as the Baseline score. A weekly score was determined based on the average of all available daily scores of the week.
Percentage of Participants With a Reduction in WI-NRS Score ≥4 From Baseline at Week 6	Baseline; Week 6	Participants were asked to rate the severity of their worst level of itching in the past 24 hours using the daily WI-NRS, an 11-point scale ranging from 0 (no itching) to 10 (worst itching imaginable). Itching severity scores collected via the WI-NRS have been categorized in the as mild (\<4), moderate (≥4 to \<7), or severe (≥7). The average WI-NRS score using the daily values from the week before the first dose of study drug (including the WI-NRS score captured on Study Day 1 of dosing) served as the Baseline score. A weekly score was determined based on the average of all available daily scores of the week.
Percentage of Participants With a WI-NRS Score <4 at Week 6	Baseline; Week 6	Participants were asked to rate the severity of their worst level of itching in the past 24 hours using the daily WI-NRS, an 11-point scale ranging from 0 (no itching) to 10 (worst itching imaginable). Itching severity scores collected via the WI-NRS have been categorized in the as mild (\<4), moderate (≥4 to \<7), or severe (≥7). The average WI-NRS score using the daily values from the week before the first dose of study drug (including the WI-NRS score captured on Study Day 1 of dosing) served as the Baseline score. A weekly score was determined based on the average of all available daily scores of the week.
Double-blind Treatment Period: Number of Participants With Any Treatment-emergent Adverse Event (TEAE), Any ≥Grade 3 TEAE, Any Related TEAE, and Any TEAE That Led to Discontinuation of Study Drug	up to the end of Week 6	An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable or unintended sign (including a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product. TEAEs are AEs with an onset after the first dose of study drug or existing events that worsened after the first dose during the study. TEAEs were graded for severity (mild \[Grade 1\], moderate \[Grade 2\], severe \[Grade 3\], life threatening \[Grade 4\], death \[Grade 5\]) using Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. The investigator assessed whether the TEAEs were related or unrelated to the study drug.
Open-label Extension Period: Number of Participants With Any TEAE, Any ≥Grade 3 TEAE, Any Related TEAE, and Any TEAE That Led to Discontinuation of Study Drug	from the beginning of Week 7 up to Week 12	An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable or unintended sign (including a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product. TEAEs are AEs with an onset after the first dose of study drug or existing events that worsened after the first dose during the study. TEAEs were graded for severity (mild \[Grade 1\], moderate \[Grade 2\], severe \[Grade 3\], life threatening \[Grade 4\], death \[Grade 5\]) using CTCAE, version 5.0. The investigator assessed whether the TEAEs were related or unrelated to the study drug.
Percentage of Participants With a Reduction in WI-NRS Score ≥2 From Baseline at Week 6	Baseline; Week 6	Participants were asked to rate the severity of their worst level of itching in the past 24 hours using the daily WI-NRS, an 11-point scale ranging from 0 (no itching) to 10 (worst itching imaginable). Itching severity scores collected via the WI-NRS have been categorized in the as mild (\<4), moderate (≥4 to \<7), or severe (≥7). The average WI-NRS score using the daily values from the week before the first dose of study drug (including the WI-NRS score captured on Study Day 1 of dosing) served as the Baseline score. A weekly score was determined based on the average of all available daily scores of the week.
Open-label Extension Period: Number of Participants With Any Serious TEAE, Any ≥Grade 3 Serious TEAE, Any Related Serious TEAE, and Any Serious TEAE That Led to Discontinuation of Study Drug	from the beginning of Week 7 up to Week 12	TEAEs are AEs with an onset after the first dose of study drug or existing events that worsened after the first dose during the study. A serious TEAE is any untoward medical occurrence, that at any dose: results in death; is life threatening; requires hospital admission or prolongs hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly/birth defect; or is a medically significant event that, based on appropriate medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent one of the previously listed outcomes. Serious TEAEs were graded for severity (mild \[Grade 1\], moderate \[Grade 2\], severe \[Grade 3\], life threatening \[Grade 4\], death \[Grade 5\]) using CTCAE, version 5.0. The investigator assessed whether the serious TEAEs were related or unrelated to the study drug.
Double-blind Treatment Period: Number of Participants With Any Treatment-emergent (TE) Adverse Event of Special Interest (AESI), Any ≥Grade 3 TE AESI, Any Related TE AESI, and Any TE AESI That Led to Discontinuation of Study Drug	up to the end of Week 6	An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. TEAEs are AEs with an onset after the first dose of study drug or existing events that worsened after the first dose during the study. AESI were considered to be any clinically meaningful new, worsening from Baseline, or abnormal laboratory findings or symptoms suggestive of acute kidney injury (AKI) (e.g., blood urea increased or protein urine present AEs as identified by the Standardized Medical Dictionary for Regulatory Activities \[MedDRA\] Query \[SMQ\] Acute renal failure). TE AESIs were graded for severity (mild \[Grade 1\], moderate \[Grade 2\], severe \[Grade 3\], life threatening \[Grade 4\], death \[Grade 5\]) using CTCAE, version 5.0. The investigator assessed whether the AE AESIs were related or unrelated to the study drug.
Open-label Extension Period: Number of Participants With Any Treatment-emergent (TE) AESI, Any ≥Grade 3 TE AESI, Any Related TE AESI, and Any TE AESI That Led to Discontinuation of Study Drug	from the beginning of Week 7 up to Week 12	An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. TEAEs are AEs with an onset after the first dose of study drug or existing events that worsened after the first dose during the study. AESI were considered to be any clinically meaningful new, worsening from Baseline, or abnormal laboratory findings or symptoms suggestive of acute kidney injury (AKI) (e.g., blood urea increased or protein urine present AEs as identified by the Standardized Medical Dictionary for Regulatory Activities \[MedDRA\] Query \[SMQ\] Acute renal failure). TE AESIs were graded for severity (mild \[Grade 1\], moderate \[Grade 2\], severe \[Grade 3\], life threatening \[Grade 4\], death \[Grade 5\]) using CTCAE, version 5.0. The investigator assessed whether the AE AESIs were related or unrelated to the study drug.
Number of Participants With Any Clinically Meaningful Changes From Baseline in Clinically Meaningful in Clinical Laboratory Test Results	up to the end of Week 12	Clinical laboratory test results included results for clinical hematology, chemistry, coagulation, and thyroid function parameters . The investigator determined if changes were clinically meaningful.
Number of Participants With Any Clinically Meaningful Changes From Baseline in Vital Sign Measurements	up to the end of Week 12	Vital sign measurements included measurements for blood pressure, pulse rate, oxygen saturation, body temperature, and respiratory rate. The investigator determined if changes were clinically meaningful.
Number of Participants With Any Clinically Significant Changes From Baseline in Electrocardiogram (ECG) Parameters	up to the end of Week 12	ECG parameters included heart rate, RR interval, PR interval, QRS duration, or QT interval. The investigator determined if changes were clinically significant.
Plasma Concentration of EP547 and Metabolites	1, 2, and 3 hours postdose on Day 1 and Week 3; predose on Weeks 1, 2, and 6	The lower level of quantitation = 0.01 micrograms per milliliter (µg/mL) for EP547 and 0.005 μg/mL for EP3583.
Double-blind Treatment Period: Number of Participants With Any Serious TEAE, Any ≥Grade 3 Serious TEAE, Any Related Serious TEAE, and Any Serious TEAE That Led to Discontinuation of Study Drug	up to the end of Week 6	TEAEs are AEs with an onset after the first dose of study drug or existing events that worsened after the first dose during the study. A serious TEAE is any untoward medical occurrence, that at any dose: results in death; is life threatening; requires hospital admission or prolongs hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly/birth defect; or is a medically significant event that, based on appropriate medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent one of the previously listed outcomes. Serious TEAEs were graded for severity (mild \[Grade 1\], moderate \[Grade 2\], severe \[Grade 3\], life threatening \[Grade 4\], death \[Grade 5\]) using CTCAE, version 5.0. The investigator assessed whether the serious TEAEs were related or unrelated to the study drug.

Countries

Belgium, Canada, France, Israel, Netherlands, Spain, United Kingdom, United States

Participant flow

Pre-assignment details

Participants were enrolled at 29 study sites across the United States, United Kingdom, France, Spain, Canada, Israel, Belgium, and the Netherlands.

Participants by arm

Arm	Count
Placebo 100 mg QD; EP547 100 mg QD Participants were randomized to receive oral placebo 100 mg QD for 6 weeks in the Double-Blind (DB) Treatment Period. Participants who completed the Double-Blind Treatment Period and were still receiving study drug switched to oral EP547 100 mg QD for 6 weeks in the Open-Label Extension Period.	30
EP547 100 mg QD; EP547 100 mg QD Participants were randomized to receive oral EP547 100 milligrams (mg) once daily (QD) for 6 weeks in the Double-Blind Treatment Period. Participants who completed the Double-Blind Treatment Period and were still receiving study drug received oral EP547 100 mg QD for an additional 6 weeks in the Open-Label Extension Period.	31
Total	61

Withdrawals & dropouts

Period	Reason	FG000	FG001
DB Treatment Period (Weeks 1-6)	Protocol Violation	1	1
DB Treatment Period (Weeks 1-6)	Withdrawal by Subject	0	2

Baseline characteristics

Characteristic	EP547 100 mg QD; EP547 100 mg QD	Total	Placebo 100 mg QD; EP547 100 mg QD
Age, Continuous	51.6 years STANDARD_DEVIATION 12.88	51.1 years STANDARD_DEVIATION 12.83	50.6 years STANDARD_DEVIATION 12.99
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants	10 Participants	4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	24 Participants	49 Participants	25 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants	2 Participants	1 Participants
Race/Ethnicity, Customized American Indian or Alaska Native/White	1 Participants	1 Participants	0 Participants
Race/Ethnicity, Customized Asian	1 Participants	1 Participants	0 Participants
Race/Ethnicity, Customized Asian/White	0 Participants	1 Participants	1 Participants
Race/Ethnicity, Customized Black or African American	3 Participants	6 Participants	3 Participants
Race/Ethnicity, Customized North African (Morocco)	1 Participants	1 Participants	0 Participants
Race/Ethnicity, Customized White	25 Participants	51 Participants	26 Participants
Sex: Female, Male Female	24 Participants	48 Participants	24 Participants
Sex: Female, Male Male	7 Participants	13 Participants	6 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 30	0 / 60
other Total, other adverse events	7 / 30	24 / 60
serious Total, serious adverse events	0 / 30	1 / 60

Outcome results

Primary

Change From Baseline in the Worst Itch Numeric Rating Scale (WI-NRS) Score up to Week 6

Participants were asked to rate the severity of their worst level of itching in the past 24 hours using the daily WI-NRS, an 11-point scale ranging from 0 (no itching) to 10 (worst itching imaginable). Itching severity scores collected via the WI-NRS have been categorized in the as mild (\<4), moderate (≥4 to \<7), or severe (≥7). The average WI-NRS score using the daily values from the week before the first dose of study drug (including the WI-NRS score captured on Study Day 1 of dosing) served as the Baseline score. A weekly score was determined based on the average of all available daily scores of the week. Change from Baseline was calculated as the post-Baseline score minus the Baseline score.

Time frame: Baseline; up to Week 6

Population: Full Analysis Set: all participants who were randomized and took at least 1 dose of randomized study drug. Participants were analyzed according to randomized treatment assignment. Only participants with available data were analyzed. MMRM=mixed effects model for repeated measures.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo 100 mg QD; EP547 100 mg QD	Change From Baseline in the Worst Itch Numeric Rating Scale (WI-NRS) Score up to Week 6	-2.20 scores on a scale	Standard Error 0.445
EP547 100 mg QD; EP547 100 mg QD	Change From Baseline in the Worst Itch Numeric Rating Scale (WI-NRS) Score up to Week 6	-1.75 scores on a scale	Standard Error 0.43

p-value: 0.457795% CI: [-0.77, 1.68]MMRM

Secondary

Change From Baseline in the 5-D Itch Scale Total Score at Week 6

The 5-D Itch Scale is a multidimensional (degree, duration, direction, disability, and distribution) questionnaire measuring changes in pruritis. The duration, degree, and direction domain scores range from 1 (no pruritus) to 5 (most severe pruritus). The disability domain includes 4 items assessing itching impact on daily activities: sleep, leisure/social activities, housework/errands, and work/school. Disability domain score=highest score on any of the 4 categories (1 \[no pruritis\] to 5 \[most severe pruritis\]). For the distribution domain, 16 body parts are listed to determine the distribution of itching over the last 2 weeks; the number of affected body parts is tallied (potential sum=0-16); the sum is sorted into 5 thresholds: 0-2 is assigned a score of 1; 3-5, a score of 2; 6-10, a score of 3; 11-13, a score of 4; 14-16, a score of 5. Higher scores indicate more severe pruritis. The 5 domain scores are summed to get a total 5-D score: 5 (no pruritus) to 25 (most severe pruritus).

Time frame: Baseline; Week 6

Population: Full Analysis Set. Only participants with available data were analyzed. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo 100 mg QD; EP547 100 mg QD	Change From Baseline in the 5-D Itch Scale Total Score at Week 6	-3.7 scores on a scale	Standard Error 0.78
EP547 100 mg QD; EP547 100 mg QD	Change From Baseline in the 5-D Itch Scale Total Score at Week 6	-3.8 scores on a scale	Standard Error 0.82

Secondary

Double-blind Treatment Period: Number of Participants With Any Serious TEAE, Any ≥Grade 3 Serious TEAE, Any Related Serious TEAE, and Any Serious TEAE That Led to Discontinuation of Study Drug

TEAEs are AEs with an onset after the first dose of study drug or existing events that worsened after the first dose during the study. A serious TEAE is any untoward medical occurrence, that at any dose: results in death; is life threatening; requires hospital admission or prolongs hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly/birth defect; or is a medically significant event that, based on appropriate medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent one of the previously listed outcomes. Serious TEAEs were graded for severity (mild \[Grade 1\], moderate \[Grade 2\], severe \[Grade 3\], life threatening \[Grade 4\], death \[Grade 5\]) using CTCAE, version 5.0. The investigator assessed whether the serious TEAEs were related or unrelated to the study drug.

Time frame: up to the end of Week 6

Population: Safety Analysis Set

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Placebo 100 mg QD; EP547 100 mg QD	Double-blind Treatment Period: Number of Participants With Any Serious TEAE, Any ≥Grade 3 Serious TEAE, Any Related Serious TEAE, and Any Serious TEAE That Led to Discontinuation of Study Drug	Any serious TEAE	0 Participants
Placebo 100 mg QD; EP547 100 mg QD	Double-blind Treatment Period: Number of Participants With Any Serious TEAE, Any ≥Grade 3 Serious TEAE, Any Related Serious TEAE, and Any Serious TEAE That Led to Discontinuation of Study Drug	Any ≥Grade 3 serious TEAE	0 Participants
Placebo 100 mg QD; EP547 100 mg QD	Double-blind Treatment Period: Number of Participants With Any Serious TEAE, Any ≥Grade 3 Serious TEAE, Any Related Serious TEAE, and Any Serious TEAE That Led to Discontinuation of Study Drug	Any related serious TEAE	0 Participants
Placebo 100 mg QD; EP547 100 mg QD	Double-blind Treatment Period: Number of Participants With Any Serious TEAE, Any ≥Grade 3 Serious TEAE, Any Related Serious TEAE, and Any Serious TEAE That Led to Discontinuation of Study Drug	Any serious TEAE that led to discontinuation of study drug	0 Participants
EP547 100 mg QD; EP547 100 mg QD	Double-blind Treatment Period: Number of Participants With Any Serious TEAE, Any ≥Grade 3 Serious TEAE, Any Related Serious TEAE, and Any Serious TEAE That Led to Discontinuation of Study Drug	Any serious TEAE that led to discontinuation of study drug	0 Participants
EP547 100 mg QD; EP547 100 mg QD	Double-blind Treatment Period: Number of Participants With Any Serious TEAE, Any ≥Grade 3 Serious TEAE, Any Related Serious TEAE, and Any Serious TEAE That Led to Discontinuation of Study Drug	Any serious TEAE	0 Participants
EP547 100 mg QD; EP547 100 mg QD	Double-blind Treatment Period: Number of Participants With Any Serious TEAE, Any ≥Grade 3 Serious TEAE, Any Related Serious TEAE, and Any Serious TEAE That Led to Discontinuation of Study Drug	Any related serious TEAE	0 Participants
EP547 100 mg QD; EP547 100 mg QD	Double-blind Treatment Period: Number of Participants With Any Serious TEAE, Any ≥Grade 3 Serious TEAE, Any Related Serious TEAE, and Any Serious TEAE That Led to Discontinuation of Study Drug	Any ≥Grade 3 serious TEAE	0 Participants

Secondary

Double-blind Treatment Period: Number of Participants With Any Treatment-emergent Adverse Event (TEAE), Any ≥Grade 3 TEAE, Any Related TEAE, and Any TEAE That Led to Discontinuation of Study Drug

An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable or unintended sign (including a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product. TEAEs are AEs with an onset after the first dose of study drug or existing events that worsened after the first dose during the study. TEAEs were graded for severity (mild \[Grade 1\], moderate \[Grade 2\], severe \[Grade 3\], life threatening \[Grade 4\], death \[Grade 5\]) using Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. The investigator assessed whether the TEAEs were related or unrelated to the study drug.

Time frame: up to the end of Week 6

Population: Safety Analysis Set: All participants who were randomized and took at least 1 dose of randomized study drug. Analysis was based on the treatment actually received.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Placebo 100 mg QD; EP547 100 mg QD	Double-blind Treatment Period: Number of Participants With Any Treatment-emergent Adverse Event (TEAE), Any ≥Grade 3 TEAE, Any Related TEAE, and Any TEAE That Led to Discontinuation of Study Drug	Any TEAE	15 Participants
Placebo 100 mg QD; EP547 100 mg QD	Double-blind Treatment Period: Number of Participants With Any Treatment-emergent Adverse Event (TEAE), Any ≥Grade 3 TEAE, Any Related TEAE, and Any TEAE That Led to Discontinuation of Study Drug	Any ≥Grade 3 TEAE	0 Participants
Placebo 100 mg QD; EP547 100 mg QD	Double-blind Treatment Period: Number of Participants With Any Treatment-emergent Adverse Event (TEAE), Any ≥Grade 3 TEAE, Any Related TEAE, and Any TEAE That Led to Discontinuation of Study Drug	Any related TEAE	5 Participants
Placebo 100 mg QD; EP547 100 mg QD	Double-blind Treatment Period: Number of Participants With Any Treatment-emergent Adverse Event (TEAE), Any ≥Grade 3 TEAE, Any Related TEAE, and Any TEAE That Led to Discontinuation of Study Drug	Any TEAE that led to discontinuation of study drug	0 Participants
EP547 100 mg QD; EP547 100 mg QD	Double-blind Treatment Period: Number of Participants With Any Treatment-emergent Adverse Event (TEAE), Any ≥Grade 3 TEAE, Any Related TEAE, and Any TEAE That Led to Discontinuation of Study Drug	Any TEAE that led to discontinuation of study drug	0 Participants
EP547 100 mg QD; EP547 100 mg QD	Double-blind Treatment Period: Number of Participants With Any Treatment-emergent Adverse Event (TEAE), Any ≥Grade 3 TEAE, Any Related TEAE, and Any TEAE That Led to Discontinuation of Study Drug	Any TEAE	18 Participants
EP547 100 mg QD; EP547 100 mg QD	Double-blind Treatment Period: Number of Participants With Any Treatment-emergent Adverse Event (TEAE), Any ≥Grade 3 TEAE, Any Related TEAE, and Any TEAE That Led to Discontinuation of Study Drug	Any related TEAE	5 Participants
EP547 100 mg QD; EP547 100 mg QD	Double-blind Treatment Period: Number of Participants With Any Treatment-emergent Adverse Event (TEAE), Any ≥Grade 3 TEAE, Any Related TEAE, and Any TEAE That Led to Discontinuation of Study Drug	Any ≥Grade 3 TEAE	0 Participants

Secondary

Double-blind Treatment Period: Number of Participants With Any Treatment-emergent (TE) Adverse Event of Special Interest (AESI), Any ≥Grade 3 TE AESI, Any Related TE AESI, and Any TE AESI That Led to Discontinuation of Study Drug

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. TEAEs are AEs with an onset after the first dose of study drug or existing events that worsened after the first dose during the study. AESI were considered to be any clinically meaningful new, worsening from Baseline, or abnormal laboratory findings or symptoms suggestive of acute kidney injury (AKI) (e.g., blood urea increased or protein urine present AEs as identified by the Standardized Medical Dictionary for Regulatory Activities \[MedDRA\] Query \[SMQ\] Acute renal failure). TE AESIs were graded for severity (mild \[Grade 1\], moderate \[Grade 2\], severe \[Grade 3\], life threatening \[Grade 4\], death \[Grade 5\]) using CTCAE, version 5.0. The investigator assessed whether the AE AESIs were related or unrelated to the study drug.

Time frame: up to the end of Week 6

Population: Safety Analysis Set

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Placebo 100 mg QD; EP547 100 mg QD	Double-blind Treatment Period: Number of Participants With Any Treatment-emergent (TE) Adverse Event of Special Interest (AESI), Any ≥Grade 3 TE AESI, Any Related TE AESI, and Any TE AESI That Led to Discontinuation of Study Drug	Any treatment-emergent (TE) AESI	0 Participants
Placebo 100 mg QD; EP547 100 mg QD	Double-blind Treatment Period: Number of Participants With Any Treatment-emergent (TE) Adverse Event of Special Interest (AESI), Any ≥Grade 3 TE AESI, Any Related TE AESI, and Any TE AESI That Led to Discontinuation of Study Drug	Any ≥Grade 3 TE AESI	0 Participants
Placebo 100 mg QD; EP547 100 mg QD	Double-blind Treatment Period: Number of Participants With Any Treatment-emergent (TE) Adverse Event of Special Interest (AESI), Any ≥Grade 3 TE AESI, Any Related TE AESI, and Any TE AESI That Led to Discontinuation of Study Drug	Any related TE AESI	0 Participants
Placebo 100 mg QD; EP547 100 mg QD	Double-blind Treatment Period: Number of Participants With Any Treatment-emergent (TE) Adverse Event of Special Interest (AESI), Any ≥Grade 3 TE AESI, Any Related TE AESI, and Any TE AESI That Led to Discontinuation of Study Drug	Any TE AESI that led to discontinuation of study drug	0 Participants
EP547 100 mg QD; EP547 100 mg QD	Double-blind Treatment Period: Number of Participants With Any Treatment-emergent (TE) Adverse Event of Special Interest (AESI), Any ≥Grade 3 TE AESI, Any Related TE AESI, and Any TE AESI That Led to Discontinuation of Study Drug	Any TE AESI that led to discontinuation of study drug	0 Participants
EP547 100 mg QD; EP547 100 mg QD	Double-blind Treatment Period: Number of Participants With Any Treatment-emergent (TE) Adverse Event of Special Interest (AESI), Any ≥Grade 3 TE AESI, Any Related TE AESI, and Any TE AESI That Led to Discontinuation of Study Drug	Any treatment-emergent (TE) AESI	0 Participants
EP547 100 mg QD; EP547 100 mg QD	Double-blind Treatment Period: Number of Participants With Any Treatment-emergent (TE) Adverse Event of Special Interest (AESI), Any ≥Grade 3 TE AESI, Any Related TE AESI, and Any TE AESI That Led to Discontinuation of Study Drug	Any related TE AESI	0 Participants
EP547 100 mg QD; EP547 100 mg QD	Double-blind Treatment Period: Number of Participants With Any Treatment-emergent (TE) Adverse Event of Special Interest (AESI), Any ≥Grade 3 TE AESI, Any Related TE AESI, and Any TE AESI That Led to Discontinuation of Study Drug	Any ≥Grade 3 TE AESI	0 Participants

Secondary

Number of Participants With Any Clinically Meaningful Changes From Baseline in Clinically Meaningful in Clinical Laboratory Test Results

Clinical laboratory test results included results for clinical hematology, chemistry, coagulation, and thyroid function parameters . The investigator determined if changes were clinically meaningful.

Time frame: up to the end of Week 12

Population: Safety Analysis Set

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Placebo 100 mg QD; EP547 100 mg QD	Number of Participants With Any Clinically Meaningful Changes From Baseline in Clinically Meaningful in Clinical Laboratory Test Results	3 Participants
EP547 100 mg QD; EP547 100 mg QD	Number of Participants With Any Clinically Meaningful Changes From Baseline in Clinically Meaningful in Clinical Laboratory Test Results	0 Participants

Secondary

Number of Participants With Any Clinically Meaningful Changes From Baseline in Vital Sign Measurements

Vital sign measurements included measurements for blood pressure, pulse rate, oxygen saturation, body temperature, and respiratory rate. The investigator determined if changes were clinically meaningful.

Time frame: up to the end of Week 12

Population: Safety Analysis Set

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Placebo 100 mg QD; EP547 100 mg QD	Number of Participants With Any Clinically Meaningful Changes From Baseline in Vital Sign Measurements	0 Participants
EP547 100 mg QD; EP547 100 mg QD	Number of Participants With Any Clinically Meaningful Changes From Baseline in Vital Sign Measurements	1 Participants

Secondary

Number of Participants With Any Clinically Significant Changes From Baseline in Electrocardiogram (ECG) Parameters

ECG parameters included heart rate, RR interval, PR interval, QRS duration, or QT interval. The investigator determined if changes were clinically significant.

Time frame: up to the end of Week 12

Population: Safety Analysis Set

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Placebo 100 mg QD; EP547 100 mg QD	Number of Participants With Any Clinically Significant Changes From Baseline in Electrocardiogram (ECG) Parameters	0 Participants
EP547 100 mg QD; EP547 100 mg QD	Number of Participants With Any Clinically Significant Changes From Baseline in Electrocardiogram (ECG) Parameters	0 Participants

Secondary

Open-label Extension Period: Number of Participants With Any Serious TEAE, Any ≥Grade 3 Serious TEAE, Any Related Serious TEAE, and Any Serious TEAE That Led to Discontinuation of Study Drug

Time frame: from the beginning of Week 7 up to Week 12

Population: Open-label Extension Analysis Set

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Placebo 100 mg QD; EP547 100 mg QD	Open-label Extension Period: Number of Participants With Any Serious TEAE, Any ≥Grade 3 Serious TEAE, Any Related Serious TEAE, and Any Serious TEAE That Led to Discontinuation of Study Drug	Any serious TEAE	1 Participants
Placebo 100 mg QD; EP547 100 mg QD	Open-label Extension Period: Number of Participants With Any Serious TEAE, Any ≥Grade 3 Serious TEAE, Any Related Serious TEAE, and Any Serious TEAE That Led to Discontinuation of Study Drug	Any ≥Grade 3 serious TEAE	1 Participants
Placebo 100 mg QD; EP547 100 mg QD	Open-label Extension Period: Number of Participants With Any Serious TEAE, Any ≥Grade 3 Serious TEAE, Any Related Serious TEAE, and Any Serious TEAE That Led to Discontinuation of Study Drug	Any related serious TEAE	0 Participants
Placebo 100 mg QD; EP547 100 mg QD	Open-label Extension Period: Number of Participants With Any Serious TEAE, Any ≥Grade 3 Serious TEAE, Any Related Serious TEAE, and Any Serious TEAE That Led to Discontinuation of Study Drug	Any serious TEAE that led to discontinuation of study drug	0 Participants
EP547 100 mg QD; EP547 100 mg QD	Open-label Extension Period: Number of Participants With Any Serious TEAE, Any ≥Grade 3 Serious TEAE, Any Related Serious TEAE, and Any Serious TEAE That Led to Discontinuation of Study Drug	Any serious TEAE that led to discontinuation of study drug	0 Participants
EP547 100 mg QD; EP547 100 mg QD	Open-label Extension Period: Number of Participants With Any Serious TEAE, Any ≥Grade 3 Serious TEAE, Any Related Serious TEAE, and Any Serious TEAE That Led to Discontinuation of Study Drug	Any serious TEAE	0 Participants
EP547 100 mg QD; EP547 100 mg QD	Open-label Extension Period: Number of Participants With Any Serious TEAE, Any ≥Grade 3 Serious TEAE, Any Related Serious TEAE, and Any Serious TEAE That Led to Discontinuation of Study Drug	Any related serious TEAE	0 Participants
EP547 100 mg QD; EP547 100 mg QD	Open-label Extension Period: Number of Participants With Any Serious TEAE, Any ≥Grade 3 Serious TEAE, Any Related Serious TEAE, and Any Serious TEAE That Led to Discontinuation of Study Drug	Any ≥Grade 3 serious TEAE	0 Participants

Secondary

Open-label Extension Period: Number of Participants With Any TEAE, Any ≥Grade 3 TEAE, Any Related TEAE, and Any TEAE That Led to Discontinuation of Study Drug

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable or unintended sign (including a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product. TEAEs are AEs with an onset after the first dose of study drug or existing events that worsened after the first dose during the study. TEAEs were graded for severity (mild \[Grade 1\], moderate \[Grade 2\], severe \[Grade 3\], life threatening \[Grade 4\], death \[Grade 5\]) using CTCAE, version 5.0. The investigator assessed whether the TEAEs were related or unrelated to the study drug.

Time frame: from the beginning of Week 7 up to Week 12

Population: Open-label Extension Analysis Set: all participants who completed the Double-Blind Treatment Period and received at least 1 dose of study drug in the Open-Label Extension Period

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Placebo 100 mg QD; EP547 100 mg QD	Open-label Extension Period: Number of Participants With Any TEAE, Any ≥Grade 3 TEAE, Any Related TEAE, and Any TEAE That Led to Discontinuation of Study Drug	Any TEAE	16 Participants
Placebo 100 mg QD; EP547 100 mg QD	Open-label Extension Period: Number of Participants With Any TEAE, Any ≥Grade 3 TEAE, Any Related TEAE, and Any TEAE That Led to Discontinuation of Study Drug	Any ≥Grade 3 TEAE	2 Participants
Placebo 100 mg QD; EP547 100 mg QD	Open-label Extension Period: Number of Participants With Any TEAE, Any ≥Grade 3 TEAE, Any Related TEAE, and Any TEAE That Led to Discontinuation of Study Drug	Any related TEAE	5 Participants
Placebo 100 mg QD; EP547 100 mg QD	Open-label Extension Period: Number of Participants With Any TEAE, Any ≥Grade 3 TEAE, Any Related TEAE, and Any TEAE That Led to Discontinuation of Study Drug	Any TEAE that led to discontinuation of study drug	0 Participants
EP547 100 mg QD; EP547 100 mg QD	Open-label Extension Period: Number of Participants With Any TEAE, Any ≥Grade 3 TEAE, Any Related TEAE, and Any TEAE That Led to Discontinuation of Study Drug	Any TEAE that led to discontinuation of study drug	0 Participants
EP547 100 mg QD; EP547 100 mg QD	Open-label Extension Period: Number of Participants With Any TEAE, Any ≥Grade 3 TEAE, Any Related TEAE, and Any TEAE That Led to Discontinuation of Study Drug	Any TEAE	15 Participants
EP547 100 mg QD; EP547 100 mg QD	Open-label Extension Period: Number of Participants With Any TEAE, Any ≥Grade 3 TEAE, Any Related TEAE, and Any TEAE That Led to Discontinuation of Study Drug	Any related TEAE	2 Participants
EP547 100 mg QD; EP547 100 mg QD	Open-label Extension Period: Number of Participants With Any TEAE, Any ≥Grade 3 TEAE, Any Related TEAE, and Any TEAE That Led to Discontinuation of Study Drug	Any ≥Grade 3 TEAE	0 Participants

Secondary

Open-label Extension Period: Number of Participants With Any Treatment-emergent (TE) AESI, Any ≥Grade 3 TE AESI, Any Related TE AESI, and Any TE AESI That Led to Discontinuation of Study Drug

Time frame: from the beginning of Week 7 up to Week 12

Population: Open-label Extension Analysis Set

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Placebo 100 mg QD; EP547 100 mg QD	Open-label Extension Period: Number of Participants With Any Treatment-emergent (TE) AESI, Any ≥Grade 3 TE AESI, Any Related TE AESI, and Any TE AESI That Led to Discontinuation of Study Drug	Any TE AESI	0 Participants
Placebo 100 mg QD; EP547 100 mg QD	Open-label Extension Period: Number of Participants With Any Treatment-emergent (TE) AESI, Any ≥Grade 3 TE AESI, Any Related TE AESI, and Any TE AESI That Led to Discontinuation of Study Drug	Any ≥Grade 3 TE AESI	0 Participants
Placebo 100 mg QD; EP547 100 mg QD	Open-label Extension Period: Number of Participants With Any Treatment-emergent (TE) AESI, Any ≥Grade 3 TE AESI, Any Related TE AESI, and Any TE AESI That Led to Discontinuation of Study Drug	Any related TE AESI	0 Participants
Placebo 100 mg QD; EP547 100 mg QD	Open-label Extension Period: Number of Participants With Any Treatment-emergent (TE) AESI, Any ≥Grade 3 TE AESI, Any Related TE AESI, and Any TE AESI That Led to Discontinuation of Study Drug	Any TE AESI that led to discontinuation of study drug	0 Participants
EP547 100 mg QD; EP547 100 mg QD	Open-label Extension Period: Number of Participants With Any Treatment-emergent (TE) AESI, Any ≥Grade 3 TE AESI, Any Related TE AESI, and Any TE AESI That Led to Discontinuation of Study Drug	Any TE AESI that led to discontinuation of study drug	0 Participants
EP547 100 mg QD; EP547 100 mg QD	Open-label Extension Period: Number of Participants With Any Treatment-emergent (TE) AESI, Any ≥Grade 3 TE AESI, Any Related TE AESI, and Any TE AESI That Led to Discontinuation of Study Drug	Any TE AESI	0 Participants
EP547 100 mg QD; EP547 100 mg QD	Open-label Extension Period: Number of Participants With Any Treatment-emergent (TE) AESI, Any ≥Grade 3 TE AESI, Any Related TE AESI, and Any TE AESI That Led to Discontinuation of Study Drug	Any related TE AESI	0 Participants
EP547 100 mg QD; EP547 100 mg QD	Open-label Extension Period: Number of Participants With Any Treatment-emergent (TE) AESI, Any ≥Grade 3 TE AESI, Any Related TE AESI, and Any TE AESI That Led to Discontinuation of Study Drug	Any ≥Grade 3 TE AESI	0 Participants

Secondary