EPICS-III

18 evidence topics · 10 sources

Objective

Biochemical-response objective

“biochemical response” (opens the source at this quote in a new tab)

Location and study date

Protocol-listed study region

“United States” (opens the source at this quote in a new tab)

Study design

EPICS-III: NCT05133336

“A multicenter, randomized, double-blind, placebo controlled, phase 2b/3 study to evaluate the efficacy and safety of saroglitazar magnesium” (opens the source at this quote in a new tab)

Eligibility criteria

EPICS-III: inclusion-criteria excerpts

Criterion	Quoted protocol text
UDCA-treated population	“Subjects on ursodeoxycholic acid (UDCA) for at least 12 months”
UDCA-intolerant population	“Subjects who are unable to tolerate UDCA”
ALP threshold	“ALP ≥ 1.67 x ULN”

Treatment

Investigational dosage and administration

“Saroglitazar Magnesium 1 mg tablet orally administered once daily in the morning before breakfast without food” (opens the source at this quote in a new tab)
“52 weeks” (opens the source at this quote in a new tab)

Study outcomes

Rationale for using ALP and bilirubin biochemical response as the primary endpoint

EPICS-III: composite biochemical-response endpoint

Component	Quoted definition
ALP threshold	“alkaline phosphatase (ALP) <1.67x upper limit of normal (ULN)”
ALP decrease relative to baseline	“≥15%”
Total bilirubin criterion	“total bilirubin ≤ ULN”
Gilbert’s syndrome alternative	“direct bilirubin ≤ULN in patients with known Gilbert's syndrome”
Assessment	“52 weeks”

Prognostic association of the biochemical markers

“Combining levels of alkaline phosphatase and bilirubin increased the ability to predict patient survival times.” (opens the source at this quote in a new tab)

Statistical analysis description

Number of participants (Planned and analyzed)

Protocol-planned enrollment

Population	Planned participants
Whole phase 2b/3 protocol	“192”

Phase 3 enrollment reported in the topline release

Population	Reported participants
Randomized phase 3 cohort	“149”

EPICS-III: phase III results

Endpoint or population	Saroglitazar	Placebo
Reported trial N	“148”

Registry-reported enrollment across the combined study

Population	Reported participants
Combined study enrollment	“196”

Description of analysis sets

No evidence found.

Results

Participant disposition

No evidence found.

Baseline characteristics

Phase 3 baseline ALP

Characteristic	Saroglitazar	Placebo
Mean ALP, U/L	“363”	“317.2”

Efficacy results

EPICS-III: phase III biochemical results

Endpoint or population	Saroglitazar	Placebo
Biochemical response at Week 52	“56.7%”	“9.8%”
ALP percentage change from baseline at Week 52	“-33.5%”	“+6.5%”

EPICS-III: treatment differences

Treatment difference	Quoted result
Biochemical response	“48% (95% CI: 35.3, 60.8) (p < 0.001)”
Least-squares mean ALP change	“-124.1 U/L (-40.1%)”

Health-related quality of life and patient-reported outcomes

EPICS-III: week 52 pruritus results

Endpoint or population	Saroglitazar	Placebo
Change in 5-D Itch Total score at Week 52	“-4.6”	“-4.4”

EPICS-III: pruritus

“statistically significant improvements observed at six months, although significance was not maintained at the 12-month assessment.” (opens the source at this quote in a new tab)

Safety results

EPICS-III: serious adverse events

Endpoint or population	Saroglitazar	Placebo
Serious adverse events	“6.3%”	“11.1%”

Study limitations

Summary

The primary endpoint is a biochemical surrogate, not a direct measure of transplantation or survival. The topline release reports 149 randomized participants, whereas the later NDA-supporting report gives a phase 3 trial population of 148; these totals are not reconciled in the retrieved evidence. The combined-study registry enrollment of 196 is a different population. Pruritus improvement was not statistically significant at 12 months.