EPICS

17 evidence topics · 5 sources

Objective

Phase II proof-of-concept study: NCT03112681

“Effect of a 16-week Treatment Regimen of Saroglitazar Magnesium 2 mg and 4 mg on Alkaline Phosphatase (ALP) Levels” (opens the source at this quote in a new tab)

Location and study date

No evidence found.

Study design

Double-blind randomized proof-of-concept design

“double-blind, phase II proof-of-concept trial” (opens the source at this quote in a new tab)

Eligibility criteria

Prior UDCA response

“UDCA) resistant or intolerant” (opens the source at this quote in a new tab)

Treatment

Randomized daily treatment groups

Treatment parameter	Saroglitazar 4 mg	Saroglitazar 2 mg	Placebo
Daily dose	“4 mg”	“2 mg”	“placebo”
Treatment duration	“16 weeks”	“16 weeks”	“16 weeks”

Study outcomes

Rationale for using ALP reduction as the primary endpoint

ALP and bilirubin as prognostic 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)

Phase II proof-of-concept study: study population

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

Randomized allocation

Group	Participants
Saroglitazar 4 mg	“13”
Saroglitazar 2 mg	“14”
Placebo	“10”

Description of analysis sets

Primary analysis population

“modified ITT analysis” (opens the source at this quote in a new tab)

Results

Participant disposition

Study-drug discontinuations because of aminotransferase increases

Group	Participants
All saroglitazar groups	“4”
Saroglitazar 4 mg	“3”
Saroglitazar 2 mg	“1”

Baseline characteristics

Baseline comparisons between treatment groups

“not significantly different” (opens the source at this quote in a new tab)

Efficacy results

Phase II proof-of-concept study: week 16 ALP endpoints

Week 16 endpoint	Saroglitazar 4 mg	Saroglitazar 2 mg	Placebo
Mean percentage ALP reduction	“49%”	“51%”	“3%”
Least-squares mean ALP change, U/L	“-163.3”	“-155.8”	“-21.1”

Health-related quality of life and patient-reported outcomes

Week 16 PBC-40 itch domain

“The mean change from baseline on the itch domain of the PBC-40 questionnaire at Week 16 was -1.52, -1.08 and -2.31, respectively, for saroglitazar 4 mg, saroglitazar 2 mg and placebo groups.” (opens the source at this quote in a new tab)
“Overall, no worsening of pruritus was observed on the itch domain of the PBC-40 questionnaire” (opens the source at this quote in a new tab)
“13 (35.1%) patients reported pruritus at baseline” (opens the source at this quote in a new tab)

Safety results

Participants with at least one treatment-emergent adverse event

Outcome	Saroglitazar 4 mg	Saroglitazar 2 mg	Placebo
Participants, n (%)	“11 (84.6%)”	“12 (85.7%)”	“8 (80%)”

Aminotransferase increases after treatment discontinuation

“due to aminotransferase increases that promptly returned to baseline values after drug discontinuation.” (opens the source at this quote in a new tab)

EPICS phase II study: conference publication

“Liver tests returned to baseline after study drug discontinuation in 3 while one patient required immune suppression for suspected overlap syndrome.” (opens the source at this quote in a new tab)

Study limitations

Summary

This 37-participant trial lasted 16 weeks and tested 2 mg and 4 mg, not the later 1 mg magnesium regimen. Four participants discontinued treatment because of aminotransferase increases. The conference report describes one participant requiring immune suppression for suspected overlap syndrome, whereas the journal abstract summarizes recovery after discontinuation. Neither report establishes a long-term clinical-outcome benefit.

Investigator-stated limitation on the pruritus finding

“There were anecdotal reports of improvement in itching while on treatment with saroglitazar, but the current study does not provide any conclusive evidence, primarily because of the low prevalence of itching in study participants and the lack of additional measurements of itch severity.” (opens the source at this quote in a new tab)