RESPONSE

17 evidence topics · 3 sources

Objective

Biochemical-response objective

“biochemical response at Month 12” (opens the source at this quote in a new tab)

Location and study date

U.S. participation

Population characteristic	Reported value
Participants enrolled in the United States	“Thirty-two percent”

Study design

Randomized, double-blind trial duration

“12-month” (opens the source at this quote in a new tab)

Eligibility criteria

Biochemical eligibility

Criterion	Quoted threshold
ALP: at least this multiple of ULN	“1.67”
Total bilirubin: at most this multiple of ULN	“2”

Treatment

Daily treatment allocation

Treatment	Dose
Seladelpar	“10 mg”
Comparator	“placebo”

Study outcomes

Rationale for using ALP and bilirubin biochemical response 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)

Randomized population

Treatment	Participants
Seladelpar	“128”
Placebo	“65”

Description of analysis sets

Early treatment discontinuation or missing month 12 data

“non-responders” (opens the source at this quote in a new tab)

Biochemical-response hypothesis test

“Cochran–Mantel–Haenszel” (opens the source at this quote in a new tab)

Results

Participant disposition

No evidence found.

Baseline characteristics

Baseline population

Characteristic	Reported value
Mean age, years	“57”
Female participants	“95%”
Mean ALP, U/L	“314”

Efficacy results

Month 12 biochemical results

Outcome	Seladelpar	Placebo
Biochemical response, n (%)	“79 (62)”	“13 (20)”
ALP normalization, n (%)	“32 (25)”	“0 (0)”

Month 12 biochemical response and alkaline phosphatase normalization: between-group differences

“A greater percentage of the patients in the seladelpar group than in the placebo group had a biochemical response (61.7% vs. 20.0%; difference, 41.7 percentage points; 95% confidence interval [CI], 27.7 to 53.4, P<0.001).” (opens the source at this quote in a new tab)
“Normalization of the alkaline phosphatase level also occurred in a greater percentage of patients who received seladelpar than of those who received placebo (25.0% vs. 0%; difference, 25.0 percentage points; 95% CI, 18.3 to 33.2, P<0.001).” (opens the source at this quote in a new tab)
“Of the 193 patients who underwent randomization and treatment, 93.8% received ursodeoxycholic acid as standard-of-care background therapy.” (opens the source at this quote in a new tab)

Health-related quality of life and patient-reported outcomes

Month 6 pruritus: baseline average score at least 4

Outcome	Seladelpar	Placebo
Analysis participants	“49”	“23”
Mean change in score, standard error	“-3.2 (0.3)”	“-1.7 (0.4)”

Month 6 pruritus: least-squares mean difference against placebo

“Seladelpar resulted in a greater reduction in the score on the pruritus numerical rating scale than placebo (least-squares mean change from baseline, −3.2 vs. −1.7; least-squares mean difference, −1.5; 95% CI, −2.5 to −0.5, P = 0.005).” (opens the source at this quote in a new tab)

Safety results

Fractures during the trial

Outcome	Seladelpar	Placebo
Participants with fractures	“4%”	“no”

Overall and serious adverse events

“Adverse events were reported in 86.7% of the patients in the seladelpar group and in 84.6% in the placebo group, and serious adverse events in 7.0% and 6.2%, respectively.” (opens the source at this quote in a new tab)
“The incidence and severity of adverse events were similar in the two groups.” (opens the source at this quote in a new tab)

Study limitations

Summary

This is comparator evidence, not a randomized comparison against saroglitazar. The primary endpoint was biochemical response after 12 months, and the pruritus analysis concerned a subgroup with baseline scores of at least 4. The prescribing information does not establish improved survival or prevention of liver decompensation.