Trial Outcomes & Findings for Trial of High-dose Urso in Primary Sclerosing Cholangitis (NCT NCT00059202)

NCT ID: NCT00059202

Last Updated: 2021-05-03

Results Overview

Treatment failure was defined as death, transplantation, meeting minimal listing criteria, development of varices, cholangiocarcinoma, or progression to cirrhosis

• Recruitment status: TERMINATED
• Study phase: PHASE2/PHASE3
• Target enrollment: 150 participants
• Primary outcome timeframe: 5 years
• Results posted on: 2021-05-03

Participant Flow

Participant milestones

Measure	Ursodeoxycholic Acid Ursodeoxycholic Acid 28-30 mg/kg/day in divided doses	Placebo Placebo for Urso
Overall Study STARTED	76	74
Overall Study COMPLETED	70	59
Overall Study NOT COMPLETED	6	15

Reasons for withdrawal

Measure	Ursodeoxycholic Acid Ursodeoxycholic Acid 28-30 mg/kg/day in divided doses	Placebo Placebo for Urso
Overall Study Withdrawal by Subject	5	9
Overall Study Protocol Violation	1	3
Overall Study drug toxicity	0	3

Baseline Characteristics

Trial of High-dose Urso in Primary Sclerosing Cholangitis

Baseline characteristics by cohort

Measure	Ursodeoxycholic Acid n=76 Participants Ursodeoxycholic Acid 28-30 mg/kg/day in divided doses	Placebo n=74 Participants Placebo for Urso	Total n=150 Participants Total of all reporting groups
Age, Continuous	47.9 years n=93 Participants	45.3 years n=4 Participants	46.6 years n=27 Participants
Sex: Female, Male Female	38 Participants n=93 Participants	26 Participants n=4 Participants	64 Participants n=27 Participants
Sex: Female, Male Male	38 Participants n=93 Participants	48 Participants n=4 Participants	86 Participants n=27 Participants
Region of Enrollment United States	76 participants n=93 Participants	74 participants n=4 Participants	150 participants n=27 Participants

PRIMARY outcome

Timeframe: 5 years

Treatment failure was defined as death, transplantation, meeting minimal listing criteria, development of varices, cholangiocarcinoma, or progression to cirrhosis

Outcome measures

Measure	Ursodeoxycholic Acid n=76 Participants Ursodeoxycholic Acid 28-30 mg/kg/day in divided doses	Placebo n=74 Participants Placebo for Urso
Number of Participants With Treatment Failure	30 Participants	19 Participants

SECONDARY outcome

Timeframe: 5 years

Death at any time up to 5 years

Outcome measures

Measure	Ursodeoxycholic Acid n=76 Participants Ursodeoxycholic Acid 28-30 mg/kg/day in divided doses	Placebo n=74 Participants Placebo for Urso
Number of Deaths	5 participants	3 participants

SECONDARY outcome

Timeframe: 5 years

Liver transplantation at any time up to 5 years

Outcome measures

Measure	Ursodeoxycholic Acid n=76 Participants Ursodeoxycholic Acid 28-30 mg/kg/day in divided doses	Placebo n=74 Participants Placebo for Urso
Number of Participants Who Have a Liver Transplantation	11 participants	5 participants

SECONDARY outcome

Timeframe: 5 years

Meeting minimal listing criteria for liver transplantation at any time up to 5 years. Minimal listing criteria are defined as a MELD score of 14 or higher. The Model For End-Stage Liver Disease (MELD) is a numeric score with a range of 6 to 40, where a higher score means worse liver disease.

Outcome measures

Measure	Ursodeoxycholic Acid n=76 Participants Ursodeoxycholic Acid 28-30 mg/kg/day in divided doses	Placebo n=74 Participants Placebo for Urso
Number of Participants Meeting Minimal Listing Criteria for Liver Transplantation	13 participants	10 participants

SECONDARY outcome

Timeframe: 5 years

Development of cholangiocarcinoma at any time up to 5 years

Outcome measures

Measure	Ursodeoxycholic Acid n=76 Participants Ursodeoxycholic Acid 28-30 mg/kg/day in divided doses	Placebo n=74 Participants Placebo for Urso
Number of Participants Who Developed Cholangiocarcinoma	2 participants	2 participants

SECONDARY outcome

Timeframe: 5 years

Development of esophogeal and/or gastric varices

Outcome measures

Measure	Ursodeoxycholic Acid n=76 Participants Ursodeoxycholic Acid 28-30 mg/kg/day in divided doses	Placebo n=74 Participants Placebo for Urso
Number of Participants Who Developed Varices	15 participants	5 participants

SECONDARY outcome

Timeframe: 5 years

Development of cirrhosis based on liver biopsy

Outcome measures

Measure	Ursodeoxycholic Acid n=76 Participants Ursodeoxycholic Acid 28-30 mg/kg/day in divided doses	Placebo n=74 Participants Placebo for Urso
Number of Participants Who Developed Cirrhosis	6 participants	4 participants

SECONDARY outcome

Timeframe: 12 months

Alkaline phosphatase divided by the upper limit of normal

Outcome measures

Measure	Ursodeoxycholic Acid n=70 Participants Ursodeoxycholic Acid 28-30 mg/kg/day in divided doses	Placebo n=63 Participants Placebo for Urso
Alkaline Phosphatase at 12 Months	1.9 Ratio Interval 0.6 to 9.1	2.9 Ratio Interval 0.6 to 13.6

SECONDARY outcome

Timeframe: 24 months

Alkaline phosphatase divided by the upper limit of normal

Outcome measures

Measure	Ursodeoxycholic Acid n=65 Participants Ursodeoxycholic Acid 28-30 mg/kg/day in divided doses	Placebo n=58 Participants Placebo for Urso
Alkaline Phosphatase at 24 Months	1.8 Ratio Interval 0.6 to 8.5	2.6 Ratio Interval 0.5 to 11.9

SECONDARY outcome

Timeframe: 36 months

Alkaline phosphatase divided by the upper limit of normal

Outcome measures

Measure	Ursodeoxycholic Acid n=56 Participants Ursodeoxycholic Acid 28-30 mg/kg/day in divided doses	Placebo n=53 Participants Placebo for Urso
Alkaline Phosphatase at 36 Months	1.7 Ratio Interval 0.6 to 16.5	2.4 Ratio Interval 0.4 to 12.1

SECONDARY outcome

Timeframe: 12 months

Aspartate aminotransferase at divided by the upper limit of normal

Outcome measures

Measure	Ursodeoxycholic Acid n=70 Participants Ursodeoxycholic Acid 28-30 mg/kg/day in divided doses	Placebo n=63 Participants Placebo for Urso
Aspartate Aminotransferase at 12 Months	1.0 Ratio Interval 0.5 to 10.5	1.9 Ratio Interval 0.6 to 8.7

SECONDARY outcome

Timeframe: 24 months

Aspartate aminotransferase at divided by the upper limit of normal

Outcome measures

Measure	Ursodeoxycholic Acid n=65 Participants Ursodeoxycholic Acid 28-30 mg/kg/day in divided doses	Placebo n=59 Participants Placebo for Urso
Aspartate Aminotransferase at 24 Months	1.1 Ratio Interval 0.4 to 8.4	1.9 Ratio Interval 0.5 to 13.3

SECONDARY outcome

Timeframe: 36 months

Aspartate aminotransferase at divided by the upper limit of normal

Outcome measures

Measure	Ursodeoxycholic Acid n=56 Participants Ursodeoxycholic Acid 28-30 mg/kg/day in divided doses	Placebo n=53 Participants Placebo for Urso
Aspartate Aminotransferase at 36 Months	1.1 Ratio Interval 0.3 to 7.2	1.7 Ratio Interval 0.5 to 14.8

SECONDARY outcome

Timeframe: 12 months

Bilirubin divided by the upper limit of normal

Outcome measures

Measure	Ursodeoxycholic Acid n=70 Participants Ursodeoxycholic Acid 28-30 mg/kg/day in divided doses	Placebo n=63 Participants Placebo for Urso
Bilirubin at 12 Months	0.8 Ratio Interval 0.2 to 6.3	0.9 Ratio Interval 0.3 to 8.2

SECONDARY outcome

Timeframe: 24 months

Bilirubin divided by the upper limit of normal

Outcome measures

Measure	Ursodeoxycholic Acid n=64 Participants Ursodeoxycholic Acid 28-30 mg/kg/day in divided doses	Placebo n=59 Participants Placebo for Urso
Bilirubin at 24 Months	0.8 Ratio Interval 0.2 to 7.2	1.0 Ratio Interval 0.2 to 8.6

SECONDARY outcome

Timeframe: 36 months

Bilirubin divided by the upper limit of normal

Outcome measures

Measure	Ursodeoxycholic Acid n=55 Participants Ursodeoxycholic Acid 28-30 mg/kg/day in divided doses	Placebo n=53 Participants Placebo for Urso
Bilirubin at 36 Months	0.8 Ratio Interval 0.2 to 15.9	0.9 Ratio Interval 0.3 to 9.6

Adverse Events

Ursodeoxycholic Acid

Serious events: 0 serious events

Other events: 0 other events

Deaths: 5 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 3 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Keith Lindor

Mayo Clinic

Phone: 507-284-2511

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place