Abstract | BACKGROUND & AIMS: METHODS: We performed a double-blind study of 165 patients with primary biliary cirrhosis (95% women) and levels of alkaline phosphatase (ALP) 1.5- to 10-fold the upper limit of normal. Patients were randomly assigned to groups given 10 mg, 25 mg, or 50 mg doses of OCA or placebo, once daily for 3 months. Patients maintained their existing dose of ursodeoxycholic acid throughout the study. The primary outcome was change in level of ALP from baseline (day 0) until the end of the study (day 85 or early termination). We also performed an open-label extension of the trial in which 78 patients were enrolled and 61 completed the first year. RESULTS: OCA was superior to placebo in achieving the primary end point. Subjects given OCA had statistically significant relative reductions in mean ALP from baseline to the end of the study (P < .0001 all OCA groups vs placebo). Levels of ALP decreased 21%-25% on average from baseline in the OCA groups and 3% in the placebo group. Sixty-nine percent (68 of 99) of patients given OCA had at least a 20% reduction in ALP compared with 8% (3 of 37) of patients given placebo (P < .0003). Among secondary end points, levels of γ- glutamyl transpeptidase decreased 48%-63%, on average, among subjects given OCA, vs a 7% decrease in the group given placebo; levels of alanine aminotransferase decreased 21%-35% on average among subjects given OCA vs none of the patients given placebo. Pruritus was the principal adverse event; incidence values in the OCA 10 mg, 25 mg, and 50 mg groups were 47% (not significantly different), 87% (P < .0003), and 80% (P < .006), respectively, vs 50% in the placebo group. In the extension study, levels of ALP continued to decrease to a mean level of 202 ± 11 U/L after 12 months vs 285 ± 15 U/L at baseline. CONCLUSIONS:
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Authors | Gideon M Hirschfield, Andrew Mason, Velimir Luketic, Keith Lindor, Stuart C Gordon, Marlyn Mayo, Kris V Kowdley, Catherine Vincent, Henry C Bodhenheimer Jr, Albert Parés, Michael Trauner, Hanns-Ulrich Marschall, Luciano Adorini, Cathi Sciacca, Tessa Beecher-Jones, Erin Castelloe, Olaf Böhm, David Shapiro |
Journal | Gastroenterology
(Gastroenterology)
Vol. 148
Issue 4
Pg. 751-61.e8
(Apr 2015)
ISSN: 1528-0012 [Electronic] United States |
PMID | 25500425
(Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Video-Audio Media)
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Copyright | Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- Cholagogues and Choleretics
- obeticholic acid
- Chenodeoxycholic Acid
- Ursodeoxycholic Acid
- gamma-Glutamyltransferase
- Alanine Transaminase
- Alkaline Phosphatase
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Topics |
- Adult
- Aged
- Alanine Transaminase
(blood)
- Alkaline Phosphatase
(blood)
- Chenodeoxycholic Acid
(administration & dosage, analogs & derivatives, therapeutic use)
- Cholagogues and Choleretics
(administration & dosage, therapeutic use)
- Dose-Response Relationship, Drug
- Double-Blind Method
- Female
- Humans
- Liver Cirrhosis, Biliary
(blood, drug therapy)
- Male
- Middle Aged
- Pruritus
(chemically induced)
- Treatment Failure
- Treatment Outcome
- Ursodeoxycholic Acid
(therapeutic use)
- gamma-Glutamyltransferase
(blood)
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