PMID- 30859149
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210109
IS  - 2471-254X (Electronic)
IS  - 2471-254X (Linking)
VI  - 3
IP  - 3
DP  - 2019 Mar
TI  - A Randomized, Controlled, Phase 2 Study of Maralixibat in the Treatment of 
      Itching Associated With Primary Biliary Cholangitis.
PG  - 365-381
LID - 10.1002/hep4.1305 [doi]
AB  - Primary biliary cholangitis (PBC) is typically associated with elevated serum 
      bile acid levels and pruritus, but pruritus is often refractory to treatment with 
      existing therapies. This phase 2 study assessed the efficacy and safety of 
      maralixibat, a selective, ileal, apical, sodium-dependent, bile acid transporter 
      inhibitor, in adults with PBC and pruritus. Adults with PBC and pruritus who had 
      received ursodeoxycholic acid (UDCA) for >/=6 months or were intolerant to UDCA 
      were randomized 2:1 to maralixibat (10 or 20 mg/day) or placebo for 13 weeks in 
      combination with UDCA (when tolerated). The primary outcome was change in Adult 
      Itch Reported Outcome (ItchRO) average weekly sum score (0, no itching; 70, 
      maximum itching) from baseline to week 13/early termination (ET). The study 
      enrolled 66 patients (maralixibat [both doses combined], n = 42; placebo, 
      n = 24). Mean ItchRO weekly sum scores decreased from baseline to week 13/ET 
      with maralixibat (-26.5; 95% confidence interval [CI], -31.8, -21.2) and placebo 
      (-23.4; 95% CI, -30.3, -16.4). The difference between groups was not significant 
      (P = 0.48). In the maralixibat and placebo groups, adverse events (AEs) were 
      reported in 97.6% and 70.8% of patients, respectively. Gastrointestinal disorders 
      were the most frequently reported AEs (maralixibat, 78.6%; placebo, 50.0%). 
      Conclusion: Reductions in pruritus did not differ significantly between 
      maralixibat and placebo. However, a large placebo effect may have confounded 
      assessment of pruritus. Lessons learned from this rigorously designed and 
      executed trial are indispensable for understanding how to approach trials 
      assessing pruritus as the primary endpoint and the therapeutic window of bile 
      acid uptake inhibition as a therapeutic strategy in PBC.
FAU - Mayo, Marlyn J
AU  - Mayo MJ
AD  - Digestive and Liver Diseases University of Texas Southwestern Medical Center 
      Dallas TX.
FAU - Pockros, Paul J
AU  - Pockros PJ
AD  - Scripps Clinic and Scripps Translational Science Institute La Jolla CA.
FAU - Jones, David
AU  - Jones D
AD  - Institute of Cellular Medicine Newcastle University Newcastle upon Tyne United 
      Kingdom.
FAU - Bowlus, Christopher L
AU  - Bowlus CL
AUID- ORCID: 0000-0002-3906-6811
AD  - Division of Gastroenterology and Hepatology University of California Davis School 
      of Medicine Sacramento CA.
FAU - Levy, Cynthia
AU  - Levy C
AD  - Division of Hepatology University of Miami Miller School of Medicine Miami FL.
FAU - Patanwala, Imran
AU  - Patanwala I
AD  - Royal Liverpool University Hospital and University of Liverpool Liverpool United 
      Kingdom.
FAU - Bacon, Bruce
AU  - Bacon B
AD  - Division of Gastroenterology and Hepatology Saint Louis University School of 
      Medicine St. Louis MO.
FAU - Luketic, Velimir
AU  - Luketic V
AD  - Division of Gastroenterology, Hepatology and Nutrition Virginia Commonwealth 
      University School of Medicine Richmond VA.
AD  - McGuire Research Institute, McGuire VA Medical Center Richmond VA.
FAU - Vuppalanchi, Raj
AU  - Vuppalanchi R
AD  - Indiana University School of Medicine Indianapolis IN.
FAU - Medendorp, Sharon
AU  - Medendorp S
AD  - Premier Research Research Triangle Park NC.
FAU - Dorenbaum, Alejandro
AU  - Dorenbaum A
AD  - Stanford University Palo Alto CA.
FAU - Kennedy, Ciara
AU  - Kennedy C
AD  - Amplyx Pharmaceuticals San Diego CA.
FAU - Novak, Patricia
AU  - Novak P
AD  - Lumena Pharmaceuticals San Diego CA (one of the Shire group of companies).
FAU - Gu, Joan
AU  - Gu J
AD  - Shire Lexington MA.
FAU - Apostol, George
AU  - Apostol G
AD  - Shire Zug Switzerland.
FAU - Hirschfield, Gideon M
AU  - Hirschfield GM
AD  - Toronto Centre for Liver Disease University Health Network, University of Toronto 
      Toronto Canada.
LA  - eng
GR  - MR/L001489/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
DEP - 20190201
PL  - United States
TA  - Hepatol Commun
JT  - Hepatology communications
JID - 101695860
PMC - PMC6396374
EDAT- 2019/03/13 06:00
MHDA- 2019/03/13 06:01
PMCR- 2019/02/01
CRDT- 2019/03/13 06:00
PHST- 2018/08/21 00:00 [received]
PHST- 2018/11/14 00:00 [accepted]
PHST- 2019/03/13 06:00 [entrez]
PHST- 2019/03/13 06:00 [pubmed]
PHST- 2019/03/13 06:01 [medline]
PHST- 2019/02/01 00:00 [pmc-release]
AID - HEP41305 [pii]
AID - 10.1002/hep4.1305 [doi]
PST - epublish
SO  - Hepatol Commun. 2019 Feb 1;3(3):365-381. doi: 10.1002/hep4.1305. eCollection 2019 
      Mar.