Moexipril for Primary Biliary Cirrhosis
Information source: Mayo Clinic
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Primary Biliary Cirrhosis
Intervention: Moexipril (Drug)
Phase: Phase 2
Sponsored by: Mayo Clinic
Official(s) and/or principal investigator(s):
Keith D Lindor, MD, Principal Investigator, Affiliation: Mayo Clinic and Foundation
The blockade of angiotensin II synthesis attenuates hepatic fibrosis in different
experimental models of chronic liver injury. We aimed to determine the safety and efficacy of
moexipril, an angiotensin-converting enzyme (ACE) inhibitor, on liver biochemistries, Mayo
risk score, and health-related quality of life in patients with primary biliary cirrhosis
(PBC) who have had a suboptimal response to ursodeoxycholic acid (UDCA).
Official title: Open-Label Pilot Investigation of Moexipril for the Treatment of Primary Biliary Cirrhosis (PBC)
Study design: Treatment, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Primary outcome: change in liver biochemistries and Mayo risk score for PBC
Secondary outcome: change in health-related quality of life in PBC
Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease of presumed autoimmune
cause characterized by progressive inflammatory destruction of interlobular and septal bile
ducts, resulting in fibrosis and eventual cirrhosis (1). In PBC patients, the most disabling
symptoms are fatigue and pruritus which diminish health-related quality of life (HRQL.
Ursodeoxycholic acid (UDCA), at a dose of 13 to 15 mg/kg per day, is a safe and effective
medical therapy for most patients with PBC. Nevertheless, UDCA therapy has not ameliorated
symptoms associated with PBC. Some UDCA-treated patients show progressive disease resulting
in the liver transplantation or death from liver-related causes. For these patients, who show
a persistent elevation of serum alkaline phosphatase at least twice the normal level after 6
months of UDCA monotherapy (incomplete responders), the evaluation of combination therapy in
clinical trials has been recommended.
Moexipril is a long-acting, nonsulfhydryl ACE inhibitor with lipophilicity, and so can
readily penetrate lipid membranes and thus target tissue ACE in addition to plasma ACE. This
drug also demonstrated antioxidative properties in addition to efficiently controlling blood
pressure in hypertensive postmenopausal subjects. Moreover, quality-of-life data suggest
favorable effects of moexipril treatment in a patient population at high cardiovascular risk.
The tolerability and safety profile of moexipril resembles that of other ACE inhibitors along
with no reports of hepatotoxicity in controlled trials. Hence, moexipril is an attractive
drug for evaluation in patients with chronic liver disease.
Minimum age: 18 Years.
Maximum age: 85 Years.
- PBC patients treated with UDCA (daily dose of 13 to 15 mg/kg for at least 6 months)
and an incomplete response defined by persistent elevation of serum alkaline
phosphatase activity at least 2 times the upper limit of normal
- age less than 18 years
- pregnancy or nursing
- anticipated need for liver transplantation within 1 year with less than a 80% one-year
survival determined by the Mayo risk score
- complications of cirrhosis such as recurrent variceal hemorrhage, portosystemic
encephalopathy, and refractory ascites
- history of coexistent severe cardiovascular disease including aortic stenosis
- history of coexistent severe renal disease (defined as elevation of serum creatinine
more than 1. 5 mg/dL) including renal artery stenosis
- history of allergy to ACE inhibitors
- current use of an ACE inhibitors or AT1 receptor antagonists in the past 3 months
- previous treatment with immunosuppressive agents or any experimental drug in the
preceding 3 months.
Locations and Contacts
Mayo Clinic, Rochester, Minnesota 55905, United States
Mayo Clinic Clinical Trials
Talwalkar JA, Lindor KD. Primary biliary cirrhosis. Lancet. 2003 Jul 5;362(9377):53-61. Review.
Starting date: June 2003
Ending date: June 2007
Last updated: December 22, 2007