A Phase 3, Double Blind, Placebo Controlled Trial and Long Term Safety Extension of Obeticholic Acid in Patients with Primary Biliary Cirrhosis
- Clements University Hospital
- UT Southwestern-Clinical Translational Research Center (CTRC)
- UT Southwestern-Other
Marlyn Mayo, M.D.
This is a phase 3, double blind (DB), placebo controlled, parallel group trial followed
by a long term safety extension (LTSe) of oCa in patients with PBC. in the DB
phase, approximately 180 patients (60 patients per arm) will be randomized in a
1:1:1 ratio to 1 of 3 treatment arms: (a) placebo, (b) 10 mg oCa, or (c) 5 mg titrating
to 10 mg oCa. Study medication will be administered orally, once daily for
12 months. During the LTSe phase, patients may receive up to 25 mg of oCa for
up to 5 years. all patients should continue their prestudy dose of ursodeoxycholic
acid (uDCa) throughout trial participation.
However, effective with Protocol Version 4, patients should be titrated to a maximum of 10 mg
daily. Patients who were titrated above 10 mg prior to Protocol Version 4 may remain
on their current dose or the dose may be decreased as clinically indicated.
1. Definite or probable PBC diagnosis (consistent with AASLD and EASL Practice
Guidelines; [Lindor 2009; EASL 2009]), as demonstrated by the presence of
>= 2 of the following 3 diagnostic factors:
* History of elevated ALP levels for at least 6 months
* Positive AMA titer or if AMA negative or in low titer (<1:80) PBC specific
antibodies (anti-GP210 and/or anti-SP100 and/or antibodies against the major
M2 components (PDC-E2, 2-oxo-glutaric acid dehydrogenase complex)
* Liver biopsy consistent with PBC
2. At least 1 of the following qualifying biochemistry values:
* ALP >= 1.67x ULN
* Total bilirubin > ULN but < 2x ULN
3. Age >= 18 years
4. Taking UDCA for at least 12 months (stable dose for >= 3 months) prior to Day 0,
or unable to tolerate UDCA (no UDCA for >= 3 months) prior to Day 0.
5. Contraception: Female patients must be postmenopausal, surgically sterile, or if
premenopausal, be prepared to use >= 1 effective (<= 1% failure rate) method of
contraception during the trial and for 30 days after the EOT visit. Effective
methods of contraception are considered to be:
* Hormonal (e.g., contraceptive pill, patch, intramuscular implant or injection);
* Double barrier method, i.e., (a) condom (male or female) or (b) diaphragm,
with spermicide; or
* Intrauterine device (IUD); or
* Vasectomy (partner)
6. Must provide written informed consent and agree to comply with the trial protocol.