Study to determine if the investigational drug obeticholic acid (also known as OCA) in combination with the investigational drug bezafibrate (BZF), has an effect on Primary Biliary Cholangitis (also known as Primary Biliary Cirrhosis or PBC).
- Conditions
- Primary Biliary Cholangitis (PBC)MedDRA version: 21.0Level: LLTClassification code 10036680Term: Primary biliary cirrhosisSystem Organ Class: 100000004871Therapeutic area: Diseases [C] - Digestive System Diseases [C06]
- Registration Number
- EUCTR2018-002575-17-PL
- Lead Sponsor
- Intercept Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 75
- A definite or probable diagnosis of PBC (consistent with the European Association for the Study of the Liver [EASL] Practice Guidelines and the American Association for the Study of Liver Diseases; [Lindor 2009a, EASL 2017])
- Qualifying ALP and/or bilirubin liver biochemistry values
- Age =18 years
- Taking UDCA for at least 12 months (stable dose for =3 months) before Day 1 or unable to tolerate or unresponsive to UDCA (no UDCA for =3 months) before Day 1
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 65
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10
- History or presence of other concomitant liver diseases
- Presence of clinical complications of PBC or clinically significant (CS) hepatic decompensation at Screening Visit 1 and 2
- Medical conditions that may cause nonhepatic increases in ALP or which may diminish life expectancy to <2 years
-Presence of any other disease or condition that interferes with the absorption, distribution, metabolism, or excretion of drugs including bile salt metabolism in the intestine
- Current or history of gallbladder disease with or without cholelithiasis and symptoms
- History of drug-induced myopathy
- Severe renal failure (serum creatinine >1.5 mg/100 mL (>135 µmol/L); creatinine clearance <60 mL/min) or undergoing dialysis
- Platelet count <100 000/ml at Screening Visits 1 and 2
- Known history of human immunodeficiency virus (HIV) infection
- History or presence of clinically concerning cardiac arrhythmias likely to affect survival during the study, or Screening (pretreatment) QT or QTc interval of >500 milliseconds
- Severe pruritus, or required systemic treatment for pruritus (eg, with bile acid sequestrants or rifampicin) within 2 months of Day 1
- History of known or suspected CS hypersensitivity to OCA, BZF, or other fibrates or any of their components
- Known photoallergic or phototoxic reactions to fibrates
- If female, known pregnancy, or has a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating
- Other CS medical conditions that are not well controlled or for which medication needs are anticipated to change during the study (eg, type 2 diabetes mellitus, hypothyroidism, nephritic syndrome, dysproteinemia,
obstructive liver disease)
- Treatment with commercially available OCA or participated in a previous study involving OCA within 6 months before Screening
- Unable to tolerate BZF or other fibrates, treatment with commercially available fibrates or participation in a previous study involving fibrates within 3 months before Screening
Note: Other protocol defined Inclusion/Exclusion criteria may apply
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective is to assess the effects of the combination of OCA and BZF on alkaline phosphatase (ALP) in comparison to BZF alone in subjects with PBC.;Secondary Objective: The secondary objectives are to assess the effects of the combination of OCA and BZF in comparison to BZF alone in subjects with PBC on the following:<br>- Response and normalization rates of biochemical disease markers<br>- Disease-specific symptoms as assessed by health-related quality of life questionnaires (PBC-40, pruritus visual analog scale [VAS], EQ-5D-5L, and SF-36)<br>- Biomarkers of bile acid synthesis and homeostasis, including 7a hydroxy 4 cholesten-3-one (C4) and bile acids<br>- Safety and tolerability ;Primary end point(s): Reduction in ALP from baseline to Week 12 in the DB Treatment Period;Timepoint(s) of evaluation of this end point: baseline toweek 12
- Secondary Outcome Measures
Name Time Method Secondary end point(s): - Response and normalization rates of biochemical disease markers<br>- Disease-specific symptoms as assessed by health-related quality of life questionnaires (PBC-40, pruritus visual analog scale [VAS], EQ-5D-5L, and SF-36)<br>- Biomarkers of bile acid synthesis and homeostasis, including 7a hydroxy 4 cholesten-3-one (C4) and bile acids<br>- Safety and tolerability ;Timepoint(s) of evaluation of this end point: Baseline to End of study