Pilot Study Of Obeticholic Acid In Portal Hypertensio

Phase 1

Active, not recruiting

Conditions: Portal Hypertension in Patients with Cirrhosis
MedDRA version: 14.1Level: PTClassification code 10036200Term: Portal hypertensionSystem Organ Class: 10019805 - Hepatobiliary disorders
Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Registration Number: EUCTR2010-023241-29-BE

Lead Sponsor: Intercept Pharmaceuticals Inc

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Not Recruiting

Sex: All

Target Recruitment: 78

Inclusion Criteria

1. Male or female age 18-70 years.
2. History of alcoholic cirrhosis with clinical or radiological and biochemical evidence of cirrhosis.
3. Evidence of a feature of portal hypertension (endoscopic, radiological or other).
4. Patients recruited into the cohort evaluation of efficacy must have significant portal hypertension defined as an HVPG = 12 mmHg.
5. Patients with large or grade 3 oesophageal varices as identified by endoscopy within 6 months of screening should be in an endoscopic band ligation program at the time of study entry.
6. Patients will be understood to be either abstaining from alcohol for at least 6 weeks, or have a stable low alcohol intake (= 4 units per day) for at least 6 weeks, and commit to stay abstinent or to consume = 4 units per day for the duration of the study.
7. Female patients must be postmenopausal, surgically sterile, or if premenopausal, must be prepared to use at least 1 effective (=1% failure rate) method of contraception during the course of the study and for 14 days after the end of dosing. Male patients with female partners of child bearing potential must be prepared to use at least 1 effective method of contraception with all sexual partners unless they have had a prior vasectomy. Effective methods of contraception are considered to be:
• Barrier method, i.e., (a) condom (male or female) or (b) diaphragm, with spermicide; orHormonal (e.g., contraceptive pill, patch, intramuscular implant or injection); or
• Intrauterine device (IUD); or
• Vasectomy (partner)
8. Must be willing and able to give written informed consent and agree to comply with the study protocol.
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 60
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 18

Exclusion Criteria

Patients will be excluded from the study if they meet any of the following:
1. Patients with co-existing disease including:
• Significant organ failure defined as:
o Respiratory: PaO2 < 8kPa
o Renal: serum creatinine > 150 µmol/L
o Cardiovascular: haemodynamic requirement for inotropic support
o CNS: hepatic encephalopathy West Haven Criteria score > 2
• Decompensated cirrhosis with a Child-Pugh score > 12 or with a requirement for organ support
• Concomitant hepatobiliary disease (except hepatitis B or C viral disease), e.g., primary sclerosing cholangitis, primary biliary cirrhosis
• Known or suspected hepatic or extra hepatic malignancy, unless adequately treated or in complete remission for = 3 years
• Concomitant acute pancreatitis
• Acute alcoholic hepatitis with sepsis, within 3 months
2. Use of treatments for hepatitis B or C virus within 12 months of randomisation, or anticipated use during the study.
3. Use of the following drugs within 6 months of randomisation:
• Immuno-modulatory treatment (including azothiaprine, methotrexate, anti-TNF therapies)
4. Use of concomitant vasoactive drugs within 4-6 weeks (as specified below) of randomisation, including:
• Beta blockers (= 6 weeks prior to randomisation or, following one-off short term treatment of up to a maximum of 6 days = 3 weeks prior to randomisation)
• Nitrates (= 6 weeks prior to randomisation)
• Vasopressin or analogues (= 6 weeks prior to randomisation)
• Phosphodiesterase-5 inhibitors (e.g., sildenafil, tadalafil, vardenafil or other drugs for erectile dysfunction) = 4 weeks prior to randomisation)
5. Use of the following drugs within 3 months of randomisation:
• Systemic corticosteroids
• Pentoxifylline
• Potentially hepatotoxic drugs (including a methyl-dopa, sodium valproic acid, isoniazide, or nitrofurantoin), unless well tolerated, and approved by the medical monitor
• Ursodeoxycholic acid (UDCA)
• Known or suspected use of illicit drugs or drugs of abuse (allowed if medically prescribed or indicated)
6. Change in dose or regimen within 3 months of randomisation of:
• Fibrates or statins
• Angiotensin II receptor antagonist or angiotensin converting enzyme (ACE) inhibitor
7. Presence of human immunodeficiency virus (HIV).
8. If female: pregnant, lactating, or positive serum or urine pregnancy test.
9. BMI = 40, or = 35 with complications.
10. Other concomitant disease or condition likely to significantly decrease life expectancy (e.g., moderate to severe congestive heart failure).
11. Any patient who has received any investigational drug or device within 4 months of dosing, or who is scheduled to receive another investigational drug or device during the course of this study.
12. Known iodine allergy or sensitivity to contrast media.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

Related Trials