Study of INT-747 as Monotherapy in Participants With Primary Biliary Cirrhosis (PBC)

Intercept Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Liver Cirrhosis, Biliary

Treatments: Drug: Placebo; Drug: Obeticholic Acid (OCA)

Study type: Interventional

Funder types: Industry

Identifiers

NCT00570765

2007-001424-12 (EudraCT Number)

747-201

Details and patient eligibility

About

The primary hypothesis was that obeticholic acid (OCA) will cause a reduction in alkaline phosphatase levels in PBC participants, over a 12-week treatment period, as compared to placebo.

Full description

The study included 2 phases: a 3-month randomized, double-blind (DB), placebo-controlled, parallel group phase, followed by a long-term safety extension (LTSE). The planned duration of the LTSE phase was country-specific, ranging from 108 months to indefinitely. On-site visits occurred at least every 6 months.

Following completion of the 3-month DB phase, participants who continued to meet protocol requirements were given the opportunity to enroll in the LTSE phase of the study at selected study sites. The participants who enrolled in the LTSE phase started OCA administration, from a starting dose (10 or 50 milligrams [mg]) based on the dose of OCA or placebo received in the DB phase or on the timing of entry into the LTSE phase.

Because the LTSE phase was not planned in the original study design, participants had varied gaps between the end of the DB phase and the start of the LTSE phase. Moreover, some participants initiated ursodeoxycholic acid during the course of that break.

Enrollment: 60 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Female participants must be postmenopausal, surgically sterile, or if premenopausal, be prepared to use 1 effective method of contraception with all sexual partners during the study and for 14 days after the end of dosing.
• Male participants must be prepared to use 1 effective method of contraception with all sexual partners during the study during the study unless they had a prior vasectomy.
• Proven or likely PBC, as demonstrated by the participant presenting with at least 2 of the following 3 diagnostic factors:
• History of increased alkaline phosphatase (ALP) levels for at least 6 months;
• Positive antimitochondrial antibody titer (>1:40 titer on immunofluorescence or M2 positive by enzyme-linked immunosorbent assay) or PBC-specific antinuclear antibodies (antinuclear dot and nuclear rim positive);
• Liver biopsy consistent with PBC
• Screening ALP level between 1.5 and 10 × upper limit of normal (ULN).

Exclusion criteria

• Administration of the following drugs at any time during the 3 months prior to screening for the study: ursodeoxycholic acid, colchicine, methotrexate, azathioprine, or systemic corticosteroids.
• Screening conjugated (direct) bilirubin >2 × ULN.
• Screening alanine aminotransferase or aspartate aminotransferase >5 × ULN.
• Screening serum creatinine >133 micromoles/liter (1.5 mg/deciliter).

History or presence of hepatic decompensation (for example, variceal bleeds, encephalopathy, or poorly controlled ascites).

• History or presence of other concomitant liver diseases including hepatitis due to hepatitis B or C virus infection, primary sclerosing cholangitis, alcoholic liver disease, definite autoimmune liver disease or biopsy proven nonalcoholic steatohepatitis.
• Pregnancy.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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60 participants in 4 patient groups, including a placebo group

DB OCA 10 mg

Experimental group

Description:

OCA 10 mg for 3 months during the DB phase.

Treatment:

Drug: Obeticholic Acid (OCA)

DB OCA 50 mg

Experimental group

Description:

OCA 50 mg for 3 months during the DB phase.

Treatment:

Drug: Obeticholic Acid (OCA)

DB OCA Placebo

Placebo Comparator group

Description:

Matching placebo for 3 months during the DB phase.

Treatment:

Drug: Placebo

LTSE OCA Total

Experimental group

Description:

After completion of the 3-month DB phase, all eligible participants were offered the opportunity to enter an open-label LTSE for up to 96 months beginning at 10 mg OCA. Doses up to 50 mg daily were evaluated.

Treatment:

Drug: Obeticholic Acid (OCA)