A Study of INT-747 (6-ECDCA) Monotherapy in Patients With Primary Biliary Cirrhosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 60
- 试验地点
- 21
- 主要终点
- DB Phase: Mean Percent Change In Serum Alkaline Phosphatase (ALP) From Baseline To Day 85
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
排除标准
- •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.
研究组 & 干预措施
DB OCA 10 mg
OCA 10 mg for 3 months during the DB phase.
干预措施: Obeticholic Acid (OCA) (Drug)
DB OCA 50 mg
OCA 50 mg for 3 months during the DB phase.
干预措施: Obeticholic Acid (OCA) (Drug)
DB OCA Placebo
Matching placebo for 3 months during the DB phase.
干预措施: Placebo (Drug)
LTSE OCA Total
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.
干预措施: Obeticholic Acid (OCA) (Drug)
结局指标
主要结局
DB Phase: Mean Percent Change In Serum Alkaline Phosphatase (ALP) From Baseline To Day 85
时间窗: Baseline, Day 85
The percent change in serum ALP from baseline to Day 85 is reported. The baseline value used was the mean of the pretreatment Screening and Day 0 evaluations.
次要结局
- DB Phase: Mean Percent Change In Gamma-glutamyl Transferase (GGT) From Baseline To Day 85(Baseline, Day 85)
- DB Phase: Mean Percent Change In Alanine Transaminase (ALT) From Baseline To Day 85(Baseline, Day 85)
- DB: Plasma Trough Concentrations Of OCA And Its Major, Known Metabolites(12 weeks)
- DB Phase: Mean Percent Change In Conjugated Bilirubin From Baseline To Day 85(Baseline, Day 85)
- LTSE Phase: Median Percent Change In Serum ALP From Baseline To Month 24, Month 48, Month 72, And Last Available Visit(Baseline (DB), Month 24, Month 48, Month 72, Last Available Visit (up to 96 months))
- LTSE: Median Percent Change In GGT From Baseline To Last Available Visit(Baseline (DB), Last Available Visit (up to 96 months))
- LTSE: Mean Percent Change In GGT From Baseline To Last Available Visit(Baseline (DB), Last Available Visit (up to 96 months))
- LTSE: Median Percent Change In ALT From Baseline To Last Available Visit(Baseline (DB), Last Available Visit (up to 96 months))
- LTSE: Median Percent Change In Conjugated Bilirubin From Baseline To Last Available Visit(Baseline (DB), Last Available Visit (up to 96 months))
- LTSE: Median Percent Change In Total Bilirubin From Baseline To Last Available Visit(Baseline (DB), Last Available Visit (up to 96 months))
- LTSE: Mean Percent Change In Total Bilirubin From Baseline To Last Available Visit(Baseline (DB), Last Available Visit (up to 96 months))
- LTSE Phase: Mean Percent Change In Serum ALP From Baseline To Month 24, Month 48, Month 72, And Last Available Visit(Baseline (DB), Month 24, Month 48, Month 72, Last Available Visit (up to 96 months))
- LTSE: Mean Percent Change In ALT From Baseline To Last Available Visit(Baseline (DB), Last Available Visit (up to 96 months))
- LTSE: Mean Percent Change In Conjugated Bilirubin From Baseline To Last Available Visit(Baseline (DB), Last Available Visit (up to 96 months))