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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01473524




Registration number
NCT01473524
Ethics application status
Date submitted
14/11/2011
Date registered
17/11/2011
Date last updated
6/05/2021

Titles & IDs
Public title
Phase 3 Study of Obeticholic Acid in Patients With Primary Biliary Cirrhosis
Scientific title
A Phase 3, Double-Blind, Placebo-Controlled Trial and Long-Term Safety Extension of Obeticholic Acid in Patients With Primary Biliary Cirrhosis
Secondary ID [1] 0 0
747-301
Universal Trial Number (UTN)
Trial acronym
POISE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Primary Biliary Cirrhosis 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 0 0 0 0
Connective tissue diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Obeticholic Acid (OCA)
Treatment: Drugs - Placebo

Experimental: DB OCA 5-10 mg - OCA 5 milligram (mg) for 6 months and then titrating up to 10 mg based on tolerability and response for remaining 6 months of the DB phase.

Experimental: DB OCA 10 mg - OCA 10 mg for 12 months during the DB phase.

Placebo Comparator: DB Placebo - Matching placebo for 12 months during the DB phase.

Experimental: LTSE OCA - After completion of the 12-month DB phase all participants were offered the opportunity to enter an open-label LTSE for up to 5 years beginning at 5 mg OCA. Initially, participants were allowed to titrate to doses up to 25 mg, however, the maximum dose was then limited to 10 mg. Participants who were previously titrated above 10 mg OCA daily were down-titrated to =10 mg OCA daily.


Treatment: Drugs: Obeticholic Acid (OCA)
OCA was administered orally once daily and provided in tablet form in 2 strengths: 5 mg and 10 mg.

Treatment: Drugs: Placebo
Matching placebo tablets were administered orally once daily.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
DB Phase: Composite Endpoint Alkaline Phosphatase (ALP) And Total Bilirubin, 10 mg OCA Versus Placebo
Timepoint [1] 0 0
DB Month 12
Primary outcome [2] 0 0
LTSE Phase: Composite Endpoint ALP And Total Bilirubin
Timepoint [2] 0 0
Baseline (DB Month 12), LTSE Months 24, 36, 48, and 60
Secondary outcome [1] 0 0
DB Phase: Composite Endpoint ALP And Total Bilirubin, 10 mg Versus Placebo
Timepoint [1] 0 0
DB Month 6
Secondary outcome [2] 0 0
DB Phase: Composite Endpoint ALP And Total Bilirubin, 5-10 mg Versus Placebo
Timepoint [2] 0 0
DB Month 12
Secondary outcome [3] 0 0
DB Phase: Composite Endpoint ALP And Total Bilirubin, 5-10 mg Versus Placebo
Timepoint [3] 0 0
DB Month 6
Secondary outcome [4] 0 0
DB Phase: ALP Absolute Change From Baseline To Month 12
Timepoint [4] 0 0
Baseline, DB Month 12
Secondary outcome [5] 0 0
DB Phase: Total Bilirubin Absolute Change From Baseline To Month 12
Timepoint [5] 0 0
Baseline, DB Month 12
Secondary outcome [6] 0 0
DB Phase: Direct Bilirubin Absolute Change From Baseline To Month 12
Timepoint [6] 0 0
Baseline, DB Month 12
Secondary outcome [7] 0 0
DB Phase: Alanine Aminotransferase (ALT) Absolute Change From Baseline To Month 12
Timepoint [7] 0 0
Baseline, DB Month 12
Secondary outcome [8] 0 0
DB Phase: Aspartate Aminotransferase (AST) Absolute Change From Baseline To Month 12
Timepoint [8] 0 0
Baseline, DB Month 12
Secondary outcome [9] 0 0
DB Phase: Gamma-glutamyltransferase (GGT) Absolute Change From Baseline To Month 12
Timepoint [9] 0 0
Baseline, DB Month 12
Secondary outcome [10] 0 0
LTSE Phase: ALP Levels
Timepoint [10] 0 0
LTSE Day 0 and LTSE Months 12, 24, 36, 48, and 60
Secondary outcome [11] 0 0
LTSE Phase: ALP Change From DB Baseline
Timepoint [11] 0 0
DB Baseline, LTSE Months 12, 24, 36, 48, and 60

Eligibility
Key inclusion criteria
1. Definite or probable PBC diagnosis (consistent with American Association for the Study
of Liver Disease [AASLD] and European Association for Study of the Liver [EASL]
Practice Guidelines; [Lindor 2009; EASL 2009]), as demonstrated by the presence of = 2
of the following 3 diagnostic factors:

- History of elevated alkaline phosphatase (ALP) levels for at least 6 months

- Positive antimitochondrial antibodies (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 (pyruvate dehydrogenase complex-E2
[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 upper limit of normal (ULN)

- Total bilirubin > ULN but < 2x ULN

3. Age = 18 years

4. Taking ursodeoxycholic acid (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 participants 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 end of treatment (EOT) visit.
Effective methods of contraception are considered to be:

- Hormonal (for example, contraceptive pill, patch, intramuscular implant or
injection); or

- Double barrier method, that is, (a) condom (male or female) or (b) diaphragm,
with spermicide; or

- Intrauterine device (IUD); or

- Vasectomy (partner); or

- Sexual abstinence

6. Must provide written informed consent and agree to comply with the trial protocol.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. History or presence of other concomitant liver diseases including:

- Hepatitis C virus (HCV) infection; participants with active hepatitis B (HBV)
infection will be excluded, however, participants who have seroconverted
(hepatitis B surface antigen [Hbs Ag] and hepatitis B e antigen [Hbe Ag]
negative) may be included after consultation with the medical monitor.

- Primary sclerosing cholangitis (PSC)

- Alcoholic liver disease

- Definite autoimmune liver disease or overlap hepatitis

- Nonalcoholic steatohepatitis (NASH)

- Gilbert's Syndrome (due to interpretability of bilirubin levels)

2. Presence of clinical complications of PBC or clinically significant hepatic
decompensation, including:

- History of liver transplantation, current placement on a liver transplant list or
current Model for End Stage Liver Disease (MELD) score = 15

- Portal hypertension with complications, including: known gastric or large
esophageal varices, poorly controlled or diuretic resistant ascites, history of
variceal bleeds or related therapeutic or prophylactic interventions (for
example, beta blockers, insertion of variceal bands or transjugular intrahepatic
portosystemic shunt [TIPS]), or hepatic encephalopathy

- Cirrhosis with complications, including history or presence of: spontaneous
bacterial peritonitis, hepatocellular carcinoma, bilirubin > 2x ULN

- Hepatorenal syndrome (type I or II) or Screening serum creatinine > 2
mg/deciliter dL) (178 micromole [µmol])/liter [L])

3. Participants with severe pruritus or those requiring systemic treatment for pruritus
(for example, with bile acid sequestrants [BAS] or rifampicin) within 2 months of Day
0 will be excluded

4. Administration of the following medications is prohibited as specified below:

- Prohibited 6 months prior to Day 0 and throughout the trial (that is, to last
dose and/or EOT): azathioprine, colchicine, cyclosporine, methotrexate,
mycophenolate mofetil, pentoxifylline; fenofibrate or other fibrates; budesonide
and other systemic corticosteroids; potentially hepatotoxic drugs (including
a-methyl-dopa, sodium valproic acid, isoniazide, or nitrofurantoin)

- Prohibited 12 months prior to Day 0 and throughout the trial (that is, to last
dose and/or EOT): antibodies or immunotherapy directed against interleukins or
other cytokines or chemokines

5. Participants who have previously participated in a clinical trial of OCA will not be
allowed to participate

6. History or presence of clinically concerning cardiac arrhythmias likely to affect
survival during the trial, or prolongation of Screening (pretreatment) QT or QTc
interval of > 500 milliseconds (msec)

7. If female: known pregnancy, or has a positive urine pregnancy test (confirmed by a
positive serum pregnancy test), or lactating

8. Known history of human immunodeficiency virus (HIV) infection

9. Presence of any other disease or condition that is interfering with the absorption,
distribution, metabolism, or excretion of drugs including bile salt metabolism in the
intestine. Participants with inflammatory bowel disease or who have undergone gastric
bypass procedures will be excluded (gastric lap band is acceptable).

10. Medical conditions that may cause nonhepatic increases in ALP (for example, Paget's
disease) or which may diminish life expectancy to < 2 years, including known cancers
(except carcinomas in situ or other stable, relatively benign conditions such as
chronic lymphatic leukemia)

11. Other clinically significant medical conditions that are not well controlled or for
which medication needs are anticipated to change during the trial

12. Anticipated changes to current concomitant medications during the course of the trial

13. History of alcohol abuse, defined as consumption of more than 210 mL of alcohol per
week (that is, the equivalent of fourteen 4-ounce (125 mL) glasses of wine or fourteen
12 ounce cans/bottles of beer), or other substance abuse within 1 year prior to Day 0

14. Participation in another investigational drug, biologic, or medical device trial
within 30 days prior to Screening

15. History of noncompliance with medical regimens, or participants who are considered to
be potentially unreliable

16. Blood or plasma donation within 30 days prior to Day 0

17. Mental instability or incompetence, such that the validity of informed consent or
compliance with the trial is uncertain

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/01/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
17/12/2018
Sample size
Target
Accrual to date
Final
217
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
Austin Hospital - Heidelberg
Recruitment hospital [3] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
3084 - Heidelberg
Recruitment postcode(s) [3] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Indiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
Missouri
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
United States of America
State/province [10] 0 0
Virginia
Country [11] 0 0
United States of America
State/province [11] 0 0
Washington
Country [12] 0 0
Austria
State/province [12] 0 0
Innsbruck
Country [13] 0 0
Austria
State/province [13] 0 0
Wien
Country [14] 0 0
Belgium
State/province [14] 0 0
Leuven
Country [15] 0 0
Canada
State/province [15] 0 0
Ontario
Country [16] 0 0
Canada
State/province [16] 0 0
Quebec
Country [17] 0 0
France
State/province [17] 0 0
Pessac
Country [18] 0 0
Germany
State/province [18] 0 0
Aachen
Country [19] 0 0
Germany
State/province [19] 0 0
Erlangen
Country [20] 0 0
Germany
State/province [20] 0 0
Frankfurt am Main
Country [21] 0 0
Germany
State/province [21] 0 0
Hamburg
Country [22] 0 0
Germany
State/province [22] 0 0
Hannover
Country [23] 0 0
Germany
State/province [23] 0 0
Heidelberg
Country [24] 0 0
Germany
State/province [24] 0 0
Herne
Country [25] 0 0
Germany
State/province [25] 0 0
Homburg
Country [26] 0 0
Germany
State/province [26] 0 0
Leipzig
Country [27] 0 0
Germany
State/province [27] 0 0
München
Country [28] 0 0
Italy
State/province [28] 0 0
Bologna
Country [29] 0 0
Italy
State/province [29] 0 0
Padova
Country [30] 0 0
Italy
State/province [30] 0 0
Rozzano (MI)
Country [31] 0 0
Netherlands
State/province [31] 0 0
Amsterdam
Country [32] 0 0
Netherlands
State/province [32] 0 0
Nijmegen
Country [33] 0 0
Netherlands
State/province [33] 0 0
Utrecht
Country [34] 0 0
Poland
State/province [34] 0 0
Katowice
Country [35] 0 0
Poland
State/province [35] 0 0
Lublin
Country [36] 0 0
Poland
State/province [36] 0 0
Szczecin
Country [37] 0 0
Poland
State/province [37] 0 0
Warszawa
Country [38] 0 0
Spain
State/province [38] 0 0
Barcelona
Country [39] 0 0
Sweden
State/province [39] 0 0
Gothenburg
Country [40] 0 0
United Kingdom
State/province [40] 0 0
Birmingham
Country [41] 0 0
United Kingdom
State/province [41] 0 0
Bristol
Country [42] 0 0
United Kingdom
State/province [42] 0 0
Dundee
Country [43] 0 0
United Kingdom
State/province [43] 0 0
Larbert
Country [44] 0 0
United Kingdom
State/province [44] 0 0
London
Country [45] 0 0
United Kingdom
State/province [45] 0 0
Manchester
Country [46] 0 0
United Kingdom
State/province [46] 0 0
Newcastle Upon Tyne
Country [47] 0 0
United Kingdom
State/province [47] 0 0
Nottingham
Country [48] 0 0
United Kingdom
State/province [48] 0 0
Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Intercept Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The main objectives of the study were to assess the effects of Obeticholic Acid (OCA) on
serum alkaline phosphatase (ALP) and total bilirubin, together as a composite endpoint and on
safety in participants with primary biliary cirrhosis (PBC).
Trial website
https://clinicaltrials.gov/ct2/show/NCT01473524
Trial related presentations / publications
Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV, Heathcote EJ; American Association for Study of Liver Diseases. Primary biliary cirrhosis. Hepatology. 2009 Jul;50(1):291-308. doi: 10.1002/hep.22906. No abstract available.
Public notes

Contacts
Principal investigator
Name 0 0
Christian Weyer, MD
Address 0 0
Intercept Pharmaceuticals, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01473524