Study to Assess Safety & Efficacy of GKT137831 in Patient... | NCT03226067

NCT03226067

ID	Type	Description	Link
2016-004599-23	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
GKT137831 400mg twice daily	Experimental	GKT137831 400mg twice daily Patients will self-administer 4 capsules in the morning and 4 capsules in the evening.	Drug: GKT137831
GKT137831 400mg once daily	Experimental	GKT137831 400mg once daily Patients will self-administer 4 capsules in the morning and 4 capsules in the evening. The capsules in the evening will be placebos.	Drug: GKT137831 Drug: Placebo oral capsule
Placebo Arm	Placebo Comparator	Patients will self-administer 4 capsules in the morning and 4 capsules in the evening. All capsules will be placebos.	Drug: Placebo oral capsule

Interventions

Name	Type	Description	Arm Group Labels	Other Names
GKT137831	Drug	GKT137831 100mg capsules. To be taken as part of two dose arms which are 400mg twice daily or 400mg once daily.	GKT137831 400mg once daily GKT137831 400mg twice daily

Outcomes Module

Measure	Description	Time Frame
The Percent Change in Serum GGT.	Percent change in serum GGT from baseline to Week 24 (serum GGT was measured in U/L)	Baseline to week 24 (visit 7)

Secondary Outcomes

Measure	Description	Time Frame
Absolute Change in Serum GGT	Absolute change in serum GGT from baseline to each assessment.	From baseline to Weeks 2, 6, 12, 18 and 24
Percent Change in Serum GGT	Percent change in serum GGT from baseline to each assessment (serum GGT was measured in U/L)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male or female aged 18 to 80 years, inclusive.
Willing and able to give written informed consent and to comply with the requirements of the study.
PBC diagnosis as demonstrated by the presence of ≥ 2 of the following 3 diagnostic factors:
- History of elevated ALP levels (> ULN) for at least 6 months
- Positive anti-mitochondrial antibody (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 [PDC-E2, 2-oxo-glutaric acid dehydrogenase complex])
- Liver biopsy consistent with PBC (based on historic liver biopsy), including non-suppurative, destructive cholangitis affecting mainly the interlobular and septal bile ducts.
Serum ALP ≥ 1.5 x ULN.
Serum GGT ≥ 1.5 x ULN.
UDCA treatment for at least 6 months and stable dose for at least 3 months prior to Visit 1.
Subjects being treated for pruritus with colestyramine must be on a stable dose of colestyramine for at least 8 weeks prior to baseline/Day 1 (Visit 2). Subjects must be willing and able to take colestyramine at least 2 hours before or after study medication.
Female subjects of childbearing potential must use a highly effective method of contraception to prevent pregnancy for 4 weeks before randomization and must agree to continue strict contraception for 90 days after last administration of investigational medicinal product (IMP). Male participants with female partners of childbearing potential must be willing to use a condom and require their partner to use an additional form of adequate contraception as approved by the Investigator. This requirement begins at the time of informed consent and ends 90 days after the last administration of IMP. Male study participants must also not donate sperm from baseline until 90 days after the last administration of IMP.

Exclusion Criteria:

A positive pregnancy test or breast-feeding for female subjects.
Any hepatic decompensation, defined as a past or current history of hepatic encephalopathy, gastrointestinal tract bleeding due to esophageal varices, or ascites.
International normalized ratio (INR) > 1.2 unless subject is on anticoagulant therapy.
ALT > 3 x ULN.
Total bilirubin > 1 x ULN.
Planned or current plasmapheresis or other extra-corporeal treatments (e.g., molecular adsorbent recirculation system (MARS)) for treatment-refractory pruritus.
History of liver transplantation, current placement on a liver transplant list or current Model for End Stage Liver Disease (MELD) score ≥ 15.
Cirrhosis with complications, including history or presence of: spontaneous bacterial peritonitis, hepatocellular carcinoma.
Hepatorenal syndrome (type I or II) or Screening serum creatinine > ULN.
Competing etiology for liver disease (e.g., hepatitis C, active hepatitis B, non-alcoholic steatohepatitis (NASH), alcoholic liver disease (ALD), autoimmune hepatitis, primary sclerosing cholangitis, Gilbert's Syndrome).
Subjects receiving prohibited medications within 3 months of Screening (Visit 1) according to the list (a, b and c) provided in Section 6.6.2.
Treatment with any investigational agent within 4 weeks of Visit 1 or 5 half-lives of the investigational medicinal product (whichever is longer).
A history of long QT syndrome.
Evidence of any of the following cardiac conduction abnormalities during the screening period:
- A QTc Fredericia interval >450 milliseconds for males and >470 milliseconds for females.
- A second or third degree atrioventricular block not successfully treated with a pacemaker.
History of cancer in the preceding 5 years, except adequately treated non-melanoma skin cancer, carcinoma in situ of the cervix, in situ prostate cancer, in situ breast ductal carcinoma, or superficial bladder cancer stage 0).
The occurrence of any acute infection requiring systemic antibiotic therapy within the 2 weeks prior the Screening Visit (Visit 1), or human immunodeficiency virus (HIV) infection.
A history of bone marrow disorder including aplastic anemia, or marked anemia defined as hemoglobin < 10.0 g/dL (or 6.2 mmol/L).
Any condition which, in the opinion of the Investigator, constitutes a risk or contraindication for the participation of the subject in the study, or which could interfere with the study objectives, conduct, or evaluation.

Contacts/Locations Module

Name	Affiliation	Role
Philippe Wiesel, MD	Calliditas Therapeutics AB	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Mayo Clinic		Phoenix	Arizona	85054	United States
University California Davis

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
37183520	Derived	Invernizzi P, Carbone M, Jones D, Levy C, Little N, Wiesel P, Nevens F; study investigators. Setanaxib, a first-in-class selective NADPH oxidase 1/4 inhibitor for primary biliary cholangitis: A randomized, placebo-controlled, phase 2 trial. Liver Int. 2023 Jul;43(7):1507-1522. doi: 10.1111/liv.15596. Epub 2023 May 15.
36809195

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	GKT137831 400mg Twice Daily	GKT137831 400mg twice daily Patients will self-administer 4 capsules in the morning and 4 capsules in the evening. GKT137831: GKT137831 100mg capsules. To be taken as part of two dose arms which are 400mg twice daily or 400mg once daily.
FG001	GKT137831 400mg Once Daily

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jul 24, 2018	Mar 10, 2020

Derived Section

Miscellaneous Info Module

Submission Tracking

Condition Browse Module

Intervention Browse Module

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	GKT137831 400mg Once Daily	Subjects randomized to the 400 mg OD dose arm self-administered IMP twice daily for 24 weeks: 4 active capsules (AM dose) and 4 placebo capsules (PM dose)
BG001	GKT137831 400mg Twice Daily	Subjects randomized to the 400 mg BID dose arm self-administered IMP twice daily for 24 weeks: 4 active capsules (AM dose) and 4 active capsules (PM dose)
BG002	Placebo Arm	Subjects randomized to the placebo arm self-administered placebo twice daily for 24 weeks: 4 placebo capsules (AM dose) and 4 placebo capsules (PM dose)
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000 BG0010 BG0020 BG003

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00056.8± 9.1 BG00155.6± 9.04 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00030 BG00134 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Race

Title	Measurements
White	BG00038 BG00136 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

Greece

Title	Measurements
	BG0004 BG0013 BG002

Disease severity level based on baseline serum GGT

Number

participants

Title

Denominators

Categories

<2.5 X ULN

Title	Measurements
	BG0008 BG0017 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

The Percent Change in Serum GGT.

Percent change in serum GGT from baseline to Week 24 (serum GGT was measured in U/L)

Number of subjects analyzed in the Intent to Treat population who have evaluable results

Posted

Mean

Standard Deviation

percent change

Baseline to week 24 (visit 7)

ID	Title	Description
OG000	GKT137831 400mg Once Daily	Subjects randomized to the 400 mg OD dose arm self-administered IMP twice daily for 24 weeks: 4 active capsules (AM dose) and 4 placebo capsules (PM dose)
OG001	GKT137831 400mg Twice Daily	Subjects randomized to the 400 mg BID dose arm self-administered IMP twice daily for 24 weeks: 4 active capsules (AM dose) and 4 active capsules (PM dose)
OG002	Placebo Arm	Subjects randomized to the placebo arm self-administered placebo twice daily for 24 weeks: 4 placebo capsules (AM dose) and 4 placebo capsules (PM dose)

Units	Counts
Participants	OG00037 OG00130 OG00235

Title

Denominators

Categories

Title	Measurements
	OG000-4.9± 59.58 OG001-19± 28.89 OG002-8.4± 21.45

Secondary

Absolute Change in Serum GGT

Absolute change in serum GGT from baseline to each assessment.

Number of subjects analyzed in the Intent to Treat population who have evaluable results

Posted

Mean

Standard Deviation

U/L

From baseline to Weeks 2, 6, 12, 18 and 24

ID	Title	Description
OG000	GKT137831 400mg Once Daily	Subjects randomized to the 400 mg OD dose arm self-administered IMP twice daily for 24 weeks: 4 active capsules (AM dose) and 4 placebo capsules (PM dose)
OG001	GKT137831 400mg Twice Daily	Subjects randomized to the 400 mg BID dose arm self-administered IMP twice daily for 24 weeks: 4 active capsules (AM dose) and 4 active capsules (PM dose)
OG002	Placebo Arm	Subjects randomized to the placebo arm self-administered placebo twice daily for 24 weeks: 4 placebo capsules (AM dose) and 4 placebo capsules (PM dose)

Units	Counts
Participants

Secondary

Percent Change in Serum GGT

Percent change in serum GGT from baseline to each assessment (serum GGT was measured in U/L)

Number of subjects analyzed in the Intent to Treat population who have evaluable results

Posted

Mean

Standard Deviation

percent change

From baseline to Weeks 2, 6, 12, 18 and 24

ID	Title	Description
OG000	GKT137831 400mg Once Daily	Subjects randomized to the 400 mg OD dose arm self-administered IMP twice daily for 24 weeks: 4 active capsules (AM dose) and 4 placebo capsules (PM dose)
OG001	GKT137831 400mg Twice Daily	Subjects randomized to the 400 mg BID dose arm self-administered IMP twice daily for 24 weeks: 4 active capsules (AM dose) and 4 active capsules (PM dose)
OG002	Placebo Arm	Subjects randomized to the placebo arm self-administered placebo twice daily for 24 weeks: 4 placebo capsules (AM dose) and 4 placebo capsules (PM dose)

Units	Counts

Secondary

Percent Change in Serum ALP

Percent change in serum ALP from baseline to each assessment (serum ALP was measured in U/L).

Number of subjects analyzed in the Intent to Treat population who have evaluable results

Posted

Mean

Standard Deviation

percent change

From baseline to Weeks 2, 6, 12, 18 and 24

ID	Title	Description
OG000	GKT137831 400mg Once Daily	Subjects randomized to the 400 mg OD dose arm self-administered IMP twice daily for 24 weeks: 4 active capsules (AM dose) and 4 placebo capsules (PM dose)
OG001	GKT137831 400mg Twice Daily	Subjects randomized to the 400 mg BID dose arm self-administered IMP twice daily for 24 weeks: 4 active capsules (AM dose) and 4 active capsules (PM dose)
OG002	Placebo Arm	Subjects randomized to the placebo arm self-administered placebo twice daily for 24 weeks: 4 placebo capsules (AM dose) and 4 placebo capsules (PM dose)

Units	Counts

Secondary

Absolute Change in Serum ALP

Absolute change in serum ALP from baseline to each assessment.

Number of subjects analyzed in the Intent to Treat population who have evaluable results

Posted

Mean

Standard Deviation

U/L

From baseline to Weeks 2, 6, 12, 18 and 24

ID	Title	Description
OG000	GKT137831 400mg Once Daily	Subjects randomized to the 400 mg OD dose arm self-administered IMP twice daily for 24 weeks: 4 active capsules (AM dose) and 4 placebo capsules (PM dose)
OG001	GKT137831 400mg Twice Daily	Subjects randomized to the 400 mg BID dose arm self-administered IMP twice daily for 24 weeks: 4 active capsules (AM dose) and 4 active capsules (PM dose)
OG002	Placebo Arm	Subjects randomized to the placebo arm self-administered placebo twice daily for 24 weeks: 4 placebo capsules (AM dose) and 4 placebo capsules (PM dose)

Units	Counts
Participants

Secondary

Absolute Change in Serum Conjugated Bilirubin.

Absolute change in serum conjugated bilirubin from baseline to each assessment.

Number of subjects analyzed in the Intent to Treat population who have evaluable results

Posted

Mean

Standard Deviation

μmol/L

From baseline to Weeks 2, 6, 12, 18 and 24

ID	Title	Description
OG000	GKT137831 400mg Once Daily	Subjects randomized to the 400 mg OD dose arm self-administered IMP twice daily for 24 weeks: 4 active capsules (AM dose) and 4 placebo capsules (PM dose)
OG001	GKT137831 400mg Twice Daily	Subjects randomized to the 400 mg BID dose arm self-administered IMP twice daily for 24 weeks: 4 active capsules (AM dose) and 4 active capsules (PM dose)
OG002	Placebo Arm	Subjects randomized to the placebo arm self-administered placebo twice daily for 24 weeks: 4 placebo capsules (AM dose) and 4 placebo capsules (PM dose)

Units	Counts

Secondary

Percent Change in Serum Conjugated Bilirubin.

Percent change in serum Conjugated bilirubin, from baseline to each assessment (serum conjugated bilirubin is measured in μmol/L).

Number of subjects analyzed in the Intent to Treat population who have evaluable results

Posted

Mean

Standard Deviation

percent change

From baseline to Weeks 2, 6, 12, 18 and 24

ID	Title	Description
OG000	GKT137831 400mg Once Daily	Subjects randomized to the 400 mg OD dose arm self-administered IMP twice daily for 24 weeks: 4 active capsules (AM dose) and 4 placebo capsules (PM dose)
OG001	GKT137831 400mg Twice Daily	Subjects randomized to the 400 mg BID dose arm self-administered IMP twice daily for 24 weeks: 4 active capsules (AM dose) and 4 active capsules (PM dose)
OG002	Placebo Arm	Subjects randomized to the placebo arm self-administered placebo twice daily for 24 weeks: 4 placebo capsules (AM dose) and 4 placebo capsules (PM dose)

Units

Secondary

Absolute Change in Serum Total Bilirubin.

Absolute change in serum total bilirubin, from baseline to each assessment.

Number of subjects analyzed in the Intent to Treat population who have evaluable results

Posted

Mean

Standard Deviation

μmol/L

from baseline to Weeks 2, 6, 12, 18 and 24

ID	Title	Description
OG000	GKT137831 400mg Once Daily	Subjects randomized to the 400 mg OD dose arm self-administered IMP twice daily for 24 weeks: 4 active capsules (AM dose) and 4 placebo capsules (PM dose)
OG001	GKT137831 400mg Twice Daily	Subjects randomized to the 400 mg BID dose arm self-administered IMP twice daily for 24 weeks: 4 active capsules (AM dose) and 4 active capsules (PM dose)
OG002	Placebo Arm	Subjects randomized to the placebo arm self-administered placebo twice daily for 24 weeks: 4 placebo capsules (AM dose) and 4 placebo capsules (PM dose)

Units	Counts

Secondary

Percent Change in Serum Total Bilirubin.

Percent change in Serum Total Bilirubin from baseline to each assessment (serum total bilirubin is measured in μmol/L).

Number of subjects analyzed in the Intent to Treat population who have evaluable results

Posted

Mean

Standard Deviation

percent change

from baseline to Weeks 2, 6, 12, 18 and 24

ID	Title	Description
OG000	GKT137831 400mg Once Daily	Subjects randomized to the 400 mg OD dose arm self-administered IMP twice daily for 24 weeks: 4 active capsules (AM dose) and 4 placebo capsules (PM dose)
OG001	GKT137831 400mg Twice Daily	Subjects randomized to the 400 mg BID dose arm self-administered IMP twice daily for 24 weeks: 4 active capsules (AM dose) and 4 active capsules (PM dose)
OG002	Placebo Arm	Subjects randomized to the placebo arm self-administered placebo twice daily for 24 weeks: 4 placebo capsules (AM dose) and 4 placebo capsules (PM dose)

Units	Counts

Secondary

Absolute Change in Liver Stiffness as Assessed by Transient Elastography (FibroScan® or Similar Technology).

Absolute change in liver stiffness as assessed by transient elastography (FibroScan® or similar technology), from baseline to Week 24, in subjects with values at baseline and Week 24.

Number of subjects analyzed in the Intent to Treat population who have evaluable results

Posted

Mean

Standard Deviation

kPa

From baseline to Week 24, in patients with values at baseline and Week 24.

ID	Title	Description
OG000	GKT137831 400mg Once Daily	Subjects randomized to the 400 mg OD dose arm self-administered IMP twice daily for 24 weeks: 4 active capsules (AM dose) and 4 placebo capsules (PM dose)
OG001	GKT137831 400mg Twice Daily	Subjects randomized to the 400 mg BID dose arm self-administered IMP twice daily for 24 weeks: 4 active capsules (AM dose) and 4 active capsules (PM dose)
OG002	Placebo Arm	Subjects randomized to the placebo arm self-administered placebo twice daily for 24 weeks: 4 placebo capsules (AM dose) and 4 placebo capsules (PM dose)

Secondary

Percent Change in Liver Stiffness as Assessed by Transient Elastography (FibroScan® or Similar Technology).

Percent change in liver stiffness as assessed by transient elastography (FibroScan® or similar technology), from baseline to Week 24, in subjects with values at baseline and Week 24 (liver stiffness is measured in kPa).

Number of subjects analyzed in the Intent to Treat population who have evaluable results

Posted

Mean

Standard Deviation

percent change

From baseline to Week 24, in patients with values at baseline and Week 24.

ID	Title	Description
OG000	GKT137831 400mg Once Daily	Subjects randomized to the 400 mg OD dose arm self-administered IMP twice daily for 24 weeks: 4 active capsules (AM dose) and 4 placebo capsules (PM dose)
OG001	GKT137831 400mg Twice Daily	Subjects randomized to the 400 mg BID dose arm self-administered IMP twice daily for 24 weeks: 4 active capsules (AM dose) and 4 active capsules (PM dose)
OG002	Placebo Arm	Subjects randomized to the placebo arm self-administered placebo twice daily for 24 weeks: 4 placebo capsules (AM dose) and 4 placebo capsules (PM dose)

Secondary

Percent Change in Serum Levels of Collagen Fragments Indicative of Collagen Formation and Degradation.

Percent change in serum levels of collagen fragments indicative of collagen formation and degradation, from baseline to Weeks 12 and 24 (serum levels of collagen fragments are measured in ng/mL).

Number of subjects analyzed in the Intent to Treat population who have evaluable results

Posted

Mean

Standard Deviation

percent change

From baseline to Weeks 12 and 24.

ID	Title	Description
OG000	GKT137831 400mg Once Daily	Subjects randomized to the 400 mg OD dose arm self-administered IMP twice daily for 24 weeks: 4 active capsules (AM dose) and 4 placebo capsules (PM dose)
OG001	GKT137831 400mg Twice Daily	Subjects randomized to the 400 mg BID dose arm self-administered IMP twice daily for 24 weeks: 4 active capsules (AM dose) and 4 active capsules (PM dose)
OG002	Placebo Arm	Subjects randomized to the placebo arm self-administered placebo twice daily for 24 weeks: 4 placebo capsules (AM dose) and 4 placebo capsules (PM dose)

Secondary

Absolute Change in Liver Stiffness as Assessed by Transient Elastography by Subgroup (FibroScan® or Similar Technology).

Absolute change in liver stiffness by subgroup (>=9.6 kPa) as assessed by transient elastography (FibroScan® or similar technology), from baseline to Week 24, in subjects with values at baseline and Week 24.

Number of subjects analyzed in the Intent to Treat population who have evaluable results

Posted

Mean

Standard Deviation

kPa

From baseline to Week 24, in patients with values at baseline and Week 24.

ID	Title	Description
OG000	GKT137831 400mg Once Daily	Subjects randomized to the 400 mg OD dose arm self-administered IMP twice daily for 24 weeks: 4 active capsules (AM dose) and 4 placebo capsules (PM dose)
OG001	GKT137831 400mg Twice Daily	Subjects randomized to the 400 mg BID dose arm self-administered IMP twice daily for 24 weeks: 4 active capsules (AM dose) and 4 active capsules (PM dose)
OG002	Placebo Arm	Subjects randomized to the placebo arm self-administered placebo twice daily for 24 weeks: 4 placebo capsules (AM dose) and 4 placebo capsules (PM dose)

Secondary

Percent Change in Liver Stiffness as Assessed by Transient Elastography by Subgroup (FibroScan® or Similar Technology).

Percent change in liver stiffness by subgroup (>=9.6 kPa) as assessed by transient elastography (FibroScan® or similar technology), from baseline to Week 24, in subjects with values at baseline and Week 24 (liver stiffness is measured in kPa).

Number of subjects analyzed in the Intent to Treat population who have evaluable results

Posted

Mean

Standard Deviation

percent change

From baseline to Week 24, in patients with values at baseline and Week 24.

ID	Title	Description
OG000	GKT137831 400mg Once Daily	Subjects randomized to the 400 mg OD dose arm self-administered IMP twice daily for 24 weeks: 4 active capsules (AM dose) and 4 placebo capsules (PM dose)
OG001	GKT137831 400mg Twice Daily	Subjects randomized to the 400 mg BID dose arm self-administered IMP twice daily for 24 weeks: 4 active capsules (AM dose) and 4 active capsules (PM dose)
OG002	Placebo Arm	Subjects randomized to the placebo arm self-administered placebo twice daily for 24 weeks: 4 placebo capsules (AM dose) and 4 placebo capsules (PM dose)

Secondary

Absolute Change in Pruritis Visual Analogue Scale (VAS) Scores

Absolute Change in Pruritis Visual Analogue Scale (VAS) scores from baseline to weeks 12 and 24- Score from 0 to 10, 0= no itch and 10= severe itch, continuous, day and night intolerable itch.

Number of subjects analyzed in the Intent to Treat population who have evaluable results

Posted

Mean

Standard Deviation

score on a scale

From baseline to Weeks 12 and 24

ID	Title	Description
OG000	GKT137831 400mg Once Daily	Subjects randomized to the 400 mg OD dose arm self-administered IMP twice daily for 24 weeks: 4 active capsules (AM dose) and 4 placebo capsules (PM dose)
OG001	GKT137831 400mg Twice Daily	Subjects randomized to the 400 mg BID dose arm self-administered IMP twice daily for 24 weeks: 4 active capsules (AM dose) and 4 active capsules (PM dose)
OG002	Placebo Arm	Subjects randomized to the placebo arm self-administered placebo twice daily for 24 weeks: 4 placebo capsules (AM dose) and 4 placebo capsules (PM dose)

Secondary

Percent Change in Pruritis Visual Analogue Scale (VAS) Scores

Percent Change in Pruritis Visual Analogue Scale (VAS) scores from baseline to weeks 12 and 24- Score from 0 to 10, 0= no itch and 10= severe itch, continuous, day and night intolerable itch.

Number of subjects analyzed in the Intent to Treat population who have evaluable results

Posted

Mean

Standard Deviation

percent change

From baseline to Weeks 12 and 24

ID	Title	Description
OG000	GKT137831 400mg Once Daily	Subjects randomized to the 400 mg OD dose arm self-administered IMP twice daily for 24 weeks: 4 active capsules (AM dose) and 4 placebo capsules (PM dose)
OG001	GKT137831 400mg Twice Daily	Subjects randomized to the 400 mg BID dose arm self-administered IMP twice daily for 24 weeks: 4 active capsules (AM dose) and 4 active capsules (PM dose)
OG002	Placebo Arm	Subjects randomized to the placebo arm self-administered placebo twice daily for 24 weeks: 4 placebo capsules (AM dose) and 4 placebo capsules (PM dose)

Secondary

Absolute Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores

Absolute Change in PBC-40 Domain scores from baseline to weeks 12 and 24 Symptoms domain: items 1 to 7 of the PBC-40 questionnaire (score from 6 to 35). Itch domain: items 8 to 10 of the PBC-40 questionnaire (score from 0 to 15). Fatigue domain: items 11 to 21 of the PBC-40 questionnaire (score from 11 to 55). Cognitive domain: items 22 to 27 of the PBC-40 questionnaire (score from 6 to 30). Emotional domain: items 28, 30 and 33 of the PBC-40 questionnaire (score from 3 to 15). Social domain: items 29, 31, 32, 34 to 40 of the PBC-40 questionnaire (score from 8 to 50). Higher scores mean worse outcome.

Number of subjects analyzed in the Intent to Treat population who have evaluable results

Posted

Mean

Standard Deviation

score on a scale

From baseline to Weeks 12 and 24

ID	Title	Description
OG000	GKT137831 400mg Once Daily	Subjects randomized to the 400 mg OD dose arm self-administered IMP twice daily for 24 weeks: 4 active capsules (AM dose) and 4 placebo capsules (PM dose)
OG001	GKT137831 400mg Twice Daily	Subjects randomized to the 400 mg BID dose arm self-administered IMP twice daily for 24 weeks: 4 active capsules (AM dose) and 4 active capsules (PM dose)
OG002	Placebo Arm

Secondary

Percent Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores

Percent Change in PBC-40 Domain scores from baseline to weeks 12 and 24 Symptoms domain: items 1 to 7 of the PBC-40 questionnaire (score from 6 to 35). Itch domain: items 8 to 10 of the PBC-40 questionnaire (score from 0 to 15). Fatigue domain: items 11 to 21 of the PBC-40 questionnaire (score from 11 to 55). Cognitive domain: items 22 to 27 of the PBC-40 questionnaire (score from 6 to 30). Emotional domain: items 28, 30 and 33 of the PBC-40 questionnaire (score from 3 to 15). Social domain: items 29, 31, 32, 34 to 40 of the PBC-40 questionnaire (score from 8 to 50). Higher scores mean worse outcome.

Number of subjects analyzed in the Intent to Treat population who have evaluable results

Posted

Mean

Standard Deviation

percent change

From baseline to Weeks 12 and 24

ID	Title	Description
OG000	GKT137831 400mg Once Daily	Subjects randomized to the 400 mg OD dose arm self-administered IMP twice daily for 24 weeks: 4 active capsules (AM dose) and 4 placebo capsules (PM dose)
OG001	GKT137831 400mg Twice Daily	Subjects randomized to the 400 mg BID dose arm self-administered IMP twice daily for 24 weeks: 4 active capsules (AM dose) and 4 active capsules (PM dose)
OG002	Placebo Arm

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	GKT137831 400mg Twice Daily	GKT137831 400mg twice daily Patients will self-administer 4 capsules in the morning and 4 capsules in the evening. GKT137831: GKT137831 100mg capsules. To be taken as part of two dose arms which are 400mg twice daily or 400mg once daily.	36	1	36	32	36
EG001	GKT137831 400mg Once Daily	GKT137831 400mg once daily Patients will self-administer 4 capsules in the morning and 4 capsules in the evening. The capsules in the evening will be placebos. GKT137831: GKT137831 100mg capsules. To be taken as part of two dose arms which are 400mg twice daily or 400mg once daily. Placebo oral capsule: Matching capsules.	38	0	38	34	38
EG002	Placebo Arm	Patients will self-administer 4 capsules in the morning and 4 capsules in the evening. All capsules will be placebos. Placebo oral capsule: Matching capsules.	37	1	37	31	37

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Multiple Fractures	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	In the Setanaxib 400 mg BID arm: One (2.8%) subject experienced CTCAE grade 3 multiple fractures, resulting from a road traffic accident.	EG0001 events1 affected36 at risk EG0010 events0 affected38 at risk EG0020 events0 affected37 at risk
Urinary Infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	One (2.7%) subject in the placebo arm experienced CTCAE grade 1 urinary tract infection. This was considered unrelated to study medication by the investigator.	EG0000 events0 affected36 at risk EG0010 events0 affected38 at risk EG0021 events1 affected37 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0007 events6 affected36 at risk EG0013 events3 affected38 at risk EG0026 events4 affected37 at risk
Abdominal Pain	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0003 events3 affected36 at risk EG0014 events3 affected38 at risk EG0020 events0 affected37 at risk
Abdominal Pain Upper	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0002 events2 affected36 at risk EG0012 events2 affected38 at risk EG0022 events2 affected37 at risk
Constipation	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0004 events3 affected36 at risk EG0011 events1 affected38 at risk EG0021 events1 affected37 at risk
Gastrooesoghageal Reflux Disease	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected36 at risk EG0014 events3 affected38 at risk EG0021 events1 affected37 at risk
Diarrhea	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0002 events2 affected36 at risk EG0011 events1 affected38 at risk EG0025 events3 affected37 at risk
Dry Mouth	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected36 at risk EG0011 events1 affected38 at risk EG0022 events2 affected37 at risk
Abdominal Distension	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0002 events2 affected36 at risk EG0010 events0 affected38 at risk EG0020 events0 affected37 at risk
Pruritis	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG00010 events8 affected36 at risk EG00111 events8 affected38 at risk EG0028 events8 affected37 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected38 at risk EG0022 events2 affected37 at risk
Nasopharyngitis	Immune system disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected36 at risk EG0013 events3 affected38 at risk EG0025 events3 affected37 at risk
Urinary Tract Infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0002 events2 affected36 at risk EG0010 events0 affected38 at risk EG0025 events4 affected37 at risk
Upper Respiratory Tract Infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0002 events2 affected36 at risk EG0010 events0 affected38 at risk EG0022 events2 affected37 at risk
Oral Herpes	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected36 at risk EG0010 events0 affected38 at risk EG0022 events2 affected37 at risk
Headache	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0004 events4 affected36 at risk EG0018 events5 affected38 at risk EG0025 events5 affected37 at risk
Dizziness	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0004 events4 affected36 at risk EG0018 events5 affected38 at risk EG0021 events1 affected37 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected36 at risk EG0012 events2 affected38 at risk EG0023 events3 affected37 at risk
Fatigue	General disorders	MedDRA 21.1	Systematic Assessment	EG0003 events3 affected36 at risk EG0011 events1 affected38 at risk EG0028 events8 affected37 at risk
Pyrexia	General disorders	MedDRA 21.1	Systematic Assessment	EG0002 events2 affected36 at risk EG0011 events1 affected38 at risk EG0023 events2 affected37 at risk
Asthenia	General disorders	MedDRA 21.1	Systematic Assessment	EG0004 events2 affected36 at risk EG0010 events0 affected38 at risk EG0020 events0 affected37 at risk
Oropharyngeal Pain	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0002 events2 affected36 at risk EG0011 events1 affected38 at risk EG0022 events1 affected37 at risk
Arthropod Bite	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected36 at risk EG0010 events0 affected38 at risk EG0022 events2 affected37 at risk

First MCP Posted Date

ID	Term
D008105	Liver Cirrhosis, Biliary

Ancestor Terms

ID	Term
D002780	Cholestasis, Intrahepatic
D002779	Cholestasis
D001649	Bile Duct Diseases
D001660	Biliary Tract Diseases
D004066	Digestive System Diseases
D008107	Liver Diseases
D008103	Liver Cirrhosis
D005355	Fibrosis
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
C576694	setanaxib

Units	Counts
Participants	OG00033 OG00126 OG00232

Units	Counts
Participants	OG00033 OG00126 OG00232

Units	Counts
Participants	OG00038 OG00133 OG00234

Units	Counts
Participants	OG00014 OG0019 OG00216