Primary Biliary Cirrhosis
Conditions
Brief summary
The purpose of this study is to assess the safety and efficacy of GKT13783 in patients with Primary Biliary Cholangitis (PBC) who are taking a stable dose of ursodeoxycholic acid (UDCA) treatment, and have persistently high levels of a liver enzyme called Alkaline Phosphatase (ALP).
Detailed description
Primary biliary cholangitis (PBC) is a disease of the liver. It is caused a sustained attack by the body's immune system on the bile ducts (canals) inside the liver. This continuous assault leads to their gradual destruction and eventual disappearance. This results in obstruction to the flow of bile which gets worse with disease progression. Once the bile duct injury has been established, the disease progresses due to ongoing obstruction of bile flow, inflammation and scarring of the liver tissue(fibrosis). The liver eventually fails. This research is looking into whether the study drug is better than a dummy drug when given to patients with PBC. This trial will monitor the patients taking part with regular blood tests and ultrasound liver scans before, during, and at the end of the trial. These measures will allow for the ongoing assessment of liver function, and liver stiffness. It is hoped that in patients in whom the study drug is beneficial, the liver function or stiffness may progress at a slower pace, or may even improve during or at the end of the trial. Liver injury, inflammation and fibrosis Participants will be randomly assigned to 1 of 3 treatment groups (active drug once daily, active drug twice daily or placebo). This is a double blinded study so neither the participants nor the staff responsible for their care will know which group they have been assigned to. During the treatment period, participants will take 4 capsules orally at home in the morning and 4 capsules in the evening for 24 weeks. Participants will be in the trial for 32 weeks in total (about 8 months) and will attend approximately 8 clinic visits.
Interventions
DRUGGKT137831
GKT137831 100mg capsules. To be taken as part of two dose arms which are 400mg twice daily or 400mg once daily.
DRUGPlacebo oral capsule
Matching capsules.
Sponsors
Calliditas Therapeutics AB
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
This is a double-blind study: the Sponsor, subjects, investigator staff, persons performing the assessments and data reviewers and statisticians will remain blinded to the identity of the study treatments.
Intervention model description
This will be a double-blind, randomized, placebo-controlled, multicenter, parallel group phase 2 trial. A total of 102 subjects will be randomized and allocated to placebo or one of the 2 active treatment arms, according to a 1:1:1 randomization ratio, stratified at study entry by disease severity defined as baseline serum gamma glutamyl transferase (GGT) \< 2.5 x ULN or ≥ 2.5 x ULN). Accordingly, approximately 34 subjects will be allocated to each of the 3 treatment arms.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female aged 18 to 80 years, inclusive. 2. Willing and able to give written informed consent and to comply with the requirements of the study. 3. 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. 4. Serum ALP ≥ 1.5 x ULN. 5. Serum GGT ≥ 1.5 x ULN. 6. UDCA treatment for at least 6 months and stable dose for at least 3 months prior to Visit 1. 7. 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. 8. 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
1. A positive pregnancy test or breast-feeding for female subjects. 2. Any hepatic decompensation, defined as a past or current history of hepatic encephalopathy, gastrointestinal tract bleeding due to esophageal varices, or ascites. 3. International normalized ratio (INR) \> 1.2 unless subject is on anticoagulant therapy. 4. ALT \> 3 x ULN. 5. Total bilirubin \> 1 x ULN. 6. Planned or current plasmapheresis or other extra-corporeal treatments (e.g., molecular adsorbent recirculation system (MARS)) for treatment-refractory pruritus. 7. History of liver transplantation, current placement on a liver transplant list or current Model for End Stage Liver Disease (MELD) score ≥ 15. 8. Cirrhosis with complications, including history or presence of: spontaneous bacterial peritonitis, hepatocellular carcinoma. 9. Hepatorenal syndrome (type I or II) or Screening serum creatinine \> ULN. 10. 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). 11. 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. 12. Treatment with any investigational agent within 4 weeks of Visit 1 or 5 half-lives of the investigational medicinal product (whichever is longer). 13. A history of long QT syndrome. 14. 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. 15. 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). 16. 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. 17. A history of bone marrow disorder including aplastic anemia, or marked anemia defined as hemoglobin \< 10.0 g/dL (or 6.2 mmol/L). 18. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percent Change in Serum GGT. | Baseline to week 24 (visit 7) | Percent change in serum GGT from baseline to Week 24 (serum GGT was measured in U/L) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Serum GGT | From baseline to Weeks 2, 6, 12, 18 and 24 | Percent change in serum GGT from baseline to each assessment (serum GGT was measured in U/L) |
| Percent Change in Serum ALP | From baseline to Weeks 2, 6, 12, 18 and 24 | Percent change in serum ALP from baseline to each assessment (serum ALP was measured in U/L). |
| Absolute Change in Serum ALP | From baseline to Weeks 2, 6, 12, 18 and 24 | Absolute change in serum ALP from baseline to each assessment. |
| Absolute Change in Serum Conjugated Bilirubin. | From baseline to Weeks 2, 6, 12, 18 and 24 | Absolute change in serum conjugated bilirubin from baseline to each assessment. |
| Percent Change in Serum Conjugated Bilirubin. | From baseline to Weeks 2, 6, 12, 18 and 24 | Percent change in serum Conjugated bilirubin, from baseline to each assessment (serum conjugated bilirubin is measured in μmol/L). |
| Absolute Change in Serum Total Bilirubin. | from baseline to Weeks 2, 6, 12, 18 and 24 | Absolute change in serum total bilirubin, from baseline to each assessment. |
| Percent Change in Serum Total Bilirubin. | from baseline to Weeks 2, 6, 12, 18 and 24 | Percent change in Serum Total Bilirubin from baseline to each assessment (serum total bilirubin is measured in μmol/L). |
| Absolute Change in Liver Stiffness as Assessed by Transient Elastography (FibroScan® or Similar Technology). | From baseline to Week 24, in patients with values at baseline and Week 24. | 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. |
| Absolute Change in Serum GGT | From baseline to Weeks 2, 6, 12, 18 and 24 | Absolute change in serum GGT from baseline to each assessment. |
| Percent Change in Serum Levels of Collagen Fragments Indicative of Collagen Formation and Degradation. | From baseline to Weeks 12 and 24. | 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). |
| Absolute Change in Liver Stiffness as Assessed by Transient Elastography by Subgroup (FibroScan® or Similar Technology). | From baseline to Week 24, in patients with values at baseline and Week 24. | 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. |
| Percent Change in Liver Stiffness as Assessed by Transient Elastography by Subgroup (FibroScan® or Similar Technology). | From baseline to Week 24, in patients with values at baseline and Week 24. | 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). |
| Absolute Change in Pruritis Visual Analogue Scale (VAS) Scores | From baseline to Weeks 12 and 24 | 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. |
| Percent Change in Pruritis Visual Analogue Scale (VAS) Scores | From baseline to Weeks 12 and 24 | 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. |
| Absolute Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | From baseline to Weeks 12 and 24 | 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. |
| Percent Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | From baseline to Weeks 12 and 24 | 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. |
| Percent Change in Liver Stiffness as Assessed by Transient Elastography (FibroScan® or Similar Technology). | From baseline to Week 24, in patients with values at baseline and Week 24. | 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). |
Countries
Belgium, Canada, Germany, Greece, Israel, Italy, Spain, United Kingdom, United States
Participant flow
Recruitment details
Recruitment started Sep 2017-Sep 2018
Participants by arm
| Arm | Count |
|---|---|
| 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) | 38 |
| 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) | 36 |
| 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) | 37 |
| Total | 111 |
Baseline characteristics
| Characteristic | Placebo Arm | Total | GKT137831 400mg Twice Daily | GKT137831 400mg Once Daily |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 20 Participants | 6 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 30 Participants | 91 Participants | 30 Participants | 31 Participants |
| Age, Continuous | 56.3 years STANDARD_DEVIATION 9.19 | 56.2 years STANDARD_DEVIATION 9.04 | 55.6 years STANDARD_DEVIATION 9.04 | 56.8 years STANDARD_DEVIATION 9.1 |
| Disease severity level based on baseline serum GGT <2.5 X ULN | 10 participants | 25 participants | 7 participants | 8 participants |
| Disease severity level based on baseline serum GGT >= 2.5 X ULN | 27 participants | 86 participants | 29 participants | 30 participants |
| Race/Ethnicity, Customized Race Black | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race White | 36 Participants | 110 Participants | 36 Participants | 38 Participants |
| Region of Enrollment Belgium | 7 participants | 14 participants | 2 participants | 5 participants |
| Region of Enrollment Canada | 1 participants | 6 participants | 2 participants | 3 participants |
| Region of Enrollment Germany | 3 participants | 7 participants | 2 participants | 2 participants |
| Region of Enrollment Greece | 3 participants | 10 participants | 3 participants | 4 participants |
| Region of Enrollment Israel | 5 participants | 13 participants | 3 participants | 5 participants |
| Region of Enrollment Italy | 1 participants | 12 participants | 6 participants | 5 participants |
| Region of Enrollment Spain | 0 participants | 6 participants | 3 participants | 3 participants |
| Region of Enrollment United Kingdom | 6 participants | 16 participants | 8 participants | 2 participants |
| Region of Enrollment United States | 11 participants | 27 participants | 7 participants | 9 participants |
| Sex: Female, Male Female | 35 Participants | 99 Participants | 34 Participants | 30 Participants |
| Sex: Female, Male Male | 2 Participants | 12 Participants | 2 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 36 | 0 / 38 | 0 / 37 |
| other Total, other adverse events | 32 / 36 | 34 / 38 | 31 / 37 |
| serious Total, serious adverse events | 1 / 36 | 0 / 38 | 1 / 37 |
Outcome results
Primary
The Percent Change in Serum GGT.
Percent change in serum GGT from baseline to Week 24 (serum GGT was measured in U/L)
Time frame: Baseline to week 24 (visit 7)
Population: Number of subjects analyzed in the Intent to Treat population who have evaluable results
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GKT137831 400mg Once Daily | The Percent Change in Serum GGT. | -4.9 percent change | Standard Deviation 59.58 |
| GKT137831 400mg Twice Daily | The Percent Change in Serum GGT. | -19 percent change | Standard Deviation 28.89 |
| Placebo Arm | The Percent Change in Serum GGT. | -8.4 percent change | Standard Deviation 21.45 |
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.
Time frame: From baseline to Week 24, in patients with values at baseline and Week 24.
Population: Number of subjects analyzed in the Intent to Treat population who have evaluable results
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GKT137831 400mg Once Daily | Absolute Change in Liver Stiffness as Assessed by Transient Elastography by Subgroup (FibroScan® or Similar Technology). | -1.9 kPa | Standard Deviation 7.49 |
| GKT137831 400mg Twice Daily | Absolute Change in Liver Stiffness as Assessed by Transient Elastography by Subgroup (FibroScan® or Similar Technology). | -2.1 kPa | Standard Deviation 2.43 |
| Placebo Arm | Absolute Change in Liver Stiffness as Assessed by Transient Elastography by Subgroup (FibroScan® or Similar Technology). | 0.4 kPa | Standard Deviation 4.65 |
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.
Time frame: From baseline to Week 24, in patients with values at baseline and Week 24.
Population: Number of subjects analyzed in the Intent to Treat population who have evaluable results
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GKT137831 400mg Once Daily | Absolute Change in Liver Stiffness as Assessed by Transient Elastography (FibroScan® or Similar Technology). | -0.5 kPa | Standard Deviation 5.24 |
| GKT137831 400mg Twice Daily | Absolute Change in Liver Stiffness as Assessed by Transient Elastography (FibroScan® or Similar Technology). | -0.3 kPa | Standard Deviation 7.9 |
| Placebo Arm | Absolute Change in Liver Stiffness as Assessed by Transient Elastography (FibroScan® or Similar Technology). | 0.7 kPa | Standard Deviation 3.63 |
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.
Time frame: From baseline to Weeks 12 and 24
Population: Number of subjects analyzed in the Intent to Treat population who have evaluable results
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GKT137831 400mg Once Daily | Absolute Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Absolute change Symptoms W12 | -0.4 score on a scale | Standard Deviation 3.34 |
| GKT137831 400mg Once Daily | Absolute Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Absolute change Symptoms W24 | 0.1 score on a scale | Standard Deviation 3.46 |
| GKT137831 400mg Once Daily | Absolute Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Absolute change Itch W12 | -0.2 score on a scale | Standard Deviation 2.61 |
| GKT137831 400mg Once Daily | Absolute Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Absolute change Itch W24 | -0.4 score on a scale | Standard Deviation 3.22 |
| GKT137831 400mg Once Daily | Absolute Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Absolute change Fatigue W12 | -1.8 score on a scale | Standard Deviation 5.76 |
| GKT137831 400mg Once Daily | Absolute Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Absolute change Fatigue W24 | -0.8 score on a scale | Standard Deviation 6.31 |
| GKT137831 400mg Once Daily | Absolute Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Absolute change Cognitive W12 | -0.1 score on a scale | Standard Deviation 5.02 |
| GKT137831 400mg Once Daily | Absolute Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Absolute change Cognitive W24 | 0.8 score on a scale | Standard Deviation 4.67 |
| GKT137831 400mg Once Daily | Absolute Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Absolute change Emotional W12 | -0.5 score on a scale | Standard Deviation 2.09 |
| GKT137831 400mg Once Daily | Absolute Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Absolute change Emotional W24 | -0.3 score on a scale | Standard Deviation 2.6 |
| GKT137831 400mg Once Daily | Absolute Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Absolute change Social W12 | 0.6 score on a scale | Standard Deviation 4.69 |
| GKT137831 400mg Once Daily | Absolute Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Absolute change Social W24 | 0.8 score on a scale | Standard Deviation 5.08 |
| GKT137831 400mg Twice Daily | Absolute Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Absolute change Social W24 | -2.2 score on a scale | Standard Deviation 4.93 |
| GKT137831 400mg Twice Daily | Absolute Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Absolute change Symptoms W12 | -0.9 score on a scale | Standard Deviation 3.19 |
| GKT137831 400mg Twice Daily | Absolute Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Absolute change Cognitive W12 | -2.4 score on a scale | Standard Deviation 5.68 |
| GKT137831 400mg Twice Daily | Absolute Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Absolute change Emotional W12 | -1.8 score on a scale | Standard Deviation 3.2 |
| GKT137831 400mg Twice Daily | Absolute Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Absolute change Symptoms W24 | -1.4 score on a scale | Standard Deviation 4.23 |
| GKT137831 400mg Twice Daily | Absolute Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Absolute change Fatigue W24 | -3.6 score on a scale | Standard Deviation 7.32 |
| GKT137831 400mg Twice Daily | Absolute Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Absolute change Social W12 | -2.1 score on a scale | Standard Deviation 5.24 |
| GKT137831 400mg Twice Daily | Absolute Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Absolute change Itch W12 | 0.6 score on a scale | Standard Deviation 2.69 |
| GKT137831 400mg Twice Daily | Absolute Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Absolute change Cognitive W24 | -1.4 score on a scale | Standard Deviation 5.34 |
| GKT137831 400mg Twice Daily | Absolute Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Absolute change Fatigue W12 | -3.2 score on a scale | Standard Deviation 8.25 |
| GKT137831 400mg Twice Daily | Absolute Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Absolute change Itch W24 | 0.1 score on a scale | Standard Deviation 2.83 |
| GKT137831 400mg Twice Daily | Absolute Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Absolute change Emotional W24 | -2.0 score on a scale | Standard Deviation 3 |
| Placebo Arm | Absolute Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Absolute change Itch W24 | 0.1 score on a scale | Standard Deviation 2.85 |
| Placebo Arm | Absolute Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Absolute change Fatigue W12 | 0.6 score on a scale | Standard Deviation 4.91 |
| Placebo Arm | Absolute Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Absolute change Emotional W24 | 0.4 score on a scale | Standard Deviation 1.78 |
| Placebo Arm | Absolute Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Absolute change Fatigue W24 | 0.6 score on a scale | Standard Deviation 5.35 |
| Placebo Arm | Absolute Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Absolute change Cognitive W12 | 1.0 score on a scale | Standard Deviation 4.35 |
| Placebo Arm | Absolute Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Absolute change Cognitive W24 | 0.3 score on a scale | Standard Deviation 3.67 |
| Placebo Arm | Absolute Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Absolute change Social W12 | 2.0 score on a scale | Standard Deviation 5.43 |
| Placebo Arm | Absolute Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Absolute change Symptoms W12 | -0.2 score on a scale | Standard Deviation 3.52 |
| Placebo Arm | Absolute Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Absolute change Symptoms W24 | -0.3 score on a scale | Standard Deviation 3.1 |
| Placebo Arm | Absolute Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Absolute change Emotional W12 | 0.4 score on a scale | Standard Deviation 2.35 |
| Placebo Arm | Absolute Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Absolute change Itch W12 | 0.4 score on a scale | Standard Deviation 2.79 |
| Placebo Arm | Absolute Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Absolute change Social W24 | 1.7 score on a scale | Standard Deviation 5.01 |
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.
Time frame: From baseline to Weeks 12 and 24
Population: Number of subjects analyzed in the Intent to Treat population who have evaluable results
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GKT137831 400mg Once Daily | Absolute Change in Pruritis Visual Analogue Scale (VAS) Scores | Absolute change W12 | -0.1 score on a scale | Standard Deviation 3.1 |
| GKT137831 400mg Once Daily | Absolute Change in Pruritis Visual Analogue Scale (VAS) Scores | Absolute change W24 | -1.0 score on a scale | Standard Deviation 2.32 |
| GKT137831 400mg Twice Daily | Absolute Change in Pruritis Visual Analogue Scale (VAS) Scores | Absolute change W24 | 0.1 score on a scale | Standard Deviation 2.3 |
| GKT137831 400mg Twice Daily | Absolute Change in Pruritis Visual Analogue Scale (VAS) Scores | Absolute change W12 | 0.3 score on a scale | Standard Deviation 2.33 |
| Placebo Arm | Absolute Change in Pruritis Visual Analogue Scale (VAS) Scores | Absolute change W12 | 0.5 score on a scale | Standard Deviation 1.79 |
| Placebo Arm | Absolute Change in Pruritis Visual Analogue Scale (VAS) Scores | Absolute change W24 | 0.7 score on a scale | Standard Deviation 1.83 |
Secondary
Absolute Change in Serum ALP
Absolute change in serum ALP from baseline to each assessment.
Time frame: From baseline to Weeks 2, 6, 12, 18 and 24
Population: Number of subjects analyzed in the Intent to Treat population who have evaluable results
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GKT137831 400mg Once Daily | Absolute Change in Serum ALP | Absolute change W18 | -27.6 U/L | Standard Deviation 62.54 |
| GKT137831 400mg Once Daily | Absolute Change in Serum ALP | Absolute change W12 | -15.3 U/L | Standard Deviation 67.79 |
| GKT137831 400mg Once Daily | Absolute Change in Serum ALP | Absolute change W2 | -19.8 U/L | Standard Deviation 35.95 |
| GKT137831 400mg Once Daily | Absolute Change in Serum ALP | Absolute change W6 | -27.3 U/L | Standard Deviation 44.13 |
| GKT137831 400mg Once Daily | Absolute Change in Serum ALP | Absolute change W24 | -32.5 U/L | Standard Deviation 65.3 |
| GKT137831 400mg Twice Daily | Absolute Change in Serum ALP | Absolute change W12 | -53 U/L | Standard Deviation 66.51 |
| GKT137831 400mg Twice Daily | Absolute Change in Serum ALP | Absolute change W2 | -45.9 U/L | Standard Deviation 75.75 |
| GKT137831 400mg Twice Daily | Absolute Change in Serum ALP | Absolute change W6 | -58.6 U/L | Standard Deviation 63.88 |
| GKT137831 400mg Twice Daily | Absolute Change in Serum ALP | Absolute change W18 | -53.2 U/L | Standard Deviation 80.01 |
| GKT137831 400mg Twice Daily | Absolute Change in Serum ALP | Absolute change W24 | -45.2 U/L | Standard Deviation 84.41 |
| Placebo Arm | Absolute Change in Serum ALP | Absolute change W24 | -12.4 U/L | Standard Deviation 53.48 |
| Placebo Arm | Absolute Change in Serum ALP | Absolute change W18 | -6 U/L | Standard Deviation 50.15 |
| Placebo Arm | Absolute Change in Serum ALP | Absolute change W2 | -17 U/L | Standard Deviation 44.4 |
| Placebo Arm | Absolute Change in Serum ALP | Absolute change W12 | -7.1 U/L | Standard Deviation 52.75 |
| Placebo Arm | Absolute Change in Serum ALP | Absolute change W6 | -14.5 U/L | Standard Deviation 59.72 |
Secondary
Absolute Change in Serum Conjugated Bilirubin.
Absolute change in serum conjugated bilirubin from baseline to each assessment.
Time frame: From baseline to Weeks 2, 6, 12, 18 and 24
Population: Number of subjects analyzed in the Intent to Treat population who have evaluable results
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GKT137831 400mg Once Daily | Absolute Change in Serum Conjugated Bilirubin. | Absolue change W18 | 0.5 μmol/L | Standard Deviation 2.1 |
| GKT137831 400mg Once Daily | Absolute Change in Serum Conjugated Bilirubin. | Absolute change W12 | 0.8 μmol/L | Standard Deviation 1.97 |
| GKT137831 400mg Once Daily | Absolute Change in Serum Conjugated Bilirubin. | Absolute change W2 | 0 μmol/L | Standard Deviation 1.32 |
| GKT137831 400mg Once Daily | Absolute Change in Serum Conjugated Bilirubin. | Absolute change W6 | -0.3 μmol/L | Standard Deviation 1.14 |
| GKT137831 400mg Once Daily | Absolute Change in Serum Conjugated Bilirubin. | Absolute change W24 | 1.1 μmol/L | Standard Deviation 3.44 |
| GKT137831 400mg Twice Daily | Absolute Change in Serum Conjugated Bilirubin. | Absolute change W12 | 0.4 μmol/L | Standard Deviation 1.28 |
| GKT137831 400mg Twice Daily | Absolute Change in Serum Conjugated Bilirubin. | Absolute change W2 | 0.3 μmol/L | Standard Deviation 1.61 |
| GKT137831 400mg Twice Daily | Absolute Change in Serum Conjugated Bilirubin. | Absolute change W6 | 0.5 μmol/L | Standard Deviation 2.06 |
| GKT137831 400mg Twice Daily | Absolute Change in Serum Conjugated Bilirubin. | Absolue change W18 | 0.6 μmol/L | Standard Deviation 1.78 |
| GKT137831 400mg Twice Daily | Absolute Change in Serum Conjugated Bilirubin. | Absolute change W24 | 1.1 μmol/L | Standard Deviation 1.76 |
| Placebo Arm | Absolute Change in Serum Conjugated Bilirubin. | Absolute change W24 | 0.3 μmol/L | Standard Deviation 2.57 |
| Placebo Arm | Absolute Change in Serum Conjugated Bilirubin. | Absolue change W18 | -0.0 μmol/L | Standard Deviation 1.91 |
| Placebo Arm | Absolute Change in Serum Conjugated Bilirubin. | Absolute change W2 | -0.1 μmol/L | Standard Deviation 1.4 |
| Placebo Arm | Absolute Change in Serum Conjugated Bilirubin. | Absolute change W12 | -0.1 μmol/L | Standard Deviation 1.55 |
| Placebo Arm | Absolute Change in Serum Conjugated Bilirubin. | Absolute change W6 | -0.3 μmol/L | Standard Deviation 1.29 |
Secondary
Absolute Change in Serum GGT
Absolute change in serum GGT from baseline to each assessment.
Time frame: From baseline to Weeks 2, 6, 12, 18 and 24
Population: Number of subjects analyzed in the Intent to Treat population who have evaluable results
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GKT137831 400mg Once Daily | Absolute Change in Serum GGT | Absolute change W18 | -19.2 U/L | Standard Deviation 134.32 |
| GKT137831 400mg Once Daily | Absolute Change in Serum GGT | Absolute change W12 | -3.9 U/L | Standard Deviation 115.13 |
| GKT137831 400mg Once Daily | Absolute Change in Serum GGT | Absolute change W2 | -14.3 U/L | Standard Deviation 112.66 |
| GKT137831 400mg Once Daily | Absolute Change in Serum GGT | Absolute change W6 | -22.2 U/L | Standard Deviation 76.68 |
| GKT137831 400mg Once Daily | Absolute Change in Serum GGT | Absolute change W24 | -17.9 U/L | Standard Deviation 117.62 |
| GKT137831 400mg Twice Daily | Absolute Change in Serum GGT | Absolute change W12 | -50.6 U/L | Standard Deviation 74.7 |
| GKT137831 400mg Twice Daily | Absolute Change in Serum GGT | Absolute change W2 | -48.5 U/L | Standard Deviation 61.83 |
| GKT137831 400mg Twice Daily | Absolute Change in Serum GGT | Absolute change W6 | -53.5 U/L | Standard Deviation 67.57 |
| GKT137831 400mg Twice Daily | Absolute Change in Serum GGT | Absolute change W18 | -37.9 U/L | Standard Deviation 93.88 |
| GKT137831 400mg Twice Daily | Absolute Change in Serum GGT | Absolute change W24 | -43.6 U/L | Standard Deviation 62.22 |
| Placebo Arm | Absolute Change in Serum GGT | Absolute change W24 | -10.7 U/L | Standard Deviation 78.2 |
| Placebo Arm | Absolute Change in Serum GGT | Absolute change W18 | -4.5 U/L | Standard Deviation 79.81 |
| Placebo Arm | Absolute Change in Serum GGT | Absolute change W2 | -11.2 U/L | Standard Deviation 45.96 |
| Placebo Arm | Absolute Change in Serum GGT | Absolute change W12 | -8.6 U/L | Standard Deviation 70.11 |
| Placebo Arm | Absolute Change in Serum GGT | Absolute change W6 | -17.9 U/L | Standard Deviation 59.01 |
Secondary
Absolute Change in Serum Total Bilirubin.
Absolute change in serum total bilirubin, from baseline to each assessment.
Time frame: from baseline to Weeks 2, 6, 12, 18 and 24
Population: Number of subjects analyzed in the Intent to Treat population who have evaluable results
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GKT137831 400mg Once Daily | Absolute Change in Serum Total Bilirubin. | Absolute change W18 | 0.1 μmol/L | Standard Deviation 3.22 |
| GKT137831 400mg Once Daily | Absolute Change in Serum Total Bilirubin. | Absolute change W12 | 0.6 μmol/L | Standard Deviation 3.35 |
| GKT137831 400mg Once Daily | Absolute Change in Serum Total Bilirubin. | Absolute change W2 | -0.2 μmol/L | Standard Deviation 2.51 |
| GKT137831 400mg Once Daily | Absolute Change in Serum Total Bilirubin. | Absolute change W6 | -0.5 μmol/L | Standard Deviation 2.35 |
| GKT137831 400mg Once Daily | Absolute Change in Serum Total Bilirubin. | Absolute change W24 | 0.5 μmol/L | Standard Deviation 3.77 |
| GKT137831 400mg Twice Daily | Absolute Change in Serum Total Bilirubin. | Absolute change W12 | 0.1 μmol/L | Standard Deviation 2.69 |
| GKT137831 400mg Twice Daily | Absolute Change in Serum Total Bilirubin. | Absolute change W2 | 0.1 μmol/L | Standard Deviation 2.76 |
| GKT137831 400mg Twice Daily | Absolute Change in Serum Total Bilirubin. | Absolute change W6 | 0.5 μmol/L | Standard Deviation 3.39 |
| GKT137831 400mg Twice Daily | Absolute Change in Serum Total Bilirubin. | Absolute change W18 | 0.5 μmol/L | Standard Deviation 2.82 |
| GKT137831 400mg Twice Daily | Absolute Change in Serum Total Bilirubin. | Absolute change W24 | 1.2 μmol/L | Standard Deviation 2.71 |
| Placebo Arm | Absolute Change in Serum Total Bilirubin. | Absolute change W24 | 0.7 μmol/L | Standard Deviation 3.23 |
| Placebo Arm | Absolute Change in Serum Total Bilirubin. | Absolute change W18 | -0.1 μmol/L | Standard Deviation 3.81 |
| Placebo Arm | Absolute Change in Serum Total Bilirubin. | Absolute change W2 | -0.4 μmol/L | Standard Deviation 3.75 |
| Placebo Arm | Absolute Change in Serum Total Bilirubin. | Absolute change W12 | 0.0 μmol/L | Standard Deviation 2.21 |
| Placebo Arm | Absolute Change in Serum Total Bilirubin. | Absolute change W6 | -0.5 μmol/L | Standard Deviation 3.29 |
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).
Time frame: From baseline to Week 24, in patients with values at baseline and Week 24.
Population: Number of subjects analyzed in the Intent to Treat population who have evaluable results
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GKT137831 400mg Once Daily | Percent Change in Liver Stiffness as Assessed by Transient Elastography by Subgroup (FibroScan® or Similar Technology). | -5.3 percent change | Standard Deviation 35.1 |
| GKT137831 400mg Twice Daily | Percent Change in Liver Stiffness as Assessed by Transient Elastography by Subgroup (FibroScan® or Similar Technology). | -16.1 percent change | Standard Deviation 20.71 |
| Placebo Arm | Percent Change in Liver Stiffness as Assessed by Transient Elastography by Subgroup (FibroScan® or Similar Technology). | 4.2 percent change | Standard Deviation 30.09 |
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).
Time frame: From baseline to Week 24, in patients with values at baseline and Week 24.
Population: Number of subjects analyzed in the Intent to Treat population who have evaluable results
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GKT137831 400mg Once Daily | Percent Change in Liver Stiffness as Assessed by Transient Elastography (FibroScan® or Similar Technology). | 3.3 percent change | Standard Deviation 34.95 |
| GKT137831 400mg Twice Daily | Percent Change in Liver Stiffness as Assessed by Transient Elastography (FibroScan® or Similar Technology). | 7.9 percent change | Standard Deviation 43.68 |
| Placebo Arm | Percent Change in Liver Stiffness as Assessed by Transient Elastography (FibroScan® or Similar Technology). | 10.1 percent change | Standard Deviation 33.11 |
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.
Time frame: From baseline to Weeks 12 and 24
Population: Number of subjects analyzed in the Intent to Treat population who have evaluable results
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GKT137831 400mg Once Daily | Percent Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Percent change Symptoms W12 | -2.8 percent change | Standard Deviation 24.68 |
| GKT137831 400mg Once Daily | Percent Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Percent change Symptoms W24 | 1.1 percent change | Standard Deviation 25.27 |
| GKT137831 400mg Once Daily | Percent Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Percent change Itch W12 | -5.6 percent change | Standard Deviation 62.92 |
| GKT137831 400mg Once Daily | Percent Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Percent change Itch W24 | -11.4 percent change | Standard Deviation 52.75 |
| GKT137831 400mg Once Daily | Percent Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Percent change Fatigue W12 | -3.4 percent change | Standard Deviation 21.11 |
| GKT137831 400mg Once Daily | Percent Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Percent change Fatigue W24 | 0.3 percent change | Standard Deviation 24.89 |
| GKT137831 400mg Once Daily | Percent Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Percent change Cognitive W12 | 6.1 percent change | Standard Deviation 56.79 |
| GKT137831 400mg Once Daily | Percent Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Percent change Cognitive W24 | 16.0 percent change | Standard Deviation 62.27 |
| GKT137831 400mg Once Daily | Percent Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Percent change Emotional W12 | -1.2 percent change | Standard Deviation 35.5 |
| GKT137831 400mg Once Daily | Percent Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Percent change Emotional W24 | 4.9 percent change | Standard Deviation 54.41 |
| GKT137831 400mg Once Daily | Percent Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Percent change Social W12 | 4.8 percent change | Standard Deviation 24.14 |
| GKT137831 400mg Once Daily | Percent Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Percent change Social W24 | 8.1 percent change | Standard Deviation 27.94 |
| GKT137831 400mg Twice Daily | Percent Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Percent change Social W24 | -7.7 percent change | Standard Deviation 18.38 |
| GKT137831 400mg Twice Daily | Percent Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Percent change Symptoms W12 | -2.7 percent change | Standard Deviation 24.48 |
| GKT137831 400mg Twice Daily | Percent Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Percent change Cognitive W12 | -9.5 percent change | Standard Deviation 32.14 |
| GKT137831 400mg Twice Daily | Percent Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Percent change Emotional W12 | -12.8 percent change | Standard Deviation 33.88 |
| GKT137831 400mg Twice Daily | Percent Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Percent change Symptoms W24 | -3.7 percent change | Standard Deviation 25.19 |
| GKT137831 400mg Twice Daily | Percent Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Percent change Fatigue W24 | -9.9 percent change | Standard Deviation 19.81 |
| GKT137831 400mg Twice Daily | Percent Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Percent change Social W12 | -6.2 percent change | Standard Deviation 21.65 |
| GKT137831 400mg Twice Daily | Percent Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Percent change Itch W12 | -9.2 percent change | Standard Deviation 43.43 |
| GKT137831 400mg Twice Daily | Percent Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Percent change Cognitive W24 | -1.9 percent change | Standard Deviation 40.79 |
| GKT137831 400mg Twice Daily | Percent Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Percent change Fatigue W12 | -6.8 percent change | Standard Deviation 26.51 |
| GKT137831 400mg Twice Daily | Percent Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Percent change Itch W24 | -9.5 percent change | Standard Deviation 41.83 |
| GKT137831 400mg Twice Daily | Percent Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Percent change Emotional W24 | -16.9 percent change | Standard Deviation 26.85 |
| Placebo Arm | Percent Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Percent change Itch W24 | -6.8 percent change | Standard Deviation 40.62 |
| Placebo Arm | Percent Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Percent change Fatigue W12 | 3.4 percent change | Standard Deviation 20.45 |
| Placebo Arm | Percent Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Percent change Emotional W24 | 8.7 percent change | Standard Deviation 34.49 |
| Placebo Arm | Percent Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Percent change Fatigue W24 | 2.4 percent change | Standard Deviation 23.07 |
| Placebo Arm | Percent Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Percent change Cognitive W12 | 11.7 percent change | Standard Deviation 51.28 |
| Placebo Arm | Percent Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Percent change Cognitive W24 | 5.2 percent change | Standard Deviation 46.11 |
| Placebo Arm | Percent Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Percent change Social W12 | 13.9 percent change | Standard Deviation 40.03 |
| Placebo Arm | Percent Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Percent change Symptoms W12 | 3.1 percent change | Standard Deviation 37.21 |
| Placebo Arm | Percent Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Percent change Symptoms W24 | 1.1 percent change | Standard Deviation 35.03 |
| Placebo Arm | Percent Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Percent change Emotional W12 | 8.7 percent change | Standard Deviation 45.99 |
| Placebo Arm | Percent Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Percent change Itch W12 | -2.5 percent change | Standard Deviation 48.47 |
| Placebo Arm | Percent Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores | Percent change Social W24 | 9.3 percent change | Standard Deviation 28.53 |
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.
Time frame: From baseline to Weeks 12 and 24
Population: Number of subjects analyzed in the Intent to Treat population who have evaluable results
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GKT137831 400mg Once Daily | Percent Change in Pruritis Visual Analogue Scale (VAS) Scores | Percent change W12 | -35.1 percent change | Standard Deviation 46.13 |
| GKT137831 400mg Once Daily | Percent Change in Pruritis Visual Analogue Scale (VAS) Scores | Percent change W24 | -36.9 percent change | Standard Deviation 58.6 |
| GKT137831 400mg Twice Daily | Percent Change in Pruritis Visual Analogue Scale (VAS) Scores | Percent change W12 | -11.7 percent change | Standard Deviation 73.87 |
| GKT137831 400mg Twice Daily | Percent Change in Pruritis Visual Analogue Scale (VAS) Scores | Percent change W24 | -0.3 percent change | Standard Deviation 92.71 |
| Placebo Arm | Percent Change in Pruritis Visual Analogue Scale (VAS) Scores | Percent change W12 | -8.3 percent change | Standard Deviation 70.68 |
| Placebo Arm | Percent Change in Pruritis Visual Analogue Scale (VAS) Scores | Percent change W24 | 27.3 percent change | Standard Deviation 72.88 |
Secondary
Percent Change in Serum ALP
Percent change in serum ALP from baseline to each assessment (serum ALP was measured in U/L).
Time frame: From baseline to Weeks 2, 6, 12, 18 and 24
Population: Number of subjects analyzed in the Intent to Treat population who have evaluable results
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GKT137831 400mg Once Daily | Percent Change in Serum ALP | Percent change W18 | -7.8 percent change | Standard Deviation 21.68 |
| GKT137831 400mg Once Daily | Percent Change in Serum ALP | Percent change W12 | -3.9 percent change | Standard Deviation 22.17 |
| GKT137831 400mg Once Daily | Percent Change in Serum ALP | Percent change W2 | -5.5 percent change | Standard Deviation 10.95 |
| GKT137831 400mg Once Daily | Percent Change in Serum ALP | Percent change W6 | -8.6 percent change | Standard Deviation 13.42 |
| GKT137831 400mg Once Daily | Percent Change in Serum ALP | Percent change W24 | -9.7 percent change | Standard Deviation 21.1 |
| GKT137831 400mg Twice Daily | Percent Change in Serum ALP | Percent change W12 | -14.6 percent change | Standard Deviation 17.89 |
| GKT137831 400mg Twice Daily | Percent Change in Serum ALP | Percent change W2 | -13.0 percent change | Standard Deviation 12.71 |
| GKT137831 400mg Twice Daily | Percent Change in Serum ALP | Percent change W6 | -16.3 percent change | Standard Deviation 13.32 |
| GKT137831 400mg Twice Daily | Percent Change in Serum ALP | Percent change W18 | -15.8 percent change | Standard Deviation 21.42 |
| GKT137831 400mg Twice Daily | Percent Change in Serum ALP | Percent change W24 | -12.9 percent change | Standard Deviation 19.55 |
| Placebo Arm | Percent Change in Serum ALP | Percent change W24 | -3.1 percent change | Standard Deviation 15.99 |
| Placebo Arm | Percent Change in Serum ALP | Percent change W18 | -0.5 percent change | Standard Deviation 15.66 |
| Placebo Arm | Percent Change in Serum ALP | Percent change W2 | -3.6 percent change | Standard Deviation 11.51 |
| Placebo Arm | Percent Change in Serum ALP | Percent change W12 | -0.6 percent change | Standard Deviation 16.41 |
| Placebo Arm | Percent Change in Serum ALP | Percent change W6 | -1.4 percent change | Standard Deviation 15.19 |
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).
Time frame: From baseline to Weeks 2, 6, 12, 18 and 24
Population: Number of subjects analyzed in the Intent to Treat population who have evaluable results
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GKT137831 400mg Once Daily | Percent Change in Serum Conjugated Bilirubin. | Percent change W18 | 6.0 percent change | Standard Deviation 28.16 |
| GKT137831 400mg Once Daily | Percent Change in Serum Conjugated Bilirubin. | Percent change W12 | 9.4 percent change | Standard Deviation 27.14 |
| GKT137831 400mg Once Daily | Percent Change in Serum Conjugated Bilirubin. | Percent change W2 | 0.9 percent change | Standard Deviation 16.81 |
| GKT137831 400mg Once Daily | Percent Change in Serum Conjugated Bilirubin. | Percent change W6 | -3.4 percent change | Standard Deviation 18.7 |
| GKT137831 400mg Once Daily | Percent Change in Serum Conjugated Bilirubin. | Percent change W24 | 12.7 percent change | Standard Deviation 36.35 |
| GKT137831 400mg Twice Daily | Percent Change in Serum Conjugated Bilirubin. | Percent change W12 | 4.8 percent change | Standard Deviation 18.55 |
| GKT137831 400mg Twice Daily | Percent Change in Serum Conjugated Bilirubin. | Percent change W2 | 5.2 percent change | Standard Deviation 22.79 |
| GKT137831 400mg Twice Daily | Percent Change in Serum Conjugated Bilirubin. | Percent change W6 | 6.3 percent change | Standard Deviation 29.4 |
| GKT137831 400mg Twice Daily | Percent Change in Serum Conjugated Bilirubin. | Percent change W18 | 8.9 percent change | Standard Deviation 19.34 |
| GKT137831 400mg Twice Daily | Percent Change in Serum Conjugated Bilirubin. | Percent change W24 | 16.1 percent change | Standard Deviation 24.85 |
| Placebo Arm | Percent Change in Serum Conjugated Bilirubin. | Percent change W24 | 6.4 percent change | Standard Deviation 32.9 |
| Placebo Arm | Percent Change in Serum Conjugated Bilirubin. | Percent change W18 | 1.8 percent change | Standard Deviation 25.98 |
| Placebo Arm | Percent Change in Serum Conjugated Bilirubin. | Percent change W2 | 1.3 percent change | Standard Deviation 28.11 |
| Placebo Arm | Percent Change in Serum Conjugated Bilirubin. | Percent change W12 | -0.7 percent change | Standard Deviation 20.81 |
| Placebo Arm | Percent Change in Serum Conjugated Bilirubin. | Percent change W6 | -3.5 percent change | Standard Deviation 17.99 |
Secondary
Percent Change in Serum GGT
Percent change in serum GGT from baseline to each assessment (serum GGT was measured in U/L)
Time frame: From baseline to Weeks 2, 6, 12, 18 and 24
Population: Number of subjects analyzed in the Intent to Treat population who have evaluable results
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GKT137831 400mg Once Daily | Percent Change in Serum GGT | Percent change W18 | -4.5 percent change | Standard Deviation 69.65 |
| GKT137831 400mg Once Daily | Percent Change in Serum GGT | Percent change W12 | 1.7 percent change | Standard Deviation 66.84 |
| GKT137831 400mg Once Daily | Percent Change in Serum GGT | Percent change W2 | -7 percent change | Standard Deviation 25.08 |
| GKT137831 400mg Once Daily | Percent Change in Serum GGT | Percent change W6 | -11.8 percent change | Standard Deviation 21.59 |
| GKT137831 400mg Once Daily | Percent Change in Serum GGT | Percent change W24 | -4.9 percent change | Standard Deviation 59.58 |
| GKT137831 400mg Twice Daily | Percent Change in Serum GGT | Percent change W12 | -18.6 percent change | Standard Deviation 27.44 |
| GKT137831 400mg Twice Daily | Percent Change in Serum GGT | Percent change W2 | -17 percent change | Standard Deviation 17.25 |
| GKT137831 400mg Twice Daily | Percent Change in Serum GGT | Percent change W6 | -22 percent change | Standard Deviation 23.4 |
| GKT137831 400mg Twice Daily | Percent Change in Serum GGT | Percent change W18 | -18.7 percent change | Standard Deviation 28.55 |
| GKT137831 400mg Twice Daily | Percent Change in Serum GGT | Percent change W24 | -19 percent change | Standard Deviation 28.89 |
| Placebo Arm | Percent Change in Serum GGT | Percent change W24 | -8.4 percent change | Standard Deviation 21.45 |
| Placebo Arm | Percent Change in Serum GGT | Percent change W18 | -5.2 percent change | Standard Deviation 22.79 |
| Placebo Arm | Percent Change in Serum GGT | Percent change W2 | -6.2 percent change | Standard Deviation 13.04 |
| Placebo Arm | Percent Change in Serum GGT | Percent change W12 | -5.5 percent change | Standard Deviation 19.44 |
| Placebo Arm | Percent Change in Serum GGT | Percent change W6 | -7.5 percent change | Standard Deviation 16.89 |
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).
Time frame: From baseline to Weeks 12 and 24.
Population: Number of subjects analyzed in the Intent to Treat population who have evaluable results
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GKT137831 400mg Once Daily | Percent Change in Serum Levels of Collagen Fragments Indicative of Collagen Formation and Degradation. | Percent change ProC3 W12 | -2.58 percent change | Standard Deviation 21.09 |
| GKT137831 400mg Once Daily | Percent Change in Serum Levels of Collagen Fragments Indicative of Collagen Formation and Degradation. | Percent change ProC3 W24 | -3.6 percent change | Standard Deviation 22.54 |
| GKT137831 400mg Once Daily | Percent Change in Serum Levels of Collagen Fragments Indicative of Collagen Formation and Degradation. | Percent change ProC5 W12 | 1.17 percent change | Standard Deviation 20.56 |
| GKT137831 400mg Once Daily | Percent Change in Serum Levels of Collagen Fragments Indicative of Collagen Formation and Degradation. | Percent change ProC5 W24 | 2.26 percent change | Standard Deviation 30.36 |
| GKT137831 400mg Once Daily | Percent Change in Serum Levels of Collagen Fragments Indicative of Collagen Formation and Degradation. | Percent change C3M W12 | -0.63 percent change | Standard Deviation 15.03 |
| GKT137831 400mg Once Daily | Percent Change in Serum Levels of Collagen Fragments Indicative of Collagen Formation and Degradation. | Percent change C3M W24 | -0.93 percent change | Standard Deviation 15.29 |
| GKT137831 400mg Once Daily | Percent Change in Serum Levels of Collagen Fragments Indicative of Collagen Formation and Degradation. | Percent change C4M W12 | 1.59 percent change | Standard Deviation 15.76 |
| GKT137831 400mg Once Daily | Percent Change in Serum Levels of Collagen Fragments Indicative of Collagen Formation and Degradation. | Percent change C4M W24 | -4.43 percent change | Standard Deviation 17.72 |
| GKT137831 400mg Once Daily | Percent Change in Serum Levels of Collagen Fragments Indicative of Collagen Formation and Degradation. | Percent change BGM W12 | -0.13 percent change | Standard Deviation 14.91 |
| GKT137831 400mg Once Daily | Percent Change in Serum Levels of Collagen Fragments Indicative of Collagen Formation and Degradation. | Percent change BGM W24 | 1.19 percent change | Standard Deviation 17.15 |
| GKT137831 400mg Twice Daily | Percent Change in Serum Levels of Collagen Fragments Indicative of Collagen Formation and Degradation. | Percent change BGM W12 | -4.3 percent change | Standard Deviation 18.81 |
| GKT137831 400mg Twice Daily | Percent Change in Serum Levels of Collagen Fragments Indicative of Collagen Formation and Degradation. | Percent change ProC3 W12 | -1.31 percent change | Standard Deviation 18.23 |
| GKT137831 400mg Twice Daily | Percent Change in Serum Levels of Collagen Fragments Indicative of Collagen Formation and Degradation. | Percent change C3M W24 | 0.17 percent change | Standard Deviation 30.1 |
| GKT137831 400mg Twice Daily | Percent Change in Serum Levels of Collagen Fragments Indicative of Collagen Formation and Degradation. | Percent change C3M W12 | -3.06 percent change | Standard Deviation 17.73 |
| GKT137831 400mg Twice Daily | Percent Change in Serum Levels of Collagen Fragments Indicative of Collagen Formation and Degradation. | Percent change ProC3 W24 | 0.69 percent change | Standard Deviation 18.17 |
| GKT137831 400mg Twice Daily | Percent Change in Serum Levels of Collagen Fragments Indicative of Collagen Formation and Degradation. | Percent change BGM W24 | 2.18 percent change | Standard Deviation 29.14 |
| GKT137831 400mg Twice Daily | Percent Change in Serum Levels of Collagen Fragments Indicative of Collagen Formation and Degradation. | Percent change C4M W24 | 3.33 percent change | Standard Deviation 37.63 |
| GKT137831 400mg Twice Daily | Percent Change in Serum Levels of Collagen Fragments Indicative of Collagen Formation and Degradation. | Percent change ProC5 W12 | -6.65 percent change | Standard Deviation 22.99 |
| GKT137831 400mg Twice Daily | Percent Change in Serum Levels of Collagen Fragments Indicative of Collagen Formation and Degradation. | Percent change C4M W12 | -4.82 percent change | Standard Deviation 18.97 |
| GKT137831 400mg Twice Daily | Percent Change in Serum Levels of Collagen Fragments Indicative of Collagen Formation and Degradation. | Percent change ProC5 W24 | -3.27 percent change | Standard Deviation 17.73 |
| Placebo Arm | Percent Change in Serum Levels of Collagen Fragments Indicative of Collagen Formation and Degradation. | Percent change C4M W24 | 0.73 percent change | Standard Deviation 21.55 |
| Placebo Arm | Percent Change in Serum Levels of Collagen Fragments Indicative of Collagen Formation and Degradation. | Percent change ProC5 W24 | -0.51 percent change | Standard Deviation 37.78 |
| Placebo Arm | Percent Change in Serum Levels of Collagen Fragments Indicative of Collagen Formation and Degradation. | Percent change C3M W12 | 1.31 percent change | Standard Deviation 20.17 |
| Placebo Arm | Percent Change in Serum Levels of Collagen Fragments Indicative of Collagen Formation and Degradation. | Percent change C3M W24 | -1.06 percent change | Standard Deviation 23.88 |
| Placebo Arm | Percent Change in Serum Levels of Collagen Fragments Indicative of Collagen Formation and Degradation. | Percent change BGM W12 | -0.12 percent change | Standard Deviation 23.07 |
| Placebo Arm | Percent Change in Serum Levels of Collagen Fragments Indicative of Collagen Formation and Degradation. | Percent change C4M W12 | 3.19 percent change | Standard Deviation 20.8 |
| Placebo Arm | Percent Change in Serum Levels of Collagen Fragments Indicative of Collagen Formation and Degradation. | Percent change ProC3 W12 | 3.64 percent change | Standard Deviation 27.86 |
| Placebo Arm | Percent Change in Serum Levels of Collagen Fragments Indicative of Collagen Formation and Degradation. | Percent change BGM W24 | 3.77 percent change | Standard Deviation 25.89 |
| Placebo Arm | Percent Change in Serum Levels of Collagen Fragments Indicative of Collagen Formation and Degradation. | Percent change ProC3 W24 | 3.10 percent change | Standard Deviation 20.78 |
| Placebo Arm | Percent Change in Serum Levels of Collagen Fragments Indicative of Collagen Formation and Degradation. | Percent change ProC5 W12 | 0.35 percent change | Standard Deviation 22.52 |
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).
Time frame: from baseline to Weeks 2, 6, 12, 18 and 24
Population: Number of subjects analyzed in the Intent to Treat population who have evaluable results
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GKT137831 400mg Once Daily | Percent Change in Serum Total Bilirubin. | Percent change W24 | 5.4 percent change | Standard Deviation 29.77 |
| GKT137831 400mg Once Daily | Percent Change in Serum Total Bilirubin. | Percent change W2 | -0.6 percent change | Standard Deviation 23.62 |
| GKT137831 400mg Once Daily | Percent Change in Serum Total Bilirubin. | Percent change W12 | 5.7 percent change | Standard Deviation 32.99 |
| GKT137831 400mg Once Daily | Percent Change in Serum Total Bilirubin. | Percent change W6 | -1.6 percent change | Standard Deviation 21.94 |
| GKT137831 400mg Once Daily | Percent Change in Serum Total Bilirubin. | Percent change W18 | 1.7 percent change | Standard Deviation 28.34 |
| GKT137831 400mg Twice Daily | Percent Change in Serum Total Bilirubin. | Percent change W6 | 8.8 percent change | Standard Deviation 41.19 |
| GKT137831 400mg Twice Daily | Percent Change in Serum Total Bilirubin. | Percent change W24 | 14.5 percent change | Standard Deviation 31.6 |
| GKT137831 400mg Twice Daily | Percent Change in Serum Total Bilirubin. | Percent change W18 | 9.6 percent change | Standard Deviation 32.56 |
| GKT137831 400mg Twice Daily | Percent Change in Serum Total Bilirubin. | Percent change W2 | 5.3 percent change | Standard Deviation 32.42 |
| GKT137831 400mg Twice Daily | Percent Change in Serum Total Bilirubin. | Percent change W12 | 7.7 percent change | Standard Deviation 37.53 |
| Placebo Arm | Percent Change in Serum Total Bilirubin. | Percent change W24 | 10.5 percent change | Standard Deviation 32.27 |
| Placebo Arm | Percent Change in Serum Total Bilirubin. | Percent change W2 | 3.3 percent change | Standard Deviation 39.98 |
| Placebo Arm | Percent Change in Serum Total Bilirubin. | Percent change W6 | 0.1 percent change | Standard Deviation 34.6 |
| Placebo Arm | Percent Change in Serum Total Bilirubin. | Percent change W18 | 4.1 percent change | Standard Deviation 29.5 |
| Placebo Arm | Percent Change in Serum Total Bilirubin. | Percent change W12 | 3.1 percent change | Standard Deviation 22.39 |