Nonalcoholic Steatohepatitis
Conditions
Brief summary
To evaluate the safety and potential efficacy of two dose levels of JKB-121 (5 mg twice daily and 10 mg twice daily) in reducing liver fat and/or liver biochemistry compared to placebo in patients with biopsy-proven nonalcoholic steatohepatitis
Detailed description
JKB-121 is a long-acting small molecule that is efficacious as a weak antagonist at the TLR-4 receptor. It is a non-selective opioid antagonist which has been shown to prevent the lipopolysaccharide (LPS) induced inflammatory liver injury in a methionine/choline deficient diet fed rat model of nonalcoholic fatty liver disease. In vitro, JKB-121 neutralized or reduced the LPS-induced release of inflammatory cytokines, deactivated hepatic stellate cells, inhibited hepatic stellate cell proliferation, and collagen expression. Inhibition of the TLR4 signaling pathway may provide an effective therapy in the prevention of inflammatory hepatic injury and hepatic fibrosis in patients with nonalcoholic steatohepatitis. This study will evaluate the safety and potential efficacy of two dose levels of JKB-121 (5 mg twice daily and 10 mg twice daily) in reducing liver fat and/or liver biochemistry compared to placebo in patients with biopsy-proven nonalcoholic steatohepatitis.
Interventions
DRUGJKB-121: 5 mg twice daily
DRUGJKB-121: 10 mg twice daily
DRUGPlacebo
Sponsors
Manal Abdelmalek
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years 2. Provision of written informed consent 3. Biopsy-proven NASH within 12 months or at screening 4. ALT \> 40 U/L for women and \> 60 U/L for men at screening and at least once in the previous 12 months. 5. HBA1C of ≤ 9.0
Exclusion criteria
1. Any chronic liver disease other than NASH 2. Cirrhosis, as assessed clinically or histologically 3. Presence of vascular liver disease 4. BMI ≤ 25 kg/m2 5. Excessive alcohol use (\> 20 g/day) within the past 2 years 6. AST or ALT \> 250 U/L. 7. Type 1 diabetes mellitus 8. Bariatric surgery in the past 5 years. 9. Weight gain of \> 5% in past 6 months or \> 10% change in past 12 months. 10. Contraindication to MRI 11. Inadequate venous access 12. HIV antibody positive, hepatitis B surface antigen positive (HBsAg), or Hepatitis C virus (HCV) RNA positive. 13. Receiving an elemental diet or parenteral nutrition 14. Chronic pancreatitis or pancreatic insufficiency 15. Any history of complications of cirrhosis 16. Concurrent conditions: * Inflammatory bowel disease * Significant cardiac disease * chronic infection or immune mediated disease * Any malignant disease * Prior solid organ transplant * Any other concurrent condition which, in the opinion of the investigator, could impact adversely on the subject participating or the interpretation of the study data. 17. Concurrent medications which may treat NASH 18. HbA1C \> 9.0% 19. Pregnancy or breastfeeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Analysis of MRI-PDFF Change From Baseline to Week 24 (Per Protocol Population) | Baseline to week 24 |
| Analysis of MRI-PDFF Change From Baseline to Week 12 (Per Protocol Population) | Baseline to Week 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Remission (in Weeks) | 24 weeks | Time to remission is the time in weeks from randomization to liver function remission, defined as two consecutive ALT values within normal range (\<40 U/L) during the treatment period. |
| Change in BMI (Body Mass Index) | Baseline, week 24 | — |
| Change in Hemoglobin A1C | Baseline, week 24 | — |
| Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) | Baseline, week 24 | HOMA-IR was calculated according to the formula: fasting insulin (microU/L) x fasting glucose (nmol/L)/22.5. Optimal Range: 1.0 (0.5-1.4). Lower values represent a better outcome. |
| Percent Change in Cholesterol | Baseline, week 24 | — |
| Percent Change in Triglycerides | Baseline, week 24 | — |
| Percent Change in Low Density Lipoprotein (LDL) Cholesterol | Baseline, week 24 | — |
| Percent Change in High Density Lipoprotein (HDL) | Baseline, week 24 | — |
| Analysis of ALT Change From Baseline to Week 24 (Per Protocol Population) | Baseline to week 24 | — |
| Mean Serum Alanine Aminotransferase (ALT) | weeks 4, 8, 12, 16, 20, and 24 | — |
| Mean Serum Gamma-glutamyl Transpeptidase (GGT) | weeks 4, 8, 12, 16, 20, and 24 | — |
| Number of Subjects With ALT in Normal Range at Week 24 | Week 24 | Normal range is \<40 U/L |
| Maximum Observed Concentrations (Cmax) | pre-dose and at 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12, and 24 hours | — |
| Minimum Observed Concentration (Cmin) | pre-dose and at 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12, and 24 hours | — |
| Area Under Concentration-time (AUC) | pre-dose and at 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12, and 24 hours | — |
| Half-life | pre-dose and at 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12, and 24 hours | — |
| Mean Serum Aspartate Aminotransferase (AST) | weeks 4, 8, 12, 16, 20, and 24 | — |
| Analysis of ALT Change From Baseline to Week 12 (Per Protocol Population) | Baseline to week 12 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| JKB 5 mg BID JKB 121, 5 mg twice daily | 21 |
| JKB 10 mg BID JKB 121, 10 mg twice daily | 22 |
| Placebo BID Identical appearing placebo | 22 |
| Total | 65 |
Baseline characteristics
| Characteristic | JKB 5 mg BID | JKB 10 mg BID | Placebo BID | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 5 Participants | 2 Participants | 9 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants | 17 Participants | 20 Participants | 56 Participants |
| Age, Continuous | 51 years STANDARD_DEVIATION 11.5 | 50.5 years STANDARD_DEVIATION 12.9 | 49.5 years STANDARD_DEVIATION 10.5 | 51 years STANDARD_DEVIATION 11.5 |
| Body Mass Index | 40.0 kg/m^2 STANDARD_DEVIATION 6.8 | 34.1 kg/m^2 STANDARD_DEVIATION 6.4 | 35.4 kg/m^2 STANDARD_DEVIATION 6.5 | 35.2 kg/m^2 STANDARD_DEVIATION 6.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 4 Participants | 5 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 18 Participants | 17 Participants | 50 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 21 Participants | 20 Participants | 21 Participants | 62 Participants |
| Region of Enrollment United States | 21 participants | 22 participants | 22 participants | 65 participants |
| Sex: Female, Male Female | 12 Participants | 15 Participants | 17 Participants | 44 Participants |
| Sex: Female, Male Male | 9 Participants | 7 Participants | 5 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 22 | 0 / 22 |
| other Total, other adverse events | 18 / 21 | 15 / 22 | 19 / 22 |
| serious Total, serious adverse events | 1 / 21 | 0 / 22 | 1 / 22 |
Outcome results
Primary
Analysis of MRI-PDFF Change From Baseline to Week 12 (Per Protocol Population)
Time frame: Baseline to Week 12
Population: The per protocol population included only those patients with non-missing baseline (ie. screening) and the specified visit are included. If missing, the last valid measurement on or prior to the first date administration of study medication is used as baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| JKB 121, 5 mg | Analysis of MRI-PDFF Change From Baseline to Week 12 (Per Protocol Population) | -1.78 percentage |
| JKB-121: 10 mg | Analysis of MRI-PDFF Change From Baseline to Week 12 (Per Protocol Population) | -1.50 percentage |
| Placebo | Analysis of MRI-PDFF Change From Baseline to Week 12 (Per Protocol Population) | -2.74 percentage |
p-value: 0.5276ANCOVA
p-value: 0.4968ANCOVA
Primary
Analysis of MRI-PDFF Change From Baseline to Week 24 (Per Protocol Population)
Time frame: Baseline to week 24
Population: The per protocol population included only those patients with non-missing baseline (ie. screening) and the specified visit are included. If missing, the last valid measurement on or prior to the first date administration of study medication is used as baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| JKB 121, 5 mg | Analysis of MRI-PDFF Change From Baseline to Week 24 (Per Protocol Population) | 0.38 percentage of fat |
| JKB-121: 10 mg | Analysis of MRI-PDFF Change From Baseline to Week 24 (Per Protocol Population) | -0.44 percentage of fat |
| Placebo | Analysis of MRI-PDFF Change From Baseline to Week 24 (Per Protocol Population) | -3.09 percentage of fat |
p-value: 0.034ANCOVA
p-value: 0.1731ANCOVA
Secondary
Analysis of ALT Change From Baseline to Week 12 (Per Protocol Population)
Time frame: Baseline to week 12
Population: The per protocol population included only those patients with non-missing baseline (ie. screening) and the specified visit are included. If missing, the last valid measurement on or prior to the first date administration of study medication is used as baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| JKB 121, 5 mg | Analysis of ALT Change From Baseline to Week 12 (Per Protocol Population) | -6.3 U/L |
| JKB-121: 10 mg | Analysis of ALT Change From Baseline to Week 12 (Per Protocol Population) | -9.9 U/L |
| Placebo | Analysis of ALT Change From Baseline to Week 12 (Per Protocol Population) | -21.7 U/L |
p-value: 0.0882ANCOVA
p-value: 0.253ANCOVA
Secondary
Analysis of ALT Change From Baseline to Week 24 (Per Protocol Population)
Time frame: Baseline to week 24
Population: The per protocol population included only those patients with non-missing baseline (ie. screening) and the specified visit are included. If missing, the last valid measurement on or prior to the first date administration of study medication is used as baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| JKB 121, 5 mg | Analysis of ALT Change From Baseline to Week 24 (Per Protocol Population) | -6.7 U/L |
| JKB-121: 10 mg | Analysis of ALT Change From Baseline to Week 24 (Per Protocol Population) | -1.3 U/L |
| Placebo | Analysis of ALT Change From Baseline to Week 24 (Per Protocol Population) | -20.9 U/L |
p-value: 0.2591ANCOVA
p-value: 0.1806ANCOVA
Secondary
Area Under Concentration-time (AUC)
Time frame: pre-dose and at 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12, and 24 hours
Population: PK Substudy Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| JKB 121, 5 mg | Area Under Concentration-time (AUC) | time 0 to infinity | 38.50 h*ng/mL | Standard Deviation 13.578 |
| JKB 121, 5 mg | Area Under Concentration-time (AUC) | time 0 to time of last quantifiable concentration | 26.29 h*ng/mL | Standard Deviation 9.443 |
| JKB 121, 5 mg | Area Under Concentration-time (AUC) | time 0 to 12 hours | 26.29 h*ng/mL | Standard Deviation 9.443 |
| JKB-121: 10 mg | Area Under Concentration-time (AUC) | time 0 to infinity | 71.24 h*ng/mL | Standard Deviation 16.562 |
| JKB-121: 10 mg | Area Under Concentration-time (AUC) | time 0 to time of last quantifiable concentration | 46.55 h*ng/mL | Standard Deviation 5.312 |
| JKB-121: 10 mg | Area Under Concentration-time (AUC) | time 0 to 12 hours | 50.44 h*ng/mL | Standard Deviation 5.388 |
Secondary
Change in BMI (Body Mass Index)
Time frame: Baseline, week 24
Population: Only patients with non-missing baseline and the specified visit are included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| JKB 121, 5 mg | Change in BMI (Body Mass Index) | -0.18 kg/m^2 |
| JKB-121: 10 mg | Change in BMI (Body Mass Index) | 0.54 kg/m^2 |
| Placebo | Change in BMI (Body Mass Index) | -0.63 kg/m^2 |
Secondary
Change in Hemoglobin A1C
Time frame: Baseline, week 24
Population: Only patients with non-missing baseline and the specified visit are included
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| JKB 121, 5 mg | Change in Hemoglobin A1C | 0.07 percentage of HbA1C |
| JKB-121: 10 mg | Change in Hemoglobin A1C | 0.23 percentage of HbA1C |
| Placebo | Change in Hemoglobin A1C | 0.45 percentage of HbA1C |
Secondary
Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)
HOMA-IR was calculated according to the formula: fasting insulin (microU/L) x fasting glucose (nmol/L)/22.5. Optimal Range: 1.0 (0.5-1.4). Lower values represent a better outcome.
Time frame: Baseline, week 24
Population: Only patients with non-missing baseline and the specified visit are included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| JKB 121, 5 mg | Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) | -1.013 HOMA-IR index |
| JKB-121: 10 mg | Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) | -0.679 HOMA-IR index |
| Placebo | Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) | -0.404 HOMA-IR index |
Secondary
Half-life
Time frame: pre-dose and at 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12, and 24 hours
Population: PK Substudy Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| JKB 121, 5 mg | Half-life | 8.55 h | Standard Deviation 1.439 |
| JKB-121: 10 mg | Half-life | 6.95 h | Standard Deviation 2.67 |
Secondary
Maximum Observed Concentrations (Cmax)
Time frame: pre-dose and at 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12, and 24 hours
Population: PK Substudy Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| JKB 121, 5 mg | Maximum Observed Concentrations (Cmax) | 5.26 ng/mL | Standard Deviation 1.731 |
| JKB-121: 10 mg | Maximum Observed Concentrations (Cmax) | 14.33 ng/mL | Standard Deviation 1.986 |
Secondary
Mean Serum Alanine Aminotransferase (ALT)
Time frame: weeks 4, 8, 12, 16, 20, and 24
Population: Number of subjects with a result at baseline and the specified visit. Baseline is defined as the measurement at Day 1.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| JKB 121, 5 mg | Mean Serum Alanine Aminotransferase (ALT) | Week 4 | 65.8 U/L | Standard Deviation 28.28 |
| JKB 121, 5 mg | Mean Serum Alanine Aminotransferase (ALT) | Week 8 | 63.8 U/L | Standard Deviation 26.03 |
| JKB 121, 5 mg | Mean Serum Alanine Aminotransferase (ALT) | Week 12 | 67.9 U/L | Standard Deviation 36.23 |
| JKB 121, 5 mg | Mean Serum Alanine Aminotransferase (ALT) | Week 16 | 61.5 U/L | Standard Deviation 29.06 |
| JKB 121, 5 mg | Mean Serum Alanine Aminotransferase (ALT) | Week 20 | 61.1 U/L | Standard Deviation 33.08 |
| JKB 121, 5 mg | Mean Serum Alanine Aminotransferase (ALT) | Week 24 | 67.3 U/L | Standard Deviation 33.8 |
| JKB-121: 10 mg | Mean Serum Alanine Aminotransferase (ALT) | Week 12 | 65.3 U/L | Standard Deviation 28.09 |
| JKB-121: 10 mg | Mean Serum Alanine Aminotransferase (ALT) | Week 4 | 70.4 U/L | Standard Deviation 26.33 |
| JKB-121: 10 mg | Mean Serum Alanine Aminotransferase (ALT) | Week 16 | 69.5 U/L | Standard Deviation 43.98 |
| JKB-121: 10 mg | Mean Serum Alanine Aminotransferase (ALT) | Week 20 | 63.8 U/L | Standard Deviation 37.96 |
| JKB-121: 10 mg | Mean Serum Alanine Aminotransferase (ALT) | Week 8 | 77.4 U/L | Standard Deviation 41.18 |
| JKB-121: 10 mg | Mean Serum Alanine Aminotransferase (ALT) | Week 24 | 68.2 U/L | Standard Deviation 46.34 |
| Placebo | Mean Serum Alanine Aminotransferase (ALT) | Week 8 | 79.4 U/L | Standard Deviation 42.62 |
| Placebo | Mean Serum Alanine Aminotransferase (ALT) | Week 12 | 69.8 U/L | Standard Deviation 39.27 |
| Placebo | Mean Serum Alanine Aminotransferase (ALT) | Week 24 | 67.6 U/L | Standard Deviation 48.06 |
| Placebo | Mean Serum Alanine Aminotransferase (ALT) | Week 20 | 70.7 U/L | Standard Deviation 43.59 |
| Placebo | Mean Serum Alanine Aminotransferase (ALT) | Week 4 | 95.0 U/L | Standard Deviation 66.36 |
| Placebo | Mean Serum Alanine Aminotransferase (ALT) | Week 16 | 68.7 U/L | Standard Deviation 33.19 |
Secondary
Mean Serum Aspartate Aminotransferase (AST)
Time frame: weeks 4, 8, 12, 16, 20, and 24
Population: Number of subjects with a result at baseline and the specified visit. Baseline is defined as the measurement at Day 1.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| JKB 121, 5 mg | Mean Serum Aspartate Aminotransferase (AST) | Week 4 | 45.7 U/L | Standard Deviation 15.11 |
| JKB 121, 5 mg | Mean Serum Aspartate Aminotransferase (AST) | Week 8 | 45.3 U/L | Standard Deviation 16.43 |
| JKB 121, 5 mg | Mean Serum Aspartate Aminotransferase (AST) | Week 12 | 47.6 U/L | Standard Deviation 17.56 |
| JKB 121, 5 mg | Mean Serum Aspartate Aminotransferase (AST) | Week 16 | 42.9 U/L | Standard Deviation 13.61 |
| JKB 121, 5 mg | Mean Serum Aspartate Aminotransferase (AST) | Week 20 | 50.1 U/L | Standard Deviation 26.34 |
| JKB 121, 5 mg | Mean Serum Aspartate Aminotransferase (AST) | Week 24 | 49.4 U/L | Standard Deviation 17.92 |
| JKB-121: 10 mg | Mean Serum Aspartate Aminotransferase (AST) | Week 24 | 49.5 U/L | Standard Deviation 33.78 |
| JKB-121: 10 mg | Mean Serum Aspartate Aminotransferase (AST) | Week 4 | 42.9 U/L | Standard Deviation 12.01 |
| JKB-121: 10 mg | Mean Serum Aspartate Aminotransferase (AST) | Week 16 | 47.5 U/L | Standard Deviation 22.29 |
| JKB-121: 10 mg | Mean Serum Aspartate Aminotransferase (AST) | Week 20 | 46.4 U/L | Standard Deviation 27.14 |
| JKB-121: 10 mg | Mean Serum Aspartate Aminotransferase (AST) | Week 8 | 47.1 U/L | Standard Deviation 15.12 |
| JKB-121: 10 mg | Mean Serum Aspartate Aminotransferase (AST) | Week 12 | 44.2 U/L | Standard Deviation 16.48 |
| Placebo | Mean Serum Aspartate Aminotransferase (AST) | Week 8 | 67.4 U/L | Standard Deviation 55.1 |
| Placebo | Mean Serum Aspartate Aminotransferase (AST) | Week 12 | 49.7 U/L | Standard Deviation 22.94 |
| Placebo | Mean Serum Aspartate Aminotransferase (AST) | Week 24 | 47.4 U/L | Standard Deviation 25.93 |
| Placebo | Mean Serum Aspartate Aminotransferase (AST) | Week 16 | 51.1 U/L | Standard Deviation 24.32 |
| Placebo | Mean Serum Aspartate Aminotransferase (AST) | Week 4 | 81.0 U/L | Standard Deviation 79.96 |
| Placebo | Mean Serum Aspartate Aminotransferase (AST) | Week 20 | 54.0 U/L | Standard Deviation 44.85 |
Secondary
Mean Serum Gamma-glutamyl Transpeptidase (GGT)
Time frame: weeks 4, 8, 12, 16, 20, and 24
Population: Number of subjects with a result at baseline and the specified visit. Baseline is defined as the measurement at Day 1.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| JKB 121, 5 mg | Mean Serum Gamma-glutamyl Transpeptidase (GGT) | Week 4 | 68.4 U/L | Standard Deviation 38.07 |
| JKB 121, 5 mg | Mean Serum Gamma-glutamyl Transpeptidase (GGT) | Week 8 | 73.7 U/L | Standard Deviation 48.74 |
| JKB 121, 5 mg | Mean Serum Gamma-glutamyl Transpeptidase (GGT) | Week 12 | 79.2 U/L | Standard Deviation 58.32 |
| JKB 121, 5 mg | Mean Serum Gamma-glutamyl Transpeptidase (GGT) | Week 16 | 78.3 U/L | Standard Deviation 54.85 |
| JKB 121, 5 mg | Mean Serum Gamma-glutamyl Transpeptidase (GGT) | Week 20 | 75.4 U/L | Standard Deviation 52.8 |
| JKB 121, 5 mg | Mean Serum Gamma-glutamyl Transpeptidase (GGT) | Week 24 | 86.6 U/L | Standard Deviation 79.47 |
| JKB-121: 10 mg | Mean Serum Gamma-glutamyl Transpeptidase (GGT) | Week 24 | 68.2 U/L | Standard Deviation 30.79 |
| JKB-121: 10 mg | Mean Serum Gamma-glutamyl Transpeptidase (GGT) | Week 4 | 83.8 U/L | Standard Deviation 48.85 |
| JKB-121: 10 mg | Mean Serum Gamma-glutamyl Transpeptidase (GGT) | Week 16 | 69.8 U/L | Standard Deviation 33.49 |
| JKB-121: 10 mg | Mean Serum Gamma-glutamyl Transpeptidase (GGT) | Week 20 | 64.1 U/L | Standard Deviation 30.65 |
| JKB-121: 10 mg | Mean Serum Gamma-glutamyl Transpeptidase (GGT) | Week 8 | 74.6 U/L | Standard Deviation 35.02 |
| JKB-121: 10 mg | Mean Serum Gamma-glutamyl Transpeptidase (GGT) | Week 12 | 74.3 U/L | Standard Deviation 36.99 |
| Placebo | Mean Serum Gamma-glutamyl Transpeptidase (GGT) | Week 8 | 147.5 U/L | Standard Deviation 123.42 |
| Placebo | Mean Serum Gamma-glutamyl Transpeptidase (GGT) | Week 12 | 133.8 U/L | Standard Deviation 115.93 |
| Placebo | Mean Serum Gamma-glutamyl Transpeptidase (GGT) | Week 24 | 109.7 U/L | Standard Deviation 92.1 |
| Placebo | Mean Serum Gamma-glutamyl Transpeptidase (GGT) | Week 16 | 134.7 U/L | Standard Deviation 139.93 |
| Placebo | Mean Serum Gamma-glutamyl Transpeptidase (GGT) | Week 4 | 165.0 U/L | Standard Deviation 149.38 |
| Placebo | Mean Serum Gamma-glutamyl Transpeptidase (GGT) | Week 20 | 132.9 U/L | Standard Deviation 144.28 |
Secondary
Minimum Observed Concentration (Cmin)
Time frame: pre-dose and at 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12, and 24 hours
Population: PK Substudy Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| JKB 121, 5 mg | Minimum Observed Concentration (Cmin) | 0.349 ng/mL | Standard Deviation 0.1595 |
| JKB-121: 10 mg | Minimum Observed Concentration (Cmin) | 1.512 ng/mL | Standard Deviation 1.0702 |
Secondary
Number of Subjects With ALT in Normal Range at Week 24
Normal range is \<40 U/L
Time frame: Week 24
Population: Number of subjects with an ALT result at the specified visit
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| JKB 121, 5 mg | Number of Subjects With ALT in Normal Range at Week 24 | 5 Participants |
| JKB-121: 10 mg | Number of Subjects With ALT in Normal Range at Week 24 | 4 Participants |
| Placebo | Number of Subjects With ALT in Normal Range at Week 24 | 7 Participants |
Secondary
Percent Change in Cholesterol
Time frame: Baseline, week 24
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| JKB 121, 5 mg | Percent Change in Cholesterol | 6.62 percent change |
| JKB-121: 10 mg | Percent Change in Cholesterol | -2.55 percent change |
| Placebo | Percent Change in Cholesterol | 2.26 percent change |
Secondary
Percent Change in High Density Lipoprotein (HDL)
Time frame: Baseline, week 24
Population: Only patients with non-missing baseline and the specified visit are included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| JKB 121, 5 mg | Percent Change in High Density Lipoprotein (HDL) | 2.70 percent change |
| JKB-121: 10 mg | Percent Change in High Density Lipoprotein (HDL) | -0.80 percent change |
| Placebo | Percent Change in High Density Lipoprotein (HDL) | 13.97 percent change |
Secondary
Percent Change in Low Density Lipoprotein (LDL) Cholesterol
Time frame: Baseline, week 24
Population: Only patients with non-missing baseline and the specified visit are included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| JKB 121, 5 mg | Percent Change in Low Density Lipoprotein (LDL) Cholesterol | 5.92 percent change |
| JKB-121: 10 mg | Percent Change in Low Density Lipoprotein (LDL) Cholesterol | -4.79 percent change |
| Placebo | Percent Change in Low Density Lipoprotein (LDL) Cholesterol | 1.50 percent change |
Secondary
Percent Change in Triglycerides
Time frame: Baseline, week 24
Population: Only patients with non-missing baseline and the specified visit are included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| JKB 121, 5 mg | Percent Change in Triglycerides | 18.12 percent change |
| JKB-121: 10 mg | Percent Change in Triglycerides | 2.62 percent change |
| Placebo | Percent Change in Triglycerides | 3.78 percent change |
Secondary
Time to Remission (in Weeks)
Time to remission is the time in weeks from randomization to liver function remission, defined as two consecutive ALT values within normal range (\<40 U/L) during the treatment period.
Time frame: 24 weeks
Population: No subjects reached remission; analysis not performed.