Alcoholic Hepatitis
Conditions
Keywords
Alcoholic Hepatitis, acute alcoholic liver disease, progressive inflammatory liver injury, IV infusion
Brief summary
This is a research trial testing DUR-928 (an experimental medication). The purpose of this trial is to assess the dose related safety, Pharmacokinetics, and Pharmacodynamics of DUR 928 in patients with moderate and severe alcoholic hepatitis (AH).
Interventions
DRUGDUR-928 30 mg
Lowest dose of 3 dose escalation arms.
DRUGDUR-928 90 mg
Middle dose of 3 dose escalation arms.
DRUGDUR-928 150 mg
Highest dose of 3 dose escalation arms.
Sponsors
CTI Clinical Trial and Consulting Services
Durect
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Staggered parallel design.
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Able to provide written informed consent (either from patient or patient's legally acceptable representative) 2. Male or female patients 21 years of age or older with BMI ≥ 20 to ≤ 40 kg/m2 3. Patients with alcoholic hepatitis defined as: 1. History of heavy alcohol abuse: \> 40 g/day in females or \> 60 g/day in males for a minimum period of 6 months, AND 2. Consumed alcohol within 12 weeks of entry into the study, AND 3. Serum bilirubin \> 3 mg/dL AND AST \> ALT, but less than 300 U/L AND 4. MELD score between 11-30, inclusive 4. No evidence of active infection as determined by the investigator. 5. Women of child-bearing potential must utilize appropriate birth control throughout the study duration. 6. Male patients must agree to use a medically acceptable method of contraception/birth control throughout the study duration
Exclusion criteria
1. Other or concomitant cause(s) of liver disease as a result of: 1. Autoimmune liver disease 2. Wilson disease 3. Vascular liver disease 4. Drug induced liver disease 2. Co-infection with human immunodeficiency virus (HIV) or Hepatitis B 3. Any active malignancies other than curatively treated skin cancer (basal cell or squamous cell carcinomas) 4. If female, known pregnancy, or has a positive serum pregnancy test, or lactating/breastfeeding 5. Serum creatinine \> 2.5 mg/dL 6. Patients who have had organ transplantation (such as liver, kidney, lung, heart, bone marrow, or stem cell etc.), other than cornea transplant 7. Stage 3 or greater encephalopathy by West Haven criteria
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Model for End Stage Liver Disease (MELD) Score - Percent Change From Baseline | Baseline (Screening or Day 1 Pre-dose), Day 7 and Day 28 | The MELD Score %change from baseline is a %change between 2 time points, baseline and value at a specific time point (Day 7 or Day 28). MELD score is a good predictor of outcome. A declining MELD score suggests disease improvement. Lab values for international normalized ratio (INR), serum creatinine (sCr) and bilirubin are used to calculate the MELD score. MELD score will be calculated using the original formula (pre-2016) which does not include serum sodium level. Original MELD Score = (0.957 x Ln(Serum Creatinine in mg/dL) + 0. 378 x Ln(Serum Bilirubin in mg/dL) + 1.120 x Ln (INR) + 0.643) x 10 Note: (1) If patient received two or more dialysis treatments within the prior 7 days, then the value for serum creatinine will be set to 4.0. (2) If any laboratory value is less than 1.0, the value will be set to 1.0 for the MELD score calculation, in order to avoid negative values resulting from taking the natural log of values less than 1. |
| Lille Model for Alcoholic Hepatitis Score | Day 7 | The Lille score predicts response of AH subjects to treatment with glucocorticoids, such as prednisolone. This score is based on age, serum albumin, creatinine, PT, and the difference in bilirubin between pre-treatment and Day 7 post-treatment. The Lille score ranges from 0.01 to 1.00. A score \>0.45 predicts a higher risk of death and the recommendation to stop steroid administration. Lille Score = Exp(-R)/(1 + Exp(-R)) Where: R = \[3.19 - (0.101 x Age in years)\] + (1.47 x Albumin in g/dL) + \[0.28215 x (Bilirubin initial - Bilirubin day 7 in mg/dL)\] - (0.206 x Creatinine in mg/dL) - (0.11115 x Bilirubin initial in mg/dL) - (0.0096 x PT in seconds) NOTE: When calculating Lille, use baseline values for ALL parameters EXCEPT bilirubin at Day 7. Baseline would be the Day 1 Pre-dose sample result, if available. If not available, then use the Screening sample result. |
| Model for End Stage Liver Disease (MELD) Score | Baseline (Screening or Day 1 Pre-dose), Day 7 and Day 28 | The MELD score at enrollment is a good predictor for AH patient prognosis. Laboratory values for international normalized ratio (INR), serum creatinine (sCr) and bilirubin are used to calculate the MELD score. The MELD score ranges from 6.0 to 40.0 (capped) with a higher score predicting a higher risk of death. A sequentially improving MELD score is associated with a better chance of recovery. MELD score will be calculated using the original formula (pre-2016) which does not include serum sodium level. Original MELD Score = (0.957 x Ln(Serum Creatinine in mg/dL) + 0. 378 x Ln(Serum Bilirubin in mg/dL) + 1.120 x Ln (INR) + 0.643) x 10 Note: (1) If patient received two or more dialysis treatments within the prior 7 days, then the value for serum creatinine will be set to 4.0. (2) If any laboratory value is less than 1.0, the value will be set to 1.0 for the MELD score calculation, in order to avoid negative values resulting from taking the natural log of values less than 1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| International Normalized Ratio (INR) - Percent Change From Baseline | Baseline (Screening or Day 1 Pre-dose), Day 7, Day 28 | ITT population. INR (international normalized ratio) is a standardized number based on the prothrombin time and calculated by the clinical lab. INR measures the time it takes for blood to clot in vitro and measures, among other things, liver synthetic function. |
| Bilirubin - Percent Change From Baseline | Baseline (Screening or Day 1 Pre-dose), Day 7, Day 28 | ITT population |
| Serum Cytokeratin 18 (M30) | Baseline (Screening or Day 1 Pre-dose), Day 7, Day 28 | Analysis Population Description: Baseline was defined as the last non-missing value prior to study drug administration, at Screening or Day 1 Pre-dose. |
| Serum Cytokeratin 18 (M65) | Baseline (Screening or Day 1 Pre-dose), Day 7, Day 28 | Analysis Population Description: Baseline was defined as the last non-missing value prior to study drug administration, at Screening or Day 1 Pre-dose. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Serum Creatinine (sCR) | Baseline (Screening or Day 1 Pre-dose) | Serum Creatinine (sCR) at baseline is provided as part of the calculation for MELD |
Countries
United States
Participant flow
Recruitment details
Part A (Moderate AH) and Part B (Severe AH) were assigned treatments in a dose escalation, staggered parallel design. Part A (Moderate AH) highest dose of dose escalation arms (150 mg) was not enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Moderate AH DUR-928 30 mg Part A (Moderate AH) Lowest dose of doses investigated: 30 mg, 90 mg, 150 mg
DUR-928: Dose escalation including 2 doses: 30mg and 90 mg (150 mg did not enroll) | 4 |
| Moderate AH DUR-928 90 mg Part A (Moderate AH) Middle dose of doses investigated: 30 mg, 90 mg, 150 mg
DUR-928: Dose escalation including 2 doses: 30mg and 90 mg (150 mg did not enroll) | 3 |
| Severe AH DUR-928 30 mg Part B (Severe AH) Lowest dose of doses investigated: 30mg, 90 mg and 150 mg
DUR-928: Dose escalation including 3 doses: 30mg, 90 mg and 150 mg | 4 |
| Severe AH DUR-928 90 mg Part B (Severe AH) Middle dose of doses investigated: 30mg, 90 mg and 150 mg
DUR-928: Dose escalation including 3 doses: 30mg, 90 mg and 150 mg | 4 |
| Severe AH DUR-928 150 mg Part B (Severe AH) Highest dose of doses investigated: 30mg, 90 mg and 150 mg
DUR-928: Dose escalation including 3 doses: 30mg, 90 mg and 150 mg | 4 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Moderate AH DUR-928 30 mg | Total | Severe AH DUR-928 150 mg | Severe AH DUR-928 90 mg | Severe AH DUR-928 30 mg | Moderate AH DUR-928 90 mg |
|---|---|---|---|---|---|---|
| Age, Continuous | 36.5 years | 41.0 years | 40.5 years | 43.5 years | 45.0 years | 42.0 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 7 Participants | 2 Participants | 2 Participants | 2 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 12 Participants | 2 Participants | 2 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 17 Participants | 3 Participants | 4 Participants | 4 Participants | 3 Participants |
| Region of Enrollment United States | 4 participants | 19 participants | 4 participants | 4 participants | 4 participants | 3 participants |
| Sex: Female, Male Female | 3 Participants | 8 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 1 Participants | 11 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 3 | 0 / 4 | 0 / 4 | 0 / 4 |
| other Total, other adverse events | 4 / 4 | 2 / 3 | 3 / 4 | 3 / 4 | 3 / 4 |
| serious Total, serious adverse events | 2 / 4 | 0 / 3 | 2 / 4 | 1 / 4 | 0 / 4 |
Outcome results
Primary
Lille Model for Alcoholic Hepatitis Score
The Lille score predicts response of AH subjects to treatment with glucocorticoids, such as prednisolone. This score is based on age, serum albumin, creatinine, PT, and the difference in bilirubin between pre-treatment and Day 7 post-treatment. The Lille score ranges from 0.01 to 1.00. A score \>0.45 predicts a higher risk of death and the recommendation to stop steroid administration. Lille Score = Exp(-R)/(1 + Exp(-R)) Where: R = \[3.19 - (0.101 x Age in years)\] + (1.47 x Albumin in g/dL) + \[0.28215 x (Bilirubin initial - Bilirubin day 7 in mg/dL)\] - (0.206 x Creatinine in mg/dL) - (0.11115 x Bilirubin initial in mg/dL) - (0.0096 x PT in seconds) NOTE: When calculating Lille, use baseline values for ALL parameters EXCEPT bilirubin at Day 7. Baseline would be the Day 1 Pre-dose sample result, if available. If not available, then use the Screening sample result.
Time frame: Day 7
Population: ITT
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Moderate AH DUR-928 30 mg | Lille Model for Alcoholic Hepatitis Score | 0.020 score on a scale |
| Moderate AH DUR-928 90 mg | Lille Model for Alcoholic Hepatitis Score | 0.050 score on a scale |
| Severe AH DUR-928 30 mg | Lille Model for Alcoholic Hepatitis Score | 0.155 score on a scale |
| Severe AH DUR-928 90 mg | Lille Model for Alcoholic Hepatitis Score | 0.195 score on a scale |
| Severe AH DUR-928 150 mg | Lille Model for Alcoholic Hepatitis Score | 0.420 score on a scale |
Primary
Model for End Stage Liver Disease (MELD) Score
The MELD score at enrollment is a good predictor for AH patient prognosis. Laboratory values for international normalized ratio (INR), serum creatinine (sCr) and bilirubin are used to calculate the MELD score. The MELD score ranges from 6.0 to 40.0 (capped) with a higher score predicting a higher risk of death. A sequentially improving MELD score is associated with a better chance of recovery. MELD score will be calculated using the original formula (pre-2016) which does not include serum sodium level. Original MELD Score = (0.957 x Ln(Serum Creatinine in mg/dL) + 0. 378 x Ln(Serum Bilirubin in mg/dL) + 1.120 x Ln (INR) + 0.643) x 10 Note: (1) If patient received two or more dialysis treatments within the prior 7 days, then the value for serum creatinine will be set to 4.0. (2) If any laboratory value is less than 1.0, the value will be set to 1.0 for the MELD score calculation, in order to avoid negative values resulting from taking the natural log of values less than 1.
Time frame: Baseline (Screening or Day 1 Pre-dose), Day 7 and Day 28
Population: ITT, baseline was defined as the last non-missing value prior to study drug administration, at Screening or Day 1 Pre-dose
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Moderate AH DUR-928 30 mg | Model for End Stage Liver Disease (MELD) Score | Day 7 | 17.0 score on a scale |
| Moderate AH DUR-928 30 mg | Model for End Stage Liver Disease (MELD) Score | Day 28 | 15.0 score on a scale |
| Moderate AH DUR-928 30 mg | Model for End Stage Liver Disease (MELD) Score | Screening | 19.5 score on a scale |
| Moderate AH DUR-928 90 mg | Model for End Stage Liver Disease (MELD) Score | Day 28 | 11.5 score on a scale |
| Moderate AH DUR-928 90 mg | Model for End Stage Liver Disease (MELD) Score | Day 1 Pre-dose | 20.0 score on a scale |
| Moderate AH DUR-928 90 mg | Model for End Stage Liver Disease (MELD) Score | Screening | 19.0 score on a scale |
| Moderate AH DUR-928 90 mg | Model for End Stage Liver Disease (MELD) Score | Day 7 | 17.0 score on a scale |
| Severe AH DUR-928 30 mg | Model for End Stage Liver Disease (MELD) Score | Day 1 Pre-dose | 23.0 score on a scale |
| Severe AH DUR-928 30 mg | Model for End Stage Liver Disease (MELD) Score | Screening | 24.5 score on a scale |
| Severe AH DUR-928 30 mg | Model for End Stage Liver Disease (MELD) Score | Day 28 | 19.0 score on a scale |
| Severe AH DUR-928 30 mg | Model for End Stage Liver Disease (MELD) Score | Day 7 | 23.5 score on a scale |
| Severe AH DUR-928 90 mg | Model for End Stage Liver Disease (MELD) Score | Day 7 | 24.0 score on a scale |
| Severe AH DUR-928 90 mg | Model for End Stage Liver Disease (MELD) Score | Day 1 Pre-dose | 24.0 score on a scale |
| Severe AH DUR-928 90 mg | Model for End Stage Liver Disease (MELD) Score | Screening | 24.5 score on a scale |
| Severe AH DUR-928 90 mg | Model for End Stage Liver Disease (MELD) Score | Day 28 | 23.5 score on a scale |
| Severe AH DUR-928 150 mg | Model for End Stage Liver Disease (MELD) Score | Day 28 | 23.0 score on a scale |
| Severe AH DUR-928 150 mg | Model for End Stage Liver Disease (MELD) Score | Screening | 25.0 score on a scale |
| Severe AH DUR-928 150 mg | Model for End Stage Liver Disease (MELD) Score | Day 1 Pre-dose | 23.0 score on a scale |
| Severe AH DUR-928 150 mg | Model for End Stage Liver Disease (MELD) Score | Day 7 | 24.0 score on a scale |
Primary
Model for End Stage Liver Disease (MELD) Score - Percent Change From Baseline
The MELD Score %change from baseline is a %change between 2 time points, baseline and value at a specific time point (Day 7 or Day 28). MELD score is a good predictor of outcome. A declining MELD score suggests disease improvement. Lab values for international normalized ratio (INR), serum creatinine (sCr) and bilirubin are used to calculate the MELD score. MELD score will be calculated using the original formula (pre-2016) which does not include serum sodium level. Original MELD Score = (0.957 x Ln(Serum Creatinine in mg/dL) + 0. 378 x Ln(Serum Bilirubin in mg/dL) + 1.120 x Ln (INR) + 0.643) x 10 Note: (1) If patient received two or more dialysis treatments within the prior 7 days, then the value for serum creatinine will be set to 4.0. (2) If any laboratory value is less than 1.0, the value will be set to 1.0 for the MELD score calculation, in order to avoid negative values resulting from taking the natural log of values less than 1.
Time frame: Baseline (Screening or Day 1 Pre-dose), Day 7 and Day 28
Population: ITT
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Moderate AH DUR-928 30 mg | Model for End Stage Liver Disease (MELD) Score - Percent Change From Baseline | Day 7 | -5.00 Percent Change |
| Moderate AH DUR-928 30 mg | Model for End Stage Liver Disease (MELD) Score - Percent Change From Baseline | Day 28 | -20.00 Percent Change |
| Moderate AH DUR-928 90 mg | Model for End Stage Liver Disease (MELD) Score - Percent Change From Baseline | Day 7 | -10.53 Percent Change |
| Moderate AH DUR-928 90 mg | Model for End Stage Liver Disease (MELD) Score - Percent Change From Baseline | Day 28 | -33.93 Percent Change |
| Severe AH DUR-928 30 mg | Model for End Stage Liver Disease (MELD) Score - Percent Change From Baseline | Day 7 | 0.00 Percent Change |
| Severe AH DUR-928 30 mg | Model for End Stage Liver Disease (MELD) Score - Percent Change From Baseline | Day 28 | -26.76 Percent Change |
| Severe AH DUR-928 90 mg | Model for End Stage Liver Disease (MELD) Score - Percent Change From Baseline | Day 28 | -8.00 Percent Change |
| Severe AH DUR-928 90 mg | Model for End Stage Liver Disease (MELD) Score - Percent Change From Baseline | Day 7 | 0.00 Percent Change |
| Severe AH DUR-928 150 mg | Model for End Stage Liver Disease (MELD) Score - Percent Change From Baseline | Day 7 | 0.00 Percent Change |
| Severe AH DUR-928 150 mg | Model for End Stage Liver Disease (MELD) Score - Percent Change From Baseline | Day 28 | 0.00 Percent Change |
Secondary
Bilirubin - Percent Change From Baseline
ITT population
Time frame: Baseline (Screening or Day 1 Pre-dose), Day 7, Day 28
Population: Baseline is defined as the last non-missing value prior to study drug administration, at Screening or Day 1 Pre-dose
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Moderate AH DUR-928 30 mg | Bilirubin - Percent Change From Baseline | Day 7 Percent Change from Baseline | -15.69 Percent Change |
| Moderate AH DUR-928 30 mg | Bilirubin - Percent Change From Baseline | Day 28 Percent Change from Baseline | -27.27 Percent Change |
| Moderate AH DUR-928 90 mg | Bilirubin - Percent Change From Baseline | Day 7 Percent Change from Baseline | -31.03 Percent Change |
| Moderate AH DUR-928 90 mg | Bilirubin - Percent Change From Baseline | Day 28 Percent Change from Baseline | -74.27 Percent Change |
| Severe AH DUR-928 30 mg | Bilirubin - Percent Change From Baseline | Day 7 Percent Change from Baseline | -25.19 Percent Change |
| Severe AH DUR-928 30 mg | Bilirubin - Percent Change From Baseline | Day 28 Percent Change from Baseline | -56.93 Percent Change |
| Severe AH DUR-928 90 mg | Bilirubin - Percent Change From Baseline | Day 28 Percent Change from Baseline | -34.82 Percent Change |
| Severe AH DUR-928 90 mg | Bilirubin - Percent Change From Baseline | Day 7 Percent Change from Baseline | -6.48 Percent Change |
| Severe AH DUR-928 150 mg | Bilirubin - Percent Change From Baseline | Day 7 Percent Change from Baseline | 4.96 Percent Change |
| Severe AH DUR-928 150 mg | Bilirubin - Percent Change From Baseline | Day 28 Percent Change from Baseline | -10.04 Percent Change |
Secondary
International Normalized Ratio (INR) - Percent Change From Baseline
ITT population. INR (international normalized ratio) is a standardized number based on the prothrombin time and calculated by the clinical lab. INR measures the time it takes for blood to clot in vitro and measures, among other things, liver synthetic function.
Time frame: Baseline (Screening or Day 1 Pre-dose), Day 7, Day 28
Population: Baseline is defined as the last non-missing value prior to study drug administration, at Screening or Day 1 Pre-dose
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Moderate AH DUR-928 30 mg | International Normalized Ratio (INR) - Percent Change From Baseline | Day 7 Percent Change from Baseline | -10.000 Percent Change |
| Moderate AH DUR-928 30 mg | International Normalized Ratio (INR) - Percent Change From Baseline | Day 28 Percent Change from Baseline | -3.676 Percent Change |
| Moderate AH DUR-928 90 mg | International Normalized Ratio (INR) - Percent Change From Baseline | Day 7 Percent Change from Baseline | -3.226 Percent Change |
| Moderate AH DUR-928 90 mg | International Normalized Ratio (INR) - Percent Change From Baseline | Day 28 Percent Change from Baseline | 0.000 Percent Change |
| Severe AH DUR-928 30 mg | International Normalized Ratio (INR) - Percent Change From Baseline | Day 7 Percent Change from Baseline | 4.768 Percent Change |
| Severe AH DUR-928 30 mg | International Normalized Ratio (INR) - Percent Change From Baseline | Day 28 Percent Change from Baseline | -19.402 Percent Change |
| Severe AH DUR-928 90 mg | International Normalized Ratio (INR) - Percent Change From Baseline | Day 28 Percent Change from Baseline | -3.180 Percent Change |
| Severe AH DUR-928 90 mg | International Normalized Ratio (INR) - Percent Change From Baseline | Day 7 Percent Change from Baseline | 0.000 Percent Change |
| Severe AH DUR-928 150 mg | International Normalized Ratio (INR) - Percent Change From Baseline | Day 7 Percent Change from Baseline | 0.000 Percent Change |
| Severe AH DUR-928 150 mg | International Normalized Ratio (INR) - Percent Change From Baseline | Day 28 Percent Change from Baseline | 0.000 Percent Change |
Secondary
Serum Cytokeratin 18 (M30)
Analysis Population Description: Baseline was defined as the last non-missing value prior to study drug administration, at Screening or Day 1 Pre-dose.
Time frame: Baseline (Screening or Day 1 Pre-dose), Day 7, Day 28
Population: Number analyzed is dependent on samples being collected and evaluable.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Moderate AH DUR-928 30 mg | Serum Cytokeratin 18 (M30) | Day 7 | 526 U/L |
| Moderate AH DUR-928 30 mg | Serum Cytokeratin 18 (M30) | Day 1-Predose | 723.5 U/L |
| Moderate AH DUR-928 90 mg | Serum Cytokeratin 18 (M30) | Day 28 | 2205.5 U/L |
| Moderate AH DUR-928 90 mg | Serum Cytokeratin 18 (M30) | Day 7 | 3112 U/L |
| Moderate AH DUR-928 90 mg | Serum Cytokeratin 18 (M30) | Day 1-Predose | 737 U/L |
| Severe AH DUR-928 30 mg | Serum Cytokeratin 18 (M30) | Day 1-Predose | 1443.5 U/L |
| Severe AH DUR-928 30 mg | Serum Cytokeratin 18 (M30) | Day 28 | 1114.0 U/L |
| Severe AH DUR-928 30 mg | Serum Cytokeratin 18 (M30) | Day 7 | 3305.5 U/L |
| Severe AH DUR-928 90 mg | Serum Cytokeratin 18 (M30) | Day 1-Predose | 1946 U/L |
| Severe AH DUR-928 90 mg | Serum Cytokeratin 18 (M30) | Day 7 | 1702.0 U/L |
| Severe AH DUR-928 90 mg | Serum Cytokeratin 18 (M30) | Day 28 | 550.5 U/L |
| Severe AH DUR-928 150 mg | Serum Cytokeratin 18 (M30) | Day 1-Predose | 931 U/L |
| Severe AH DUR-928 150 mg | Serum Cytokeratin 18 (M30) | Day 28 | 161.0 U/L |
| Severe AH DUR-928 150 mg | Serum Cytokeratin 18 (M30) | Day 7 | 1012.5 U/L |
Secondary
Serum Cytokeratin 18 (M65)
Analysis Population Description: Baseline was defined as the last non-missing value prior to study drug administration, at Screening or Day 1 Pre-dose.
Time frame: Baseline (Screening or Day 1 Pre-dose), Day 7, Day 28
Population: Number analyzed is dependent on samples being collected and evaluable.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Moderate AH DUR-928 30 mg | Serum Cytokeratin 18 (M65) | Day 7 | 353.0 U/L |
| Moderate AH DUR-928 30 mg | Serum Cytokeratin 18 (M65) | Day 1-Predose | 252.5 U/L |
| Moderate AH DUR-928 90 mg | Serum Cytokeratin 18 (M65) | Day 7 | 4697.0 U/L |
| Moderate AH DUR-928 90 mg | Serum Cytokeratin 18 (M65) | Day 1-Predose | 1791.0 U/L |
| Moderate AH DUR-928 90 mg | Serum Cytokeratin 18 (M65) | Day 28 | 4771.5 U/L |
| Severe AH DUR-928 30 mg | Serum Cytokeratin 18 (M65) | Day 7 | 7303.0 U/L |
| Severe AH DUR-928 30 mg | Serum Cytokeratin 18 (M65) | Day 1-Predose | 3033.5 U/L |
| Severe AH DUR-928 30 mg | Serum Cytokeratin 18 (M65) | Day 28 | 2426.0 U/L |
| Severe AH DUR-928 90 mg | Serum Cytokeratin 18 (M65) | Day 7 | 4397.5 U/L |
| Severe AH DUR-928 90 mg | Serum Cytokeratin 18 (M65) | Day 1-Predose | 4071.5 U/L |
| Severe AH DUR-928 90 mg | Serum Cytokeratin 18 (M65) | Day 28 | 1224.5 U/L |
| Severe AH DUR-928 150 mg | Serum Cytokeratin 18 (M65) | Day 7 | 3994.5 U/L |
| Severe AH DUR-928 150 mg | Serum Cytokeratin 18 (M65) | Day 28 | 1987.0 U/L |
| Severe AH DUR-928 150 mg | Serum Cytokeratin 18 (M65) | Day 1-Predose | 1999.0 U/L |
Other Pre-specified
Serum Creatinine (sCR)
Serum Creatinine (sCR) at baseline is provided as part of the calculation for MELD
Time frame: Baseline (Screening or Day 1 Pre-dose)
Population: Baseline was defined as the last non-missing value prior to study drug administration, at Screening or Day 1 Pre-dose.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Moderate AH DUR-928 30 mg | Serum Creatinine (sCR) | Baseline (Screening) | 0.620 mg/dL |
| Moderate AH DUR-928 90 mg | Serum Creatinine (sCR) | Baseline (Day 1-Pre dose) | 0.660 mg/dL |
| Moderate AH DUR-928 90 mg | Serum Creatinine (sCR) | Baseline (Screening) | 0.710 mg/dL |
| Severe AH DUR-928 30 mg | Serum Creatinine (sCR) | Baseline (Day 1-Pre dose) | 0.640 mg/dL |
| Severe AH DUR-928 30 mg | Serum Creatinine (sCR) | Baseline (Screening) | 0.795 mg/dL |
| Severe AH DUR-928 90 mg | Serum Creatinine (sCR) | Baseline (Screening) | 0.765 mg/dL |
| Severe AH DUR-928 90 mg | Serum Creatinine (sCR) | Baseline (Day 1-Pre dose) | 0.580 mg/dL |
| Severe AH DUR-928 150 mg | Serum Creatinine (sCR) | Baseline (Day 1-Pre dose) | 0.520 mg/dL |
| Severe AH DUR-928 150 mg | Serum Creatinine (sCR) | Baseline (Screening) | 0.610 mg/dL |