Skip to main content
OpenTrials
Completed

NCT Number: NCT03432260

A Research Study to Assess the Safety, Pharmacokinetics and Pharmacodynamics of DUR-928 in Patients With Alcoholic Hepatitis

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).

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Alcoholic Hepatitis Alcohol-Induced Disorders Alcohol-Related Disorders Chemically-Induced Disorders Digestive System Diseases Hepatitis Hepatitis, Alcoholic Liver Diseases Liver Diseases, Alcoholic Substance-Related Disorders

Age range

21 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

DURECT Study Site 0001, San Diego, California, United States

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Able to provide written informed consent (either from patient or patient's legally acceptable representative)
  • Male or female patients 21 years of age or older with BMI ≥ 20 to ≤ 40 kg/m2
  • Patients with alcoholic hepatitis defined as:
  • History of heavy alcohol abuse: > 40 g/day in females or > 60 g/day in males for a minimum period of 6 months, AND
  • Consumed alcohol within 12 weeks of entry into the study, AND
  • Serum bilirubin > 3 mg/dL AND AST > ALT, but less than 300 U/L AND
  • MELD score between 11-30, inclusive
  • No evidence of active infection as determined by the investigator.
  • Women of child-bearing potential must utilize appropriate birth control throughout the study duration.
  • Male patients must agree to use a medically acceptable method of contraception/birth control throughout the study duration

Exclusion criteria

  • Other or concomitant cause(s) of liver disease as a result of:
  • Autoimmune liver disease
  • Wilson disease
  • Vascular liver disease
  • Drug induced liver disease
  • Co-infection with human immunodeficiency virus (HIV) or Hepatitis B
  • Any active malignancies other than curatively treated skin cancer (basal cell or squamous cell carcinomas)
  • If female, known pregnancy, or has a positive serum pregnancy test, or lactating/breastfeeding
  • Serum creatinine > 2.5 mg/dL
  • Patients who have had organ transplantation (such as liver, kidney, lung, heart, bone marrow, or stem cell etc.), other than cornea transplant
  • Stage 3 or greater encephalopathy by West Haven criteria

Treatment and study plan

DUR-928 30 mg

Drug

Lowest dose of 3 dose escalation arms.

DUR-928 90 mg

Drug

Middle dose of 3 dose escalation arms.

DUR-928 150 mg

Drug

Highest dose of 3 dose escalation arms.

Primary outcomes

  1. Lille Model for Alcoholic Hepatitis Score

    Time frame: 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.

  2. Model for End Stage Liver Disease (MELD) Score

    Time frame: 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.

  3. Model for End Stage Liver Disease (MELD) Score - Percent Change From Baseline

    Time frame: 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.

Secondary outcomes

  1. Serum Cytokeratin 18 (M30)

    Time frame: 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.

  2. Serum Cytokeratin 18 (M65)

    Time frame: 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.

  3. International Normalized Ratio (INR) - Percent Change From Baseline

    Time frame: 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.

  4. Bilirubin - Percent Change From Baseline

    Time frame: Baseline (Screening or Day 1 Pre-dose), Day 7, Day 28

    ITT population

Other outcomes

  1. Serum Creatinine (sCR)

    Time frame: Baseline (Screening or Day 1 Pre-dose)

    Serum Creatinine (sCR) at baseline is provided as part of the calculation for MELD

Sponsors and collaborators

Lead sponsor

Durect

Industry

Collaborators

  • CTI Clinical Trial and Consulting Services

Registry information

Official study title

An Open- Label, Dose Escalation Study to Assess the Safety, Pharmacokinetics and Pharmacodynamic Signals of DUR-928 in Patients With Alcoholic Hepatitis

Acronym: AH

Important dates

Study start
2018
Primary completion
2019
Study completion
2019
First posted
Feb 14, 2018
Registry last updated
Sep 24, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.