Primary Sclerosing Cholangitis
Conditions
Brief summary
This is a research trial testing DUR-928 (an experimental medication). The purpose of the trial is to assess whether treatment with DUR-928 has any effect on the treatment of Primary Sclerosing Cholangitis (PSC). This trial will also assess safety (side effects).
Interventions
DRUGDUR-928
oral suspension daily for 28 days
Sponsors
Durect
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Verified diagnosis of primary sclerosing cholangitis (PSC) for at least 12 months, with or without inflammatory bowel disease (IBD). * Serum alkaline phosphatase (ALP) ≥ 1.5 times ULN and with no \>15% fluctuation in the past 3 months. * In subjects receiving treatment with ursodeoxycholic acid (UDCA), therapy must be stable for at least 3 months and at a dose not greater than 20 mg/kg/day. * Subjects of childbearing potential must agree to use a medically acceptable method of contraceptive to prevent pregnancy in the subject and/or the partner for the duration of their participation in the trial up to 2 months after the last study drug dosing.
Exclusion criteria
* Presence of documented secondary sclerosing cholangitis or small duct PSC * Bacterial cholangitis within 30 days prior to Screening * Presence of percutaneous drain or endoscopic bile duct stent * History of, or suspicion of cholangiocarcinoma. * Prior liver transplantation, or currently listed for liver transplantation * Presence of other concomitant liver diseases * Moderate to Severe active IBD or flare in colitis activity within the last 3 months * Any severe and/or untreated concomitant cardiovascular, renal, endocrine or psychiatric disorder * Any active malignant disease (within 3 years), other than non-melanomatous skin cancer * Human immunodeficiency virus (HIV) infection * Existing or intended pregnancy, or breast feeding * Has received medication from another clinical trial within the past 30 days
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent Change of Alkaline Phosphatase (ALP) From Baseline | Day 28 (end of treatment) and Day 56 (end of study/early termination) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change of Liver Enzymes and Serum Bile Acids (sBA) | Day 28 and Day 56 | Liver enzymes include alanine transaminase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), bilirubin. Percent change from baseline through the end of study treatment (Day 28) and throughout the follow-up period (Day 56). |
| Percent of Subjects With Reduction of Serum Alkaline Phosphatase (ALP) From Baseline | Day 28 (end of treatment) and Day 56 (end of follow-up) | — |
| Percent Change of Selected Biomarkers From Baseline Through the End of Study Treatment and Throughout the Follow-up Period. | Day 28 and Day 56 | — |
Countries
United States
Participant flow
Recruitment details
Study was terminated early due to lack of enrollment.
Participants by arm
| Arm | Count |
|---|---|
| DUR-928 10 mg 10 mg oral suspension
DUR-928: oral suspension daily for 28 days | 3 |
| DUR-928 50 mg 50 mg oral suspension
DUR-928: oral suspension daily for 28 days | 2 |
| Total | 5 |
Baseline characteristics
| Characteristic | DUR-928 10 mg | DUR-928 50 mg | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 1 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 2 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 3 Participants | 1 Participants | 4 Participants |
| Region of Enrollment United States | 3 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 2 |
| other Total, other adverse events | 2 / 3 | 1 / 2 |
| serious Total, serious adverse events | 0 / 3 | 0 / 2 |
Outcome results
Primary
Percent Change of Alkaline Phosphatase (ALP) From Baseline
Time frame: Day 28 (end of treatment) and Day 56 (end of study/early termination)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DUR-928 10 mg | Percent Change of Alkaline Phosphatase (ALP) From Baseline | Percent change of ALP from baseline to Day 28 | 23.7 percent change | Standard Deviation 10.7 |
| DUR-928 10 mg | Percent Change of Alkaline Phosphatase (ALP) From Baseline | Percent change of ALP from baseline to Day 56 | 10.7 percent change | Standard Deviation 17.04 |
| DUR-928 50 mg | Percent Change of Alkaline Phosphatase (ALP) From Baseline | Percent change of ALP from baseline to Day 56 | 11.05 percent change | Standard Deviation 8.68 |
| DUR-928 50 mg | Percent Change of Alkaline Phosphatase (ALP) From Baseline | Percent change of ALP from baseline to Day 28 | 16.8 percent change | Standard Deviation 2.97 |
Secondary
Percent Change of Liver Enzymes and Serum Bile Acids (sBA)
Liver enzymes include alanine transaminase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), bilirubin. Percent change from baseline through the end of study treatment (Day 28) and throughout the follow-up period (Day 56).
Time frame: Day 28 and Day 56
Population: Study terminated early due to lack of enrollment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DUR-928 10 mg | Percent Change of Liver Enzymes and Serum Bile Acids (sBA) | percent GGT change from baseline to Day 28 | 7.3 percent change | Standard Deviation 4.16 |
| DUR-928 10 mg | Percent Change of Liver Enzymes and Serum Bile Acids (sBA) | percent ALT change from baseline to Day 56 | -9.77 percent change | Standard Deviation 15.3 |
| DUR-928 10 mg | Percent Change of Liver Enzymes and Serum Bile Acids (sBA) | percent direct bilirubin change from baseline to Day 28 | 14.2 percent change | Standard Deviation 24.61 |
| DUR-928 10 mg | Percent Change of Liver Enzymes and Serum Bile Acids (sBA) | percent AST change from baseline to Day 56 | -16.23 percent change | Standard Deviation 9.17 |
| DUR-928 10 mg | Percent Change of Liver Enzymes and Serum Bile Acids (sBA) | percent GGT change from baseline to Day 56 | -7.10 percent change | Standard Deviation 11.87 |
| DUR-928 10 mg | Percent Change of Liver Enzymes and Serum Bile Acids (sBA) | percent total bilirubin change from baseline to Day 28 | 12.03 percent change | Standard Deviation 23.09 |
| DUR-928 10 mg | Percent Change of Liver Enzymes and Serum Bile Acids (sBA) | percent direct bilirubin change from baseline to Day 56 | -12.90 percent change | — |
| DUR-928 10 mg | Percent Change of Liver Enzymes and Serum Bile Acids (sBA) | percent AST change from baseline to Day 28 | 24.10 percent change | Standard Deviation 35.03 |
| DUR-928 10 mg | Percent Change of Liver Enzymes and Serum Bile Acids (sBA) | percent total bilirubin change from baseline to Day 56 | -24.60 percent change | Standard Deviation 20.46 |
| DUR-928 10 mg | Percent Change of Liver Enzymes and Serum Bile Acids (sBA) | percent serum bile acids change from baseline to Day 28 | -13.93 percent change | Standard Deviation 15 |
| DUR-928 10 mg | Percent Change of Liver Enzymes and Serum Bile Acids (sBA) | percent serum bile acids change from baseline to Day 56 | 35.23 percent change | Standard Deviation 79.79 |
| DUR-928 10 mg | Percent Change of Liver Enzymes and Serum Bile Acids (sBA) | percent ALT change from baseline to Day 28 | 32.87 percent change | Standard Deviation 48.87 |
| DUR-928 50 mg | Percent Change of Liver Enzymes and Serum Bile Acids (sBA) | percent serum bile acids change from baseline to Day 56 | -35.75 percent change | Standard Deviation 72.9 |
| DUR-928 50 mg | Percent Change of Liver Enzymes and Serum Bile Acids (sBA) | percent ALT change from baseline to Day 28 | 3.0 percent change | Standard Deviation 29.56 |
| DUR-928 50 mg | Percent Change of Liver Enzymes and Serum Bile Acids (sBA) | percent AST change from baseline to Day 28 | -20.25 percent change | Standard Deviation 3.23 |
| DUR-928 50 mg | Percent Change of Liver Enzymes and Serum Bile Acids (sBA) | percent GGT change from baseline to Day 28 | 8.15 percent change | Standard Deviation 1.49 |
| DUR-928 50 mg | Percent Change of Liver Enzymes and Serum Bile Acids (sBA) | percent direct bilirubin change from baseline to Day 28 | 34.6 percent change | — |
| DUR-928 50 mg | Percent Change of Liver Enzymes and Serum Bile Acids (sBA) | percent total bilirubin change from baseline to Day 28 | 23.85 percent change | Standard Deviation 33.73 |
| DUR-928 50 mg | Percent Change of Liver Enzymes and Serum Bile Acids (sBA) | percent serum bile acids change from baseline to Day 28 | -44.10 percent change | Standard Deviation 46.95 |
| DUR-928 50 mg | Percent Change of Liver Enzymes and Serum Bile Acids (sBA) | percent ALT change from baseline to Day 56 | -12.7 percent change | Standard Deviation 5.66 |
| DUR-928 50 mg | Percent Change of Liver Enzymes and Serum Bile Acids (sBA) | percent AST change from baseline to Day 56 | -9.70 percent change | Standard Deviation 19.09 |
| DUR-928 50 mg | Percent Change of Liver Enzymes and Serum Bile Acids (sBA) | percent GGT change from baseline to Day 56 | -3.2 percent change | Standard Deviation 2.26 |
| DUR-928 50 mg | Percent Change of Liver Enzymes and Serum Bile Acids (sBA) | percent direct bilirubin change from baseline to Day 56 | 19.20 percent change | — |
| DUR-928 50 mg | Percent Change of Liver Enzymes and Serum Bile Acids (sBA) | percent total bilirubin change from baseline to Day 56 | 19.14 percent change | Standard Deviation 15.61 |
Secondary
Percent Change of Selected Biomarkers From Baseline Through the End of Study Treatment and Throughout the Follow-up Period.
Time frame: Day 28 and Day 56
Population: The samples were not assayed to generate data for this Outcome Measure due to early study termination.
Secondary
Percent of Subjects With Reduction of Serum Alkaline Phosphatase (ALP) From Baseline
Time frame: Day 28 (end of treatment) and Day 56 (end of follow-up)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DUR-928 10 mg | Percent of Subjects With Reduction of Serum Alkaline Phosphatase (ALP) From Baseline | subjects with ≥ 40% reduction of serum ALP from baseline at day 28/end of treatment | 0 Participants |
| DUR-928 10 mg | Percent of Subjects With Reduction of Serum Alkaline Phosphatase (ALP) From Baseline | subjects with ≥ 40% reduction of serum ALP from baseline at day 56/end of follow-up | 0 Participants |
| DUR-928 50 mg | Percent of Subjects With Reduction of Serum Alkaline Phosphatase (ALP) From Baseline | subjects with ≥ 40% reduction of serum ALP from baseline at day 28/end of treatment | 0 Participants |
| DUR-928 50 mg | Percent of Subjects With Reduction of Serum Alkaline Phosphatase (ALP) From Baseline | subjects with ≥ 40% reduction of serum ALP from baseline at day 56/end of follow-up | 0 Participants |