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Astra Zeneca notified Dr. Rita Basu that they will not manufacture new drug due to business reasons and study was stopped.
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| Name | Class |
|---|---|
| AstraZeneca | INDUSTRY |
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Does the novel drug decrease liver fat in subjects with NASH or NAFLD as compared to placebo
We propose to evaluate hepatic fat and hepatic fibrosis using magnetic resonance elastography (MRE) liver (pre vs. post). We will also establish glucose tolerance status by our established labeled oral glucose tolerance test (OGTT) (6,6 ²H2 glucose). Following baseline evaluation subjects with biopsy/MRE proven NASH will be randomized to one of two groups and treated either with active drug (AZ compound) or placebo for 12 weeks (plus or minus 1 week). Subjects with history suggestive of non-alcoholic fatty liver disease (NAFLD) or NASH will be invited to participate. If they meet criteria following initial screening they will be included in the study. OGTT, liver MRE will be repeated. Liver enzymes [aspartate aminotransferase (AST), alanine aminotransferase (ALT),alkaline phosphatase (ALP)] as well as other safety tests [creatine phosphokinase (CPK), thyroid stimulating hormone (TSH), international normalized ratio (INR),total bilirubin] will be measured before, monthly during therapy and at one month following therapy. Furthermore, we will also do the subgroup analysis in NASH/NAFLD subjects with and without diabetes to see the effect of the drug.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Active drug AZ compound | Experimental | AZ compound 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg). |
|
| Placebo | Placebo Comparator | Placebo 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AZ compound | Drug | AZ compound 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg). |
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| Measure | Description | Time Frame |
|---|---|---|
| Percentage Change in Hepatic Fat | Percentage Hepatic fat measured using Magnetic Resonance Imaging (Proton Density Fat Fraction). A cut-off of <5% is used to distinguish between normal and fatty liver. | baseline, approximately 12 weeks |
| Number of Participants With no Conversion of [13C] Cortisone to [13C] Cortisol | Hepatic conversion of [13C] cortisone to [13C] cortisol was assessed before and after the treatment in both groups using the triple tracer cortisol test. | baseline, approximately 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Liver Fibrosis Measured With MRE in kPa | Liver fibrosis will be measured with Magnetic Resonance Enterography (MRE) at baseline and then compared after ~12 weeks of treatment. A clinical cut-off of 2.93 kPa was used to classify the results as either normal or elevated liver stiffness. Change in Liver fibrosis (kPa) is compared in between the groups. | baseline, approximately 12 weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Rita Basu, MD | University of Virginia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Yogesh Yadav | Charlottesville | Virginia | 22908 | United States |
No: There is not a plan to make IPD available
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| ID | Title | Description |
|---|---|---|
| FG000 | Active Drug AZ Compound | AZ compound 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg). AZ compound: AZ compound 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg). |
| FG001 | Placebo |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 8, 2019 |
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| Placebo | Other | Placebo 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg). |
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| Total Insulin Sensitivity (Si) and Hepatic Insulin Sensitivity (Si Liver) | Total insulin sensitivity (Si) and hepatic insulin sensitivity (Si liver) will be measured with an Oral glucose Tolerance test at baseline and after ~12 weeks of treatment. | baseline, approximately 12 weeks |
Placebo 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg). Placebo: Placebo 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg). |
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| NOT COMPLETED |
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The overall number of baseline participants does not differ from the number assigned to the arm or comparison group.
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| ID | Title | Description |
|---|---|---|
| BG000 | Active Drug AZ Compound | AZ compound 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg). AZ compound: AZ compound 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg). |
| BG001 | Placebo | Placebo 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg). Placebo: Placebo 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg). |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
| ||||||||||||||||
| Number of baseline particpants | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage Change in Hepatic Fat | Percentage Hepatic fat measured using Magnetic Resonance Imaging (Proton Density Fat Fraction). A cut-off of <5% is used to distinguish between normal and fatty liver. | Posted | Mean | Standard Deviation | Percentage change in liver fat fraction | baseline, approximately 12 weeks |
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| Primary | Number of Participants With no Conversion of [13C] Cortisone to [13C] Cortisol | Hepatic conversion of [13C] cortisone to [13C] cortisol was assessed before and after the treatment in both groups using the triple tracer cortisol test. | Posted | Count of Participants | Participants | baseline, approximately 12 weeks |
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| Secondary | Liver Fibrosis Measured With MRE in kPa | Liver fibrosis will be measured with Magnetic Resonance Enterography (MRE) at baseline and then compared after ~12 weeks of treatment. A clinical cut-off of 2.93 kPa was used to classify the results as either normal or elevated liver stiffness. Change in Liver fibrosis (kPa) is compared in between the groups. | Posted | Mean | Standard Deviation | kPa | baseline, approximately 12 weeks |
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| Secondary | Total Insulin Sensitivity (Si) and Hepatic Insulin Sensitivity (Si Liver) | Total insulin sensitivity (Si) and hepatic insulin sensitivity (Si liver) will be measured with an Oral glucose Tolerance test at baseline and after ~12 weeks of treatment. | Insulin Sensitivity was measured in the participants that completed the oral glucose tolerance test . | Posted | Mean | Standard Deviation | 10^-4 dl/kg/min per uU/ml | baseline, approximately 12 weeks |
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3 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Active Drug AZ Compound | AZ compound 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg). AZ compound: AZ compound 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg). | 0 | 46 | 0 | 46 | 20 | 46 |
| EG001 | Placebo | Placebo 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg). Placebo: Placebo 800 mg/day for 12 weeks (plus or minus 1 week) in two divided doses morning (400 mg) and evening (400 mg). | 0 | 47 | 0 | 47 | 10 | 47 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | General disorders | Systematic Assessment | Headache |
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| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
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| Increased TSH | Endocrine disorders | Systematic Assessment |
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The study was stopped after enrolling 93 patients. The sponsor recalled the batch of AZD4017 /placebo that was provided to the study investigator after the batch of the investigational product failed a routine stability retest that was performed to support potential shelflife extension. Ten patients who were taking either AZD4017 or a placebo were asked to stop taking their drug. Since eight of the10 patients were close to reaching study completion, their data were included in the ITT analyses.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Rita Basu | University of Virginia | 434-924-5183 | rb4vd@virginia.edu |
| Oct 4, 2021 |
| Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | May 9, 2019 | Mar 2, 2022 | ICF_001.pdf |
| ID | Term |
|---|---|
| D065626 | Non-alcoholic Fatty Liver Disease |
| ID | Term |
|---|---|
| D005234 | Fatty Liver |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| C000622345 | MeRho-Az compound |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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