A phase II, randomized, double-blind, parallel-group, placebo-controlled, 12-week treatment, adaptive proof-of-principle study of twice daily oral dosing of a novel PDE4 inhibitor (ASP9831) in subjects with non-alcoholic steatohepatitis (NASH) - ASTER

• Conditions: on-alcoholic Steatohepatitis (NASH); MedDRA version: 9.1Level: LLTClassification code 10053219Term: Non-alcoholic steatohepatitis

• Registration Number: EUCTR2007-002114-19-DE
• Lead Sponsor: Astellas Pharma Europe B.V.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-11-30
• Last Update Posted: 7 January 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 105

Inclusion Criteria

Inclusion Criteria Part 1:
1. Subject has signed written informed consent prior to screening
2. Subject is male or female and 18 years of age or above
3. For Part 1a: Subject has NASH, fibrosis stage F3 (zone 3 perisinusoidal/pericellular fibrosis and portal fibrosis with focal or extensive bridging fibrosis), histologically confirmed by a liver biopsy performed within 1 year prior to first dose
For Part 1b: Subject has NASH, fibrosis stage F0-F3, histologically confirmed by a liver biopsy performed within 1 year prior to randomization
4. Subject has serum ALT levels at screening below 300 U/l according to central laboratory analysis
5. Subject has had elevated serum ALT levels on two occasions tested within 1 year prior to screening according to local laboratory normal ranges

Inclusion Criteria Part 2:
1. Subject has signed written informed consent prior to screening
2. Subject is male or female and 18 years of age or above
3. Subject has NASH, fibrosis stage F0-F3, histologically confirmed by a liver biopsy performed within 1 year prior to randomization
4. Subject has elevated serum ALT levels at screening of at least 1.5 x the upper limit of normal range with a maximum of 300 U/l according to central laboratory analyses.
5. Subject has had elevated serum ALT >1.5 ULN or >60 IU/L (local laboratory) on one occasion in the past 6 months and no documented normal value in the past year
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Subject is diagnosed with hepatic cirrhosis
2. Subject has confirmed positive HCV and/or positive HCB serology
3. Subject has known genetic or secondary hemochromatosis
4. Subject has other known cause of liver disease (autoimmune, viral, genetic, drug induced, alcoholic liver disease or storage disease)
5. Subject has an unstable metabolic condition: i.e. weight change > 5% in the 6 months prior to screening and/or diagnosis of diabetes mellitus type 2 within 4 months prior to screening and/or initiation and subsequent continuous use of anti-diabetic drugs (including insulin sensitizing agents), anti-hypertensives and / or lipid-lowering drugs within 4 months prior to screening
6. Subject has uncontrolled diabetes mellitus type 2, i.e. HbA1c > 8.5%
7. Subject suffers from clinically significant gastrointestinal disease, or has a history of inflammatory bowel disease (Crohn's disease, ulcerative colitis and undetermined inflammatory colitis) or has a currently symptomatic gastric ulcer or erosive gastritis
8. Irritable bowel syndrome
9. Subject has known lipodystrophy
10. Subject has had a malignancy in the last 10 years, except for adequately treated basal or squamous cell carcinoma of the skin
11. Subject has known HIV infection
12. Subject has had previous bowel resection
13. Subject has a positive history of tuberculosis or a positive PPD skin test which is not explained by previous BCG vaccination
14. Subject has any other disorder that is uncontrolled by therapy and clinically significant as deemed relevant by the investigator
15. Subject has a history of excessive alcohol abuse within 5 years prior to screening or a current average alcohol intake of more than 20 g/day (2 units) for females or more than 30 g/day (3 units) for males
16. Female subject is pregnant, lactating or pre-menopausal with positive serum pregnancy test (hCG) or has an intention of becoming pregnant and/or does not use a medically acceptable method of birth control
17. Subject has used drugs associated with steatohepatitis within 6 months prior to screening (corticosteroids, high dose estrogens, methotrexate, amiodarone, anti-HIV drugs, tamoxifen)
18. Subject used other PDE4 inhibitors within 6 months prior to screening
19. Subject started or changed the dose of one or more of the following drugs/food supplements within 1 month before randomization: insulin sensitizing agents (e.g. biguanides, thiazolinediones), ursodeoxycholic acid, anti-obesity drugs (e.g. orlistat, sibutramin, rimonabant), pentoxifylline, phosphatidylcholin, ginseng, selenium, vitamin C, vitamin E
20. Subject uses concomitant medications which are mainly metabolized by CYP2C8/9 and which have a narrow safety margin (warfarin, phenytoin, paclitaxel and tolbutamide)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified