Trial Outcomes & Findings for Phase II Trial of Silymarin for Non-Cirrhotic Patients With Non-Alcoholic Steatohepatitis (NCT NCT00680407)
NCT ID: NCT00680407
Last Updated: 2019-07-17
Results Overview
Histological Scoring System for Nonalcoholic Fatty Liver Disease ranges from 0-8 with the increase in number representing a worse outcome. Therefore the efficacy improvement was to be at least 2 points in lowering the score.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
78 participants
Primary outcome timeframe
48-50 week treatment period
Results posted on
2019-07-17
Participant Flow
Patients were recruited at 5 sites; first observation April 30, 2008, last observation Nov 12, 2012.
Participant milestones
| Measure |
Silymarin 420 mg
420 mg Legalon (silymarin) three times daily
Silymarin 420 mg: 420 mg dose (5 pills, three times daily) for 48-50 week treatment period
|
Silymarin 700 mg
700 mg of Legalon (silymarin) three times daily
Silymarin 700 mg: 700 mg dose (5 pills, three times daily) for 48-50 week treatment period
|
Placebo
Placebo (lactose pill)
Placebo: Placebo (5 pills, three times daily) for 48-50 week treatment period
|
|---|---|---|---|
|
Overall Study
STARTED
|
26
|
27
|
25
|
|
Overall Study
COMPLETED
|
18
|
22
|
22
|
|
Overall Study
NOT COMPLETED
|
8
|
5
|
3
|
Reasons for withdrawal
| Measure |
Silymarin 420 mg
420 mg Legalon (silymarin) three times daily
Silymarin 420 mg: 420 mg dose (5 pills, three times daily) for 48-50 week treatment period
|
Silymarin 700 mg
700 mg of Legalon (silymarin) three times daily
Silymarin 700 mg: 700 mg dose (5 pills, three times daily) for 48-50 week treatment period
|
Placebo
Placebo (lactose pill)
Placebo: Placebo (5 pills, three times daily) for 48-50 week treatment period
|
|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
3
|
3
|
1
|
|
Overall Study
Withdrawal by Subject
|
5
|
2
|
2
|
Baseline Characteristics
Phase II Trial of Silymarin for Non-Cirrhotic Patients With Non-Alcoholic Steatohepatitis
Baseline characteristics by cohort
| Measure |
Silymarin 420 mg
n=26 Participants
420 mg Legalon (silymarin) three times daily
Silymarin 420 mg: 420 mg dose (5 pills, three times daily) for 48-50 week treatment period
|
Silymarin 700 mg
n=27 Participants
700 mg of Legalon (silymarin) three times daily
Silymarin 700 mg: 700 mg dose (5 pills, three times daily) for 48-50 week treatment period
|
Placebo
n=25 Participants
Placebo (lactose pill)
Placebo: Placebo (5 pills, three times daily) for 48-50 week treatment period
|
Total
n=78 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
47.3 years
STANDARD_DEVIATION 10.83 • n=5 Participants
|
48.2 years
STANDARD_DEVIATION 11.43 • n=7 Participants
|
49.51 years
STANDARD_DEVIATION 10.89 • n=5 Participants
|
48.3 years
STANDARD_DEVIATION 10.95 • n=4 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
33 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
45 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 48-50 week treatment periodHistological Scoring System for Nonalcoholic Fatty Liver Disease ranges from 0-8 with the increase in number representing a worse outcome. Therefore the efficacy improvement was to be at least 2 points in lowering the score.
Outcome measures
| Measure |
Silymarin 420 mg
n=26 Participants
420 mg Legalon (silymarin) three times daily
Silymarin 420 mg: 420 mg dose (5 pills, three times daily) for 48-50 week treatment period
|
Silymarin 700 mg
n=27 Participants
700 mg of Legalon (silymarin) three times daily
Silymarin 700 mg: 700 mg dose (5 pills, three times daily) for 48-50 week treatment period
|
Placebo
n=25 Participants
Placebo (lactose pill)
Placebo: Placebo (5 pills, three times daily) for 48-50 week treatment period
|
|---|---|---|---|
|
Efficacy - Improvement by at Least 2 Points in Histology (NAS)
|
5 participants
|
4 participants
|
3 participants
|
SECONDARY outcome
Timeframe: 48-50 week treatment periodOutcome measures
| Measure |
Silymarin 420 mg
n=26 Participants
420 mg Legalon (silymarin) three times daily
Silymarin 420 mg: 420 mg dose (5 pills, three times daily) for 48-50 week treatment period
|
Silymarin 700 mg
n=27 Participants
700 mg of Legalon (silymarin) three times daily
Silymarin 700 mg: 700 mg dose (5 pills, three times daily) for 48-50 week treatment period
|
Placebo
n=25 Participants
Placebo (lactose pill)
Placebo: Placebo (5 pills, three times daily) for 48-50 week treatment period
|
|---|---|---|---|
|
Safety - Occurrence of a Dose-limiting Toxicity
|
2 participants
|
0 participants
|
0 participants
|
POST_HOC outcome
Timeframe: 48-50 week treatment periodPopulation: Subgroup of ITT (Intent to Treat) Patients with NASH and without cirrhosis population
This outcome measure excludes the substantial percentage (62.8%) of patients with baseline biopsies that were deemed ineligible (per inclusion criteria) by the central pathologist due to NAS \<4 or absence of NASH (nonalcoholic steatohepatitis) (n=34), NASH with presence of cirrhosis (n=1), or slides unavailable/not evaluable for reading (n=14).
Outcome measures
| Measure |
Silymarin 420 mg
n=10 Participants
420 mg Legalon (silymarin) three times daily
Silymarin 420 mg: 420 mg dose (5 pills, three times daily) for 48-50 week treatment period
|
Silymarin 700 mg
n=9 Participants
700 mg of Legalon (silymarin) three times daily
Silymarin 700 mg: 700 mg dose (5 pills, three times daily) for 48-50 week treatment period
|
Placebo
n=10 Participants
Placebo (lactose pill)
Placebo: Placebo (5 pills, three times daily) for 48-50 week treatment period
|
|---|---|---|---|
|
Efficacy - Improvement by at Least 2 Points in Histology (NAS) - With NAS Without Cirrhosis
|
3 participants
|
4 participants
|
1 participants
|
Adverse Events
Silymarin 420 mg
Serious events: 1 serious events
Other events: 17 other events
Deaths: 0 deaths
Silymarin 700 mg
Serious events: 2 serious events
Other events: 14 other events
Deaths: 0 deaths
Placebo
Serious events: 1 serious events
Other events: 11 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Silymarin 420 mg
n=26 participants at risk
420 mg Legalon (silymarin) three times daily
Silymarin 420 mg: 420 mg dose (5 pills, three times daily) for 48-50 week treatment period
|
Silymarin 700 mg
n=27 participants at risk
700 mg of Legalon (silymarin) three times daily
Silymarin 700 mg: 700 mg dose (5 pills, three times daily) for 48-50 week treatment period
|
Placebo
n=25 participants at risk
Placebo (lactose pill)
Placebo: Placebo (5 pills, three times daily) for 48-50 week treatment period
|
|---|---|---|---|
|
Hepatobiliary disorders
ACUTE HEMATOMA POST TREATMENT LIVER BIOPSY
|
3.8%
1/26 • Number of events 1
|
0.00%
0/27
|
0.00%
0/25
|
|
Nervous system disorders
HOSPITALIZED FOR SEVERE HEADACHE
|
0.00%
0/26
|
3.7%
1/27 • Number of events 1
|
0.00%
0/25
|
|
Blood and lymphatic system disorders
LOW PLATELET COUNT
|
0.00%
0/26
|
3.7%
1/27 • Number of events 1
|
0.00%
0/25
|
|
Musculoskeletal and connective tissue disorders
BACK SURGERY L5/S1
|
0.00%
0/26
|
0.00%
0/27
|
4.0%
1/25 • Number of events 1
|
Other adverse events
| Measure |
Silymarin 420 mg
n=26 participants at risk
420 mg Legalon (silymarin) three times daily
Silymarin 420 mg: 420 mg dose (5 pills, three times daily) for 48-50 week treatment period
|
Silymarin 700 mg
n=27 participants at risk
700 mg of Legalon (silymarin) three times daily
Silymarin 700 mg: 700 mg dose (5 pills, three times daily) for 48-50 week treatment period
|
Placebo
n=25 participants at risk
Placebo (lactose pill)
Placebo: Placebo (5 pills, three times daily) for 48-50 week treatment period
|
|---|---|---|---|
|
Gastrointestinal disorders
Gasto-intestinal
|
19.2%
5/26
|
14.8%
4/27
|
16.0%
4/25
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory
|
7.7%
2/26
|
11.1%
3/27
|
8.0%
2/25
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal
|
7.7%
2/26
|
3.7%
1/27
|
16.0%
4/25
|
|
Cardiac disorders
Cardiac
|
11.5%
3/26
|
3.7%
1/27
|
8.0%
2/25
|
|
Nervous system disorders
Depression
|
3.8%
1/26
|
7.4%
2/27
|
4.0%
1/25
|
|
Skin and subcutaneous tissue disorders
Dermatologic
|
0.00%
0/26
|
7.4%
2/27
|
4.0%
1/25
|
|
General disorders
Headache
|
7.7%
2/26
|
3.7%
1/27
|
8.0%
2/25
|
|
Investigations
Hyperglycemia
|
3.8%
1/26
|
7.4%
2/27
|
0.00%
0/25
|
|
Psychiatric disorders
Neurological
|
0.00%
0/26
|
3.7%
1/27
|
8.0%
2/25
|
|
Renal and urinary disorders
Urological
|
3.8%
1/26
|
3.7%
1/27
|
8.0%
2/25
|
Additional Information
Associate Director, Clinical Research and Operations
Meda Pharmaceuticals, Inc.
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place