Study to Investigate the Effects of Different Doses of S-... | NCT01754714

ID	Type	Description	Link
2012-000975-18	EudraCT Number

Status Module

Name	Class
PPD Development, LP	INDUSTRY

Label	Type	Intervention Names
1000 mg SAMe (S-adenosyl-L-methionine)	Experimental	Drug: SAMe 1000 mg
1500 mg SAMe	Experimental	Drug: SAMe 1500 mg
2000 mg SAMe	Experimental	Drug: SAMe 2000 mg
No treatment	No Intervention

Name	Type	Description	Arm Group Labels	Other Names
SAMe 1000 mg	Drug	1000 mg dose group: one 500 mg capsule fasting in the morning and one 500 mg capsule before dinner	1000 mg SAMe (S-adenosyl-L-methionine)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Methionine Elimination Half-life Measured in Blood.	After the methionine load, blood samples will be obtained at 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours. Plasma will be analyzed for methionine.	0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hoursat Week 7

Secondary Outcomes

Measure	Description	Time Frame
Fasting Methionine Concentration of Average Methionine Concentration Versus Time Curve.	After the methionine load, blood samples will be obtained at 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours. Plasma will be analyzed for methionine.	0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hoursat Week 7
13 Carbon (Natural, Stable Isotope of Carbon) Methionine Breath Test

Other Outcomes

Measure	Description	Time Frame
Immunological/Anti-oxidant Panel (Immunological and Anti-oxidant Laboratory Parameters)	Cytokine profile ( Interleukin-6, IL-8, IL-10 (IL), Tumor Necrosis Factor (TNF -α), monocyte chemoattractant protein (MCP-1), and Granulocyte-colony stimulating factor (G-CSF ).	change from baseline at 6 weeks
Fibrosis and Apoptosis Markers (Fibrosis and Apoptosis Laboratory Markers)

Eligibility Module

Eligibility Criteria

Inclusion Criteria

Subjects with non-alcoholic steatohepatitis based on histology in medical history within the last 3 years
Subjects in a stable metabolic condition since histology for NASH (Non-alcoholic Steatohepatitis)

Exclusion Criteria

Subjects with extrahepatic biliary obstruction
Subjects with primary sclerosing cholangitis (PSC)
Subjects with primary biliary cirrhosis (PBC)
Any form of malignancy within the past 5 years and/or basal cell carcinoma and squamous cell carcinoma of the skin within the past two years
History of active substance abuse (oral, inhaled or injected) within one year prior to the study
Subjects with renal impairment (creatinine level of >2.0 mg/dL)
Subjects with a known hypersensitivity to the active substance (ademetionine) or methionine or to any of the inactive ingredients
Subjects with known genetic defects affecting the methionine cycle and/or causing homocystinuria and/or hyperhomocysteinemia (e.g., cystathionine beta-synthase deficiency, Vitamin B12 metabolism defect)
Subjects on total parenteral nutrition in the year prior to screening
Subjects after or planned for bariatric surgery (jejunoileal bypass or gastric weight loss surgery)
Extrahepatic cholestasis (proven by ultrasound)
Subjects with alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 5 upper limit of normal (ULN)
Subject with serum total bilirubin (STB) > 5 ULN
Subjects after liver transplantation and subjects on the waiting list for liver transplantation
Subjects with any of the following disease in medical history:
Viral hepatitis (serum positive HBcAb (hepatitis B core antibody) or Hepatitis C Virus (HCV) ribonucleic acid (RNA)
Evidence of autoimmune liver disease
Wilson's disease
Hemochromatosis
Alpha-1-antitrypsin deficiency
Known positivity for antibody to human immunodeficiency virus (HIV)
Known heart failure of New York heart Association class 3 or 4
Current or history of significant alcohol consumption for a period of more than three consecutive months within five years prior to screening (significant alcohol consumption is defined as > 3 U (unit)/day for men and > 2 U/day for women, on average) or binge drinking or inability to reliably quantify alcohol consumption.
Clinical or histological evidence of cirrhosis F4
Subjects with history of biliary diversion
Subjects with uncontrolled diabetes mellitus defined by HbA1c (hemoglobin A1c) > 8.0 % at screening
Concomitant medication of B12, folate, betaine or choline
Concomitant treatment with glitazone within the past year prior to the study
Subjects with known folate or B12 deficiency
BMI (body mass index) > 40 kg/m2
History of major depression diagnostic and statistical manual of mental disorders (DSM-IV) or bipolar disease
Women of childbearing potential: positive urine pregnancy test during screening or unwillingness to use an effective form of birth control during the study.
Breastfeeding women
Any condition that, in the opinion of the investigator, does not justify the patient's inclusion into the study
Investigational drug intake within one month prior to the study
Active, serious medical disease with likely life-expectancy less than five years
Uncooperative attitude or reasonable likelihood for non-compliance with the protocol or any other reason that, in the investigator's opinion, prohibits the inclusion of the subject into the study
Legal incapacity or limited legal capacity, or who are incarcerated.
Inability to return for scheduled visits.
Inability to understand and follow the requirements of the protocol in the local language

Name	Affiliation	Role
Suntje Sander-Struckmeier, PhD	Abbott	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Site Reference ID 93914		Amiens		80054	France
Site Reference ID 93895

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	1000 mg SAMe (S-adenosyl-L-methionine)	SAMe 1000 mg: 1000 mg dose group: one 500 mg capsule fasting in the morning and one 500 mg capsule before dinner
FG001	1500 mg SAMe	SAMe 1500 mg: 1500 mg dose group: two 500 mg capsules fasting in the morning and one 500 mg capsule before dinner

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

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

Methionine Elimination Half-life Measured in Blood.

After the methionine load, blood samples will be obtained at 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours. Plasma will be analyzed for methionine.

Posted

Mean

Standard Deviation

hour

0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*

ID	Title	Description
OG000	1000 mg SAMe (S-adenosyl-L-methionine)	SAMe 1000 mg: 1000 mg dose group: one 500 mg capsule fasting in the morning and one 500 mg capsule before dinner
OG001	1500 mg SAMe	SAMe 1500 mg: 1500 mg dose group: two 500 mg capsules fasting in the morning and one 500 mg capsule before dinner
OG002	2000 mg SAMe	SAMe 2000 mg: 2000 mg dose group: two 500 mg capsules fasting in the morning and two 500 mg capsules before dinner
OG003	No Treatment	No study drug was administered

Units	Counts
Participants	OG00027 OG00126 OG00224 OG003

Title

Denominators

Categories

Title	Measurements
	OG0004.29± 1.86 OG0014.66± 1.57 OG0024.25± 1.64 OG003

Secondary

Fasting Methionine Concentration of Average Methionine Concentration Versus Time Curve.

After the methionine load, blood samples will be obtained at 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours. Plasma will be analyzed for methionine.

Posted

Mean

Standard Deviation

mcg/mL

0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*

ID	Title	Description
OG000	1000 mg SAMe (S-adenosyl-L-methionine)	SAMe 1000 mg: 1000 mg dose group: one 500 mg capsule fasting in the morning and one 500 mg capsule before dinner
OG001	1500 mg SAMe	SAMe 1500 mg: 1500 mg dose group: two 500 mg capsules fasting in the morning and one 500 mg capsule before dinner
OG002	2000 mg SAMe	SAMe 2000 mg: 2000 mg dose group: two 500 mg capsules fasting in the morning and two 500 mg capsules before dinner
OG003	No Treatment	No study drug was administered

Secondary

13 Carbon (Natural, Stable Isotope of Carbon) Methionine Breath Test

parameters cumulative percentage dose of 13 carbon recovered after 30, 60, 90 minutes (cPDR30, cPDR60, cPDR 90) will be evaluated

Posted

Mean

Standard Deviation

percentage of recovery

0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*

ID	Title	Description
OG000	1000 mg SAMe (S-adenosyl-L-methionine)	SAMe 1000 mg: 1000 mg dose group: one 500 mg capsule fasting in the morning and one 500 mg capsule before dinner
OG001	1500 mg SAMe	SAMe 1500 mg: 1500 mg dose group: two 500 mg capsules fasting in the morning and one 500 mg capsule before dinner
OG002	2000 mg SAMe	SAMe 2000 mg: 2000 mg dose group: two 500 mg capsules fasting in the morning and two 500 mg capsules before dinner
OG003	No Treatment	No study drug was administered

Secondary

Hepatic Panel (Liver Laboratory Parameters)

Serum Total Bilirubin (STB), Serum Conjugated Bilirubin (SCB), liver-alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), Gamma Glutamyl Transpeptidase (GGT)

Posted

Mean

Standard Deviation

U/L

change from baseline at 6 weeks

ID	Title	Description
OG000	1000 mg SAMe (S-adenosyl-L-methionine)	SAMe 1000 mg: 1000 mg dose group: one 500 mg capsule fasting in the morning and one 500 mg capsule before dinner
OG001	1500 mg SAMe	SAMe 1500 mg: 1500 mg dose group: two 500 mg capsules fasting in the morning and one 500 mg capsule before dinner
OG002	2000 mg SAMe	SAMe 2000 mg: 2000 mg dose group: two 500 mg capsules fasting in the morning and two 500 mg capsules before dinner
OG003	No Treatment	No study drug was administered

Secondary

Metabolic Panel (Metabolic Laboratory Parameters)

Fasting lipid profile (cholesterol, HDL (High Density Lipoprotein), LDL (Low Density Lipoprotein)), amino acid profile, homeostasis model assessment (HOMA-R) and fasting glucose.

Posted

Mean

Standard Deviation

mmol/L

change from baseline at 6 weeks

ID	Title	Description
OG000	1000 mg SAMe (S-adenosyl-L-methionine)	SAMe 1000 mg: 1000 mg dose group: one 500 mg capsule fasting in the morning and one 500 mg capsule before dinner
OG001	1500 mg SAMe	SAMe 1500 mg: 1500 mg dose group: two 500 mg capsules fasting in the morning and one 500 mg capsule before dinner
OG002	2000 mg SAMe	SAMe 2000 mg: 2000 mg dose group: two 500 mg capsules fasting in the morning and two 500 mg capsules before dinner
OG003	No Treatment	No study drug was administered

Other Pre-specified

Immunological/Anti-oxidant Panel (Immunological and Anti-oxidant Laboratory Parameters)

Cytokine profile ( Interleukin-6, IL-8, IL-10 (IL), Tumor Necrosis Factor (TNF -α), monocyte chemoattractant protein (MCP-1), and Granulocyte-colony stimulating factor (G-CSF ).

Posted

Mean

Standard Deviation

pg/mL

change from baseline at 6 weeks

ID	Title	Description
OG000	1000 mg SAMe (S-adenosyl-L-methionine)	SAMe 1000 mg: 1000 mg dose group: one 500 mg capsule fasting in the morning and one 500 mg capsule before dinner
OG001	1500 mg SAMe	SAMe 1500 mg: 1500 mg dose group: two 500 mg capsules fasting in the morning and one 500 mg capsule before dinner
OG002	2000 mg SAMe	SAMe 2000 mg: 2000 mg dose group: two 500 mg capsules fasting in the morning and two 500 mg capsules before dinner
OG003	No Treatment	No study drug was administered

Other Pre-specified

Fibrosis and Apoptosis Markers (Fibrosis and Apoptosis Laboratory Markers)

Non-invasive test for liver disease (ActiTest)/Fibrotest

FibroTest® : diagnoses hepatic fibrosis ActiTest® : assesses viral necro-inflammatory activity Scores between 0 and 1, the higher the score the worse

The FibroTest score is calculated from the results of a six-parameter blood test, combining six serum markers with the age and gender of the patient:Alpha-2-macroglobulin, Haptoglobin, Apolipoprotein A1, Gamma-glutamyl transpeptidase (GGT), Total bilirubin, and Alanine transaminase (ALT). ALT is used in a second assessment called ActiTest that is part of FibroTest.

Posted

Mean

Standard Deviation

scores on a scale

change from baseline at 6 weeks

ID	Title	Description
OG000	1000 mg SAMe (S-adenosyl-L-methionine)	SAMe 1000 mg: 1000 mg dose group: one 500 mg capsule fasting in the morning and one 500 mg capsule before dinner
OG001	1500 mg SAMe	SAMe 1500 mg: 1500 mg dose group: two 500 mg capsules fasting in the morning and one 500 mg capsule before dinner
OG002	2000 mg SAMe	SAMe 2000 mg: 2000 mg dose group: two 500 mg capsules fasting in the morning and two 500 mg capsules before dinner

Secondary

The Metabolic Clearance Rate Measured in the Blood.

After the methionine load, blood samples will be obtained at 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours. Plasma will be analyzed for methionine.

Posted

Mean

Standard Deviation

L/h

0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*

ID	Title	Description
OG000	1000 mg SAMe (S-adenosyl-L-methionine)	SAMe 1000 mg: 1000 mg dose group: one 500 mg capsule fasting in the morning and one 500 mg capsule before dinner
OG001	1500 mg SAMe	SAMe 1500 mg: 1500 mg dose group: two 500 mg capsules fasting in the morning and one 500 mg capsule before dinner
OG002	2000 mg SAMe	SAMe 2000 mg: 2000 mg dose group: two 500 mg capsules fasting in the morning and two 500 mg capsules before dinner
OG003	No Treatment

Units	Counts

Secondary

Methionine Volume of Distribution at Week 7 (L)

After the methionine load, blood samples will be obtained at 0.5, 1, 1.5, 3, 4, 5, 6, 7.5 and 9 hours. Plasma will be analyzed for methionine.

Posted

Mean

Standard Deviation

0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*

ID	Title	Description
OG000	1000 mg SAMe (S-adenosyl-L-methionine)	SAMe 1000 mg: 1000 mg dose group: one 500 mg capsule fasting in the morning and one 500 mg capsule before dinner
OG001	1500 mg SAMe	SAMe 1500 mg: 1500 mg dose group: two 500 mg capsules fasting in the morning and one 500 mg capsule before dinner
OG002	2000 mg SAMe	SAMe 2000 mg: 2000 mg dose group: two 500 mg capsules fasting in the morning and two 500 mg capsules before dinner
OG003	No Treatment	No study drug was administered

Secondary

13 Carbon (Natural, Stable Isotope of Carbon) Methionine Breath Test

Peak

Posted

Mean

Standard Deviation

Atom %C13

0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*

ID	Title	Description
OG000	1000 mg SAMe (S-adenosyl-L-methionine)	SAMe 1000 mg: 1000 mg dose group: one 500 mg capsule fasting in the morning and one 500 mg capsule before dinner
OG001	1500 mg SAMe	SAMe 1500 mg: 1500 mg dose group: two 500 mg capsules fasting in the morning and one 500 mg capsule before dinner
OG002	2000 mg SAMe	SAMe 2000 mg: 2000 mg dose group: two 500 mg capsules fasting in the morning and two 500 mg capsules before dinner
OG003	No Treatment	No study drug was administered

Units	Counts

Secondary

13 Carbon (Natural, Stable Isotope of Carbon) Methionine Breath Test

Time to peak

Posted

Median

Inter-Quartile Range

minutes

0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*

ID	Title	Description
OG000	1000 mg SAMe (S-adenosyl-L-methionine)	SAMe 1000 mg: 1000 mg dose group: one 500 mg capsule fasting in the morning and one 500 mg capsule before dinner
OG001	1500 mg SAMe	SAMe 1500 mg: 1500 mg dose group: two 500 mg capsules fasting in the morning and one 500 mg capsule before dinner
OG002	2000 mg SAMe	SAMe 2000 mg: 2000 mg dose group: two 500 mg capsules fasting in the morning and two 500 mg capsules before dinner
OG003	No Treatment	No study drug was administered

Units	Counts

Secondary

Metabolic Panel (Metabolic Laboratory Parameters)

Fasting plasma insulin

Posted

Mean

Standard Deviation

pmol/L

Change from baseline at 6 weeks

ID	Title	Description
OG000	1000 mg SAMe (S-adenosyl-L-methionine)	SAMe 1000 mg: 1000 mg dose group: one 500 mg capsule fasting in the morning and one 500 mg capsule before dinner
OG001	1500 mg SAMe	SAMe 1500 mg: 1500 mg dose group: two 500 mg capsules fasting in the morning and one 500 mg capsule before dinner
OG002	2000 mg SAMe	SAMe 2000 mg: 2000 mg dose group: two 500 mg capsules fasting in the morning and two 500 mg capsules before dinner
OG003	No Treatment	No study drug was administered

Units	Counts

Secondary

Metabolic Panel (Metabolic Laboratory Parameters)

glycosylated hemoglobin (HbA1c)

Posted

Mean

Standard Deviation

Percentage

change from baseline at 6 weeks

ID	Title	Description
OG000	1000 mg SAMe (S-adenosyl-L-methionine)	SAMe 1000 mg: 1000 mg dose group: one 500 mg capsule fasting in the morning and one 500 mg capsule before dinner
OG001	1500 mg SAMe	SAMe 1500 mg: 1500 mg dose group: two 500 mg capsules fasting in the morning and one 500 mg capsule before dinner
OG002	2000 mg SAMe	SAMe 2000 mg: 2000 mg dose group: two 500 mg capsules fasting in the morning and two 500 mg capsules before dinner
OG003	No Treatment	No study drug was administered

Units	Counts

Secondary

Metabolic Panel (Metabolic Laboratory Parameters)

Adiponectin

Posted

Mean

Standard Deviation

mcg/mL

change from baseline at 6 weeks

ID	Title	Description
OG000	1000 mg SAMe (S-adenosyl-L-methionine)	SAMe 1000 mg: 1000 mg dose group: one 500 mg capsule fasting in the morning and one 500 mg capsule before dinner
OG001	1500 mg SAMe	SAMe 1500 mg: 1500 mg dose group: two 500 mg capsules fasting in the morning and one 500 mg capsule before dinner
OG002	2000 mg SAMe	SAMe 2000 mg: 2000 mg dose group: two 500 mg capsules fasting in the morning and two 500 mg capsules before dinner
OG003	No Treatment	No study drug was administered

Units	Counts
Participants

Secondary

Immunological/Anti-oxidant Panel (Immunological and Anti-oxidant Laboratory Parameters)

C-reactive Protein (CRP)

Posted

Mean

Standard Deviation

nmol/L

change from baseline at 6 weeks

ID	Title	Description
OG000	1000 mg SAMe (S-adenosyl-L-methionine)	SAMe 1000 mg: 1000 mg dose group: one 500 mg capsule fasting in the morning and one 500 mg capsule before dinner
OG001	1500 mg SAMe	SAMe 1500 mg: 1500 mg dose group: two 500 mg capsules fasting in the morning and one 500 mg capsule before dinner
OG002	2000 mg SAMe	SAMe 2000 mg: 2000 mg dose group: two 500 mg capsules fasting in the morning and two 500 mg capsules before dinner
OG003	No Treatment	No study drug was administered

Units	Counts

Secondary

Immunological/Anti-oxidant Panel (Immunological and Anti-oxidant Laboratory Parameters)

glutathione in erythrocytes

Posted

Mean

Standard Deviation

mcmol/g

change from baseline at 6 weeks

ID	Title	Description
OG000	1000 mg SAMe (S-adenosyl-L-methionine)	SAMe 1000 mg: 1000 mg dose group: one 500 mg capsule fasting in the morning and one 500 mg capsule before dinner
OG001	1500 mg SAMe	SAMe 1500 mg: 1500 mg dose group: two 500 mg capsules fasting in the morning and one 500 mg capsule before dinner
OG002	2000 mg SAMe	SAMe 2000 mg: 2000 mg dose group: two 500 mg capsules fasting in the morning and two 500 mg capsules before dinner
OG003	No Treatment	No study drug was administered

Units	Counts

Secondary

Immunological/Anti-oxidant Panel (Immunological and Anti-oxidant Laboratory Parameters)

oxidative stress marker (isoprostane level)

Posted

Mean

Standard Deviation

ng/mg Crea

change from baseline at 6 weeks

ID	Title	Description
OG000	1000 mg SAMe (S-adenosyl-L-methionine)	SAMe 1000 mg: 1000 mg dose group: one 500 mg capsule fasting in the morning and one 500 mg capsule before dinner
OG001	1500 mg SAMe	SAMe 1500 mg: 1500 mg dose group: two 500 mg capsules fasting in the morning and one 500 mg capsule before dinner
OG002	2000 mg SAMe	SAMe 2000 mg: 2000 mg dose group: two 500 mg capsules fasting in the morning and two 500 mg capsules before dinner
OG003	No Treatment	No study drug was administered

Units	Counts

Secondary

Fibrosis and Apoptosis Markers (Fibrosis and Apoptosis Laboratory Markers)

Caspase-cleaved cytokeratin (CK 18)

Posted

Mean

Standard Deviation

U/L

change from baseline at 6 weeks

ID	Title	Description
OG000	1000 mg SAMe (S-adenosyl-L-methionine)	SAMe 1000 mg: 1000 mg dose group: one 500 mg capsule fasting in the morning and one 500 mg capsule before dinner
OG001	1500 mg SAMe	SAMe 1500 mg: 1500 mg dose group: two 500 mg capsules fasting in the morning and one 500 mg capsule before dinner
OG002	2000 mg SAMe	SAMe 2000 mg: 2000 mg dose group: two 500 mg capsules fasting in the morning and two 500 mg capsules before dinner
OG003	No Treatment	No study drug was administered

Units	Counts

Secondary

Fibrosis and Apoptosis Markers (Fibrosis and Apoptosis Laboratory Markers)

Hyaluronic acid

Posted

Mean

Standard Deviation

ng/mL

change from baseline at 6 weeks

ID	Title	Description
OG000	1000 mg SAMe (S-adenosyl-L-methionine)	SAMe 1000 mg: 1000 mg dose group: one 500 mg capsule fasting in the morning and one 500 mg capsule before dinner
OG001	1500 mg SAMe	SAMe 1500 mg: 1500 mg dose group: two 500 mg capsules fasting in the morning and one 500 mg capsule before dinner
OG002	2000 mg SAMe	SAMe 2000 mg: 2000 mg dose group: two 500 mg capsules fasting in the morning and two 500 mg capsules before dinner
OG003	No Treatment	No study drug was administered

Units	Counts

Secondary

Area Under Curve (AUC) of Average Methionine Concentration Versus Time Curve

After the methionine load, blood samples will be obtained at 0.5, 1, 1.5, 3, 4, 5, 6, 7.5 and 9 hours. Plasma will be analyzed for methionine.

Posted

Mean

Standard Deviation

mcg/mL

0.5, 1, 1.5, 3, 4, 5, 6, 7.5 and 9 hours *at Week 7*

ID	Title	Description
OG000	1000 mg SAMe (S-adenosyl-L-methionine)	SAMe 1000 mg: 1000 mg dose group: one 500 mg capsule fasting in the morning and one 500 mg capsule before dinner
OG001	1500 mg SAMe	SAMe 1500 mg: 1500 mg dose group: two 500 mg capsules fasting in the morning and one 500 mg capsule before dinner
OG002	2000 mg SAMe	SAMe 2000 mg: 2000 mg dose group: two 500 mg capsules fasting in the morning and two 500 mg capsules before dinner
OG003	No Treatment	No study drug was administered

Secondary

Hepatic Panel (Liver Laboratory Parameters)

ALT/AST ratio

Posted

Mean

Standard Deviation

Ratio

change from baseline at 6 weeks

ID	Title	Description
OG000	1000 mg SAMe (S-adenosyl-L-methionine)	SAMe 1000 mg: 1000 mg dose group: one 500 mg capsule fasting in the morning and one 500 mg capsule before dinner
OG001	1500 mg SAMe	SAMe 1500 mg: 1500 mg dose group: two 500 mg capsules fasting in the morning and one 500 mg capsule before dinner
OG002	2000 mg SAMe	SAMe 2000 mg: 2000 mg dose group: two 500 mg capsules fasting in the morning and two 500 mg capsules before dinner
OG003	No Treatment	No study drug was administered

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	1000 mg SAMe (S-adenosyl-L-methionine)	SAMe 1000 mg: 1000 mg dose group: one 500 mg capsule fasting in the morning and one 500 mg capsule before dinner	0	27	7	27
EG001	1500 mg SAMe	SAMe 1500 mg: 1500 mg dose group: two 500 mg capsules fasting in the morning and one 500 mg capsule before dinner	0	27	4	27
EG002	2000 mg SAMe	SAMe 2000 mg: 2000 mg dose group: two 500 mg capsules fasting in the morning and two 500 mg capsules before dinner	0	24	7	24
EG003	No Treatment	No study drug was administered	1	28	2	28

Term	Organ System	Statistical Information
DIARRHOEA	Gastrointestinal disorders	EG0003 events3 affected27 at risk EG0012 events2 affected27 at risk EG0024 events4 affected24 at risk EG0030 events0 affected28 at risk
Abdominal Pain	Gastrointestinal disorders	EG0000 events0 affected27 at risk EG0011 events1 affected27 at risk EG0023 events3 affected24 at risk EG003
Headache	Nervous system disorders	EG0002 events2 affected27 at risk EG0011 events1 affected27 at risk EG0021 events1 affected24 at risk EG003
Fatigue	General disorders	EG0002 events2 affected27 at risk EG0010 events0 affected27 at risk EG0020 events0 affected24 at risk EG003

ID	Term
D065626	Non-alcoholic Fatty Liver Disease
D005234	Fatty Liver

ID	Term
D008107	Liver Diseases
D004066	Digestive System Diseases

ID	Term
D008715	Methionine
D000603	Amino Acids, Sulfur
D013457	Sulfur Compounds
D009930	Organic Chemicals
D000241	Adenosine
D011684	Purine Nucleosides
D011687	Purines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D000596	Amino Acids
D000602	Amino Acids, Peptides, and Proteins
D009705	Nucleosides
D009706	Nucleic Acids, Nucleotides, and Nucleosides
D012263	Ribonucleosides

ID	Title	Description
BG000	1000 mg SAMe (S-adenosyl-L-methionine)	SAMe 1000 mg: 1000 mg dose group: one 500 mg capsule fasting in the morning and one 500 mg capsule before dinner
BG001	1500 mg SAMe	SAMe 1500 mg: 1500 mg dose group: two 500 mg capsules fasting in the morning and one 500 mg capsule before dinner
BG002	2000 mg SAMe	SAMe 2000 mg: 2000 mg dose group: two 500 mg capsules fasting in the morning and two 500 mg capsules before dinner
BG003	No Treatment	no study drug was administered
BG004	Total	Total of all reporting groups