Please select the eligibility criteria that correspond to the clinical trial below.
Title: An Exploratory Study of INT-747 in Patients With Type 2 Diabetes Mellitus and Presumed Nonalcoholic Fatty Liver Disease
Brief Summary: The primary objectives of this study are to assess, in patients with Type 2 diabetes mellitus (DM) and presumed nonalcoholic fatty liver disease (NAFLD), the following:

* The safety and tolerability of multiple doses of INT 747;
* The effects of 2 dose levels (25 mg and 50 mg) of INT 747 on insulin resistance and glucose homeostasis;
* Effects of INT-747 on hepatocellular function as measured by assessment of liver enzymes and biochemical markers of hepatic and metabolic function and inflammation, and;
* Trough concentrations of INT-747 and its metabolites, glyco 6-ethyl chenodeoxycholic acid (6-EDCA) and tauro 6-ECDCA.


Options:
A: Inclusion Criteria:

* Type 2 diabetes, defined by the American Diabetes Association (ADA), as one of the following criteria:
* Symptoms of diabetes plus casual plasma glucose concentration \>200 mg/dL (11.1 mmol/L) or
* Fasting plasma glucose \>126 mg/dL (7.0 mmol/L) or
* 2-hour post-load glucose \>200 mg/dL (11.1 mmol/L) during a 75 g oral glucose tolerance test (GTT).
* Presumed NAFLD, defined by one of the following criteria:
* Alanine aminotransferase (ALT) ≥47 U/L for females and ≥56 U/L for males
* Aspartate aminotransferase (AST) ≥47 U/L for females and ≥60 U/L for males
* Enlarged liver (demonstrated by ultrasound or other imaging technique)
* Diagnostic histological findings shown on prior biopsy (in the last 5 years).

Exclusion Criteria:

* Bilirubin \>2 × ULN
* ALT \>155 U/L for females and \>185 U/L for males.
* AST \>155 U/L for females and \>200 U/L for males.
* Patients taking any antidiabetic medications, with the exception of metformin and sulfonylureas. If the HbA1c is \<11%, patients may be enrolled who have been withdrawn from all other diabetic medications as specified in the protocol, at the discretion of the Principal Investigator.
B: Inclusion Criteria:

* Age 18 and older;
* Evidence of nonalcoholic steatohepatitis with steatosis grade higher or equal to 1 in ultrasonography;
* No history of Alcohol consumption or consuming less than 10 grams alcohol per day in women and less than 20 grams per day in men;
* Absence of other liver disorders, malignancies, cardiovascular, respiratory, and kidney disorders;
* Absence of pregnancy or lactation;
* Absence of taking any medications in the past three months;
* Absence of weight loss in the recent three months;
* Absence of endocrine and metabolism disorders.

Exclusion Criteria:

* Weight loss more than 10% of baseline body weight during the intervention period.
* Pregnancy;
* Disliking to continue the study.
C: Inclusion Criteria:

* Histologically proven NAFLD less than 18 months prior to inclusion. For those with pure steatosis, ALAT or aspartate aminotransferase (ASAT) must be elevated above the upper limits of normal, and impaired glucose tolerance or diabetes mellitus type 2 must be present.
* Body weight within +/- 5 kg compared with the weight at the time of biopsy.

Exclusion Criteria:

* Treatment for more than 1 week with metformin or glitazones the last 6 months before inclusion.
* Treatment with insulin.
* Hypersensitivity to metformin.
* Treatment with cimetidine.
* Heart failure requiring pharmacological treatment.
* Coronary heart disease (New York Heart Association \[NYHA\] class 3 or 4).
* Chronic obstructive lung disease (moderate or severe).
* Breast-feeding or pregnant.
* Metabolic acidosis.
* Renal failure (male \[♂\]: creatinine \> 135 micromol/L, female \[♀\] \> 110 micromol/L).
* Average alcohol consumption \> 24 g/day the last year.
* Serum ALAT or serum ASAT \> 5 x upper limit of normal (ULN) at screening.
* Cirrhosis.
* Platelets \< 100 000.
* Haemochromatosis.
* Alfa-1-antitrypsin-deficiency.
* Wilson's disease.
* Thyroid dysfunction (0.2 mU/L \< thyroid stimulating hormone \[TSH\] \< 5.0 mU/L).
* Chronic infection with hepatitis B or C virus or HIV.
* Autoimmune hepatitis (antinuclear antibodies \[ANA\] \> 1/256 or smooth muscle antibodies \[SMA\] \> 1/128).
* Primary biliary cirrhosis (antimitochondrial antibodies \[AMA\] \> 1/64).
* Primary sclerosing cholangitis.
* Previous participation in another clinical trial the last 6 months.
* Legal incapability.
D: Inclusion Criteria:

* Liver biopsy obtained no more than 24 months before randomization with a pathology report confirming that the histological diagnosis is consistent with NASH
* Compensated liver disease with the following laboratory parameters at the entry visit:

  * Hemoglobin values of greater than or equal to 12 gm/dl for females or 13 gm/dl for males
  * WBC count \> 3,000/mm3
  * Neutrophil count \> 1,500/mm3
  * Platelets \> 70,000/mm3
  * Albumin \>3.0 g/dl
* Serum creatinine \<1.4mg/dl
* Ability to give informed consent
* Alanine aminotransferase (ALT) greater than or equal to 40 U/L
* BMI \> or equal to 27 kg/m2
* Patients who receive orlistat must agree to participate in Xenicare, a free dietary counseling program provided by Roche (sponsor)

Exclusion Criteria:

* Any cause for chronic liver disease other than NASH
* Evidence of decompensated liver disease such as a history of or presence of ascites, bleeding varices, or spontaneous encephalopathy
* History of alcohol consumption of greater than 20 grams per day in the past 2 years
* Prior surgical procedures to include gastroplasty, jejunoileal or jejunocolic bypass
* TPN within the past 6 months
* History of prior organ transplantation
* Concurrent enrollment in other experimental treatment protocols
* Use of ursodeoxycholic acid, rosiglitazone, pioglitazone, or metformin within the 6-month period before enrollment
* Women who are pregnant or breast-feeding

Answer: A