Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Crossover, Open-label Phase 1 Study of Glyceryl Tri-(4-phenylbutyrate) (GT4P)
Brief Summary: To determine the safety and tolerability of single oral doses of HPN-100 as a formulation (GT4P-F) and GT4P as the active pharmaceutical ingredient (GT4P-API) administered to healthy male subjects.


Options:
A: Inclusion Criteria:

* Subjects aged 18 and over
* Clinical diagnosis of cirrhosis of any cause
* Potential to benefit from HE treatment
* History of greater than or equal to 2 documented episodes of WH Grade 2 or more HE within the past 6 months, at least one of which occurred within the preceding 3 months
* No change in other HE-specific medications within 1 week before randomization
* Able to give informed consent and comply with study activities
* Availability of at least one designated family member or caregiver who is capable of and willing to assume responsibility for facilitating subject compliance with study procedures
* All females of childbearing age and all sexually active males must agree to use an acceptable method of contraception throughout the study.

Exclusion Criteria:

* Use of any investigational drug within 30 days
* Use of prohibited medications
* Uncontrolled infection
* Active GI bleeding or a history of GI bleeding requiring blood transfusion (\> 2 units) within 3 months
* Transjugular intrahepatic portosystemic shunt (TIPS) placement or revision within the past 90 days
* Recreational drug use or alcohol consumption for subjects with a history of alcohol or drug abuse within 6 months
* Lactating and/or pregnant females
* Active malignancy
* Clinically significant bowel disease, including obstruction, inflammatory bowel disease, or malabsorption
* Expected to undergo transplantation within 6 months
* Model for end-stage liver disease (MELD) score of \> 25
B: Inclusion Criteria:

Subjects were required to fulfill the following criteria in order to participate in the study:

* Males aged 18 to 45 years of age
* Ability to provide written, informed consent before any study-related procedures, and ability, in the opinion of the investigator, to comply with all the requirements of the study
* Subjects who were in good health as determined by a medical history, physical examination, serum chemistry, hematology, urinalysis, 12 lead ECG, and vital signs
* Weight within the range of 60-120 kg

Exclusion Criteria:

Subjects who fulfilled any of the following criteria were excluded from the study:

* Clinically significant history or evidence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, neurologic, immunologic, or psychiatric disorder(s), as determined by the investigator
* Clinically significant abnormal laboratory values (as determined by the investigator)
* Significant illness within 14 days prior to screening
* Any disorder that might significantly interfere with the absorption, distribution, metabolism, or excretion of any drug
* Use of any prescription medication within 14 days prior to screening
* Use of dietary supplements, herbal medicines, vitamins, or over-the-counter medication(s) (with the exception of acetaminophen ≤ 500 mg/day) within 10 days prior to first dosing
* Positive drugs of abuse urine test at screening or pre-dose day (cocaine, amphetamines, barbiturates, opiates, benzodiazepines, cannabinoids, methadone)
* Positive alcohol breath test at screening or pre-dose day
* Donation or loss of blood (500 ml or more) within 30 days prior to first dosing, or during the study
* Donation or loss of plasma within 7 days prior to first dosing, or during the study
* History of or current hepatitis or carriers of hepatitis B surface antigen (HBsAg) and/or hepatitis C antibodies (anti-HC)
* History of acquired immunodeficiency syndrome (AIDS) or determined HIV positive at screening
* Use of any investigational drug within 12 weeks prior to first dosing
* Known hypersensitivity to sodium phenylbutyrate or similar drugs
* Previous exposure to sodium phenylbutyrate
C: Inclusion Criteria:

1. Ages 18-80
2. Male and female subjects of all races and ethnicities including Spanish speaking subjects
3. Cirrhosis of any cause
4. Any grade of hepatic encephalopathy (1-4)
5. A legally authorized representative has to be able and willing to comply with all protocol procedures and to understand, sign and date an informed consent document, and authorize access to protected health information on the subjects behalf

Exclusion Criteria:

1. Acute liver failure
2. Structural brain lesions (as indicated by computed tomography imaging if available and confirmed by neurological exam)
3. Other causes of altered mental status (i.e. not meeting the definition of hepatic encephalopathy)
4. Previous use of rifaximin or neomycin in past 7 days
5. Prisoners
6. Pregnancy
7. \<18 years old
8. Serum sodium \<125 mEq/L
9. Receiving \> 1 dose of lactulose prior to enrollment
10. Uncontrolled infection with hemodynamic instability requiring vasopressors
D: Inclusion Criteria:

Subjects were required to fulfill the following criteria in order to participate in the study:

Screening:

* Males or females aged ≥ 18 years of age
* Able to provide written informed consent before any study-related procedures, and ability, in the opinion of the Investigator, to comply with all the requirements of the study
* Classification to one of the following:

  * current diagnosis of hepatic impairment with cirrhosis
  * healthy subject
* Subjects with hepatic impairment with cirrhosis were classifiable to one of the following groups:

  * Child-Pugh score A
  * Child-Pugh score B
  * Child-Pugh score C
* Subjects with hepatic impairment with cirrhosis who were on a therapeutic regimen of lactulose must have been on a stable dose for ≥ 30 days prior to screening
* If female, a negative pregnancy test at screening and pre-dose on day 0, or a documented sterilization procedure; a female of child-bearing potential must have been using a medically approved birth control method and must have agreed to use the same method of contraception during the full course of the study (on pre-dose day 0 as well as at screening)
* Weight within the range of 60-100 kg (at screening and pre-dose on day 0)
* Willing to stop taking any medication that the Sponsor and the Investigator felt was not appropriate for use during the study, beginning 2 days before dosing and throughout the study

Exclusion Criteria:

Subjects who fulfilled any of the following criteria were excluded from the study:

Screening:

* Clinically significant history or evidence of cardiovascular, respiratory, renal, gastrointestinal, endocrine, neurological, immunological, or psychiatric disorder(s), as determined by the Investigator
* Serum sodium \< 120 mEq/L
* Serum creatinine ≥ 1.5 upper limit of normal
* Potassium ≤ 3.5 mEq/L
* Other laboratory values outside the normal range which were determined to be clinically significant by the Investigator
* Significant illness within the last 14 days
* Oral temperature \> 38.5°C or \< 36°C and/or a suspected site of active infection
* Inflammatory bowel disease or malabsorption defined with steatorrhea
* Active gastrointestinal bleeding, defined as melena, hematochezia, or hematemesis requiring hospitalization within the last 30 days
* Use of probenecid, valproate, or corticosteroids within the last 24 hours
* Use of any medication, other than those approved by the Sponsor and Investigator, in the last 48 hours
* History of seizures within the last 72 hours
* Positive drugs of abuse urine test
* Positive alcohol breath test
* Donation or loss of blood (500 mL or more) within the last 30 days
* Donation or loss of plasma within the last 7 days
* History of acquired immunodeficiency syndrome (AIDS) or determined human immunodeficiency virus (HIV) positive
* Hepatitis B or C (HBV; HCV) positive (healthy volunteers only)
* Use of any investigational drug within the last 30 days
* Known hypersensitivity to sodium phenylbutyrate or similar drugs
* Emergency hospitalization within the last 90 days
* Intake of alcohol in the last 7 days

Pre-dose (days 0 and 7):

* Significant illness or emergency hospitalization since the last study visit
* Oral temperature \> 38.5°C or \< 36°C and/or a suspected site of active infection
* Use of probenecid, valproate, or corticosteroids within the last 24 hours
* Use of any non-approved medication (by the Sponsor/Investigator) within the 48 hours before dosing
* History of seizures within the last 72 hours
* Positive drugs of abuse urine test
* Positive alcohol breath test
* Donation or loss of blood (500 mL or more) or plasma since the last study visit
* Use of any investigational drug since the last study visit
* Intake of alcohol in the last 7 days

Answer: B