A Pharmacokinetic Study of Simufilam in Subjects With Impaired Hepatic Function

Exclusion Criteria

• •The subject has a clinically significant electrocardiogram (ECG) abnormality including, but not necessarily limited to, a confirmed QT interval by the Fridericia correction formula (QTcF) \> 470 msec (females) or \> 450 msec (males) based on WHO 2016 guidelines.
• •The subject has had a clinically significant illness within 30 days prior to the Screening Visit.
• •The subject has a medically significant comorbid illness that would impact the successful conduct of the study or achieving its objectives in the opinion of the Investigator and/or Medical Monitor.
• •The subject has used a known strong CYP2C19 inhibitor (fluconazole, fluoxetine, fluvoxamine or ticlopidine) or inducer (rifampin) within 28 days prior to admission, or 5 half-lives (whichever is longer).
• •The subject has consumed alcohol, grapefruit, grapefruit juice, caffeine- or xanthine-containing products within 72 hours before dosing or intends to use any of these products during the study.
• •The subject has smoked more than 10 cigarettes per day on average for the past 6 months.
• •The subject has a history of substance abuse within 12 months of the Screening Visit.
• •The subject tests positive on the urine drug screen for drugs of abuse at either the Screening Visit or the Check-In Visit (Note - Subjects with hepatic impairment who are prescribed medications assessed in the urine drug screen \[e.g, opiates, benzodiazepines\] need not be excluded based on a positive urine drug screen).
• •The subject has a positive ethanol breath test at either the Screening Visit or the Check-In Visit.
• •The subject has a history of regular alcohol consumption defined as greater than 7 drinks per week for women and 14 drinks per week for men within six months prior to the Screening Visit.
• •The subject has a positive serum hepatitis B surface antigen test at the Screening Visit.
• •The subject has a positive human immunodeficiency virus (HIV) test at the Screening Visit.
• •The subject is pregnant or breastfeeding.
• •The subject has received an investigational drug within 30 days or five half-lives - whichever is longer - prior to Study Day 1.
• •The subject has previously received simufilam.
• •The subject has donated or lost a significant volume of blood (\>500 mL) within a 90 day period prior to the Screening Visit. This does not include plasma donation.
• •Subjects with poor peripheral venous access.
• •Subjects who, in the opinion of the Investigator (or designee), should not participate in this study.
• •The subject with normal hepatic function has or has had hepatitis C, as confirmed by a positive hepatitis C virus (HCV) antibody test at the Screening Visit.
• •The subject with normal hepatic function has used prescription or over the counter (OTC) medication within 7 days prior to the Check-In visit, or intends to use any prescription or OTC medication during the study, with the following exceptions:
• •* Hormonal contraceptives,
• •* Over-the-counter analgesics, stool softeners, and/or multivitamins up to 48 hours prior to study drug administration.
• •The subject with hepatic impairment has used prescription or OTC medication within 7 days prior to the Check-In Visit except for the management of their hepatic impairment or stable, chronic medical conditions. Such medications must have a stable dose regiment and be approved by the Medical Monitor (Note - over-the-counter analgesics, stool softeners, and/or multivitamins up to 48 hours prior to study drug administration are acceptable).
• •The subject with hepatic impairment has a hemoglobin level \< 9.0 (g/dL) or a platelet count \< 35×109/L.
• •The hepatically impaired subject with type 2 diabetes on standard oral medication has a HbA1C \> 9.5% at either the Screening Visit or the Check-In Visit (Note - use of insulin is not acceptable).
• •The subject with hepatic impairment who has a positive hepatitis C virus (HCV) antibody test also has a positive HCV RNA test (that confirms chronic infection upon reflex testing).
• •The subject with hepatic impairment has evidence of active hepatic encephalopathy \> Grade 2 or history of \>Grade 2 within the last 6 months. Subject with a history of \> Grade 2 hepatic encephalopathy more than 6 months prior to Screening and who currently receives medication for treatment may be allowed, but should be assigned the pre-treatment Child-Pugh score of hepatic encephalopathy.
• •The subject with hepatic impairment has acute hepatitis, severe ascites (defined by the need for frequent paracentesis), hepatocellular carcinoma, current unstable hematological condition, recent upper gastrointestinal bleed, surgical portosystemic shunts, or evidence of hepatorenal syndrome.
• •The subject with hepatic impairment has history of pancreatitis within 4 months of Screening.
• •The subject with hepatic impairment has had a liver transplant prior to Screening.