Hepatic Insufficiency
Conditions
Brief summary
Evaluate simufilam levels in the blood of hepatically impaired individuals compared to Healthy individuals of similar demographics
Detailed description
This is a Phase I, open label, single-dose study of simufilam 100 mg. Up to 34 subjects may be enrolled; 10 subjects with moderate hepatic impairment, 10 healthy volunteers with normal hepatic function (with the potential of 4 more), and if needed 10 subjects with mild hepatic impairment. Both males and females will be enrolled. The study will be conducted in 2 groups (with the potential of a third) assigned based on degree of hepatic impairment as follows: up to 10 subjects with moderate hepatic impairment (Child-Pugh score of 7-9) up to 10 health volunteers (matched to each hepatic impairment severity group) If needed up to 10 subjects with mild hepatic impairment (Child-Pugh score of 5-6), and an additional 4 healthy volunteers if needed to match the mild group
Interventions
DRUGSimufilam
100 mg PTI-125
Sponsors
Cassava Sciences, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* The subject is willing and able to speak, read, and understand English and is willing to provide written informed consent. * Male or female subjects between 18 and 75 years of age, inclusive. * The subject has a body mass index (BMI) within 18-40 kg/m2. * The subject must have renal function that is normal or consistent with mild renal insufficiency. * The subject has normal/acceptable mental status for study participation in the opinion of the Investigator. * Male subjects and female subjects of childbearing potential must agree to their respective birth control requirements. Females of non-childbearing potential must satisfy the definition of permanent sterility or postmenopausal status * The subject must agree to comply with the drawing of blood samples for the pharmacokinetics (PK) assessments. * The subject is willing and able to comply with all testing and requirements defined in the protocol. * The subject is willing and able to remain at the study site unit for the duration of the study. * The subject must be negative for the COVID virus at both the Screening Visit and the Check-In Visit. Additional inclusion criteria specific for subjects with normal hepatic function: * The subject with normal hepatic function is in reasonably good health, determined by no clinically significant findings from medical history, physical examination, 12-lead electrocardiogram (ECG), vital sign measurements, and clinical laboratory evaluations in the opinion of the Investigator and/or Medical Monitor. Additional inclusion criteria specific for subjects with hepatic impairment: * Subjects with hepatic impairment with other stable, chronic medical conditions (e.g., hypertension, hyperlipidemia, diabetes) may be included if, in the opinion of the Investigator and Medical Monitor, the abnormality will not significantly alter the disposition of the drug and will not interfere with interpretation of the data. * The subject with moderate or mild hepatic impairment has been diagnosed at least 6 months prior to Screening. * Moderate: Child-Pugh Class B (7 to 9 points) * Mild: Child-Pugh Class A (5 to 6 points) (if a decision is taken to enroll) * The subject with hepatic impairment has clinical laboratory tests that are considered clinically stable and consistent with the subject's disease, in the opinion of the investigator.
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. Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve; moderate vs. normal and mild vs. normal | 5 Days | Area Under the Curve of simufilam concentration in plasma in Moderate and Mild Impairment vs. Normal (each separately) |
| Concentration max; moderate vs. normal and mild vs. normal | 5 Days | Maximum simufilam concentration in plasma in Moderate and Mild Impairment vs. Normal (each separately) |
| Time max; moderate vs. normal and mild vs. normal | 5 Days | Time to maximum simufilam concentration in plasma in Moderate and Mild Impairment vs. Normal (each separately) |
| Half-life; moderate vs. normal and mild vs. normal | 5 Days | Half-life of simufilam concentration in plasma in Moderate and Mild Impairment vs. Normal (each separately) |
| Elimination rate constant; moderate vs. normal and mild vs. normal | 5 Days | Elimination rate constant of simufilam concentration in plasma in Moderate and Mild Impairment vs. Normal (each separately) |
Countries
United States
Outcome results
None listed