A Pharmacokinetic Study of Simufilam in Subjects With Impaired Hepatic Function

NCT06390410 | Completed Phase 1 FDA Drug

• 1 other identifier: PTI-125-11
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 3

Brief Summary

Evaluate simufilam levels in the blood of hepatically impaired individuals compared to Healthy individuals of similar demographics

Conditions

Hepatic Insufficiency

Outcome Measures

Primary Outcomes (5)

• Area Under the Curve; moderate vs. normal and mild vs. normal

  Area Under the Curve of simufilam concentration in plasma in Moderate and Mild Impairment vs. Normal (each separately)

  5 Days

• Concentration max; moderate vs. normal and mild vs. normal

  Maximum simufilam concentration in plasma in Moderate and Mild Impairment vs. Normal (each separately)

  5 Days

• Time max; moderate vs. normal and mild vs. normal

  Time to maximum simufilam concentration in plasma in Moderate and Mild Impairment vs. Normal (each separately)

  5 Days

• Half-life; moderate vs. normal and mild vs. normal

  Half-life of simufilam concentration in plasma in Moderate and Mild Impairment vs. Normal (each separately)

  5 Days

• Elimination rate constant; moderate vs. normal and mild vs. normal

  Elimination rate constant of simufilam concentration in plasma in Moderate and Mild Impairment vs. Normal (each separately)

  5 Days

Study Arms (3)

Moderate Hepatic Impairment

EXPERIMENTAL

Drug: Simufilam

Healthy Volunteer

EXPERIMENTAL

Drug: Simufilam

Mild Hepatic Impairment

EXPERIMENTAL

Drug: Simufilam

Interventions

Simufilam DRUG

100 mg PTI-125

Healthy Volunteer; Mild Hepatic Impairment; Moderate Hepatic Impairment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Cassava Sciences, Inc.: lead

Study Sites (3)

Orange County Research Center

Lake Forest, California, 92630, United States

Location

Clinical Pharmacology of Miami

Miami, Florida, 33014, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

MeSH Terms

Conditions

Hepatic Insufficiency

Interventions

Simufilam

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2024
• First Posted: April 30, 2024
• Study Start: June 26, 2024
• Primary Completion: December 7, 2024
• Study Completion: December 7, 2024
• Last Updated: January 7, 2025

Record last verified: 2025-01

Locations

US (3)