Food Effect and Bioequivalence Study of Simufilam Tablets in Healthy Volunteers

A Four-way Crossover Food Effect and Bioequivalence Pharmacokinetic Study of Simufilam in Healthy Volunteers

This study will compare the pharmacokinetics of the Phase 3 simufilam 100 mg oral tablet when taken fasted versus following a high-fat or low-fat meal. Additionally, the Phase 3 oral tablet will be compared to the Phase 2 oral tablet for bioequivalence under fasted conditions.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: simufilam

Detailed Description

This is a single-center, randomized, four-treatment, four-sequence crossover study in healthy volunteers to estimate the effect of food on the pharmacokinetics of simufilam following oral 100 mg Phase 3 oral tablets. Additionally, the relative bioavailability of the Phase 3 100 mg tablet will be compared to the earlier Phase 2 100 mg tablet in the fasted state. A total of twenty four (24) healthy volunteers (12 male and 12 female) will be enrolled into this study. Subjects will be randomly assigned to one of four treatment sequences (6 subjects/sequence).

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78217
      • Worldwide Clinical Trials Phase I Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Male or female subjects, Ages ≥ 18 and ≤ 45 years
2. BMI of 18 - 30 Kg/m²
3. Informed consent form (ICF) signed by the subject
4. General health status acceptable for participation in the study as determined by medical history, review of current medication, physical examination, and laboratory results
5. Fluency (oral and written) in English
6. The patient must agree to comply with the drawing of blood samples for the PK assessments, laboratory assessments and plasma biomarkers
7. The subject is willing and able to remain at the study site for the duration of the study

Exclusion Criteria:

1. The subject has any relevant deviations from normal in physical examination, electrocardiogram (ECG), or clinical laboratory tests, as evaluated by the investigator.
2. The subject has had a clinically significant illness within 30 days of this study.
3. The subject has a history of significant neurological, hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, or metabolic disease.
4. Subject is taking prescription CNS medication.
5. The subject has used alcohol, grapefruit, grapefruit juice, caffeine or xanthinecontaining products 48 h before dosing or intends to use any of these products during the study.
6. The subject has a history of substance abuse or a current positive ethanol breath test or positive urine drug screen.
7. The subject has a positive serum hepatitis B surface antigen or positive HCV antibody test.
8. The subject has a positive HIV test.
9. The subject has a current positive urine cotinine test.
10. The subject has participated in another drug study in the past 30 days.
11. The subject has donated or lost a significant volume of blood (>450 mL) within 4 weeks of the study.
12. The subject is unwilling to reside in the study unit for the duration of the study or to cooperate fully with the investigator or site personnel.
13. Covid-19 infection within the past 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Sequence A; This arm received Phase 2 tablet fasted (Period 1), Phase 3 tablet fasted (Period 2), Phase 3 tablet after a high-fat meal (Period 3), and Phase 3 tablet after a low-fat meal (Period 4).	Drug: simufilam; Simufilam 100 mg oral tablets: the Phase 3 oral tablet for the first 3 arms and the Phase 2 tablet for the 4th arm.; Other Names: PTI-125
Other: Sequence B; This arm received Phase 3 tablet after a low-fat meal (Period 1), Phase 2 tablet fasted (Period 2), Phase 3 tablet fasted (Period 3), and Phase 3 tablet after a high-fat meal (Period 4).	Drug: simufilam; Simufilam 100 mg oral tablets: the Phase 3 oral tablet for the first 3 arms and the Phase 2 tablet for the 4th arm.; Other Names: PTI-125
Other: Sequence C; This arm received Phase 3 tablet fasted (Period 1), Phase 3 tablet after a high-fat meal (Period 2), Phase 3 tablet after a low-fat meal (Period 3), and Phase 2 tablet fasted (Period 4).	Drug: simufilam; Simufilam 100 mg oral tablets: the Phase 3 oral tablet for the first 3 arms and the Phase 2 tablet for the 4th arm.; Other Names: PTI-125
Other: Sequence D; This arm received Phase 3 tablet after a high-fat meal (Period 1), Phase 3 tablet after a low-fat meal (Period 2), Phase 2 tablet fasted (Period 3), and Phase 3 tablet fasted (Period 4).	Drug: simufilam; Simufilam 100 mg oral tablets: the Phase 3 oral tablet for the first 3 arms and the Phase 2 tablet for the 4th arm.; Other Names: PTI-125

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	The maximum concentration determined directly from individual concentration-time data	0, 0.33, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours
AUClast	Area under the curve to the time of the last quantifiable concentration, calculated using the linear trapezoidal method	0, 0.33, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours
AUCinf	Area under the curve extrapolated to infinity; calculated as: AUCinf = AUClast + Clast/λz	0, 0.33, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours

Collaborators and Investigators

• Sponsor: Cassava Sciences, Inc.
• Collaborators: Worldwide Clinical Trials
• Investigators: Principal Investigator: Robert G Bass, MD, Worldwide Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): May 4, 2021
• Primary Completion (Actual): May 11, 2021
• Study Completion (Actual): May 11, 2021

Study Registration Dates

• First Submitted: May 19, 2021
• First Submitted That Met QC Criteria: June 12, 2021
• First Posted (Actual): June 21, 2021

Study Record Updates

• Last Update Posted (Actual): August 22, 2023
• Last Update Submitted That Met QC Criteria: October 6, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: PTI-125-05

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No