Food Effect and Bioequivalence Study of Simufilam Tablets in Healthy Volunteers

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

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

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: simufilam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects, Ages ≥ 18 and ≤ 45 years BMI of 18 - 30 Kg/m² Informed consent form (ICF) signed by the subject General health status acceptable for participation in the study as determined by medical history, review of current medication, physical examination, and laboratory results Fluency (oral and written) in English The patient must agree to comply with the drawing of blood samples for the PK assessments, laboratory assessments and plasma biomarkers The subject is willing and able to remain at the study site for the duration of the study Exclusion Criteria: The subject has any relevant deviations from normal in physical examination, electrocardiogram (ECG), or clinical laboratory tests, as evaluated by the investigator. The subject has had a clinically significant illness within 30 days of this study. The subject has a history of significant neurological, hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, or metabolic disease. Subject is taking prescription CNS medication. 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. The subject has a history of substance abuse or a current positive ethanol breath test or positive urine drug screen. The subject has a positive serum hepatitis B surface antigen or positive HCV antibody test. The subject has a positive HIV test. The subject has a current positive urine cotinine test. The subject has participated in another drug study in the past 30 days. The subject has donated or lost a significant volume of blood (>450 mL) within 4 weeks of the study. 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. Covid-19 infection within the past 3 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Four-way crossover of Phase 3 tablets under fasted or high-fat or low-fat conditions and the Phase 2 tablet under fasted conditions. Subjects are randomized to a sequence.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Sequence A<br>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<br>* Simufilam 100 mg oral tablets: the Phase 3 oral tablet for the first 3 arms and the Phase 2 tablet for the 4th arm.<br>* Other names: PTI-125;|
| Other: Sequence B<br>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<br>* Simufilam 100 mg oral tablets: the Phase 3 oral tablet for the first 3 arms and the Phase 2 tablet for the 4th arm.<br>* Other names: PTI-125;|
| Other: Sequence C<br>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<br>* Simufilam 100 mg oral tablets: the Phase 3 oral tablet for the first 3 arms and the Phase 2 tablet for the 4th arm.<br>* Other names: PTI-125;|
| Other: Sequence D<br>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<br>* Simufilam 100 mg oral tablets: the Phase 3 oral tablet for the first 3 arms and the Phase 2 tablet for the 4th arm.<br>* Other names: PTI-125;|

What is the study measuring?
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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 |