Healthy Volunteers
Conditions
Brief summary
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
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).
Interventions
DRUGsimufilam
Simufilam 100 mg oral tablets: the Phase 3 oral tablet for the first 3 arms and the Phase 2 tablet for the 4th arm.
Sponsors
Worldwide Clinical Trials
Cassava Sciences, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax | 0, 0.33, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours | The maximum concentration determined directly from individual concentration-time data |
| AUClast | 0, 0.33, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours | Area under the curve to the time of the last quantifiable concentration, calculated using the linear trapezoidal method |
| AUCinf | 0, 0.33, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours | Area under the curve extrapolated to infinity; calculated as: AUCinf = AUClast + Clast/λz |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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). | 6 |
| 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). | 6 |
| 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). | 6 |
| 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). | 6 |
| Total | 24 |
Baseline characteristics
| Characteristic | Sequence A | Sequence B | Sequence C | Sequence D | Total |
|---|---|---|---|---|---|
| Age, Continuous | 31.8 years STANDARD_DEVIATION 2.14 | 38.0 years STANDARD_DEVIATION 3.52 | 30.3 years STANDARD_DEVIATION 4.18 | 34.7 years STANDARD_DEVIATION 7.09 | 33.7 years STANDARD_DEVIATION 5.23 |
| BMI | 26.63 Kg/m^2 STANDARD_DEVIATION 1.85 | 24.62 Kg/m^2 STANDARD_DEVIATION 3.49 | 24.35 Kg/m^2 STANDARD_DEVIATION 3.51 | 26.45 Kg/m^2 STANDARD_DEVIATION 2.55 | 25.51 Kg/m^2 STANDARD_DEVIATION 2.93 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 1 Participants | 4 Participants | 1 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 5 Participants | 2 Participants | 5 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height | 172.08 cm STANDARD_DEVIATION 10.24 | 174.95 cm STANDARD_DEVIATION 6.37 | 168.70 cm STANDARD_DEVIATION 10.65 | 173.62 cm STANDARD_DEVIATION 14.43 | 172.34 cm STANDARD_DEVIATION 10.36 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 4 Participants | 1 Participants | 4 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 2 Participants | 4 Participants | 1 Participants | 11 Participants |
| Region of Enrollment United States | 6 participants | 6 participants | 6 participants | 6 participants | 24 participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 4 Participants | 2 Participants | 9 Participants |
| Sex: Female, Male Male | 4 Participants | 5 Participants | 2 Participants | 4 Participants | 15 Participants |
| Weight | 79.25 Kg STANDARD_DEVIATION 11.7 | 75.77 Kg STANDARD_DEVIATION 14.63 | 69.78 Kg STANDARD_DEVIATION 15.92 | 80.58 Kg STANDARD_DEVIATION 18.7 | 76.35 Kg STANDARD_DEVIATION 15.02 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 |
| other Total, other adverse events | 4 / 24 | 4 / 24 | 3 / 24 | 2 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 |
Outcome results
Primary
AUCinf
Area under the curve extrapolated to infinity; calculated as: AUCinf = AUClast + Clast/λz
Time frame: 0, 0.33, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fasted Phase 3 Simufilam | AUCinf | 3980 h*ng/mL | Standard Deviation 1130 |
| Phase 3 High-fat Fed Simufilam | AUCinf | 3900 h*ng/mL | Standard Deviation 1030 |
| Phase 3 Low-fat Fed Simufilam | AUCinf | 3930 h*ng/mL | Standard Deviation 1050 |
| Fasted Phase 2 Simufilam | AUCinf | 3960 h*ng/mL | Standard Deviation 1060 |
90% CI: [96.33, 100.71]
90% CI: [96.85, 101.26]
90% CI: [98.05, 102.5]
Primary
AUClast
Area under the curve to the time of the last quantifiable concentration, calculated using the linear trapezoidal method
Time frame: 0, 0.33, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fasted Phase 3 Simufilam | AUClast | 3890 h*ng/mL | Standard Deviation 1050 |
| Phase 3 High-fat Fed Simufilam | AUClast | 3810 h*ng/mL | Standard Deviation 951 |
| Phase 3 Low-fat Fed Simufilam | AUClast | 3830 h*ng/mL | Standard Deviation 971 |
| Fasted Phase 2 Simufilam | AUClast | 3860 h*ng/mL | Standard Deviation 978 |
90% CI: [96.33, 100.65]
90% CI: [96.74, 101.07]
90% CI: [98.15, 102.54]
Primary
Cmax
The maximum concentration determined directly from individual concentration-time data
Time frame: 0, 0.33, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fasted Phase 3 Simufilam | Cmax | 698 ng/mL | Standard Deviation 190 |
| Phase 3 High-fat Fed Simufilam | Cmax | 715 ng/mL | Standard Deviation 156 |
| Phase 3 Low-fat Fed Simufilam | Cmax | 755 ng/mL | Standard Deviation 149 |
| Fasted Phase 2 Simufilam | Cmax | 680 ng/mL | Standard Deviation 193 |
90% CI: [96.88, 109.98]
90% CI: [102.9, 116.82]
90% CI: [96.57, 109.64]