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| ID | Type | Description | Link |
|---|---|---|---|
| 1R44AG056166 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Aging (NIA) | NIH |
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A Phase I, Single Center, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose, Pharmacokinetic and Safety Study of PTl-125 in Healthy Volunteers
This was a Phase I, single center, randomized, double-blind, placebo-controlled, single ascending dose (SAD) study in healthy volunteers, 18 to 45 years of age. A total of twenty-four (24) subjects were enrolled into the study in one of three dose cohorts. Each cohort contained eight subjects; six subjects received PTI-125 and two received placebo. Three doses of PTI-125 oral solution (50, 100, and 200 mg) or placebo solution were administered to respective cohorts.
The study included a screening period (Day -28 to Day -1), an inpatient treatment period (Day 0 through Day 4), and a follow-up visit (Day 7). Subjects reported to the clinic on the day before dosing and were randomized to receive either a single dose of orally administered PTI-125 or placebo. Each dose was administered following an overnight fast of at least 10 hours.
For each dose level, dosing was staggered such that two subjects (one active and one placebo) were dosed prior to the rest of the group. After a minimum of 24 hours and review of all 24-hour safety assessments (electrocardiogram [ECG], a brief physical examination, vital signs, and laboratory assessments) an independent Data Safety Monitoring Board/Data Monitoring Committee (DSMB/DMC) determined whether the remaining 6 subjects were to be dosed.
Pharmacokinetic blood samples were obtained prior to dosing and at specified intervals during the study (0-72 hours post-dose). Blood draws for laboratory testing were performed prior to dosing and at 24 hours post dose. After safety assessments of ECG, vital signs, and a brief physical exam at 72 hours, subjects were discharged from the clinic and returned 7 days post-dose for a final safety assessment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 50 mg PTI-125 | Active Comparator | Six (6) subjects will receive a single orally administered dose of 50 mg PTI-125 in this cohort. |
|
| 50 mg PTI-125 Placebo | Placebo Comparator | Two (2) subjects will receive a single orally administered dose of 50 mg Placebo PTI-125 in this cohort. |
|
| 100 mg PTI-125 | Active Comparator | Six (6) subjects will receive a single orally administered dose of 100 mg PTI-125 in this cohort. |
|
| 100 mg PTI-125 Placebo | Placebo Comparator | Two (2) subjects will receive a single orally administered dose of 100 mg Placebo PTI-125 in this cohort. |
|
| 200 mg PTI-125 | Active Comparator | Six (6) subjects will receive a single orally administered dose of 200 mg PTI-125 in this cohort. |
|
| 200 mg PTI-125 Placebo |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 50 mg PTI-125 | Drug | PTI-125 50 mg Oral Solution |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Plasma Concentration (Cmax) | The peak drug concentration will be obtained directly from the data without interpolation. | Blood samples will be drawn on Day 1 after dosing at 20, 40, and 60 minutes and at 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours. |
| Time to Maximum Plasma Concentration (Tmax) (Tmax) | The time to peak drug concentration will be obtained directly from the data without interpolation | Blood samples will be drawn on Day 1 after dosing at 20, 40, and 60 minutes and at 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours. |
| Time to Last Quantifiable Plasma Concentration (Tlast) | The time to the last quantifiable drug concentration will be obtained directly from the data without interpolation. | Blood samples will be drawn on Day 1 after dosing at 20, 40, and 60 minutes and at 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours. |
| Last Quantifiable Plasma Concentration (Clast) | The concentration of the last quantifiable drug will be obtained directly from the data without interpolation concentration | Blood samples will be drawn on Day 1 after dosing at 20, 40, and 60 minutes and at 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours. |
| Elimination Rate Constant (λz) | The elimination rate constant (λz) will be calculated. | Blood samples will be drawn on Day 1 after dosing at 20, 40, and 60 minutes and at 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours. |
| Termination Elimination Half-Life (T1/2) | The terminal elimination half-life (T1/2) will be calculated. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| George J Atiee, MD | Worldwide Clinical Trials | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Worldwide Clinical Trials | San Antonio | Texas | 78217 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 50 mg PTI-125 | Six (6) subjects will receive a single orally administered dose of 50 mg PTI-125 in this cohort. 50 mg PTI-125: PTI-125 50 mg Oral Solution |
| FG001 | 50 mg PTI-125 Placebo | Two (2) subjects will receive a single orally administered dose of 50 mg Placebo PTI-125 in this cohort. 50 mg PTI-125: PTI-125 50 mg Oral Solution |
| FG002 | 100 mg PTI-125 | Six (6) subjects will receive a single orally administered dose of 100 mg PTI-125 in this cohort. 100 mg PTI-125: PTI-125 100 mg Oral Solution |
| FG003 | 100 mg PTI-125 Placebo | Two (2) subjects will receive a single orally administered dose of 100 mg Placebo PTI-125 in this cohort. 100 mg PTI-125: PTI-125 100 mg Oral Solution |
| FG004 | 200 mg PTI-125 | Six (6) subjects will receive a single orally administered dose of 200 mg PTI-125 in this cohort. 200 mg PTI-125: PTI-125 200 mg Oral Solution |
| FG005 | 200 mg PTI-125 Placebo | Two (2) subjects will receive a single orally administered dose of 200 mg Placebo PTI-125 in this cohort. 200 mg PTI-125: PTI-125 200 mg Oral Solution |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 50 mg PTI-125 | Six (6) subjects will receive a single orally administered dose of 50 mg PTI-125 in this cohort. 50 mg PTI-125: PTI-125 50 mg Oral Solution |
| BG001 | 50 mg PTI-125 Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Maximum Plasma Concentration (Cmax) | The peak drug concentration will be obtained directly from the data without interpolation. | Separate dose cohorts of 6 active and 2 placebo received 50, 100, or 200 mg. A sentinel dose group of 1 active and 1 placebo preceded each full dose cohort. | Posted | Mean | Standard Deviation | ng/mL | Blood samples will be drawn on Day 1 after dosing at 20, 40, and 60 minutes and at 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours. |
|
7 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 50 mg PTI-125 | Six (6) subjects will receive a single orally administered dose of 50 mg PTI-125 in this cohort. 50 mg PTI-125: PTI-125 50 mg Oral Solution |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| lightheadedness | Nervous system disorders | medDRA | Systematic Assessment | lightheadedness upon standing was resported for a subject in the 100 mg group at 1 h post-dose |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Michael R Marsman, PharmD | Cassava Sciences | 5125822173 | mmarsman@cassavasciences.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP_ICF | Yes | Yes | Yes | Study Protocol, Statistical Analysis Plan, and Informed Consent Form | Jun 15, 2017 | Dec 17, 2018 | Prot_SAP_ICF_000.pdf |
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| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| C000719508 | Simufilam |
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Single center, randomized, double-blind, placebo controlled, SAD study of three escalating doses of PTI-125. A total of 24 healthy subjects enrolled in one of three dose cohorts. Each cohort will contain 8 subjects; six receive PTI-125 and two receive placebo. Three SAD does of PTI-125 oral solution (50, 100 or 200 mg) or placebo solution will be administered.
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Two (2) subjects will receive a single orally administered dose of 200 mg Placebo PTI-125 in this cohort. |
|
| 100 mg PTI-125 |
| Drug |
PTI-125 100 mg Oral Solution |
|
| 200 mg PTI-125 | Drug | PTI-125 200 mg Oral Solution |
|
| Blood samples will be drawn on Day 1 after dosing at 20, 40, and 60 minutes and at 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours. |
| Area Under the Curve (AUC) | The AUC from time zero to the time of the last quantifiable concentration (AUClast) will be calculated. | Blood samples will be drawn on Day 1 after dosing at 20, 40, and 60 minutes and at 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours. |
| Area Under the Curve to Infinity (AUCinf) | The AUC from time zero extrapolated to infinity (AUCinf) will be calculate. | Blood samples will be drawn on Day 1 after dosing at 20, 40, and 60 minutes and at 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours. |
| Percent Extrapolated of Area Under the Curve to Infinity (AUCextrap[%]). | The percentage of AUCinf based on extrapolation (AUCextrap[%]). | Blood samples will be drawn on Day 1 after dosing at 20, 40, and 60 minutes and at 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours. |
| Oral Clearance (Cl/F) | The apparent oral clearance will be calculated. | Blood samples will be drawn on Day 1 after dosing at 20, 40, and 60 minutes and at 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours. |
| Volume of Distribution (Vz/F) | Vz/F, apparent volume of distribution will be calculated. | Blood samples will be drawn on Day 1 after dosing at 20, 40, and 60 minutes and at 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours. |
Two (2) subjects will receive a single orally administered dose of 50 mg Placebo PTI-125 in this cohort.
50 mg PTI-125: PTI-125 50 mg Oral Solution
| BG002 | 100 mg PTI-125 | Six (6) subjects will receive a single orally administered dose of 100 mg PTI-125 in this cohort. 100 mg PTI-125: PTI-125 100 mg Oral Solution |
| BG003 | 100 mg PTI-125 Placebo | Two (2) subjects will receive a single orally administered dose of 100 mg Placebo PTI-125 in this cohort. 100 mg PTI-125: PTI-125 100 mg Oral Solution |
| BG004 | 200 mg PTI-125 | Six (6) subjects will receive a single orally administered dose of 200 mg PTI-125 in this cohort. 200 mg PTI-125: PTI-125 200 mg Oral Solution |
| BG005 | 200 mg PTI-125 Placebo | Two (2) subjects will receive a single orally administered dose of 200 mg Placebo PTI-125 in this cohort. 200 mg PTI-125: PTI-125 200 mg Oral Solution |
| BG006 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Full Range | Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
Two (2) subjects will receive a single orally administered dose of 50 mg Placebo PTI-125 in this cohort.
50 mg PTI-125: PTI-125 50 mg Oral Solution
| OG002 | 100 mg PTI-125 | Six (6) subjects will receive a single orally administered dose of 100 mg PTI-125 in this cohort. 100 mg PTI-125: PTI-125 100 mg Oral Solution |
| OG003 | 100 mg PTI-125 Placebo | Two (2) subjects will receive a single orally administered dose of 100 mg Placebo PTI-125 in this cohort. 100 mg PTI-125: PTI-125 100 mg Oral Solution |
| OG004 | 200 mg PTI-125 | Six (6) subjects will receive a single orally administered dose of 200 mg PTI-125 in this cohort. 200 mg PTI-125: PTI-125 200 mg Oral Solution |
| OG005 | 200 mg PTI-125 Placebo | Two (2) subjects will receive a single orally administered dose of 200 mg Placebo PTI-125 in this cohort. 200 mg PTI-125: PTI-125 200 mg Oral Solution |
|
|
| Primary | Time to Maximum Plasma Concentration (Tmax) (Tmax) | The time to peak drug concentration will be obtained directly from the data without interpolation | Separate dose cohorts of 6 active and 2 placebo received 50, 100, or 200 mg. A sentinel dose group of 1 active and 1 placebo preceded each full dose cohort. | Posted | Mean | Standard Deviation | hours | Blood samples will be drawn on Day 1 after dosing at 20, 40, and 60 minutes and at 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours. |
|
|
|
| Primary | Time to Last Quantifiable Plasma Concentration (Tlast) | The time to the last quantifiable drug concentration will be obtained directly from the data without interpolation. | Separate dose cohorts of 6 active and 2 placebo received 50, 100, or 200 mg. A sentinel dose group of 1 active and 1 placebo preceded each full dose cohort. | Posted | Mean | Standard Deviation | hours | Blood samples will be drawn on Day 1 after dosing at 20, 40, and 60 minutes and at 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours. |
|
|
|
| Primary | Last Quantifiable Plasma Concentration (Clast) | The concentration of the last quantifiable drug will be obtained directly from the data without interpolation concentration | Separate dose cohorts of 6 active and 2 placebo received 50, 100, or 200 mg. A sentinel dose group of 1 active and 1 placebo preceded each full dose cohort. | Posted | Mean | Standard Deviation | ng/mL | Blood samples will be drawn on Day 1 after dosing at 20, 40, and 60 minutes and at 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours. |
|
|
|
| Primary | Elimination Rate Constant (λz) | The elimination rate constant (λz) will be calculated. | Separate dose cohorts of 6 active and 2 placebo received 50, 100, or 200 mg. A sentinel dose group of 1 active and 1 placebo preceded each full dose cohort. | Posted | Mean | Standard Deviation | 1/hour | Blood samples will be drawn on Day 1 after dosing at 20, 40, and 60 minutes and at 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours. |
|
|
|
| Primary | Termination Elimination Half-Life (T1/2) | The terminal elimination half-life (T1/2) will be calculated. | Separate dose cohorts of 6 active and 2 placebo received 50, 100, or 200 mg. A sentinel dose group of 1 active and 1 placebo preceded each full dose cohort. | Posted | Mean | Standard Deviation | hours | Blood samples will be drawn on Day 1 after dosing at 20, 40, and 60 minutes and at 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours. |
|
|
|
| Primary | Area Under the Curve (AUC) | The AUC from time zero to the time of the last quantifiable concentration (AUClast) will be calculated. | Separate dose cohorts of 6 active and 2 placebo received 50, 100, or 200 mg. A sentinel dose group of 1 active and 1 placebo preceded each full dose cohort. | Posted | Mean | Standard Deviation | h*ng/mL | Blood samples will be drawn on Day 1 after dosing at 20, 40, and 60 minutes and at 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours. |
|
|
|
| Primary | Area Under the Curve to Infinity (AUCinf) | The AUC from time zero extrapolated to infinity (AUCinf) will be calculate. | Separate dose cohorts of 6 active and 2 placebo received 50, 100, or 200 mg. A sentinel dose group of 1 active and 1 placebo preceded each full dose cohort. | Posted | Mean | Standard Deviation | h*ng/mL | Blood samples will be drawn on Day 1 after dosing at 20, 40, and 60 minutes and at 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours. |
|
|
|
| Primary | Percent Extrapolated of Area Under the Curve to Infinity (AUCextrap[%]). | The percentage of AUCinf based on extrapolation (AUCextrap[%]). | Separate dose cohorts of 6 active and 2 placebo received 50, 100, or 200 mg. A sentinel dose group of 1 active and 1 placebo preceded each full dose cohort. | Posted | Mean | Standard Deviation | percent extrapolated | Blood samples will be drawn on Day 1 after dosing at 20, 40, and 60 minutes and at 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours. |
|
|
|
| Primary | Oral Clearance (Cl/F) | The apparent oral clearance will be calculated. | Separate dose cohorts of 6 active and 2 placebo received 50, 100, or 200 mg. A sentinel dose group of 1 active and 1 placebo preceded each full dose cohort. | Posted | Mean | Standard Deviation | (L/h) | Blood samples will be drawn on Day 1 after dosing at 20, 40, and 60 minutes and at 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours. |
|
|
|
| Primary | Volume of Distribution (Vz/F) | Vz/F, apparent volume of distribution will be calculated. | Separate dose cohorts of 6 active and 2 placebo received 50, 100, or 200 mg. A sentinel dose group of 1 active and 1 placebo preceded each full dose cohort. | Posted | Mean | Standard Deviation | (L) | Blood samples will be drawn on Day 1 after dosing at 20, 40, and 60 minutes and at 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours. |
|
|
|
| 0 |
| 6 |
| 0 |
| 6 |
| 0 |
| 6 |
| EG001 | 50 mg PTI-125 Placebo | Two (2) subjects will receive a single orally administered dose of 50 mg Placebo PTI-125 in this cohort. 50 mg PTI-125: PTI-125 50 mg Oral Solution | 0 | 2 | 0 | 2 | 0 | 2 |
| EG002 | 100 mg PTI-125 | Six (6) subjects will receive a single orally administered dose of 100 mg PTI-125 in this cohort. 100 mg PTI-125: PTI-125 100 mg Oral Solution | 0 | 6 | 0 | 6 | 1 | 6 |
| EG003 | 100 mg PTI-125 Placebo | Two (2) subjects will receive a single orally administered dose of 100 mg Placebo PTI-125 in this cohort. 100 mg PTI-125: PTI-125 100 mg Oral Solution | 0 | 2 | 0 | 2 | 0 | 2 |
| EG004 | 200 mg PTI-125 | Six (6) subjects will receive a single orally administered dose of 200 mg PTI-125 in this cohort. 200 mg PTI-125: PTI-125 200 mg Oral Solution | 0 | 6 | 0 | 6 | 1 | 6 |
| EG005 | 200 mg PTI-125 Placebo | Two (2) subjects will receive a single orally administered dose of 200 mg Placebo PTI-125 in this cohort. 200 mg PTI-125: PTI-125 200 mg Oral Solution | 0 | 2 | 0 | 2 | 0 | 2 |
|
| transient musculoskeletal wall pain | Musculoskeletal and connective tissue disorders | medDRA | Systematic Assessment | One subject in the 200 mg group reported transient musculoskeletal wall pain |
|
| Acne | Skin and subcutaneous tissue disorders | medDRA | Systematic Assessment | The same subject in the 200 mg group who reported transient musculoskeletal wall pain, also reported acne |
|
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| D024801 |
| Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |