A Safety Study of PTI-125 in Healthy Volunteers

NCT03784300 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: PTI-125-011R44AG056166
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

A Phase I, Single Center, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose, Pharmacokinetic and Safety Study of PTl-125 in Healthy Volunteers

Conditions

Alzheimer Disease, Early Onset; Alzheimer Disease

Outcome Measures

Primary Outcomes (11)

• 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.

  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.

Study Arms (6)

50 mg PTI-125

ACTIVE COMPARATOR

Six (6) subjects will receive a single orally administered dose of 50 mg PTI-125 in this cohort.

Drug: 50 mg PTI-125

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.

Drug: 50 mg PTI-125

100 mg PTI-125

ACTIVE COMPARATOR

Six (6) subjects will receive a single orally administered dose of 100 mg PTI-125 in this cohort.

Drug: 100 mg PTI-125

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.

Drug: 100 mg PTI-125

200 mg PTI-125

ACTIVE COMPARATOR

Six (6) subjects will receive a single orally administered dose of 200 mg PTI-125 in this cohort.

Drug: 200 mg PTI-125

200 mg PTI-125 Placebo

PLACEBO COMPARATOR

Two (2) subjects will receive a single orally administered dose of 200 mg Placebo PTI-125 in this cohort.

Drug: 200 mg PTI-125

Interventions

50 mg PTI-125 DRUG

PTI-125 50 mg Oral Solution

50 mg PTI-125; 50 mg PTI-125 Placebo

100 mg PTI-125 DRUG

PTI-125 100 mg Oral Solution

100 mg PTI-125; 100 mg PTI-125 Placebo

200 mg PTI-125 DRUG

PTI-125 200 mg Oral Solution

200 mg PTI-125; 200 mg PTI-125 Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female subjects between 18 and 45 years of age, inclusive.
• The subject has a body mass index (BMI) within 18-30 kg/m2 (inclusive).
• The subject is in good health as determined by medical history and physical examination and clinical laboratory parameters.
• The subject is willing and able to speak, read, and understand English and provide written informed consent.
• The subject is a non-smoker for at least 12 months. If a former smoker, the reason for stopping must be evaluated.
• Females who are physically incapable of childbearing defined as postmenopausal, or surgically sterile (hysterectomy, bilateral tubal ligation, bilateral oophorectomy or an Essure procedure). Appropriate documentation (ex; medical record) of the surgical sterilization procedure to be obtained and held within the subject's study file.
• The subject must agree to comply with the drawing of blood samples for the 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 confinement period and return for the outpatient visit.

You may not qualify if:

• 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 Check-in.
• The subject has a history of significant neurological, hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, or metabolic disease.
• The subject has used any prescription medication within 14 days of dosing or overthe- counter (OTC) medication within 48 h of dosing or intends to use any prescription medication or OTC medication during the study that may interfere with the evaluation of study medication.
• The subject has used alcohol, caffeine or xanthine-containing products 48 h before dosing or intends to use any of these products during the study.
• The subject has used grapefruit, grapefruit juice, or grapefruit-containing products days before dosing or intends to use any of these products during the study.
• The subject has a history of substance abuse or a positive ethanol breath test, urine cotinine, or urine drug screen at screening or at check-in. The subject has a positive serum hepatitis B surface antigen or positive HCV antibody test at the Screening Visit.
• The subject has a positive HIV test at the Screening Visit.
• Female subject is pregnant or breastfeeding.
• The subject has received an investigational drug within 30 days of Check-in.
• The subject has donated or lost a significant volume of blood (\>450 mL) within 4 weeks prior to 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.
• The subject has an AST/ALT or total bilirubin greater than the ULN. One repeat test will be allowed.

Sponsors & Collaborators

• Pain Therapeutics: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Worldwide Clinical Trials

San Antonio, Texas, 78217, United States

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Simufilam

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: Michael R Marsman, PharmD
• Organization: Cassava Sciences

mmarsman@cassavasciences.com

5125822173

Study Officials

• George J Atiee, MD

  Worldwide Clinical Trials

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: December 18, 2018
• First Posted: December 21, 2018
• Study Start: August 18, 2017
• Primary Completion: October 9, 2017
• Study Completion: March 27, 2018
• Last Updated: May 10, 2021
• Results First Posted: May 10, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)