Phase I Single Ascending Dose and Multiple Ascending Doses of Oral AFA-281 in Healthy Volunteers

A Double-blind, Placebo-controlled, Study of the Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses of Oral AFA-281 (Phase I Part 1) and Multiple Ascending Doses of Oral AFA-281 (Phase I Part 2) in Healthy Volunteers

Phase I Part 1 (single ascending dose):

Double-blind dosing will occur in healthy volunteers in 4 cohorts of 8 subjects each. Six subjects in each cohort will be randomized to receive AFA-281 and 2 subjects will be randomized to receive the matching placebo. At the end of the Part 1 study is to evaluate the safety and tolerability of AFA-281. Following completion of each cohort, bioanalytical analyses will be conducted to evaluate the pharmacokinetic profile.

Phase I Part 2 (multiple dose for 14 days):

Pending the results from Part 1, healthy volunteers will be administered AFA-281 for 14 to 21 consecutive days in 3 cohorts. At scheduled intervals after dosing, and at the end of the cohort's study period to evaluate the safety and tolerability and the pharmacokinetic profile of AFA-281.

Study Overview

• Status: Completed
• Conditions: Pain, Neuropathic; Pain, Inflammatory
• Intervention / Treatment: Drug: AFA-281

Detailed Description

Phase I Part 1 (single ascending dose):

Healthy volunteers will be admitted to the clinical research unit on Day -1. There will be five cohorts with 8 subjects per cohort. Six subjects per cohort will receive AFA-281 at one of 4 doses and 2 will receive placebo. Oral capsules will be administered on the morning of Day 1, following a 10-hour fast. Blood draws for assessment of Pharmacokinetic parameters will occur 0.2-1 hr pre-dose and at 0.5-, 1-, 2-, 3-, 4-, 8-, 10, 12-, 16-, 24-, 36-, 48-hr, and up to 72-hr post-dose. Vital signs will be collected at scheduled times following dosing. A 12-lead ECG will be obtained pre-dose and scheduled at 2, 4, 8, 24 hr, and 3- or 4 days post- dose. Various clinical laboratory tests will be drawn on Day -1, within 1 hr prior to dosing, and at scheduled timepoints after dosing while the volunteer is housed in the research center. Subjects of Cohorts 1 - 3 will be released following completion of blood draws and safety assessments up to 48 hours and Cohorts 4 and 5 subjects will return for 72-hour blood draws and Day 4 ECG and safety assessment.

Phase I Part 2 (multiple ascending doses - 14 days):

After assessment of the safety data from the single dose Phase I Part 1, healthy volunteers will be randomized into 3 cohorts with 8 subjects per cohort. Five subjects per cohort will receive AFA-281 and 3 will receive placebo. Oral capsules will be administered in dose titration and split daily dose in fours time daily (QID) for 14 - 21 consecutive days. Routine clinical monitoring will occur as in Part 1. Baseline physical examination, vital signs, clinical lab tests, and ECGs will be performed prior to dosing, at scheduled intervals after dosing, and at the end of the cohort's study period to evaluate the safety and tolerability, and the pharmacokinetic profile of AFA-281. Reports of potential adverse events will be elicited, and vital signs and 12-lead ECG will be measured in a similar manner to Part 1. Similarly, clinical laboratory tests will be drawn prior to and after dosing.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Alamitos, California, United States, 90720
      • CenExcel CNS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Participants must be in good general health with no significant medical history and have no clinically significant abnormalities on physical examination at screening and/or before administration of the initial dose of study drug.

  • Participants must have a Body Mass Index (BMI) between 18.0 and 30.0 kg/m2 inclusive.
  • Participants must have clinical laboratory values within normal range as specified by the testing laboratory, unless deemed not clinically significant by the Investigator or delegate.
  • Participants must have an ECG without clinically significant pathologic abnormalities.

Exclusion Criteria:

• Participants with significant medical history or clinically significant abnormalities
• Participants with clinically significantly pathologic abnormalities
• Participants with ECG abnormalities

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Control; Double blind placebo control	Drug: AFA-281; Part 1: AFA-281 will be administered as a single dose at 4 dose levels (TBD) Part 2: AFA-281 will be administered twice daily for 14 - 21 days at 3 dose levels (TBD)
Experimental: AFA-281; Part 1: AFA-281 administered as an oral capsule at 5 dose levels for one day. Part 2: AFA-281 administered as an oral capsule at 3 dose levels twice daily for 14 consecutive days. Doses will be determined after completion of Part 1.	Drug: AFA-281; Part 1: AFA-281 will be administered as a single dose at 4 dose levels (TBD) Part 2: AFA-281 will be administered twice daily for 14 - 21 days at 3 dose levels (TBD)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart rate	Heart rate as one of vital signs will be measured	Predose and Up to 72 hours after dose
Body temperature	Body temperature (0C) as one of vital signs will be measured	Predose and Up to 72 hours after dose
Blood Pressure	Blood pressure as one of vital signs will be measured	Predose and Up to 72 hours after dose
Electrocardiogram (ECG)	Triplicate 12-lead ECG will be measured to evaluate electrical activity of the heart	Pre-dose and up to 72 hours after dose
Blood chemistry	Blood chemistry parameters will be measured	Pre-dose and up to 72 hours after dose
Hematology	Hematology parameters will be measured	Pre-dose and up to 72 hours after dose
Coagulation	Coagulation parameters (PT/INR, PTT) will be measured	Pre-dose and up to 72 hours after dose
Urinalysis	Urinalysis parameters will be measured using dipstick and microscopic examination.	Pre-dose and up to 72 hours after dose
Blood maximum plasma concentration (Cmax) of the study drug	Pharmacokinetics parameter Cmax will be measured to assess drug exposure levels in blood	Pre-dose and up to 72 hours after dose
Blood study drug half-life (t1/2)	Pharmacokinetics parameter t1/2 will be measured to evaluate drug half-life in the blood	Pre-dose and up to 72 hours after dose
Area under the plasma concentration versus time curve (AUC) of the study drug	Pharmacokinetics parameter AUC will be measured	Pre-dose and up to 72 hours after dose
Treatment-Related Adverse Events	Number of participants with treatment-related adverse events will be assessed using CTCAE v5.0	Predose and Up to 72 hours after dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
A dose and exposure relationship	Doses of study drug and blood exposure levels will be analyzed to determine dose proportionality.	Pre-dose and up to 72 hours after dose
Plasma Concentration (Cmax) of the major metabolite in blood	Pharmacokinetics parameter Cmax of a major metabolite will be measured.	Up to 72 hours after dose
Area under the plasma concentration versus time curve (AUC) of the major metabolite in blood	Pharmacokinetics parameter AUC of a major metabolite will be measured.	Up to 72 hours after dose
Tmax of the study drug (parent compound) in blood	Pharmacokinetics parameter Time at which Cmax of the study drug appeared will be determined.	Up to 72 hours after dose
The major metabolite half-life (t1/2) in blood	Pharmacokinetics parameter t1/2 of a major metabolite will be measured.	Up to 72 hours after dose

Collaborators and Investigators

• Sponsor: Afasci Inc
• Collaborators: Cognitive Research Corporation
• Investigators: Study Chair: Xinmin Xie, MD, PhD, Afasci Inc

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2023
• Primary Completion (Actual): December 4, 2024
• Study Completion (Actual): May 14, 2025

Study Registration Dates

• First Submitted: September 14, 2022
• First Submitted That Met QC Criteria: September 16, 2022
• First Posted (Actual): September 21, 2022

Study Record Updates

• Last Update Posted (Estimated): October 21, 2025
• Last Update Submitted That Met QC Criteria: October 18, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain; Neuralgia
• Other Study ID Numbers: AFA-281-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: One year after completion of the study and 6 months after publication
• IPD Sharing Time Frame: One year after completion of the study and 6 months after publication
• IPD Sharing Access Criteria: To be added
• IPD Sharing Supporting Information Type: SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No