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

Pain, Neuropathic Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05547503
• Other study ID #: AFA-281-001
• Status: Recruiting
• Phase: Phase 1
• Start date: April 11, 2023
• Est. completion date: September 30, 2024

Study information

• Verified date: August 2023
• Source: Afasci Inc
• Contact: Dennis Gilman, PhD
• Phone: 7752250561
• Email: dpgilman[@]clindm-llc.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Phase I Part 1 (single ascending dose):

Double-blind dosing will occur in healthy volunteers in 5 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 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 of AFA-281 and the pharmacokinetic profile of AFA-281.

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. Five subjects per cohort will receive AFA-281 at either 20, 40, 80, 160 or 300 mg and 3 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 twice daily for 14 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 of AFA-281 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 64
• Est. completion date: September 30, 2024
• Est. primary completion date: August 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Neuralgia
• Pain, Inflammatory
• Pain, Neuropathic

Intervention

Drug:
• AFA-281
Part 1: AFA-281 will be administered as a single dose at 5 dose levels (TBD) Part 2: AFA-281 will be administered twice daily for 14 days at 3 dose levels (TBD)

Locations

Country	Name	City	State
United States	CenExcel CNS	Los Alamitos	California

Sponsors (1)

Lead Sponsor	Collaborator
Afasci Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Heart rate	Heart rate as one of vital signs will be measured	Predose and Up to 72 hours after dose
Primary	Body temperature	Body temperature (0C) as one of vital signs will be measured	Predose and Up to 72 hours after dose
Primary	Blood Pressure	Blood pressure as one of vital signs will be measured	Predose and Up to 72 hours after dose
Primary	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
Primary	Blood chemistry	Blood chemistry parameters will be measured	Pre-dose and up to 72 hours after dose
Primary	Hematology	Hematology parameters will be measured	Pre-dose and up to 72 hours after dose
Primary	Coagulation	Coagulation parameters (PT/INR, PTT) will be measured	Pre-dose and up to 72 hours after dose
Primary	Urinalysis	Urinalysis parameters will be measured using dipstick and microscopic examination.	Pre-dose and up to 72 hours after dose
Primary	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
Primary	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
Primary	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
Secondary	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
Secondary	Tmax of the major metabolite in blood	Pharmacokinetics parameter Time at which Cmax of a major metabolite appeared will be determined.	Up to 72 hours after dose
Secondary	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
Secondary	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
Secondary	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