Clinical trial NCT05547503: Phase I Single Ascending Dose and Multiple Ascending Doses of Oral AFA-281 in Healthy Volunteers
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Pain, Neuropathic
Pain, Inflammatory
Lead sponsor: Afasci Inc
Sponsor class: INDUSTRY
Collaborators: name: Cognitive Research Corporation
First posted: 2022-09-21
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Part 1: Single escalation dose Part 2: Multiple escalation doses for 14 days
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Treatment-Related Adverse Events
timeFrame: Predose and Up to 72 hours after dose
measure: Heart rate
timeFrame: Predose and Up to 72 hours after dose
measure: Body temperature
timeFrame: Predose and Up to 72 hours after dose
measure: Blood Pressure
timeFrame: Predose and Up to 72 hours after dose
measure: Electrocardiogram (ECG)
timeFrame: Pre-dose and up to 72 hours after dose
measure: Blood chemistry
timeFrame: Pre-dose and up to 72 hours after dose
measure: Hematology
timeFrame: Pre-dose and up to 72 hours after dose
measure: Coagulation
timeFrame: Pre-dose and up to 72 hours after dose
measure: Urinalysis
timeFrame: Pre-dose and up to 72 hours after dose
measure: Blood maximum plasma concentration (Cmax) of the study drug
timeFrame: Pre-dose and up to 72 hours after dose
measure: Blood study drug half-life (t1/2)
timeFrame: Pre-dose and up to 72 hours after dose
measure: Area under the plasma concentration versus time curve (AUC) of the study drug
timeFrame: Pre-dose and up to 72 hours after dose
Secondary outcomes:
measure: A dose and exposure relationship
timeFrame: Pre-dose and up to 72 hours after dose
measure: Tmax of the study drug (parent compound) in blood
timeFrame: Up to 72 hours after dose
measure: Plasma Concentration (Cmax) of the major metabolite in blood
timeFrame: Up to 72 hours after dose
measure: Area under the plasma concentration versus time curve (AUC) of the major metabolite in blood
timeFrame: Up to 72 hours after dose
measure: The major metabolite half-life (t1/2) in blood
timeFrame: Up to 72 hours after dose
Other outcomes:
Locations:
city: Los Alamitos
country: United States
facility: CenExcel CNS
state: California
Study officials:
affiliation: Afasci Inc
name: Xinmin Xie, MD, PhD
role: STUDY_CHAIR
References: