A Formulation Bridging and Food Effect Study of PBI-200 in Healthy Volunteers

Study Overview
=================
Brief Summary
-----------------
This is a single-dose, two-part, crossover formulation bridging and food effect study to assess the effect of formulation and food on the absorption and bioavailability of PBI-200 in normal, healthy volunteers.

Detailed Description
-----------------
This is a single-dose, two-part crossover formulation bridging (Part A) and tablet food effect (Part B) study in normal, healthy volunteers. Part A will be conducted to evaluate the pharmacokinetics (PK) and relative bioavailability of 3 formulations of PBI-200; each volunteer will serve as their own control. In Part B, PBI-200 tablets will be dosed under fasting and fed (low-fat and high-fat meals) conditions to evaluate the effect of food on the PK of PBI-200.

Official Title
-----------------
A Single-Dose, Open-Label, Two-Part, Randomized, Crossover Formulation Bridging and Food Effect Study to Assess the Effect of Formulation and Food on the Absorption and Bioavailability of PBI-200 in Normal Healthy Volunteers

Conditions
-----------------
Formulation Bridging, Food Effect

Intervention / Treatment
-----------------
* Drug: PBI-200 Tablet
* Drug: PBI-200 Capsule
* Drug: PBI-200 Suspension


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or non-pregnant, non-lactating female between 18 and 55 years of age (inclusive). Body Mass Index (BMI) between 18.0 and 32.0 kg/m² (inclusive). Non-smoking/non-vaping, healthy, with no history of clinically relevant medical illness. Exclusion Criteria: History or presence of clinically significant cardiovascular, pulmonary, respiratory, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease which, in the opinion of the Investigator, would jeopardize the safety of the volunteer or impact the validity of the study results. History of gastrointestinal/hepatobiliary or other surgery that may affect PK profiles (i.e., hepatectomy, gastric, bypass, or digestive organ resection). Intolerance to repeated venipuncture. Smoking or use of tobacco products (including vaping) within 3 months prior to the first study drug administration. Have a positive drug/alcohol screen, or history or presence of alcoholism or drug abuse within 6 months of first study drug administration. Volunteers with a corrected QT using Fridericia's formula (QTcF) prolongation over 450 milliseconds at Screening.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Single-dose, open-label, randomized, three-way crossover design
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Capsule<br>Study drug will be administered with water after an overnight fast. | Drug: PBI-200 Capsule<br>* Single dose of PBI-200 capsule<br>|
| Experimental: Tablet<br>Study drug will be administered with water after an overnight fast. | Drug: PBI-200 Tablet<br>* Single dose of PBI-200 tablet<br>|
| Experimental: Suspension<br>Study drug will be administered with water after an overnight fast. | Drug: PBI-200 Suspension<br>* Single dose of PBI-200 suspension<br>|
| Experimental: Fasted<br>Study drug will be administered with water after an overnight fast. | Drug: PBI-200 Tablet<br>* Single dose of PBI-200 tablet<br>|
| Experimental: Low-fat Meal<br>Study drug will be administered with water after an overnight fast, after which time a standard low-fat breakfast will be given. | Drug: PBI-200 Tablet<br>* Single dose of PBI-200 tablet<br>|
| Experimental: High-fat Meal<br>Study drug will be administered with water after an overnight fast, after which time a standard high-fat breakfast will be given. | Drug: PBI-200 Tablet<br>* Single dose of PBI-200 tablet<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration [C(max)] of PBI-200 | Maximum (peak) plasma drug concentration | 8 days | 
| Area Under the Concentration-Time Curve (AUC) of PBI-200 from time zero to the time of th last measurable concentration [AUC(0-t)] | AUC, calculated using linear up / log down trapezoidal method from time zero to time t, where t is the time of the last measurable concentration. | 8 days | 
| AUC of PBI-200 from time zero to infinity [AUC(0-inf)] | AUC from time zero to infinity, AUC(0-inf) = AUC(0-t) + Ct/kel, where kel is the terminal rate constant and Ct is the last measurable concentration. | 8 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Maximum Concentration [T(max)] of PBI-200 | T(max) will be determined from the observed plasma concentration data | 8 days | 
| Terminal elimination half-life [T(1/2)] | Apparent terminal elimination half-life, calculated as ln(2)/kel | 8 days | 
| Incidence, frequency and severity of adverse events (AEs) |  | 14 days |