A Safety, Tolerability, and Pharmacokinetics Study of AP303 in Healthy Subjects

Study Overview
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Brief Summary
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This is a single-center, randomized, double-blind, placebo-controlled, first-in-human study in which the safety, tolerability, and pharmacokinetics of orally administered AP303 will be assessed in healthy adult subjects.

Detailed Description
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The study will consist of 2 parts: Part A is a single ascending doses (SAD) phase enrolling a total of 4 cohorts of healthy subjects; Part B is a multiple ascending doses (MAD) phase enrolling 3 cohorts of healthy subjects. One cohort of Part A will receive AP303 under both fasted and fed conditions to investigate the effect of food.

Official Title
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A Single-center Randomized Double-blind Placebo-controlled Study to Investigate the Safety Tolerability and PK of SAD and MAD of AP303 Following Oral Administration and the Effect of Food on the PK of AP303 in Healthy Subjects

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: AP303 50 μg
* Drug: AP303 150 μg
* Drug: AP303 300 μg
* Drug: AP303 600 μg
* Drug: Placebo 50 μg
* Drug: Placebo 150 μg
* Drug: Placebo 300 μg
* Drug: Placebo 600 μg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female subjects, 18 to 55 years of age, inclusive. Body Mas index(BMI) between 18 to 32 kg/m2 inclusive. Female subjects of child-bearing potential must have a negative pregnancy test result and agree to use highly effective contraception consisting of two forms of birth control Subjects and their partners of childbearing potential must use two medically approved methods of contraception and the subjects should refrain from sperm/egg donation for the duration of the study and for 3 months after drug administration Exclusion Criteria: Pregnant (positive pregnancy test) or lactating women, and male subjects with partners who are or plan to be pregnant or lactating. History or symptoms of any clinically significant gastrointestinal, renal, hepatic, broncho-pulmonary, neurological, psychiatric, cardio-vascular, endocrinological, ophthalmologic, hematological or allergic disease, metabolic disorder, cancer or cirrhosis. People with a history of specific allergies, or allergic conditions or known allergies to any ingredient of the investigational medicinal product (IMP). History of having received or currently receiving any systemic anti-neoplastic or immune-modulatory treatment ≤ 6 months prior to the first dose of study drug or the expectation that such treatment will be needed at any time during the study. Positive test at screening of any of the following: Hepatitis B (HBsAg), Hepatitis C (HCVAb) or human immunodeficiency virus (HIV Ab). Received an investigational drug within 30 days or 5 xT1/2 whichever is longer prior to the first dose of our study for small molecule; or within 90 days or 5 x T1/2 whichever is longer prior to the first dose of our study drug; or device study within 90 days prior to screening or more than 4 times per year. History of drug and/or alcohol abuse or addiction. Use of >5 cigarettes or equivalent nicotine-containing product per day.

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AP303<br>AP303 | Drug: AP303 50 μg<br>* AP303 tablet<br>Drug: AP303 150 μg<br>* AP303 tablet<br>Drug: AP303 300 μg<br>* AP303 tablet<br>Drug: AP303 600 μg<br>* AP303 tablet<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo 50 μg<br>* Placebo tablet<br>Drug: Placebo 150 μg<br>* Placebo tablet<br>Drug: Placebo 300 μg<br>* Placebo tablet<br>Drug: Placebo 600 μg<br>* Placebo tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Single Dose and Food Effect Safety Outcome Measures | Incidence and severity of adverse events (AEs), laboratory, ECG, and vital sign changes | From baseline to Day 14 (Day 29 for Food Effect) | 
| Multiple Dose Safety Outcome Measures | Incidence and severity of AEs, laboratory, ECG, and vital sign changes. | From baseline to Day 28 | 
| Cmax after single dose | PK characteristics after single dose | Pre-dose to 96 hours post-dose | 
| Tmax after single dose | PK characteristics after single dose | Pre-dose to 96 hours post-dose | 
| AUC0-last after single dose | PK characteristics after single dose | Pre-dose to 96 hours post-dose | 
| AUC0-inf after single dose | PK characteristics after single dose | Pre-dose to 96 hours post-dose | 
| t1/2 after single dose | PK characteristics after single dose | Pre-dose to 96 hours post-dose | 
| CL/F after single dose | PK characteristics after single dose | Pre-dose to 96 hours post-dose | 
| Ae and CLR (if warranted) after single dose | PK characteristics after single dose | Pre-dose to 96 hours post-dose | 
| V/F after single dose | PK characteristics after single dose | Pre-dose to 96 hours post-dose | 
| Cmax after multiple dose | PK characteristics after multiple dose | Pre-dose to 12 hours post dose on Day 1; pre-dose to 96 hours post-dose on Day 14 | 
| Tmax after multiple dose | PK characteristics after multiple dose | Pre-dose to 12 hours post dose on Day 1; pre-dose to 96 hours post-dose on Day 14 | 
| AUC0-τ after multiple dose | PK characteristics after multiple dose | Pre-dose to 12 hours post dose on Day 1; pre-dose to 96 hours post-dose on Day 14 | 
| Cav after multiple dose | PK characteristics after multiple dose | Pre-dose to 12 hours post dose on Day 1; pre-dose to 96 hours post-dose on Day 14 | 
| t1/2 after multiple dose | PK characteristics after multiple dose | Pre-dose to 12 hours post dose on Day 1; pre-dose to 96 hours post-dose on Day 14 | 
| Rac after multiple dose | PK characteristics after multiple dose | Pre-dose to 12 hours post dose on Day 1; pre-dose to 96 hours post-dose on Day 14 | 
| Ae and CLR (if warranted) after multiple dose | PK characteristics after multiple dose | Pre-dose to 12 hours post dose on Day 1; pre-dose to 96 hours post-dose on Day 14 | 
| V/F after multiple dose | PK characteristics after multiple dose | Pre-dose to 12 hours post dose on Day 1; pre-dose to 96 hours post-dose on Day 14 | 
| Ctrough after multiple dose | PK characteristics after multiple dose | Pre-dose on Days 2, 3, 4, 5, 7, 12, and 13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of Food on the single dose Cmax | Effect of food on the single dose PK | Pre-dose to 96 hours post-dose | 
| Effect of Food on the single dose Tmax | Effect of food on the single dose PK | Pre-dose to 96 hours post-dose | 
| Effect of Food on the single dose AUC0-last | Effect of food on the single dose PK | Pre-dose to 96 hours post-dose | 
| Effect of Food on the single dose AUC0-inf | Effect of food on the single dose PK | Pre-dose to 96 hours post-dose | 
| Effect of Food on the single dose t1/2 | Effect of food on the single dose PK | Pre-dose to 96 hours post-dose | 
| Effect of Food on the single dose CL/F | Effect of food on the single dose PK | Pre-dose to 96 hours post-dose | 
| Effect of Food on the single dose Ae and CLR (if warranted) | Effect of food on the single dose PK | Pre-dose to 96 hours post-dose | 
| Effect of Food on the single dose V/F | Effect of food on the single dose PK | Pre-dose to 96 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, Tolerability, Pharmacokinetics, AP303, Healthy Subjects