Safety, Tolerability, PK and PD of SAD or MAD of APX-115 in Healthy Male Volunteers

Study Overview
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Brief Summary
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This study aims to evaluate the safety, tolerabilty, pharmacokinetics and pharmacodynamics of single ascending doses and multiple ascending doses of APX-115 in healthy males. This study also aims to evaluate the effect of food consumption on the pharmacokinetics of APX-115 and potential interaction between caffeine and APX-115 in healthy males.

Official Title
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Double Blind, Randomized Study Assessing the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Ascending Doses or Multiple Ascending Doses of APX-115 in Healthy Male Volunteers.

Conditions
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Safety, Healthy

Intervention / Treatment
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* Drug: SAD: APX-115
* Drug: SAD: Placebo
* Drug: MAD: APX-115
* Drug: MAD: Placebo
* Other: Food effect: fasted and fed
* Other: Metabolic probe with or without APX-115


Participation Criteria
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Eligibility Criteria
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Inclusion: Healthy male subject, aged between 18 and 45 years inclusive Certified as healthy by a comprehensive clinical assessment Normal dietary habits Normal ECG recording on a 12-lead ECG Signing a written informed consent prior to selection Exclusion: Any history or presence of cardiovascular, pulmonary, gastro-intestinal, hepatic, renal, metabolic, haematological, neurologic, psychiatric, systemic, infectious or ocular disease Frequent headaches and / or migraine, recurrent nausea and / or vomiting Symptomatic hypotension whatever the decrease of blood pressure or asymptomatic postural hypotension defined by a decrease in SBP or DBP equal to or greater than 20 mmHg within two minutes when changing from the supine to the standing position Blood donation (including in the frame of a clinical trial) within 2 months before administration General anaesthesia within 3 months before administration Presence or history of drug hypersensitivity, or allergic disease diagnosed and treated by a physician Inability to abstain from intensive muscular effort No possibility of contact in case of emergency Any drug intake (except paracetamol or contraception) during the last month prior to the first administration History or presence of drug or alcohol abuse (alcohol consumption > 30 grams / day) Excessive consumption of beverages with xanthine bases (> 4 cups or glasses / day) Positive Hepatitis B surface (HBs) antigen or anti Hepatitis C Virus (HCV) antibody, or positive results for Human Immunodeficiency Virus (HIV) 1 or 2 tests Positive results of screening for drugs of abuse Subject who, in the judgment of the Investigator, is likely to be non-compliant or uncooperative during the study, or unable to cooperate because of a language problem, poor mental development Administrative or legal supervision

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

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: Parallel Assignment
Interventional Model Description: Parallel design for SAD and MAD studies Crossover design for Food and Drug interaction studies
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SAD: APX-115<br>Experimental: APX-115 SAD group | Drug: SAD: APX-115<br>* Drug: APX-115 SAD APX-115 SAD for 1day<br>|
| Placebo Comparator: SAD: Placebo<br>Experimental: Placebo group | Drug: SAD: Placebo<br>* Drug: Placebo Placebo for 1day<br>|
| Experimental: MAD: APX-115<br>Experimental: APX-115 MAD group | Drug: MAD: APX-115<br>* Drug: APX-115 MAD APX-115 MAD repeatedly administered.<br>|
| Placebo Comparator: MAD: Placebo<br>Experimental: Placebo group | Drug: MAD: Placebo<br>* Matching study drug will be repeatedly administered.<br>|
| Active Comparator: Food effect - Fasting condition<br>Experimental: APX-115 under fasting condition | Other: Food effect: fasted and fed<br>* A single dose of APX-115, selected from the SAD study, will be administered under fasted and fed condition.<br>|
| Active Comparator: Food effect - fed condition<br>Experimental: APX-115 under fed condition | Other: Food effect: fasted and fed<br>* A single dose of APX-115, selected from the SAD study, will be administered under fasted and fed condition.<br>|
| Placebo Comparator: Drug Interaction - metabolic probe<br>Experimental: metabolic probe | Other: Metabolic probe with or without APX-115<br>* A metabolic probe will be administered with and without APX-115.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SAD: incidence of treatment emergent adverse events |  | Up to Day 8 | 
| SAD: number of clinically significant abnormal findings from vital signs (blood pressure, pulse) |  | Up to Day 8 | 
| SAD: number of clinically significant abnormal findings from physical exam |  | Up to Day 8 | 
| SAD: number of clinically significant abnormal findings from electrocardiogram |  | Up to Day 8 | 
| SAD: number of clinically significant abnormal findings from biological tests |  | Up to Day 8 | 
| MAD: incidence of treatment emergent adverse events |  | Up to Day 17 | 
| MAD: number of clinically significant abnormal findings from vital signs (blood pressure, pulse) |  | Up to Day 17 | 
| MAD: number of clinically significant abnormal findings from physical exams |  | Up to Day 17 | 
| MAD: number of clinically significant abnormal findings from electrocardiogram |  | Up to Day 17 | 
| Food effect: peak serum concentration (Cmax) of APX-115 under fasting and fed conditions |  | Up to Day 4 post-dose | 
| Food effect: time to reach the Cmax (Tmax) of APX-115 under fasting and fed conditions |  | Up to Day 4 post-dose | 
| Food effect: area under the curve (AUC) of APX-115 under fasting and fed conditions |  | Up to Day 4 post-dose | 
| Food effect: elimination rate constant (Kel) of APX-115 under fasting and fed conditions |  | Up to Day 4 post-dose | 
| Food effect: ratio AUCfed/AUCfasted |  | Up to Day 4 post-dose | 
| Drug interaction: peak serum concentration (Cmax) of a metabolic probe or APX-115 |  | Up to Day 4 post-dose | 
| Drug interaction: Time to reach the Cmax (tmax) of a metabolic probe or APX-115 |  | Up to Day 4 post-dose | 
| Drug interaction study: Area under the Curve (AUC) of a metabolic probe or APX-115 |  | Up to Day 4 post-dose | 
| Drug interaction: elimination rate constant (Kel) of a metabolic probe or APX-115 |  | Up to Day 4 post-dose | 
| Drug interaction: half-life (t1/2) of a metabolic probe or APX-115 |  | Up to Day 4 post-dose | 
| Drug interaction: volume of distribution (Vd/f) of a metabolic probe or APX-115 |  | Up to Day 4 post-dose | 
| Drug interaction: clearance of a metabolic probe or APX-115 |  | Up to Day 4 post-dose | 
| Drug interaction: Incidences of treatment emergent adverse events |  | Up to Day 4 post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SAD: time to reach Cmax (Tmax) of APX-115 |  | Up to Day 5 | 
| SAD: peak serum concentration (Cmax) of APX-115 |  | Up to Day 5 | 
| SAD: lowest plasma concentration before next dosing (Ctrough) |  | Up to Day 5 | 
| SAD: Area Under the Curve (AUC) of APX-115 |  | Up to Day 5 | 
| SAD: volume of distribution (Vd/F) of APX-115 |  | Up to Day 5 | 
| SAD: clearance (CL/F) of APX-115 |  | Up to Day 5 | 
| MAD: peak serum concentration (Cmax) of APX-115 |  | Up to Day 11 | 
| MAD: time to reach the Cmax (Tmax) of APX-115 |  | Up to Day 11 | 
| MAD: Area Under the Curve (AUC) of APX-115 |  | Up to Day 11 | 
| MAD: lowest plasma concentration of APX-115 before next dosing (Ctrough) |  | Up to Day 11 | 
| MAD: volume of distribution (Vd/F) of APX-115 |  | Up to Day 11 | 
| MAD: Clearance (CL/F) of APX-115 |  | Up to Day 11 | 
| MAD: accumulation ratio |  | Up to Day 11 | 
| Food effect & drug interaction: incidence of treatment emergent adverse events |  | Up to Day 4 post-dose | 
| Food effect & drug interaction: number of clinically significant findings from vital signs (blood pressure and pulse) |  | Up to Day 4 post-dose | 
| Food effect & drug interaction: number of clinically significant findings from physical exam |  | Up to Day 4 post-dose | 
| Food effect & drug interaction: number of clinically significant findings from electrocardiogram |  | Up to Day 4 post-dose | 
| Food effect & drug interaction: number of clinically significant findings from biological tests |  | Up to Day 4 post-dose |