Clinical trial NCT03694041: Safety, Tolerability, PK and PD of SAD or MAD of APX-115 in Healthy Male Volunteers
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Safety
Lead sponsor: Aptabio Therapeutics, Inc.
Sponsor class: INDIV
First posted: 2018-10-03
Enrollment: 88
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel design for SAD and MAD studies Crossover design for Food and Drug interaction studies
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: SAD: incidence of treatment emergent adverse events
timeFrame: Up to Day 8
measure: SAD: number of clinically significant abnormal findings from vital signs (blood pressure, pulse)
timeFrame: Up to Day 8
measure: SAD: number of clinically significant abnormal findings from physical exam
timeFrame: Up to Day 8
measure: SAD: number of clinically significant abnormal findings from electrocardiogram
timeFrame: Up to Day 8
measure: SAD: number of clinically significant abnormal findings from biological tests
timeFrame: Up to Day 8
measure: MAD: incidence of treatment emergent adverse events
timeFrame: Up to Day 17
measure: MAD: number of clinically significant abnormal findings from vital signs (blood pressure, pulse)
timeFrame: Up to Day 17
measure: MAD: number of clinically significant abnormal findings from physical exams
timeFrame: Up to Day 17
measure: MAD: number of clinically significant abnormal findings from electrocardiogram
timeFrame: Up to Day 17
measure: Food effect: peak serum concentration (Cmax) of APX-115 under fasting and fed conditions
timeFrame: Up to Day 4 post-dose
measure: Food effect: time to reach the Cmax (Tmax) of APX-115 under fasting and fed conditions
timeFrame: Up to Day 4 post-dose
measure: Food effect: area under the curve (AUC) of APX-115 under fasting and fed conditions
timeFrame: Up to Day 4 post-dose
measure: Food effect: elimination rate constant (Kel) of APX-115 under fasting and fed conditions
timeFrame: Up to Day 4 post-dose
measure: Food effect: ratio AUCfed/AUCfasted
timeFrame: Up to Day 4 post-dose
measure: Drug interaction: peak serum concentration (Cmax) of a metabolic probe or APX-115
timeFrame: Up to Day 4 post-dose
measure: Drug interaction: Time to reach the Cmax (tmax) of a metabolic probe or APX-115
timeFrame: Up to Day 4 post-dose
measure: Drug interaction study: Area under the Curve (AUC) of a metabolic probe or APX-115
timeFrame: Up to Day 4 post-dose
measure: Drug interaction: elimination rate constant (Kel) of a metabolic probe or APX-115
timeFrame: Up to Day 4 post-dose
measure: Drug interaction: half-life (t1/2) of a metabolic probe or APX-115
timeFrame: Up to Day 4 post-dose
measure: Drug interaction: volume of distribution (Vd/f) of a metabolic probe or APX-115
timeFrame: Up to Day 4 post-dose
measure: Drug interaction: clearance of a metabolic probe or APX-115
timeFrame: Up to Day 4 post-dose
measure: Drug interaction: Incidences of treatment emergent adverse events
timeFrame: Up to Day 4 post-dose
Secondary outcomes:
measure: SAD: time to reach Cmax (Tmax) of APX-115
timeFrame: Up to Day 5
measure: SAD: peak serum concentration (Cmax) of APX-115
timeFrame: Up to Day 5
measure: SAD: lowest plasma concentration before next dosing (Ctrough)
timeFrame: Up to Day 5
measure: SAD: Area Under the Curve (AUC) of APX-115
timeFrame: Up to Day 5
measure: SAD: volume of distribution (Vd/F) of APX-115
timeFrame: Up to Day 5
measure: SAD: clearance (CL/F) of APX-115
timeFrame: Up to Day 5
measure: MAD: peak serum concentration (Cmax) of APX-115
timeFrame: Up to Day 11
measure: MAD: time to reach the Cmax (Tmax) of APX-115
timeFrame: Up to Day 11
measure: MAD: Area Under the Curve (AUC) of APX-115
timeFrame: Up to Day 11
measure: MAD: lowest plasma concentration of APX-115 before next dosing (Ctrough)
timeFrame: Up to Day 11
measure: MAD: volume of distribution (Vd/F) of APX-115
timeFrame: Up to Day 11
measure: MAD: Clearance (CL/F) of APX-115
timeFrame: Up to Day 11
measure: MAD: accumulation ratio
timeFrame: Up to Day 11
measure: Food effect & drug interaction: incidence of treatment emergent adverse events
timeFrame: Up to Day 4 post-dose
measure: Food effect & drug interaction: number of clinically significant findings from vital signs (blood pressure and pulse)
timeFrame: Up to Day 4 post-dose
measure: Food effect & drug interaction: number of clinically significant findings from physical exam
timeFrame: Up to Day 4 post-dose
measure: Food effect & drug interaction: number of clinically significant findings from electrocardiogram
timeFrame: Up to Day 4 post-dose
measure: Food effect & drug interaction: number of clinically significant findings from biological tests
timeFrame: Up to Day 4 post-dose
Other outcomes:
Locations:
city: Gières
country: France
facility: Eurofins Optimed
Study officials:
affiliation: Eurofins Optimed
name: Yves Donazzolo, MD
role: PRINCIPAL_INVESTIGATOR
References: