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

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.

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.

Study Overview

• Status: Completed
• Conditions: Healthy; Safety
• Intervention / Treatment: 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

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Gières, France, 38610
    • Eurofins Optimed

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

7

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Aptabio Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 28, 2018
• Primary Completion (ACTUAL): March 6, 2019
• Study Completion (ACTUAL): March 6, 2019

Study Registration Dates

• First Submitted: September 20, 2018
• First Submitted That Met QC Criteria: October 2, 2018
• First Posted (ACTUAL): October 3, 2018

Study Record Updates

• Last Update Posted (ACTUAL): March 11, 2019
• Last Update Submitted That Met QC Criteria: March 7, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: OP101817.APT; 2017-004252-30 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No