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

NCT03694041 | Completed Phase 1 DMC

• 2 other identifiers: OP101817.APT2017-004252-30
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy; Safety

Outcome Measures

Primary Outcomes (22)

• 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 Outcomes (18)

• 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

Study Arms (7)

SAD: APX-115

EXPERIMENTAL

Experimental: APX-115 SAD group

Drug: SAD: APX-115

SAD: Placebo

PLACEBO COMPARATOR

Experimental: Placebo group

Drug: SAD: Placebo

MAD: APX-115

EXPERIMENTAL

Experimental: APX-115 MAD group

Drug: MAD: APX-115

MAD: Placebo

PLACEBO COMPARATOR

Experimental: Placebo group

Drug: MAD: Placebo

Food effect - Fasting condition

ACTIVE COMPARATOR

Experimental: APX-115 under fasting condition

Other: Food effect: fasted and fed

Food effect - fed condition

ACTIVE COMPARATOR

Experimental: APX-115 under fed condition

Other: Food effect: fasted and fed

Drug Interaction - metabolic probe

PLACEBO COMPARATOR

Experimental: metabolic probe

Other: Metabolic probe with or without APX-115

Interventions

SAD: APX-115 DRUG

Drug: APX-115 SAD APX-115 SAD for 1day

SAD: APX-115

SAD: Placebo DRUG

Drug: Placebo Placebo for 1day

SAD: Placebo

MAD: APX-115 DRUG

Drug: APX-115 MAD APX-115 MAD repeatedly administered.

MAD: APX-115

MAD: Placebo DRUG

Matching study drug will be repeatedly administered.

MAD: Placebo

Food effect: fasted and fed OTHER

A single dose of APX-115, selected from the SAD study, will be administered under fasted and fed condition.

Food effect - Fasting condition; Food effect - fed condition

Metabolic probe with or without APX-115 OTHER

A metabolic probe will be administered with and without APX-115.

Drug Interaction - metabolic probe

Eligibility Criteria

• Age: 18 Years - 45 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Aptabio Therapeutics, Inc.: lead

Study Sites (1)

Eurofins Optimed

Gières, 38610, France

Location

MeSH Terms

Interventions

isuzinaxib

Study Officials

• Yves Donazzolo, MD

  Eurofins Optimed

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDIV
• Responsible Party: SPONSOR

Model Details: Parallel design for SAD and MAD studies Crossover design for Food and Drug interaction studies

Study Record Dates

• First Submitted: September 20, 2018
• First Posted: October 3, 2018
• Study Start: May 28, 2018
• Primary Completion: March 6, 2019
• Study Completion: March 6, 2019
• Last Updated: March 11, 2019

Record last verified: 2019-03

Locations

FR (1)