Clinical trial NCT05921929: First-In-Human (FIH), Single Ascending Dose (SAD) Study of FluoroEthylNorMemantine (FENM)
Official title: Safety and Pharmacokinetics of a Novel NMDA Receptor Antagonist Against Brain Related Diseases in Healthy Adult Volunteers: First-in-human, Phase I, Single Dose-escalating, Open Label Study
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: PTSD
Alzheimer Disease
Brain Diseases
Neuro-Degenerative Disease
Major Depressive Disorder
Treatment Resistant Depression
Keywords: NMDA
PTSD
Alzheimer's disease
Brain Diseases
Neuro-Degenerative Disease
Major Depressive Disorder
Treatment Resistant Depression
Lead sponsor: ReST Therapeutics
Sponsor class: INDUSTRY
First posted: 2023-06-27
Enrollment: 0
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: The goal of this First-In-Human (FIH) trial is to learn about safety and PharmacoKinetics (PK) in healthy adult volunteers. The main questions it aims to answer are:

* What is the safety of single ascending doses of the FluoroEthylNorMemantine (FENM)?
* What is the PK profile of single ascending doses of the FENM in human?
* What is the preliminary exploratory time course of Brain Disease Neurotrophic Factor (BDNF) plasmatic levels of single ascending doses of the FENM? Participants will receive one single oral dose of FENM.


Eligibility criteria: Inclusion Criteria:

* willing and able to sign written informed consent,
* Body Mass Index (BMI) of 17.5 to 30.5 kg/m2, a total body weight \>65 kg,
* efficient contraceptive mean,
* no major psychiatric disorder per the Mini-International Neuropsychiatric Interview (MINI) questionnaire,
* normal laboratory tests results, arterial Blood Pressure/pulse rate, 12-lead Electrocardiogram recording.

Exclusion Criteria:

* evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, allergic disease including drug allergies, or other severe acute or chronic medical or psychiatric condition or laboratory abnormality,
* history of febrile illness within 5 days prior to administration,
* any condition possibly affecting drug absorption,
* using of prescription drugs, vaccine, routine or as needed consumption of medications or herbal supplements,
* having positive serology, positive urine test for drugs of abuse, a general medical or psychological condition or behavior, including current substance dependence or abuse,
* history of drug or alcohol abuse within 1 year before screening,
* consuming currently of nicotine containing products, any food or any beverage containing grapefruit or grapefruit juice within 48 h prior to administration,
* having blood donation or loss of significant amount of blood within 2 months prior to study.

Primary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: From single dose administration to the end of the study follow-up (2 weeks later)
Secondary outcomes:
measure: To assess maximum plasma concentration [Cmax]
timeFrame: At pre-dose and at 2, 4, 6, 8, 10, 12, 24, 48, 96, 189, 264 and 336hours post-dose
measure: To assess time to Cmax [Tmax]
timeFrame: At pre-dose and at 2, 4, 6, 8, 10, 12, 24, 48, 96, 189, 264 and 336hours post-dose
measure: To assess minimum concentration within the dosing interval [Cmin]
timeFrame: At pre-dose and at 2, 4, 6, 8, 10, 12, 24, 48, 96, 189, 264 and 336hours post-dose
measure: To assess last observed plasma concentration [Clast]
timeFrame: At pre-dose and at 2, 4, 6, 8, 10, 12, 24, 48, 96, 189, 264 and 336hours post-dose
measure: To assess time of the minimum concentration [Tmax]
timeFrame: At pre-dose and at 2, 4, 6, 8, 10, 12, 24, 48, 96, 189, 264 and 336hours post-dose
measure: To assess area under the plasma concentration-time curve from 0 to the end of the dose interval [AUC 0-tau]
timeFrame: At pre-dose and at 2, 4, 6, 8, 10, 12, 24, 48, 96, 189, 264 and 336hours post-dose
measure: To assess area under the plasma concentration-time curve from dosing (time 0) to the time of last measured concentration [AUC 0-last]
timeFrame: At pre-dose and at 2, 4, 6, 8, 10, 12, 24, 48, 96, 189, 264 and 336hours post-dose
measure: To assess total area under the plasma concentration-time curve from dosing (time 0) taken to the limit as the end time becomes arbitrarily large (infinity) [AUC 0-∞]
timeFrame: At pre-dose and at 2, 4, 6, 8, 10, 12, 24, 48, 96, 189, 264 and 336hours post-dose
measure: To assess terminal half-life, apparent elimination half-life [T1/2]
timeFrame: At pre-dose and at 2, 4, 6, 8, 10, 12, 24, 48, 96, 189, 264 and 336hours post-dose
measure: To assess apparent oral clearance [CL/F]
timeFrame: At pre-dose and at 2, 4, 6, 8, 10, 12, 24, 48, 96, 189, 264 and 336hours post-dose
measure: To assess apparent volume of distribution [Vz/F]
timeFrame: At pre-dose and at 2, 4, 6, 8, 10, 12, 24, 48, 96, 189, 264 and 336hours post-dose
measure: To assess preliminary exploratory time course of Brain Disease Neurotrophic Factor plasmatic levels of single ascending doses of the FENM
timeFrame: At pre-dose, at Cmax (estimated at 6-8hours post-dose) and at 48, 72 and 264hours post-dose
Other outcomes:
Locations:
city: Liège
country: Belgium
facility: CHU of Liège - Clinical Pharmacology Unit
Study officials:
References: