Clinical trial NCT03698695: A Pharmacodynamics, Safety, and Pharmacokinetics Study of THN201 Versus Donepezil in Healthy Male Volunteers
Official title: A Double Blind, Placebo-controlled, Randomized, 15-day Treatment, Pharmacodynamics, Safety, and Pharmacokinetics Study of THN201 Versus Donepezil Administered Orally to Healthy Male Volunteers Including a Scopolamine Challenge
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cognitive Impairment
Alzheimer Disease
Lead sponsor: Theranexus
Sponsor class: INDUSTRY
First posted: 2018-10-09
Enrollment: 152
Sex: MALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study explores the safety, pharmacodynamics and pharmacokinetics of THN201 a combination of donepezil and mefloquine to improve cognitive function in healthy male volunteers after impairment by a scopolamine challenge.

Detailed description: This is a double-blind, 3-arm, parallel group study of 15 days duration including a scopolamine challenge at D15. Healthy male subjects will receive daily doses of THN201 (donepezil 5 mg and mefloquine), donepezil 5 mg or placebo and one subcutaneous injection of scopolamine 0.5 mg on D15. Cognitive function, EEG and P300 will be assessed at baseline and before and after scopolamine challenge at D15. A final safety evaluation will be performed 2 weeks after the end of the treatment period. Pharmacokinetic assessments will be performed to obtain a time/concentration profile of donepezil and mefloquine.

Eligibility criteria: Inclusion Criteria:

* A body mass index (BMI), calculated as weight in kg/(height in m)², from 18 to 30 kg/m², inclusive
* Healthy as determined by the investigator after a comprehensive clinical assessment based on medical history, physical examination, clinical laboratory test results, vital sign measurements, blood pressure (BP), heart rate (HR) and digital 12-lead ECG readings (all results should be normal or, if out of range, they should be non-clinically significant as determined by the investigator)

Exclusion Criteria:

* Any significant cardiovascular (e.g. heart failure), pulmonary (including asthma), hepatic, renal, respiratory (e.g. asthma), gastrointestinal, endocrine (e.g. diabetes, dyslipidaemia), immunologic, dermatological, haematological, neurologic, psychiatric disease, history of any clinically important drug allergy, systemic or presence of infectious disease.
* Current suicide risk or history of suicide risk (C-SSRS baseline: "yes" answer to items 4 and/or 5).
* Brain imaging (MRI) at screening showing anatomical or vascular abnormality of any type.
* EEG examination at screening showing abnormal (epileptiform) activities.
* Symptomatic hypotension,
* Participants with, or with a history of cardiac arrhythmia or cardiac disease or a personal or family history of long QT syndrome or a family history of sudden death.
* Presence or history of drug hypersensitivity, or allergic disease diagnosed and treated by a physician.
* Antimalarial medicine intake or returning from a malaria-endemic area within the 12 last months before the first IMP administration.
* Planning to visit a country requiring antimalarial chemoprophylaxis during the study period.
* History of adverse reaction after a previous mefloquine intake.
* Contraindication for the use of Aricept® or for one of its excipients.
* Contraindication for the use of piperidine derivative compounds or for other cholinesterase inhibitors.
* Contraindication for the use of Lariam® or for one of its excipients.
* Contraindication for the use of scopolamine S.C. injection.
* History or presence of drug or alcohol abuse (alcohol consumption \> 21 units / week).

Primary outcomes:
measure: Pharmacodynamics: Cognitive function measured with the Cognitive Drug Research (CDR) test battery
timeFrame: 15 days
Secondary outcomes:
measure: Safety Adverse events
timeFrame: 29 days
Other outcomes:
measure: Pharmacokinetics Plasma concentration of donepezil and mefloquine
timeFrame: 29 days
measure: Pharmacodynamics measured by quantitative EEG (qEEG)
timeFrame: 15 days
measure: Pharmacodynamics measured by event related EEG potentials (P300)
timeFrame: 15 days
Locations:
city: Bordeaux
country: France
facility: CHU Bordeaux
city: Clermont-Ferrand
country: France
facility: CHU Clermont Ferrand
city: Grenoble
country: France
facility: CHU Grenoble
city: Lille
country: France
facility: CHU Lille
city: Marseille
country: France
facility: CHU Marseille
city: Rennes
country: France
facility: Biotrial
city: Toulouse
country: France
facility: CHU Toulouse
Study officials:
affiliation: CHU Lille
name: Régis Bordet, Prof.
role: PRINCIPAL_INVESTIGATOR
References: