A Pharmacodynamics, Safety, and Pharmacokinetics Study of THN201 Versus Donepezil in Healthy Male Volunteers

Phase 1

Completed

• Conditions: Cognitive Impairment; Alzheimer Disease
• Interventions: Drug: Placebo; Drug: THN 201; Drug: Donepezil

• Registration Number: NCT03698695
• Lead Sponsor: Theranexus

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.

Study Timeline

• Study Start: 2018-09-27
• Study First Submitted: 2018-10-02
• Study First Submitted QC: 2018-10-03
• Study First Posted: 2018-10-09
• Primary Completion: 2019-10-20
• Study Completion: 2019-12-20
• Status Verified: 2020-01
• Last Update Submitted: 2020-01-21
• Last Update Posted: 2020-01-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 152

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Donepezil placebo capsule and Mefloquine placebo capsule once daily for 15 days
THN201	THN 201	THN201: Donepezil 5mg capsule and Mefloquine 10mg capsule once daily for 15 days
Donepezil	Donepezil	Donepezil 5mg capsule and Mefloquine placebo capsule once daily for 15 days

Primary Outcome Measures

Name	Time	Method
Pharmacodynamics: Cognitive function measured with the Cognitive Drug Research (CDR) test battery	15 days	Main variable: Power of attention is the sum of the speed scores (msec) from three tests: Simple Reaction Time, Choice Reaction Time, and Digital Vigilance. Low values indicate better performance

Secondary Outcome Measures

Name	Time	Method
Safety Adverse events	29 days	Number of subjects with spontaneously reported treatment related adverse events

Trial Locations

Locations (7)

CHU Grenoble; 🇫🇷 Grenoble, France

CHU Bordeaux; 🇫🇷 Bordeaux, France

CHU Clermont Ferrand; 🇫🇷 Clermont-Ferrand, France

CHU Marseille; 🇫🇷 Marseille, France

Biotrial; 🇫🇷 Rennes, France

CHU Lille; 🇫🇷 Lille, France

CHU Toulouse; 🇫🇷 Toulouse, France