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

Alzheimer Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03698695
• Other study ID #: THN201-101
• Status: Completed
• Phase: Phase 1
• Start date: September 27, 2018
• Est. completion date: December 20, 2019

Study information

• Verified date: January 2020
• Source: Theranexus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 152
• Est. completion date: December 20, 2019
• Est. primary completion date: October 20, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 40 Years

Eligibility

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).

Related Conditions & MeSH terms

• Alzheimer Disease
• Cognitive Dysfunction
• Cognitive Impairment

Intervention

Drug:
• THN 201
THN 201: Donepezil 5 mg and Mefloquine 10 mg/d
• Donepezil
Donepezil 5 mg/d and Mefloquine placebo
• Placebo
Donepezil placebo and Mefloquine placebo

Locations

Country	Name	City	State
France	CHU Bordeaux	Bordeaux
France	CHU Clermont Ferrand	Clermont-Ferrand
France	CHU Grenoble	Grenoble
France	CHU Lille	Lille
France	CHU Marseille	Marseille
France	Biotrial	Rennes
France	CHU Toulouse	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
Theranexus

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pharmacokinetics Plasma concentration of donepezil and mefloquine	Time profile of plasma concentrations of donepezil and mefloquine	29 days
Other	Pharmacodynamics measured by quantitative EEG (qEEG)	Spectral analysis of absolute and/or relative amplitude in delta, theta, alpha, beta and gamma bands;	15 days
Other	Pharmacodynamics measured by event related EEG potentials (P300)	Auditory P300 parameters (amplitude, latency and AUC)	15 days
Primary	Pharmacodynamics: Cognitive function measured with the Cognitive Drug Research (CDR) test battery	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	15 days
Secondary	Safety Adverse events	Number of subjects with spontaneously reported treatment related adverse events	29 days