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

NCT03698695 | Completed Phase 1

• 1 other identifier: THN201-101
• Study Type: interventional
• Target: 152
• Locations: 1 country
• Sites: 7

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.

Conditions

Cognitive Impairment; Alzheimer Disease

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Safety Adverse events

  29 days

Other Outcomes (3)

• Pharmacokinetics Plasma concentration of donepezil and mefloquine

  29 days

• Pharmacodynamics measured by quantitative EEG (qEEG)

  15 days

• Pharmacodynamics measured by event related EEG potentials (P300)

  15 days

Study Arms (3)

THN201

EXPERIMENTAL

THN201: Donepezil 5mg capsule and Mefloquine 10mg capsule once daily for 15 days

Drug: THN 201

Donepezil

ACTIVE COMPARATOR

Donepezil 5mg capsule and Mefloquine placebo capsule once daily for 15 days

Drug: Donepezil

Placebo

PLACEBO COMPARATOR

Donepezil placebo capsule and Mefloquine placebo capsule once daily for 15 days

Drug: Placebo

Interventions

THN 201 DRUG

THN 201: Donepezil 5 mg and Mefloquine 10 mg/d

Also known as: Donepezil, Mefloquine

THN201

Donepezil DRUG

Donepezil 5 mg/d and Mefloquine placebo

Donepezil

Placebo DRUG

Donepezil placebo and Mefloquine placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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).

Sponsors & Collaborators

• Theranexus: lead

Study Sites (7)

CHU Bordeaux

Bordeaux, France

Location

CHU Clermont Ferrand

Clermont-Ferrand, France

Location

CHU Grenoble

Grenoble, France

Location

CHU Lille

Lille, France

Location

CHU Marseille

Marseille, France

Location

Biotrial

Rennes, France

Location

CHU Toulouse

Toulouse, France

Location

MeSH Terms

Conditions

Cognitive Dysfunction; Alzheimer Disease

Interventions

Donepezil; Mefloquine

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Régis Bordet, Prof.

  CHU Lille

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: October 2, 2018
• First Posted: October 9, 2018
• Study Start: September 27, 2018
• Primary Completion: October 20, 2019
• Study Completion: December 20, 2019
• Last Updated: January 22, 2020

Record last verified: 2020-01

Locations

FR (7)