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

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ClinicalTrials.gov Identifier: NCT03698695
Recruitment Status : Active, not recruiting
First Posted : October 8, 2018
Last Update Posted : September 26, 2019
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Cognitive Impairment Alzheimer Disease Drug: THN 201 Drug: Donepezil Drug: Placebo Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 152 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : September 27, 2018
Estimated Primary Completion Date : October 20, 2019
Estimated Study Completion Date : December 20, 2019


Arm Intervention/treatment
Experimental: THN201
THN201: Donepezil 5mg capsule and Mefloquine 10mg capsule once daily for 15 days
Drug: THN 201
THN 201: Donepezil 5 mg and Mefloquine 10 mg/d
Other Names:
  • Donepezil
  • Mefloquine

Active Comparator: Donepezil
Donepezil 5mg capsule and Mefloquine placebo capsule once daily for 15 days
Drug: Donepezil
Donepezil 5 mg/d and Mefloquine placebo

Placebo Comparator: Placebo
Donepezil placebo capsule and Mefloquine placebo capsule once daily for 15 days
Drug: Placebo
Donepezil placebo and Mefloquine placebo




Primary Outcome Measures :
  1. Pharmacodynamics: Cognitive function measured with the Cognitive Drug Research (CDR) test battery [ Time Frame: 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 :
  1. Safety Adverse events [ Time Frame: 29 days ]
    Number of subjects with spontaneously reported treatment related adverse events


Other Outcome Measures:
  1. Pharmacokinetics Plasma concentration of donepezil and mefloquine [ Time Frame: 29 days ]
    Time profile of plasma concentrations of donepezil and mefloquine

  2. Pharmacodynamics measured by quantitative EEG (qEEG) [ Time Frame: 15 days ]
    Spectral analysis of absolute and/or relative amplitude in delta, theta, alpha, beta and gamma bands;

  3. Pharmacodynamics measured by event related EEG potentials (P300) [ Time Frame: 15 days ]
    Auditory P300 parameters (amplitude, latency and AUC)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03698695


Locations
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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, France
Sponsors and Collaborators
Theranexus
Investigators
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Principal Investigator: Régis Bordet, Prof. CHU Lille

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Responsible Party: Theranexus
ClinicalTrials.gov Identifier: NCT03698695     History of Changes
Other Study ID Numbers: THN201-101
First Posted: October 8, 2018    Key Record Dates
Last Update Posted: September 26, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Donepezil
Alzheimer Disease
Cognitive Dysfunction
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Cognition Disorders
Mefloquine
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Nootropic Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents