Back to resultsA Pharmacodynamics, Safety, and Pharmacokinetics Study of THN201 Versus Donepezil in Healthy Male Volunteers
Primary Purpose
Cognitive Impairment, Alzheimer Disease
Status
Completed
Phase
Phase 1
Locations
France
Study Type
Interventional
Intervention
THN 201
Donepezil
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Cognitive Impairment
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).
Sites / Locations
- CHU Bordeaux
- CHU Clermont Ferrand
- CHU Grenoble
- CHU Lille
- CHU Marseille
- Biotrial
- CHU Toulouse
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
Placebo Comparator
Arm Label
THN201
Donepezil
Placebo
Arm Description
THN201: Donepezil 5mg capsule and Mefloquine 10mg capsule once daily for 15 days
Donepezil 5mg capsule and Mefloquine placebo capsule once daily for 15 days
Donepezil placebo capsule and Mefloquine placebo capsule once daily for 15 days
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Safety Adverse events
Number of subjects with spontaneously reported treatment related adverse events
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03698695
Brief Title
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
2. Study Status
Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
September 27, 2018 (Actual)
Primary Completion Date
October 20, 2019 (Actual)
Study Completion Date
December 20, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Theranexus
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cognitive Impairment, Alzheimer Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
152 (Actual)
8. Arms, Groups, and Interventions
Arm Title
THN201
Arm Type
Experimental
Arm Description
THN201: Donepezil 5mg capsule and Mefloquine 10mg capsule once daily for 15 days
Arm Title
Donepezil
Arm Type
Active Comparator
Arm Description
Donepezil 5mg capsule and Mefloquine placebo capsule once daily for 15 days
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Donepezil placebo capsule and Mefloquine placebo capsule once daily for 15 days
Intervention Type
Drug
Intervention Name(s)
THN 201
Other Intervention Name(s)
Donepezil, Mefloquine
Intervention Description
THN 201: Donepezil 5 mg and Mefloquine 10 mg/d
Intervention Type
Drug
Intervention Name(s)
Donepezil
Intervention Description
Donepezil 5 mg/d and Mefloquine placebo
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Donepezil placebo and Mefloquine placebo
Primary Outcome Measure Information:
Title
Pharmacodynamics: Cognitive function measured with the Cognitive Drug Research (CDR) test battery
Description
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
Time Frame
15 days
Secondary Outcome Measure Information:
Title
Safety Adverse events
Description
Number of subjects with spontaneously reported treatment related adverse events
Time Frame
29 days
Other Pre-specified Outcome Measures:
Title
Pharmacokinetics Plasma concentration of donepezil and mefloquine
Description
Time profile of plasma concentrations of donepezil and mefloquine
Time Frame
29 days
Title
Pharmacodynamics measured by quantitative EEG (qEEG)
Description
Spectral analysis of absolute and/or relative amplitude in delta, theta, alpha, beta and gamma bands;
Time Frame
15 days
Title
Pharmacodynamics measured by event related EEG potentials (P300)
Description
Auditory P300 parameters (amplitude, latency and AUC)
Time Frame
15 days
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Régis Bordet, Prof.
Organizational Affiliation
CHU Lille
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU Bordeaux
City
Bordeaux
Country
France
Facility Name
CHU Clermont Ferrand
City
Clermont-Ferrand
Country
France
Facility Name
CHU Grenoble
City
Grenoble
Country
France
Facility Name
CHU Lille
City
Lille
Country
France
Facility Name
CHU Marseille
City
Marseille
Country
France
Facility Name
Biotrial
City
Rennes
Country
France
Facility Name
CHU Toulouse
City
Toulouse
Country
France
12. IPD Sharing Statement
Learn more about this trial
A Pharmacodynamics, Safety, and Pharmacokinetics Study of THN201 Versus Donepezil in Healthy Male Volunteers
We'll reach out to this number within 24 hrs