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

Theranexus

Status and phase: Completed; Phase 1

Conditions: Alzheimer Disease; Cognitive Impairment

Treatments: Drug: THN 201; Drug: Placebo; Drug: Donepezil

Study type: Interventional

Funder types: Industry

Identifiers

NCT03698695

THN201-101

Details and patient eligibility

About

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.

Full 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.

Enrollment: 152 patients

Sex: Male

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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152 participants in 3 patient groups, including a placebo group

THN201

Experimental group

Description:

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

Treatment:

Drug: THN 201

Donepezil

Active Comparator group

Description:

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

Treatment:

Drug: Donepezil

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo