A double-blind, placebo-controlled, five-way partial crossover study with EVP-6124 and donepezil in the scopolamine challenge model in healthy elderly volunteers
- Conditions
- Alzheimer's Diseasedementia10057167
- Registration Number
- NL-OMON37445
- Lead Sponsor
- EnVivo Pharmaceuticals
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 36
1.Age between 65 and 85 years (inclusive) ;
2.Body mass index between 18 and 32 kg/m2;
3.Able to read and understand the written consent form, complete study-related procedures, and communicate with the study staff;
4.Non-smokers;
5.Willing to comply with study restrictions;
1. Clinically relevant history of abnormal physical or mental health interfering with the study as determined by medical history taking and physical examinations obtained during the screening visit and/or at the start of the first study day for each period as judged by the investigator;;2. Clinically relevant abnormal laboratory results, electrocardiogram (ECG) and vital signs, or physical findings at screening and/or at the start of the first study day for each period (as judged by the investigator);;3. Mini-Mental State Examination (MMSE) lower than 27;;4. Positive test for hepatitis B, C or HIV;;5. History of alcoholism or substance abuse within three years prior to screening;;6. Subjects unable to refrain from alcohol use from 24hours prior to dosing on Day 1 Periods 1-5 until discharge from the CRU for each study period; ;7. Used tobacco and/or nicotine-containing products within 90 days of dosing on Day 1 Period 1;;8. Have a hemoglobin value of <8.0 mmol/L at screening;;9. Have aspartate transaminase (AST), alanine transaminase (ALT), gamma glutamyl transferase (GGT) or total bilirubin levels >1.5 times the upper limit of normal at screening;;10. Have evidence of significant renal insufficiency, indicated by a serum creatinine greater than the upper limit of normal at screening;;11. Evidence of elevated blood pressure at screening or baseline of >160 mmHg systolic or >100 mmHg diastolic;;12. Have a screening ECG with a corrected QT (QTc) interval using Bazett*s formula >450 msec for males and >470 msec for females or the presence of any clinically significant cardiac abnormalities, including but not limited to patterns consistent with myocardial ischemia, electrolyte abnormalities, or atrial or ventricular dysrhythmia or significant conduction abnormalities;;13. Subject is a habitual and heavy consumer of caffeinated beverages (more than 6 cups of coffee or equivalent/day) at screening and/or is not able to refrain from use of (methyl) xanthines (e.g. coffee, tea, cola, chocolate) from 12 hours prior to dosing on Day 1 until discharge from the CRU for each study period;;14. Positive urine drug screen (UDS) or alcohol or cotinine test at screening and/or Day -1 of each period;;15. Concomitant use of inhibitors of CYP2D6 (e.g., kinidine, paroxetine, fluoxetine) or of CYP3A4 (e.g., ketoconazol, ritonavir) within 21 days of randomization on Day 1 Period 1;;16. Subject is unable to refrain from the use of concomitant medication which, in the opinion of the investigator, interferes with their ability to participate in the trial, from 7 days prior to dosing on Day 1 Period 1 until the follow-up study visit;;17. Subject has a history of severe allergies, or has had an anaphylactic reaction to prescription or non-prescription drugs or food;;18. History or clinical evidence of any disease and/or existence of any surgical or medical condition which might interfere with the absorption, distribution, metabolism or excretion of the study drugs (EVP-6124, donepezil or scopolamine);;19. Participation in an investigational drug trial in the 3 months prior to administration of the initial dose of study drug (Day 1 Period 1) or more than 4 times per year;;20. Donation of blood/plasma outside limits of Sanquin Blood Supply Foundation guidelines of approximately 500 mL or significant blood loss;;21. Have participated as a plasma donor in a plasmapheresis program within 7 days before screening;;22. Have received treatment with othe
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Pharmacodynamics:<br /><br>* Saccadic eye movements<br /><br>* Smooth pursuit eye movements<br /><br>* Adaptive tracking<br /><br>* Visual analogue scales (VAS) for alertness, mood, calmness and psychedelic<br /><br>effects<br /><br>* Body sway<br /><br>* Finger tapping<br /><br>* Pharmaco-Electroencephalography EEG (pEEG)<br /><br>* Visual verbal memory test (VVLT)<br /><br>* Stroop color-word interference<br /><br>* Pupil size<br /><br>* N-back test<br /><br>* Symbol digit substitution test<br /><br>* Simple reaction time<br /><br><br /><br>Pharmacokinetics:<br /><br>* Plasma PK EVP-6124: Cmax, Tmax<br /><br>* Plasma PK donepezil: Cmax, Tmax<br /><br>* Plasma PK scopolamine: Cmax, AUC0-last, AUC0-*, Tmax, t1/2β<br /><br><br /><br>Determination of genes related to acetylcoline receptor and<br /><br>acetylcholinesterase transcription</p><br>
- Secondary Outcome Measures
Name Time Method <p>- the difference in respons of tumor necrosis factor a (TNFa) to a<br /><br>lipopolisacharide (LPS) challenge between treatment regimens will be assessed.<br /><br><br /><br>- Safety parameters: Adverse events (AEs), vital signs including blood pressure<br /><br>measurements and weight, physical examinations including a neurological<br /><br>assessment, 12-lead electrocardiograms (ECGs), and clinical laboratory tests </p><br>