Cognitive impairment dementia
Conditions
Interventions
• IV biperiden lactate (Akineton®) 2.6 mg 
• Donepezil hydrochloride 10 mg (Sulbenin®)
• Placebo
Sponsors
Centre for Human Drug Research
Eligibility
Age
65 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1) Healthy male or female subjects >=65 to 80 years of age, inclusive at screening 2) Subjects must have a body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive. Subjects should weigh 50 kilograms at a minimum. 3) Subjects must meet heart rate (HR) requirements: 45 - 100 bpm as measured at screening in a resting position (after the subject has been supine for >=5 minutes). 4) Male subjects must agree not to donate sperm from screening until 90 days after the last dose of study treatment. 5) Subjects must agree not to donate blood or blood products during the study and for up to 3 weeks, after the last dose of study treatment. 6) Subjects must be able to understand the commitments of the study and communicate effectively with the investigator and site staff. 7) Subjects must be able to participate, willing to give written informed consent, and willing to comply with all study procedures and restrictions.
Exclusion criteria
Exclusion criteria: 1) Evidence of any active or chronic disease or condition that could interfere with, or for which the treatment of might interfere with, the conduct of the study, or that would pose an unacceptable risk to the subject in the opinion of the investigator (following a detailed medical history, physical examination, vital signs (systolic and diastolic BP, pulse rate, respiratory rate, body temperature) and 12-lead electrocardiogram (ECG)). Minor deviations from the normal range may be accepted, if judged by the Investigator to have no clinical relevance. 2) Clinically significant abnormalities, as judged by the investigator, in laboratory test results (including hepatic and renal panels, complete blood count, chemistry panel and urinalysis). In the case of uncertain or questionable results, tests performed during screening may be repeated before randomization to confirm eligibility or judged to be clinically irrelevant for healthy subjects. 3) Subjects have a current or history of any clinically relevant psychiatric disorder as classified according to DSMIV or DSM 5 (e.g. psychotic disorder e.g. schizophrenia/schizo-affective disorder, bipolar disorder Type I or Type II, personality disorder, major depressive disorder/persistent depressive disorder, obsessive-compulsive disorder, panic disorder, anorexia nervosa, bulimia nervosa, generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), autism spectrum disorder (ASD) sleep disorders and previous delirium). 4) Subjects have history or clinical evidence of any disease and/or existence of any surgical or medical condition (e.g., stomach bypass) that might interfere with the ADME of the study treatment. 5) Subjects have a personal or family history of congenital long QT syndrome (QT interval corrected for HR using Friderica*s formula [QTcF] of >450 milliseconds for male subjects or >470 milliseconds for female subjects during resting ECG at screening) or sudden death. 6) Subjects have a Mini Mental State Examination (MMSE) score 5 cigarettes (or equivalent) per day or use tobacco or any
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adaptive Tracking: • Average adaptive tracking performance (%) | — |
Secondary
| Measure | Time frame |
|---|---|
| Plasma PK parameters derived by non-compartmental analysis: • Donepezil: Cmax, AUC0-24, tmax • Biperiden: Cmax, AUC0-last, tmax Adaptive Tracking: • Average adaptive tracking performance (%) Static Pupillometry: • Left and right pupil:iris ratios N-Back Task (0-, 1-, and 2-back): • Average reaction time (msec) • Accuracy ([number correct * number incorrect] / total) Salivary flow assessment • (g/3 minutes) Adaptive Tracking: • Average adaptive tracking performance (%) Static Pupillometry: • Left and right pupil:iris ratios N-Back Task (0-, 1-, and 2-back): • Average reaction time (msec) • Accuracy ([number correct * number incorrect] / total) Salivary flow assessment • (g/3 minutes) Adaptive Tracking: • Average adaptive tracking performance (%) Saccadic eye movements: • Saccadic peak velocity (degrees/second) • Saccadic inaccuracy (%) • Saccadic reaction time (sec) Smooth Pursuit Eye Movement: • Percentage of time the subject*s eyes are in smooth pursuit of the target Static Pupillometry: • Left and right pupil:iris ratios Body Sway: • Antero-posterior sway (mm) N-Back Task (0-, 1-, and 2-back): • Average reaction time (msec) • Accuracy ([number correct * number incorrect] / total) Visual Verbal Learning Test (VVLT): • Immediate Recall (number correct) • Delayed Recall (number correct) • Delayed Recognition (number correct and reaction time) Quantitative electroencephalography (qEEG): • Power in alpha frequency bands [dB] • Power in beta frequency bands [dB] • Power in gamma frequency bands [dB] • Power in delta frequency bands [dB] • Power in theta frequency bands [dB] Auditory event-related potentials (ERPs): • MMN (amplitude [µV2]; latency [msec]) • P300, P3a (amplitude [µV2]; latency [msec]) • P300, P3b (amplitude [µV2]; latency [msec]) • ASSR (amplitude [µV2]; phase locking factor) | — |
Countries
Netherlands
Contacts
Public ContactP.H.C. Kremer
Centre for Human Drug Research
Outcome results
None listed