Randomized, double-blind, placebo-controlled, 2-way crossover study to characterize pharmacological reversal of biperiden-induced cognitive effects by donepezil in healthy elderly subjects

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.

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 <25 at screening
7) Subjects have any disease associated with cognitive impairment.
8) Subjects have a history of severe allergies, or history of an anaphylactic
reaction to prescription or non-prescription drugs or food (non-active hay
fever is acceptable; active, medically untreated hay fever is allowed, if
deemed acceptable by the investigator).
9) Subjects have a history of hypersensitivity to biperiden or to the
excipients used in the biperiden formulation.
10) Subjects have a history of hypersensitivity to donepezil and piperidine
derivates or to the excipients used in the donepezil formulation.
11) Subjects have a history of hypersensitivity to other acetylcholinesterase
inhibitors.
12) Subjects have a positive test for Hepatitis B surface antigen (HBsAg),
Hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV
Ab) at screening.
13) Subjects have a positive urine drug screen (UDS), or alcohol test at
screening or admission to the inpatient unit, confirmed by repeat testing.
14) Subjects consume more than an average of 2 alcoholic beverages daily or
more than 14 alcoholic beverages weekly within <=7 days of Day *1 or consume any
alcohol within 24 hours of Day -1.
15) Subjects smoke >5 cigarettes (or equivalent) per day or use tobacco or any
nicotine-containing products (including e-cigarettes and patches) prior to
screening. Smoking is prohibited from within 14 days before dosing until EOS.
16) Subjects have an excessive caffeine consumption, defined as >800 mg per day
from 7 days before each study drug administration until 24 hours prior to
dosing. Subjects will abstain from caffeine containing products for 24 hours
prior to each dosing and whilst in the study until discharge from the clinical
unit. At other times throughout the study, subjects should not consume more
than 800 mg caffeine per day. Caffeine quantities are defined as follows: one
cup of coffee contains 100 mg of caffeine; one cup of tea, or one glass of
cola, or potion of chocolate (dark:100 g, milk 200 g) contains approximately 40
mg of caffeine; one bottle of Red Bull contains approximately 80 mg of caffeine.
17) Subjects have used any prescription or OTC medications as outlined in
section 4.4.2, except paracetamol (up to 4 g/day) and ibuprofen (up to 1200
mg/day), <=14 days or <5 t1/2 (whichever is longer) before Day 1. Other
exceptions may be made at the discretion of the investigator.
18) Subjects have used alternative/complementary medicine products (e.g.,
herbal supplements, creatine, sports supplements) <=7 days before Day 1.
19) Subjects have any other concurrent disease or condition that could
interfere with, or for which the concomitant treatment might interfere with,
the conduct of the study, or that would, in the opinion of the Investigator,
pose an unacceptable risk to the subject in this study.
20) Subjects have participated in an investigational drug study within 90 days
of the first dose of study treatment or more than 4 times per year.
21) Subjects have donated or lost blood of more than 500 mL within 90 days
before screening.
22) A subject, in the investigator*s opinion, has any condition that might
indicate that the subject is unsuitable for the study.