In this study we will investigate how safe the new compound deramciclane is, when it is given alone and in combination with the existing medication dextromethorphan (Part B), and how well it is tolerated when it is used by healthy elderly…
ID
Source
Brief title
Condition
- Dementia and amnestic conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To assess the pharmacokinetics (PK) of multiple doses of deramciclane in
healthy elderly subjects
To assess the PK of multiple doses of dextromethorphan in healthy elderly
subjects
To assess the PK of multiple doses of dextromethorphan and deramciclane
combined in healthy elderly subjects
To assess the safety and tolerability of multiple doses of deramciclane,
dextromethorphan, and deramciclane combined with dextromethorphan,
in healthy elderly subjects
Secondary outcome
Not applicable.
Background summary
Deramciclane is a new compound that originally was being developed for the
treatment of anxiety disorders. However clinical studies in patients were
stopped early when the compound was not effective in reducing anxiety. Now
deramciclane is repurposed for the possible treatment of behavioral symptoms of
dementia, like agitation, aggression, disturbed emotions, and mood
disturbances. These symptoms are very common in people with different forms of
dementia, and are very stressful for both patients and their caregivers.
Dextromethorphan is an existing medication and is mostly used as a cough
suppressant in cough medication. But recently it is also being developed as
compound for the treatment of diseases of the central nervous system (the
brain). Dextromethorphan is broken down really fast by the liver by certain
enzymes. One of the breakdown products is thought to cause the symptoms that
occur with dextromethorphan overdose (hallucinations, agitation, or sedation).
Therefore, in these studies into the effects of dextromethorphan on brain
function, dextromethorphan is given in combination with quinidine. Quinidine
slows down these liver enzymes, resulting in a slower breakdown of
dextromethorphan. Deramciclane has a similar effect as quinidine, and it is
expected to have additional therapeutic effects.It is thought that the
combination treatment of deramciclane and dextromethorphan will reduce the
behavioral symptoms in patients with dementia.
Study objective
In this study we will investigate how safe the new compound deramciclane is,
when it is given alone and in combination with the existing medication
dextromethorphan (Part B), and how well it is tolerated when it is used by
healthy elderly participants. In Part A only deramciclane will be given, and in
Part B both deramciclane and dextromethorphan will be given. We also
investigate how quickly and to what extent deramciclane is absorbed,
transported, and eliminated from the body. Deramciclane has been administered
to humans before. In addition, it has been extensively tested in the laboratory
and on animals.
Study design
Part A:
The study lasts a maximum of 8 weeks from the inspection to the follow-up
check. For the research it is necessary that the volunteers stay in the
research center for 2 periods; 1 period of 4 days (3 nights), and 1 period of 3
days (2 nights).
Day 1 is the first day of receiving the study drug. We expect the subjects to
be 2 days prior to the day of the first study drug administration at the study
center (i.e. Day -2). You must then report at approximately 14:00 in the
afternoon.
One leaves the research center on Day 2 of the research. For the second period,
we expect the VW on Day 10. You must then report at approximately 14:00 in the
afternoon. They leave the research center on Day 12 of the study. The arrival
times can be adjusted
While at the research center, deramciclane is given as capsules by mouth with
240 milliliters (ml) of (tap) water. After taking the study drug, one of the
researchers will inspect the hands and mouth. This is to check whether the
study drug has been taken.
Mne will take deramciclane at home for a few days (from the evening on Day 2
until the morning of Day 10). At home you can eat and drink as usual, with the
exception of a number of research-related restrictions. Please note that 48
hours (2 days) prior to each entry (Day -2 and Day 10), no beverages or food
containing caffeine such as coffee, (ice) tea, cola, chocolate (milk), mocha
may be consumed drinks/sweets, energy drinks.
One is requested to take the morning dose of deramciclane immediately after
breakfast and the evening dose approximately 12 hours later. They are given
instructions for dosing at home and a diary in which to record the time of each
dose of deramciclane and any side effects. You will receive a text message
and/or phone call twice a day as a reminder to take Deramciclane at home.
Part B:
The study takes a maximum of 9 weeks from the inspection to the follow-up check.
For the research it is necessary to stay in the research center for 2 periods;
1 period of 7 days (6 nights), and 1 period of 3 days (2 nights).
Day 1 is the first day of receiving the study drug. We expect the volunteers to
be 2 days prior to the day of the first study drug administration at the study
center (this is Day -2). You must then report at approximately 14:00 in the
afternoon.
The volunteer leaves the study center on Day 5 of the study. For the second
period we expect the volunteers on Day 13.
You must then report at approximately 14:00 in the afternoon. They leave the
research center on Day 15 of the study.
At the research center, dextromethorphan, and deramciclane, or placebo are
given twice daily as capsules by mouth with 240 milliliters (ml) of (tap)
water. After taking the study drug, one of the researchers will inspect your
hands and mouth. This is to check whether the study drug has been taken.
Deramciclane and dextromethorphan will also be taken twice daily as capsules at
home for several days (from the evening of Day 5 to the morning of Day 13). At
home you can eat and drink as usual, with the exception of a number of
research-related restrictions.
The morning dose of deramciclane and dextromethorphan is requested to be taken
immediately after breakfast and the evening dose approximately 12 hours later.
Dosing instructions are given and a diary is given in which to record the time
of each dose of deramciclane and dextromethorphan and any side effects. You
will receive a text or text message and/or phone call twice a day as a reminder
to take deramciclane and dextromethorphan at home.
Intervention
Not applicable.
Study burden and risks
Blood draws may hurt or cause bruising. Using an indwelling cannula can
sometimes cause inflammation, swelling, hardening of the artery, or blood
clotting and bleeding around the puncture site. In some individuals, a blood
draw can sometimes cause paleness, nausea, sweating, slow heart rate, or drop
in blood pressure with dizziness or fainting.
All in all, we will no longer take 270 milliliters (ml) of blood from you. This
amount does not cause any problems in adults. If the researcher does this
necessary to ensure the safety of the participant, additional samples can be
taken for any additional testing. If this happens, the total amount of blood
drawn will be more than the amount indicated above.
To make a heart film, electrodes are placed on the arms, chest and legs.
Prolonged use of these electrodes may cause skin irritation.
Samples for the coronavirus test will be taken with cotton swabs at the back of
the nose and throat. Taking the samples only takes a few seconds, but can cause
discomfort and discomfort. Taking a sample from the back of the throat may
result in gagging. When the sample is taken at the back of the nose, you may
experience a stinging sensation and the eyes may water.
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Heidelberg 69117
DE
Listed location countries
Age
Inclusion criteria
1. Sex: male or postmenopausal female.
2. Age: 65 to 85 years, inclusive, at screening.
3. BMI :18.0 to 35.0 kg/m2 , inclusive, at screening.
4. Status: healthy subjects.
5. Good physical and mental health based on medical history, physical
examination, clinical laboratory, ECG, and vital signs, or the absence of any
medical condition which, in the opinion of the Investigator, might prevent
compliance with study procedures or completion.
6. Subjects must have a score of >=23 on the Mini-Mental State Exam (MMSE).
Exclusion criteria
1. Evidence of any active or chronic disease or condition that could interfere
with, or the treatment of which could 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 (SBP) and diastolic blood pressure (BP), pulse rate, body
temperature], 12lead ECG, and clinical laboratory parameters [hematology,
blood chemistry, and urinalysis]). Minor deviations of laboratory values from
the normal range may be accepted, if judged by the Investigator as clinically
irrelevant.
2. Previous participation in the current study.
3. Employee of PRA or the Sponsor.
4. History of relevant drug and/or food allergies.
5. History of alcohol abuse or drug addiction (including soft drugs like
cannabis products) in the previous 2 years.
6. Positive drug and alcohol screen (opiates, methadone, cocaine, amphetamines
[including ecstasy], cannabinoids, barbiturates, benzodiazepines, gamma
hydroxybutyric acid [GHB], tricyclic antidepressants, and alcohol) at screening
or at the first admission.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2021-002665-17-NL |
| CCMO | NL78397.056.21 |