The Primary objective is to confirm the maintenance of vigilance with SENS-111.Secondary objectives are:* to confirm the maintenance of working memory, and cognitive function; * to confirm the pharmacodynamics effect of SENS-111 on symptoms…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
bij gezonde proefpersonen; mate van misselijkheid en behoud van alertheid na inname medicatie
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoints reflecting sedation will be assessed by the change of
performance over time, compared to baseline, including all test parameters of
the
* Vigilance & Tracking test
* Pepsy psychomotor test battery;
Secondary outcome
The main secondary endpoints reflecting sedation will be assessed by the change
over time, compared to baseline, of
* Subjective alertness measured by the Stanford Sleepiness Scale.
The main secondary endpoint reflecting efficacy will be assessed by
* The severity of nausea and associated symptoms assessed by the MISC during
the rotary chair run and by the change over time, compared to baseline.
* The change over time, compared to baseline, of balance performance as
measured by the Balance Test.
Other study end-point
Includes the change versus baseline in the diameter of the pupil measured by
static pupillometry test and the following safety endpoints:
* Overall tolerability: incidence, severity and nature of adverse events and
SAE throughout the study course
* Clinical chemistry and hematology parameters
In order to send subject home safely, different medical checks will be done
during intake and end of trial day (follow finger movement with eyes, Romberg
test, Hand-eye coordination test and misery). Also a short 5 minutes
psychomotor vigilance task (PVT) will be conducted. See document K End of trial
day medical check.pdf.
Background summary
Sensorion is developing SENS-111, a H4 antagonist, 100mg and 200mg as a
treatment of acute unilateral vertigo (AUV), a rare vestibular disorder. Based
on preclinical and clinical studies, SENS-111 was confirmed to modulate the
peripheral vestibular apparatus; to reduce symptoms (such as vertigo and
nystagmus) associated with vestibular dysfunction; and to be safe and well
tolerated. The proposed study is aiming at confirming that SENS-111 (at the
potential therapeutic doses) is devoid of anticholinergic properties in an
experimental situation of an example of a sensory conflict between parts of the
vestibular system, and can therefore be used safely in this population.
Based on the underlying mechanism of action, preclinical safety and clinical
safety studies, it is expected/assumed that SENS-111 will maintain cognitive
performance and avoid sedation. While other antihistaminines (such as Meclizine
as an antihistamine H1) causes major sides effects including sedation, and
cognitive disturbances.
Study objective
The Primary objective is to confirm the maintenance of vigilance with SENS-111.
Secondary objectives are:
* to confirm the maintenance of working memory, and cognitive function;
* to confirm the pharmacodynamics effect of SENS-111 on symptoms experimentally
induced by motion
* assess the safety of SENS-111
Study design
The study is a 4-period, 4-treatment (SENS-111 100mg, SENS-111 200mg, placebo
and meclizine) double-blind, double dummy, cross over design with a randomized
sequence order.
Intervention
Subjects will receive the following treatment once, one week apart, in a random
order
SENS-111 100mg: 1 ODT100mg SENS-111 and 1 ODT placebo and 4 placebo meclizine
oral capsules
SENS-111 200mg: 2 ODT 100mg SENS-111 and 4 placebo meclizine oral capsules
Placebo: 2 ODT placebo and 4 placebo meclizine oral capsules
Meclizine 50mg: 2 ODT Placebo and and 4 meclizine 12,5mg oral encapsulated
tablets
During the trial days, they will be exposed to a rotatory movement, while
sitting in a chair for induction of nausea.
Study burden and risks
The study will include a total of 6 visits: a screening visit, 4 experimental
visits when the subjects will receive the study drug and will be exposed to an
experimental rotation (rotating chair), and a follow up visit by phone call to
confirm the safety of the patient. The tests will be conducted one week apart.
Subjects will be requested to fill in questionnaires and scales, and tests on a
screen during the inclusion visit and during the experimental visits to assess
the severity of symptoms induced by motion, cognition and vigilance. Usual
laboratory tests will be performed at entry and at the end of the study.
SENS-111 has been given to more than 170 subjects, healthy or with allergic
rhinitis or with AUV, at 500mg single dose or up to 250mg for 7 days. SENS-111
was well tolerated and only mild to moderate adverse events were reported. The
most frequent adverse events reported both in SENS-111 and placebo were nausea,
vomiting, somnolence, abdominal pain, abnormal faeces, diarrhoea and headache.
Meclizine has been widely used and is sold as an over the counter medication
for the treatment of vertigo and nausea/ vomiting induced by motion. Risks
associated with the intake of the drug are well known and includes
hypersensitivity to the drug and adverse effects related to the anticholinergic
properties. Subjects will be warned of the possibility of drowsiness and
cautioned against driving a car or operating dangerous machinery. Also,
alcoholic beverages are to be avoided while taking this drug. Subjects with
asthma, glaucoma, or enlargement of the prostate gland will be excluded from
the study due to the risk of worsening. Anaphylactoid reactions, drowsiness,
dry mouth, headache, fatigue, vomiting and, on rare occasions, blurred vision
have been reported.
The subjects will be exposed to a rotatory movement sitting in a chair. This is
expected to induce mild to moderate nausea/vomiting and other motion associated
symptoms. Patient will be constantly followed, and monitored to avoid dramatic
effects.
No individual benefit is expected from participating in this study for a given
subject. It is expected that conducting the study in a homogeneous population,
in standardized condition, using a calibrator will provide reliable evaluation
of the effect of SENS-111 on vigilance, and potential activity in a model of
sensory conflict.
Rue du Professeur Joseph Blayac 375
Montpellier 34080
FR
Rue du Professeur Joseph Blayac 375
Montpellier 34080
FR
Listed location countries
Age
Inclusion criteria
1. Male
2. Aged *18 years and * 45 years
3. Susceptible to motion sickness defined as MSSQ*short within 10th to 95th percentiles
4. Signed and dated written informed consent.
Exclusion criteria
1. History of acute or chronic vestibular disorder, tinnitus or hearing loss, or inner ear problem
2. Past history of seizures or convulsions
3. Past history of migraine or hyperemesis
4. Subjects with known allergy to meclizine, or to any other histamine antagonist
5. Known severe adverse drug reaction e.g. clinical symptoms of cardiac rhythm disturbances
6. Subjects with known asthma
7. History of alcohol or drug abuse
8. Current smoker
9. Current participation in another clinical trial
10. Treatment with any investigational agent within 4 weeks prior to randomization or 5 half-lives of the investigational drug (whichever is longer)
11. Subject with known narrow angle glaucoma,
12. Subject with known prostate enlargement or history of urine retention
13. Subject with infection or inflammatory process during screening or at inclusion
14. Positive urine screening for drugs
15. Any abnormality on 12-lead electrocardiogram (ECG), in particular QTc prolongation defined by: QTc >470 ms
16. Clinically significant abnormal blood pressure (>140/90 mmHg) or significant abnormal heart rate (arrhythmia, or tachycardia or bradycardia).
17. Known history of, or concomitant hepatic, gastrointestinal, cardiovascular, respiratory, neurological, psychiatric, hematological, renal, or dermatological disease, or any condition, psychiatric, substance abuse, or otherwise, that, in the opinion of the Investigator might interfere with the evaluation of study treatment or warrant exclusion.
18. Abnormal laboratory findings:
a. Creatininemia >1.5 upper limit of normal (ULN))
b. ALAT and/or ASAT > 1.5 x ULN
c. Hemoglobin 10 g/ml and/or
d. Neutrophils <1500/ml and/or
e. Platelets <100 000 /ml
19. Subject is unavailable to complete the study (including all follow-up visits) and comply with study restrictions.
20. Subjects who, in the opinion of the Investigator, have significant medical or psychosocial findings that warrant exclusion. Examples of significant problems include, but are not limited to other serious non-malignancy-associated medical conditions that may be expected to limit life expectancy or significantly increase the risk of SAEs and any condition, psychiatric, substance abuse, or otherwise, that, in the opinion of the Investigator, would preclude informed consent, consistent follow-up, or compliance with any aspect of the study
21. Subject is the Investigator or any Sub-Investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol.
22. Any treatment within 72 hours prior to inclusion
23. Prior participation in a clinical trial with SENS-111
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 | EUCTR2018-000777-80-NL |
| CCMO | NL65239.056.18 |