1. To investigate the safety and tolerability of single oral doses of NS11821 in healthy male subjects and estimate a maximum tolerated dose.2. To investigate the pharmacokinetics (PK) of single ascending oral doses of NS11821.
ID
Source
Brief title
Condition
- Anxiety disorders and symptoms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Safety parameters
1. Adverse events.
2. Vital signs (supine and orthostatic blood pressure, heart rate, body
temperature, respiratory rate).
3. Electro-cardiogram (ECG).
4. Safety laboratory assays (clinical chemistry, haematology, and
urine-analysis).
Pharmacokinetics:
1. Plasma concentration of NS11821.
2. Urine concentration of NS11821.
Secondary outcome
Pharmacodynamics:
Saccadic eye movements: peak velocity, reaction time, inaccuracy.
Smooth pursuit.
Visual analogue scales (VAS) according to Bond and Lader: alertness, mood and
calmness.
VAS Bowdle: item *feeling high*, and composite factors *internal perception*
and *external perception*.
Body sway.
Adaptive tracking (tracking performance).
Power spectral changes in ph-EEG.
Cognitive function (Cognition (Visual Verbal Learning Test)).
Tapping.
Pharmacokinetics:
Plasma and urine concentration NS11821 metabolites.
Background summary
NS11821 is a new investigational drug that is being developed for the treatment
of anxiety disorders. This drug is not yet registered and in this study will be
administered to humans for the first time. Due to its more selective action in
the brain, this compound is expected to cause less side effects than the
current drugs in the market, such as lorazepam.
Study objective
1. To investigate the safety and tolerability of single oral doses of NS11821
in healthy male subjects and estimate a maximum tolerated dose.
2. To investigate the pharmacokinetics (PK) of single ascending oral doses of
NS11821.
Study design
This is a single-dose, parallel, double blind, placebo-controlled, randomized,
dose-escalation study in healthy male subjects.
Intervention
Three ascending single oral doses (i.e. 10, 30, and 50 mg) are planned with a
dose escalation factor of approximately 2. However, based on safety,
pharmacokinetic or pharmacodynamic findings, further decisions can be dose
escalation, dose de-escalation, or dose repetition. It may also be possible to
terminate the study prematurely. After the first three dose levels the
scientific review committee will review all data and may decide to either
continue or discontinue the study. An additional 2 cohorts may be rectuited.
The maximum dose of NS11821 is 150mg.
Study burden and risks
Screening: medical history taking, physical examination, venapuntion
(haematology, chemistry, virology), drugs screening.
Studyday: repeated performance of several tests, insertion of intravenous
catheter for repeated blood sampling,
ECG.
Follow-up: physical examination, ECG
Restrictions: during the study period, restriction will be applied to living
pattern and the use of alcohol, tobacco,
cafeine, recreational drugs and medication.
Side-effects: as this study is with a new drug, not all of the side effects are
known. It is possible that unexpected side effects occur during the study.
Pederstrupvej 93
2750 Ballerup
Denmark
Pederstrupvej 93
2750 Ballerup
Denmark
Listed location countries
Age
Inclusion criteria
1. Voluntary provision of written informed consent prior to any study procedure, indicative of understanding the purpose of the study and willing to participate in the study and comply with the study procedures and restrictions.
2. Male.
3. Aged 18-45 years (both inclusive).
Exclusion criteria
1. Subject is unhealthy according to medical history, physical examination, ECG, blood pressure and heart rate, and laboratory profile of blood and urine. A volunteer with a clinical abnormality may be included only if the investigator or his designee considers that the abnormality will not introduce additional risk factor for the subject's health, or interfere with the study objectives.
2. Presence or history of clinical significant psychiatric diseases, as judged by the investigator.
3. Any clinically relevant acute or chronic diseases which according to the investigator could interfere with the subject*s safety during the trial, or expose them to undue risk, or which could interfere with the study objectives.
4. Presence or history of clinical significant diseases of the renal, hepatic, gastrointestinal, cardiovascular, musculoskeletal system or presence of history of clinical significant immunological, endocrine, metabolic diseases, or other condition known to interfere with the absorption, distribution, metabolism or excretion of drugs, as judged by the investigator.
5. Presence or history of clinically significant allergy or known hypersensitivity to any component of the investigational product.
6. Has a Body Mass Index (BMI) < 18 or > 30 kg/m2.
7. Has positive serology for HIV-1, HIV-2, hepatitis B (surface antigen), and/or hepatitis C.
8. Has planned medical treatments (including dental care) from screening to follow-up visit.
9. Use of prescribed medication or over-the-counter (OTC) medication within two weeks prior to dosing, except for paracetamol.
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10. Enrolment in any investigational study or intake of an investigational drug within 3 months prior to the start of the study or more than 4 times a year.
11. Current regular user of any illicit drugs or history of drug or alcohol abuse. Subjects who have a positive drug screen at screening and/or pre-dose or subjects who have a positive alcohol breath test at pre-dose will be excluded.
12. Donation of blood/plasma outside limits of Sanquin Blood Supply Foundation guidelines.
13. Previous randomization in this study.
14. Has any barrier (language, mental incapacity, etc.) that could interfere with the psychomotor or cognitive tests.
15. Unlikely to co-operate in the study, and/or has poor compliance anticipated by the investigator. Or not consistently reachable in case of emergency.
16. Daily consumption of xanthine-containing products more than 6 units. Unwilling or unable to refrain from consumption of xanthine-containing foods or drinks from 2 days prior to admission and during the stay in the research unit. One caffeine unit is contained in the following items: one cup of coffee, two cans of cola, one glass of tea, * cup of energy drink (e.g. Red Bull) or three chocolate bars.
17. Unwilling or unable to refrain from intensive physical exercise from screening until the follow-up visit.
18. Unwilling or unable to refrain from products containing alcohol from 2 days before admission and during the stay in the research unit.
19. Unwilling or unable to refrain from products containing grapefruit from 2 days before admission and during the stay in the research unit.
20. Smokes more than 5 cigarettes (or equivalent as judged by the investigator) a day, or unwilling or unable to refrain from smoking from 24 hours before admission and during the stay in the research unit.
21. Unwilling to abstain from having unprotected sexual intercourse or donating sperm during the study and for 3 months after study.
22. Is unsuitable, in the opinion of the investigator, to participate in the study for any other reason.
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 | EUCTR2009-012373-35-NL |
| CCMO | NL28807.058.09 |