The study will be performed in 2 parts, Parts A and B. The purpose of the study is to investigate to what extent BN201 is tolerated. It will also be investigated how quickly and to what extent BN201 is absorbed and eliminated from the body (this is…
ID
Source
Brief title
Condition
- Ocular neuromuscular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Safety : In both study parts: adverse events (AEs; including infusion site
reactions), clinical laboratory, vital signs, 12 lead electrocardiogram (ECG),
telemetry and physical examination
In Part A only: Holter monitoring and electroencephalogram (EEG)
In Part B only: Columbia-Suicide Severity Rating Scale (C-SSRS)
questionnaire, quantitative sensory testing (QST) for mechano-sensitivity, and
visual analog scale (VAS) for spontaneous pain
PK : Plasma BN201 concentrations
Plasma PK parameters estimated using noncompartmental analysis, as
appropriate: Cmax, tmax, kel, t1/2, AUC0-t, AUC0-24, AUC0-inf, %AUCextra, CL,
Vz and dose linearity (Parts A and B), and Ctrough and Rac (Part B only)
PD : Translocation of Foxo3 from nucleus to cytoplasm in peripheral blood
mononuclear cells (PBMCs)
Secondary outcome
n/a
Background summary
BN201 is a new investigational compound that may eventually be used for the
treatment of acute optic neuritis. Optic neuritis is an inflammation of the
optic nerve, the bundle of nerve fibers that transmits visual information from
your eye to your brain. BN201 is a compound that activates the enzyme called
*serum glucocorticoid kinase-2* (SGK2) which promotes the survival of cells by
changing the cellular localization of the forkhead transcription factor Foxo-3,
thus inhibiting cell death.
Study objective
The study will be performed in 2 parts, Parts A and B. The purpose of the study
is to investigate to what extent BN201 is tolerated. It will also be
investigated how quickly and to what extent BN201 is absorbed and eliminated
from the body (this is called pharmacokinetics). In addition, the effect of the
compound on the location of the protein Foxo-3 in white blood cells will be
investigated (this is called pharmacodynamics).
This study will be performed in 32 healthy male and female volunteers, divided
over 4 groups.
For each group, the study will consist of 2 periods. In each period you will
receive a single dose of BN201 or a single dose of placebo. A placebo is the
same formulation without the active ingredient. BN201 and placebo will be given
in the form of an intravenous (iv) infusion. The duration of the iv infusion
will be approximately 1 hour. There will be at least 14 days between each time
you will receive the research compound.
Study design
Part 1:
The actual study will consist of 2 periods during which the volunteer will stay
in the clinical research center in Groningen for
3 days (2 nights). There will be a resting period of at least 14 days between
each period. In each period, the volunteer will
receive the study compound on Day 1 and will leave the clinical research center
on Day 2.
Part 2:
The actual study will consist of 1 period. The volunteer will stay in the
clinical research center in Groningen for 7 days (6 nights). The volunteer
will receive the study compound 5 days (once a day) and will leave the clinical
research center on Day 6.
Intervention
Part 1:
During the study you will receive BN201 or placebo after an overnight fast (at
least 10 hours no eating and drinking) as an iv infusion. The duration of the
iv infusion will be approximately 1 hour.
Part 2:
During the study you will receive BN201 or placebo after an overnight fast (at
least 10 hours no eating and drinking) as an iv infusion. The duration of the
iv infusion will be approximately 1 hour.
For all groups it is applicable that fasting will continue until 2 hours after
the start of the iv infusion. Then you will receive breakfast. During fasting
and after intake of the study compound, you are allowed to drink water with the
exception of 2 hours prior to until 1 hour after drug administration.
Study burden and risks
As BN201 will be administered to humans for the first time in this study,
adverse effects of BN201 in humans have not been reported to date. However,
BN201 has been studied in animals. BN201 was welltolerated in rats (at a dose
level of 50 mg per kg body weight per day) and dogs (at dose levels up to 18 mg
per kg body weight per day), when administered once-daily as an iv infusion for
14 consecutive days. In dogs, the most frequently observed adverse effects
after once-daily administration of BN201 (36 mg per kg body weight per day) for
14 consecutive days were: incoordination, body tremors and/or shaking,
decreased activity, convulsions, and increase in heart rate. All observed
adverse effects were of short duration and generally resolved within 1 day
after administration of the study compound.
In each group and in each period, initially 2 volunteers will be dosed (1
volunteer will receive BN201 and 1 volunteer will receive placebo). After
dosing, the safety and tolerability of BN201 in these 2 volunteers will be
closely monitored for 24 hours. If there are no unacceptable adverse reactions
and both PRA and the Sponsor agree on the safety and tolerability of the study
compound in the first 2 volunteers, the remaining 6 volunteers of the group
will be dosed.
Dalmases 27
Barcelona Local 1 08017
ES
Dalmases 27
Barcelona Local 1 08017
ES
Listed location countries
Age
Inclusion criteria
- healthy male or female
- 18-55 years old inclusive
- BMI between 18.0 - 32 kg/m2
- smokes less than 6 cigarettes per day (or 1 cigar or pipe)
Exclusion criteria
strenuous activity (e.g. sports) is not allowed from 96 hours (4 days) prior to entry into the clinical research center and during your stay in the clinical research center. you are not allowed to eat or drink (fast) from 4 hours prior to the pre-study screening, from 4 hours prior to entry into the clinical research center and from 4 hours prior to the poststudy screening .you are not allowed to consume any methylxanthine-containing beverages or food (coffee, tea, cola, chocolate, *powerdrinks*) or alcohol, from 48 hours (2 days) prior to entry into the clinical research center and during your stay in the clinical research center. you are not allowed to consume any foods containing poppy seeds from 48 hours (2 days) prior to the prestudy screening and entry into the clinical research center as this could cause a false-positive drug screen result. you are not allowed to use any prescribed medication during 30 days prior to entry into the clinical research center until the poststudy screening .you are not allowed to use any over-the-counter medication, vitamin preparations and other food supplements, or herbal medications (e.g. St. John*s Wort), from 14 days prior to entry into the clinical research center until the poststudy screening. you are not allowed to have had a serious infection (e.g., pneumonia) within 2 months before the pre-study screening. you are not allowed to have had an active bacterial or viral infection and fever (body temperature >38°C) within 48 hours (2 days) prior to the first administration of the study compound.
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 | EUCTR2015-002722-39-NL |
| CCMO | NL54253.056.15 |