The webinar is directed toward all clinical trial professionals who work on the development of CNS-active drugs and plan a new early or late phase clinical trial. Electroencephalography (EEG), including Event-Related Potentials (ERP), can be an objective endpoint of choice in many cases – this webinar will make clear why, when and with what benefit. Contents: Main EEG paradigms and endpoints Brain disorders and drug action as seen in the EEG The key-lock principle PD/PK modeling with EEG EEG topographies How The Siesta Group can support clinical trial EEG

1. www.thesiestagroup.com
The Siesta Group Webinar
What EEG can do for your trial
Georg Dorffner
Peter Anderer
P t A d

2. Electroencephalography (EEG)
International 10/20 system
4 minutes each
eyes open/eyes closed
y p y
Repeated stimuli
Long-term (e.g. sleep)
2

3. Stimuli for event-related potentials
Visual (VEP) Acoustic (AEP)
e.g. checker pattern e.g. oddball
paradigm
3

4. Core paradigms of Pharmaco-EEG
Single channel topography tomography
(LORETA)
nalysis
pectral
EEG)
(qE
Sp
An
elated
3
2
1
t-values
Potntials
0
(ERP)
-1
-2
Event-re
-3
N1- P2- N2- P300-
LATENCY LATENCY LATENCY LATENCY
E
4

5. Main endpoints: qEEG
Power per
band
Absolute
and relative
Dominant
frequencies
ratios
5

6. Main endpoints: ERP
Latency
Amplitude
N1 N2 P2
N1, N2, P2,
P3
components
6

7. Why EEG?
It‘s an objective measurement
It helps you answer questions like
Is my drug active in the brain?
How does it act?
Where does it act?
When does it act?
At which dose does it act?
in a very cost-efficient manner 7

8. How …
stimulant sedative
8

9. Drug-induced
Drug induced EEG changes are related to
behavioral changes (Fink 1964)
Perceptual discrimination ,
EEG slow activity  (with or motor activity , mood ,
without amplitude )
ith t lit d ht intensity and rate 
thought i t
th it d t ,
recall 
EEG beta activity  (with
y ( sleep duration , affect , fear
amplitude ) and anxiety 
EEG beta activity (with mood , perception of stimuli 
amplitude )
EEG beta + slow activity  delirium, perceptual acuity +
recall , psychomotor
tl
restlessness
EEG alpha activity  relaxation, reveries, pleasant
fantasies, feelings of well-being,
euphoria, mood 
9

10. How:
Effect on perception and cognition
20
10
0
Differecnes in ms
-10
10
n
MID (n=16,16)
SDAT (n=18,17)
-20
-30
30 Nicergoline
-40
*
(8 weeks, 20x30mg)
**
-50
50 * p<0 05 t-test
p<0.05 t test vs. Placebo
N1 P2 N2 P300 ** p<0.01
Shortening of latency points toward cognitive
improvement 10

11. Where … (electrode)
Topographic map
(19 electrodes,
l t d
interpolated)
Depicts changes
(drug/placebo) or
significance (p values)
Univariate or several
variables
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12. Where … (brain area): LORETA
12

13. When …
Riba et al. 2002
PK/PD modeling
13

14. At which dose …
DIFFERENCES BETWEEN DRUG AND
DRUG-AND
PLACEBO-INDUCED CHANGES IN ABSULUTE
POWER VARIABLES AFTER 0.1mg, 0.2 mg AND
0.4mg SURICLONE AND 1mg ALPRAZOLAM 2
g g
HOURS
AFTER ORAL ADMINSTRATION (N=15)
Saletu et al 1994
al,
14

15. Cost-effectiveness
Wilson 2012 15

16. Other advantages
Unobtrusive
No radiation or additional exposure to drugs
ethically without problems
Short measurement without too many y
burdens
Effects with n = 10 .. 40
16

17. Key-Lock Principle (Saletu)
Representative drugs of the main
psychopharmacological classes i d
h h l i l l induce – as
compared to placebo – significant and typical
changes i th EEG
h in the
In many variables these changes are
opposite to differences between p
pp patients
suffering from mental disorders
17

18. Saletu et al. 2006 18

19. Saletu et al. 2006 19

20. Key-lock – example
Saletu et al. 1997
20

21. EEG in the development cycle
Dose-efficacy relations
Preclinical
Therapeutic outcome
Relation to clinical
variables
Phase I
R d t EEG
Rodent
Rodent sleep
Translational Phase II
hypotheses
yp
21

22. Data quality
EEG is a very sensitive instrument
Data quality must be high and constant
q y g
Proper patching
Proper devices
Avoidance of artifacts
Subject must be awake
No disturbance
22

23. Artifacts - example
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24. Artifact after reduction
24

25. The Siesta Group
Clinical trial service provider
specialised in sleep and/or
Electroencephalography (EEG)
Large scientific background,
p y
physician co-owned
Tight network of partners and
associates
Headquarter :
Vienna, Austria, Europe
US operations through Philips-
Respironics
Developer of Somnolyzer24x7,
purchased by Philips Respironics
Philips-Respironics,
Feb 2010
25

26. Pharmaco-EEG: Services we offer
Consulting and protocol development
Trial feasibility and set-up
Site identification, preparation, training, management
p p g g
Centralized data analysis, such as sleep scoring,
EEG spectral analysis, and other endpoint calculation
PSG and EEG data quality monitoring and
harmonization
Biomarker research and exploratory data analysis
Device rentals
26

27. Pharmaco-EEG: Our strengths
Covering full spectrum of pharmaco-EEG
High level quality control
g q y
Superior artefact treatment
>30 years of experience
State-of-the-art technology
Top experts in psychiatry and neurology
Following latest IPEG standards
g
27

28. Scoring/Reading center – data flow
Endpoint variable
Sponsor table
CRF
S esta
Siesta
reports
Online SDex
PSG/EEG data (edf)
Inv. site
Inv. site
Main variables Inv. site Secure ftp
Inv.
Inv site
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29. Special offer for US trials:
Partnership with Community Research
Dedicated Clinical Research Site (Since 1995)
Three Locations in Greater Cincinnati, OH
Th L ti i G t Ci i ti
60 Bed Phase 1 Unit Located on Hospital Campus
Phase 1 Experience Includes: First-in-Human, SAD/MAD, Patient/Special
Populations,
Populations Food Effect EEG/PSG Vaccines
Effect, EEG/PSG,
18 Year History of Excellence in Sleep Research
8 Bed Sleep Laboratory in Phase 1 Unit; (14 total PSG beds)
Sleep Studies Include: Insomnia, Narcolepsy, Sl
Sl St di I l d I i N l Sleep A
Apnea, R tl
Restless L
Leg
Syndrome, Shift Work Sleep Disorder, Non-Restorative Sleep Syndrome,
Jet Lag, Sleep and Human Performance
Recruitment Database of 60,000 NHV and Patient Populations
60 000
CNS Populations: Depression, Bipolar, GAD, OCD, Binge Eating,
Alzheimer's Disease, Parkinson's Disease, Pain (Chronic, OA/RA,
Fibromyalgia, Migraine)
y g g )
Excellent Inspection History: 3 FDA Audits Without 483 Findings
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30. Your advantage
EEG expertise, investigator, and trial
manager in one
Utmost quality through joint SOPs
Reduced costs and quicker study start
Combined experience in almost every field of
p y
CNS-active drugs
30

31. Our offer until March 31, 2013
Free Feasibility:
Costs d ff t f i l di
C t and efforts for including EEG
You provide: real or mock protocol
We
W provide: a cost estimate for additional
id t ti t f dditi l
EEG costs
31

32. Contact
The Siesta Group
Vienna,
Vienna Austria:
Phone: +43 1 9551213
info@thesiestagroup.com
@ g p
www.thesiestagroup.com
USA: Philips Respironics
Bend, Oregon:
Phone: 1-541-598-3800, 1-800-685-2999
respironics.minimitter@philips.com
clinicaltrials.respironics.com
clinicaltrials respironics com
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33. References
Riba J, Anderer P, Morte A, Urbano G, Jané F, Saletu B, Barbanoj MJ.:
Topographic pharmaco-EEG mapping of the effects of the South American
psychoactive b
h ti beverage ayahuasca i h lth volunteers. B J Cli Ph
h in healthy l t Br Clin Pharmacol. l
2002 Jun;53(6):613-28.
Saletu B, Anderer P, Saletu-Zyhlarz GM.: EEG topography and tomography
(LORETA) in the classification and evaluation of the pharmacodynamics of
psychotropic drugs. Clin EEG Neurosci. 2006 Apr;37(2):66-80.
Saletu B, Saletu-Zyhlarz G, Anderer P, Brandstätter N, Frey R, Gruber G,
Klösch G, Mandl M, Grünberger J, Linzmayer L.: Nonorganic insomnia in
, , g , y g
generalized anxiety disorder. 2. Comparative studies on sleep, awakening,
daytime vigilance and anxiety under lorazepam plus diphenhydramine
(Somnium) versus lorazepam alone, utilizing clinical, polysomnographic and
EEG mapping methods Neuropsychobiology 1997;36(3):130 52
methods. Neuropsychobiology. 1997;36(3):130-52.
Saletu B, Grünberger J, Linzmayer L, Semlitsch HV, Anderer P, Chwatal K.:
Pharmacokinetic and -dynamic studies with a new anxiolytic, suriclone, utilizing
EEG mapping and psychometry Br J Clin Pharmacol 1994 Feb;37(2):145 56.
psychometry. Pharmacol. Feb;37(2):145-56
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