eeg awareness weeks - what eeg can co for your trial

www.thesiestagroup.com

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What EEG can do for your trial

Georg DorffnerP t A dPeter Anderer

Electroencephalography (EEG)

International 10/20 systemInternational 10/20 system

4 minutes eacheyes open/eyes closedy p yRepeated stimuliLong-term (e.g. sleep)

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Stimuli for event-related potentials

Visual (VEP) Acoustic (AEP)Visual (VEP)e.g. checker pattern

Acoustic (AEP)e.g. oddballparadigmparadigm

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Core paradigms of Pharmaco-EEG

Single channel topography tomography(LORETA)

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Sp

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(qE

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-2

-1

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2

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t-val

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edia

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N1-LATENCY

P2-LATENCY

N2-LATENCY

P300-LATENCY

Eve

nt-re

Pot

nt(E

R

4

E

Main endpoints: qEEG

Power per bandAbsolute and relativeDominant frequenciesfrequenciesratios

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Main endpoints: ERP

LatencyAmplitudeN1 N2 P2N1, N2, P2, P3 componentscomponents

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Why EEG?

It‘s an objective measurement

It helps you answer questions likeIs my drug active in the brain?How does it act?Where does it act?When does it act?At which dose does it act?

7in a very cost-efficient manner

How …

stimulant sedative

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Drug induced EEG changes are related toDrug-induced EEG changes are related to behavioral changes (Fink 1964)

EEG slow activity (with or ith t lit d )

Perceptual discrimination , motor activity , mood , th ht i t it d t without amplitude )

EEG beta activity (with

thought intensity and rate , recall sleep duration , affect , fear y (

amplitude )EEG beta activity (with amplitude )

and anxiety mood , perception of stimuli

amplitude )EEG beta + slow activity delirium, perceptual acuity +

recall , psychomotor tl

EEG alpha activity restlessness relaxation, reveries, pleasant fantasies, feelings of well-being,

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euphoria, mood

How:How: Effect on perception and cognition

10

20

10

0

10

n m

s

30

-20

-10

Diff

erec

nes

in MID (n=16,16)SDAT (n=18,17)

Nicergoline

50

-40

-30

* p<0 05 t-test

*

**

Nicergoline (8 weeks, 20x30mg) vs. Placebo

Shortening of latency points toward cognitive

-50N1 P2 N2 P300

p<0.05 t test** p<0.01

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Shortening of latency points toward cognitiveimprovement

Where … (electrode)

Topographic map(19 l t d(19 electrodes, interpolated)Depicts changes (drug/placebo) or significance (p values)Univariate or several variables

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Where … (brain area): LORETA

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When …

Riba et al. 2002

13PK/PD modeling

At which dose …

DIFFERENCES BETWEEN DRUG ANDDIFFERENCES BETWEEN DRUG-AND PLACEBO-INDUCED CHANGES IN ABSULUTE POWER VARIABLES AFTER 0.1mg, 0.2 mg AND 0.4mg SURICLONE AND 1mg ALPRAZOLAM 2 g gHOURS AFTER ORAL ADMINSTRATION (N=15)

Saletu et al 1994

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Saletu et al, 1994

Cost-effectiveness

15Wilson 2012

Other advantages

UnobtrusiveUnobtrusiveNo radiation or additional exposure to drugsethically without problemsShort measurement without too many yburdensEffects with n = 10 .. 40Effects with n 10 .. 40

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Key-Lock Principle (Saletu)

Representative drugs of the main h h l i l l i dpsychopharmacological classes induce – as

compared to placebo – significant and typical h i th EEGchanges in the EEG

In many variables these changes are opposite to differences between patients pp psuffering from mental disorders

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18Saletu et al. 2006

19Saletu et al. 2006

Key-lock – example

Saletu et al. 1997

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EEG in the development cycle

Dose-efficacy relationsPreclinical Therapeutic outcome

Relation to clinical

Preclinical

variables

R d t EEGPhase I

Rodent EEGRodent sleepTranslationalhypotheses

Phase II

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yp

Data quality

EEG is a very sensitive instrument

Data quality must be high and constantq y gProper patchingProper devicesProper devicesAvoidance of artifactsSubject must be awakeSubject must be awakeNo disturbance

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Artifacts - example

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Artifact after reduction

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The Siesta Group

Clinical trial service provider specialised in sleep and/or Electroencephalography (EEG)Large scientific background, physician co-ownedp yTight network of partners and associatesHeadquarter :Headquarter :Vienna, Austria, EuropeUS operations through Philips-RespironicsRespironics

Developer of Somnolyzer24x7,purchased by Philips Respironics

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purchased by Philips-Respironics, Feb 2010

Pharmaco-EEG: Services we offer

Consulting and protocol developmentTrial feasibility and set-upSite identification, preparation, training, managementp p g gCentralized data analysis, such as sleep scoring, EEG spectral analysis, and other endpoint calculationPSG and EEG data quality monitoring and harmonizationBiomarker research and exploratory data analysisDevice rentals

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Pharmaco-EEG: Our strengths

Covering full spectrum of pharmaco-EEGHigh level quality controlg q ySuperior artefact treatment>30 years of experience>30 years of experienceState-of-the-art technologyTop experts in psychiatry and neurologyFollowing latest IPEG standards

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g

Scoring/Reading center – data flow

Sponsor Endpoint variabletable

SiestaCRF

S esta

reports

PSG/EEG data (edf)Online SDex

reports

Inv. siteInv. site

Inv. siteInv site

Secure ftpMain variables

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Inv. site

Special offer for US trials:Special offer for US trials:Partnership with Community Research

Dedicated Clinical Research Site (Since 1995)Th L ti i G t Ci i ti OHThree Locations in Greater Cincinnati, OH60 Bed Phase 1 Unit Located on Hospital CampusPhase 1 Experience Includes: First-in-Human, SAD/MAD, Patient/Special Populations Food Effect EEG/PSG VaccinesPopulations, Food Effect, EEG/PSG, Vaccines18 Year History of Excellence in Sleep Research8 Bed Sleep Laboratory in Phase 1 Unit; (14 total PSG beds)Sl St di I l d I i N l Sl A R tl LSleep Studies Include: Insomnia, Narcolepsy, Sleep Apnea, Restless Leg Syndrome, Shift Work Sleep Disorder, Non-Restorative Sleep Syndrome, Jet Lag, Sleep and Human PerformanceRecruitment Database of 60 000 NHV and Patient PopulationsRecruitment Database of 60,000 NHV and Patient PopulationsCNS Populations: Depression, Bipolar, GAD, OCD, Binge Eating, Alzheimer's Disease, Parkinson's Disease, Pain (Chronic, OA/RA, Fibromyalgia, Migraine)

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y g g )Excellent Inspection History: 3 FDA Audits Without 483 Findings

Your advantage

EEG expertise, investigator, and trial manager in onemanager in oneUtmost quality through joint SOPsReduced costs and quicker study startCombined experience in almost every field of p yCNS-active drugs

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Our offer until March 31, 2013

Free Feasibility: C t d ff t f i l di EEGCosts and efforts for including EEG

You provide: real or mock protocolYou provide: real or mock protocol

W id t ti t f dditi lWe provide: a cost estimate for additional EEG costs

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Contact

The Siesta GroupVienna Austria:Vienna, Austria:Phone: +43 1 9551213info@thesiestagroup.com@ g pwww.thesiestagroup.com

USA: Philips RespironicsBend, Oregon:Phone: 1-541-598-3800, 1-800-685-2999respironics.minimitter@philips.comclinicaltrials respironics com

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clinicaltrials.respironics.com

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

h ti b h i h lth l t B J Cli Ph lpsychoactive beverage ayahuasca in healthy volunteers. Br J Clin Pharmacol. 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(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 ggeneralized 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 52EEG mapping 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

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EEG mapping and psychometry. Br J Clin Pharmacol. 1994 Feb;37(2):145 56.