CNS, LLC CLINICAL PHARMACOLOGY UNIT 2600 Redondo Avenue, Suite 500 Long Beach, CA 90806

CNS, LLCCLINICAL PHARMACOLOGY

UNIT2600 Redondo Avenue, Suite 500

Long Beach, CA 90806

Bobbie TheodoreAlliance Director

[email protected]

Annie SpenoOperations Manager

[email protected]

www.clinicaltrialcenters.com


State-of-the-Art Clinical Pharmacology Unit

Facility60+ bed CPU dedicated and designed specifically for early phase clinical researchTargeted healthy normal volunteers, stable psychiatric, CNS, medical and ethno-bridging special patient population trialsAdditional 20 beds in separate PHF unit (Psychiatric Health Facility) licensed by the state of California for acute psychiatric patient population trialsPrivate and semi-private rooms for double occupancy to accommodate caregiver or significant otherLocated within a medical HMO building with a 7 day/week urgent care; acute hospital within 5 milesNumber of offices to accommodate monitors/CRA’s with internet access and copy/fax servicesBuilding has video surveillance that can be monitored in all nurses stationsSecure offsite automatic data back upEasy access to regional Long Beach airport for monitors and visitorsReverse airflow room for smoking breaks, or if protocol allows, patients are accompanied outside of facility for smoking breakContracted with trained pharmacist in compounding procedures; capabilities include encapsulating powder


Staff

Full Time Experienced StaffPrincipal and Sub-Investigators Board Certified in Psychiatry, Neurology, Internal Medicine and Family Practice, and Licensed Clinical PsychologistsMultiple certified doctorate-level raters with comprehensive cognitive rating scales experience24 hour staffing includes licensed ACLS certified nurse’s (RNs, LVNs) on all shiftsDirector of nursing, charge nurse and director of social servicesMultiple dedicated early phase experienced CCRCs and research assistantsLab technicians IATA certifiedDedicated medication dispensary with a Pharm.D. supervisorDedicated outreach and recruitment specialistsRecreational therapistOperations manager provides continuous staff training on GCP, SOPsDedicated internal QA staff conducts internal auditsCaterer provides daily meals, and dietician for special meals or protocol mandated dietary requests


Experience

Healthy normal volunteers (HNV)First in human (FIM) patient populations – Alzheimer’s, schizophreniaSAD/MAD, single, and multiple dose escalation TQT, Qtc, single and continuous ECGTelemetry, holter and ambulatory cardiac monitoringEEG/qEEG, evoked potentialsDrug-drug interaction (DDI), food effect, fed and fastedSerial PK, 24 to 36 hour draws, on the hour and or ½ hourImaging, fMRI , 1.5 and 3T, Arterial Spin Labeling (ASL), and PET imagingCSF collection (conducted by Neurologists and Internists on site. Additional access to anesthesiologists that perform and monitor the setting of spinal catheters)

Proof-of-concept (POC), pilot, pivotal and crossover designsLarge cohorts, and competitive enrollments Up to 8 week inpatient staysDelivery system methods – oral, IV infusion, intravenous, injectable, device, patchBioequivalence


Therapeutic Areas

Psychiatric special patient populations - Addictions (smoking cessation, alcohol dependence, eating disorders, opioid dependence), ADHD, bipolar disorders, cognitive dysfunction, MCI, depression, schizophrenia, stable and acute Non-psychiatric CNS and medical special patient populations - Alzheimer's, pain disorders (headache, migraine, diabetic neuropathy, chronic, PHN, fibromyalgia, osteoarthritis), Parkinson's, type 2 diabetes, hypertension, high cholesterol, women’s health, asthma, multiple sclerosis, OIC, asthma, and IBSBioequivalence and biosimilar Ethno-bridging


Emergency Capabilities, Lab and Data Collection

Emergency Capabilities and TrainingEach unit has an emergency cart which includes an AED and emergency medications checked at every shiftStaff ACLS certified and qualified in use of emergency crash cart, CPR, AED, oxygen tank Automatic defibrillators on site tested and calibrated annually8AM-8PM Urgent Care on site (1st floor)ER ½ mile awayAdmitting privileges at Pacific Hospital (2 miles)

Clinical/Analytical Specimens and LaboratoryRelationship with local laboratory for services24/7 Pick-upSTAT capabilities analyze within 1-2 hoursElectronic transmission capabilitiesRefrigerated and ambient centrifugesAlarmed refrigerators/freezers (-20, -70 and -80 degrees)CLIA waivered labDiesel generator provides 24-hour battery back up

Data CollectionAll data collected by experienced licensed staff, with strict adherence to the protocol, timely and accuratelyData entry between 24-48 hours


Phase I Trials

Phase I: (includes Dr. Mark Leibowitz’ trial experience)70+ healthy normal subject trials, 40+ FIM, 200+ bioequivalence and ethno-bridging50+ patient populations – Alzheimer’s, depression, diabetes, epilepsy, gastrointestinal disorders, hypertension, insomnia, migraine, multiple sclerosis, obesity, Parkinson’s, and schizophrenia

Cognition: 20+ targeting cognitive primary endpointsCognitive dysfunction in schizophrenia, depression, MCI and Alzheimer’sCANTAB administered over 300+ times in 3 yrs (additional rating scale experience on slide 18)


Phase II – III Trials

Psychiatry: 300+ studies, inpatient and outpatient200+ Schizophrenia and schizoaffective disorders - acute, negative symptoms, stable, cognition 50+ Depression – MDD, refractory/treatment resistant, depression with sexual dysfunction 20+ Bipolar mania and mixed 5+ Other indications – ADHD, anxiety, PTSD, chemical dependency

Neurology: 80+ studies, inpatient and outpatient, broad range of indications30+ Alzheimer’s - MCI, mild-to-moderate, severe25+ Pain studies - migraine, diabetic neuropathy, OA, chronic back/knee pain, fibromyalgia15+ Parkinson’s trials - early stage and advanced 8+ Epilepsy - adjunctive therapy and monotherapy 8+ MS – relapsing remitting 5+ Sleep disorders – insomnia, restless legs syndrome

Dr. Mark Leibowitz:20+ patient populations

200+ Bioequivalence15+ Japanese bridging

General Medical:10+ across broad range of indications –

type 2 diabetes, NOH, hypercholesterolemia, OIC, IBS, asthma, crohn’s, women’s health


Phase I Sample Metrics

Study Title# of

Cohorts Contracted# of Cohorts

EnrolledLength of

Enrollment Year StatusA Phase I, Randomized, Single Blind, Placebo Controlled, Ascending Multiple Oral Dose Study Assessing the Safety, Tolerability, and Pharmacokinetics of XXX in Male and Female Subjects with Schizophrenia.

Up to 60 (5 cohorts of 12)

1(12) enrolled in

1 week

ongoing 2014 RESCUE SITE

Active – 1 site

A Phase I, Randomized, Single-Blind, Placebo-Controlled, Ascending Single Oral Dose Study Assessing the Safety, Tolerability, and Pharmacokinetics of XXX in Male and Female Subjects with Schizophrenia


1(12) enrolled in

1 week

ongoing 2014 RESCUE SITE

Active – 1 site

A Phase I, Randomized, Double-blinded, Multiple Ascending Dose Study in Patients with Early-stage Parkinson’s Disease to Evaluate the Pharmacokinetics and Safety of XXX following Intramuscular Injections

Up to 20 (5 max per cohort)

Cohort 1 currently enrolling

2 months 2014 Active


Phase I Sample Metrics (cont'd)

Study Title# of

Cohorts Contracted# of Cohorts

EnrolledLength of

Enrollment Year Status

A Phase I, Prospective, Randomized, Double-blind, Placebo-controlled, Sequential-cohort, Escalating, Single-dose Study designed to determine the maximum tolerated oral dose of XXX in Healthy, Male volunteers – 3 days/2 overnights

45 (3 cohorts of 12) 4th and 5th cohorts

added

3 (36)Cohort 4 enrolling

6 months 20132014

Active – 1 site

Phase I/II Randomized, Double-blind, Placebo-controlled, Sequential Dose Escalation Cohort Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of XXX in Psychiatrically Stable Schizophrenia Subjects – 2 weeks inpatient


5th cohort added

4 (32)Cohort 5 currently enrolling

5 months 20132014

Active – 1 site

A Phase I, Randomized, Double-blind, Placebo-controlled, Combined Single Ascending Dose and Multiple Ascending Dose Study to Assess Safety, Tolerability, Immunogenicity, Pharmacodynamic Response, and Pharmacokinetics of Intravenous Infusions of XXX in Subjects With Mild to Moderate Alzheimer’s Disease

1 (5 patients) 2 (10 patients)

12 months 2012 2013

TOP ENROLLING

SITE



Study Title# of Patients

Screened# of Patients Randomized

Length of Enrollment Year Status

A Phase I, Randomized, Double-blind, Placebo-controlled, Sequential Dose Escalation Cohort Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of XXX in Psychiatrically Stable Schizophrenia Subjects

57 41 5 months 2014 Active

A Phase I, Open-label, Multiple Dose, Safety and Tolerability Study of XXX Administered in the Deltoid Muscle in Adult Subjects with Schizophrenia

40 28 1 month 2013 Active

A Phase I, Evaluation of the Effects of Sequential Multiple-dose Regimens of XXX on Cardiac Repolarization in Patients with Schizophrenia

58 30 6 months 2012 Closed

A Phase I, Placebo-and Positive-controlled Study of the Electrophysiological Effects on the QT Interval after a Supratherapeutic Dose of XXX in Subjects with Schizophrenia

22 15 3 weeks 2012 Closed

A Phase Ib, Randomized, Double-Blind, Placebo-Controlled, Sponsor-Open, Study to Examine the Safety, Tolerability and Pharmacokinetics of XXX in Psychiatrically Stable Subjects with Schizophrenia


A Phase I, Open-Label, Single Group, Multiple-Dose, Study to Evaluate the Pharmacokinetics of XXX Drug Delivery System following 24-hr Application in Patients Diagnosed with Parkinson’s Disease




Study Title# of Patients

Screened# of Patients Randomized


A Phase I, 2-part, open label, inpatient study to assess the safety and tolerability of multiple ascending doses of XXX in subjects with Schizophrenia


Phase I, Open-Label, Randomized, Parallel Group, Crossover Study to Compare the Pharmacokinetcs of XXX in Migraine Subjects During an Acute Migraine Attack and During a Non-Migraine Period

54 20 (SFs due to pts not having a migraine in req’d window)

8 months 2012 TOP ENROLLING

SITE

A Phase I Parallel-group, Double-blind, Placebo and Positive Controlled Multiple Oral Dose Administration Trial to Evaluate the Effects of XXX on QT/QTc in Subjects with Schizophrenia or Schizoaffective Disorder

34 25 1 month 2012 Closed

A Phase I, Open-Label, Single Group, Multiple-Dose, Study to Evaluate the Pharmacokinetics of XXX Patch (XXX Transdermal Drug Delivery System) following 24-hr Application in Patients Diagnosed with Parkinson’s Disease


A Phase I, Double-Blind, Randomized, Placebo-Controlled, Multiple, Escalating Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of XXX in Elderly Volunteers and in Subjects With Mild Alzheimer's Disease (included CSF and PET)

11 7 4 months 2011 RESCUE SITE

A Phase I Randomized, Double-Blind, Placebo-Controlled Study of Safety and Pharmacodynamic Effects of XXX in Major Depressive Disorder Subjects


A Phase I Randomized, Double-blind, Placebo-controlled, Ascending Dose Study of Safety and Tolerability of XXX in Adult Patients With Parkinson’s Disease Who Are Receiving XXX



Phase IIa Sample Metrics

Study Title

# of Patients Screened

# of Patients Randomized


A Phase IIa Randomized, Double-blind, Crossover Study Comparing the Tolerability of Two Dose Regimens of XXX in Adult Patients with Parkinson's Disease who are receiving XXX

11 10 1 month 2010 RESCUE SITE

A Phase IIa, Multicenter, Double-Blind, Randomized, Parallel Group, 4-week Inpatient Treatment Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Two Fixed Doses of XXX Compared to Placebo, Using XXX as an Active Control, in the Treatment of Acute Exacerbation of Schizophrenia


A Phase IIa, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Assess Pharmacodynamics, Pharmacokinetics, Safety and Tolerability of Oral Multiple Ascending Doses for XXX in Patients with Schizophrenia (included 24 hours telemetry and holter monitoring)



Recruitment

Located within three large metropolitan areas, strategically situated to recruit from a very diverse ethnic population of over 15 million people (Los Angeles County – 9MM, Orange County – 3M, and Riverside/San Bernardino Counties – 3M). There are also several major universities and community colleges nearby for healthy normal volunteer recruitmentPartnered with PIs that are part of large psychiatric mental health facilities (serving 5,000 schizophrenia patients), group neurology practice of over 4,000 patients, and a 15 physician family practice with access to thousands of patients Extensive site and practice databases of over 40,000 subjects across a variety of therapeutic areas, established over 13+ years of clinical researchDedicated, 15+ recruitment specialists including field-based outreach staff with established community relationships that visit referring physicians, residential facilities and senior communities, provide free seminars, lunch and learns, distribute flyers and attend community eventsEstablished relationships with media buyers; discounted print and radio ad pricing and preferred placementsRecruitment plans tailored to each study, consistently meet or exceeds enrollment goals in a timely and efficient manner Ads contain number that directs callers straight to our internal call center staff of trained specialists who conduct prescreening over the phoneAbility to pre-qualify patients via IRB-approved pre-screen consent form


Retention

Investigators treat research patients in their practices which promotes retention, and allows for ease in transition and follow upUnits designed specifically for research, with patient comfort and safety in mindPrivate rooms for caregiver accommodations as needed32” LCD flat screen TVs with cable in every room, and in lounge areasWireless internet for personal lab tops and community computers allows patients to keep in touchBoard games, and video systems for video games and movies (DVDs)Recreation Therapist provides ongoing activities for longer inpatient staysLounge, break room, dining room with full kitchenFulltime caterer and dietician provide meals and protocol mandated special dietary requestsSite owned vans and town car service provides patient transportation to and from visits, including to and from the imaging facility, as neededDedicated staff for regular contact with patient and family


Advantages

Swift start up – Central IRBCNS and healthy subject expertise – thought leaders provide clinical feedback, vendor vetting, and CRO recommendations during development process if neededAbility to recruit quality patients for low drop out/high retentionProven study metricsProven placebo separation resultsParticipation in many pharmaceutical and CRO preferred site programs13+ years experienced staff, low turnover

Rating Scale Experience:ACDSACRADAS-COGADCS-ADLADCS-CGIADFACSADMACQADRAIMSAISRS/ADHD RS-IVASEXBACSBAIBARSBASBDIBESBIS11BPI-SFBPRSBSSBVMTCAADID CAARS CADSS CAI

CANTABCBQCCTCDISCDRCDR-SOBCDRS-RCDSCDSSCFCGDSCGI-BP/I/S/SCA-SCIBICCIBIS-plusCOG STATECOWSCPRSCPTCRTTCSDDCSFQC-SSRSCVLTDADDCSQDEQDESS

DSDSISDSM-IV DiagnosisDSSTEDE-QEDSSEQ-5D 5L and 3L proxyESRSESSFAQFASTFCSRT-IRFIQFMSFOSQFrSBeGAFGASGBIGDSGo/ No Go TaskHADSHAM-AHAM-DHISHoehn & Yahr

HRUQHUIHVLTIADCQISIKBITKellgren-LawrenceKSQK-SADSLHIB-Q20LSEQMADRSMCCB (Matrics)MCQMGH ATRQMGH CPFQMINImMIDIMMSEMNSI Part bMoCAModified HachinskiMOS/ MOS-SSMSLT NABNC070

NDSNDTNINCDSNPINPSNPSINSANTBNTSS-6NYPRSPAC-QoLPANSSPDQPDSS-2PGAPGICPI NRSPOMSPPSQAPQASP-R CSAPSPPSQIPUTSPWCPWI

QIDS-16QL21, QL 98Q-LES-QQOL/ QOL-ADRAVLTRBANSRey Cpx FigureRoland-MorrisRSQ – D/WRUD-LiteRUSPRUQSANSSASSASSSBQ-RSCIDSCL-90SCOPASCoRSSDSSF-12SFISGI-CogSIBSIGH-DSIS

SLOFSOWSSQLMSRTTSTSSWNTMTP 1, 2 TrailsTNSn ScoringTooLTOVATSQMTSSRUPDRSUPSAVASWAIS/R/SWCSTWMSWOMACWoRQWPAIWRAADSWTARYBOCSYGTSSYMRS

Certified, experienced raters, including M.D., Ph.D. and M.A.-level


Curriculum Vitae

Click on names to view CVs:David P. Walling, Ph.D. – CEO and PIMark Leibowitz, M.D. - PIArmen K. Goenjian, M.D., D.F.A.P.A., F.A.C.G.S. – PI Omid Omidvar, M.D. – PI Nirav S. Patel, M.D. – PI Steven H. Reynolds, D.O. – PISeanglong Te, M.D. – Sub-I Kim Lorine, Ph.D. – RaterSara Deering, Ph.D. – RaterThanh Ho, Ph.D. – RaterChristopher Webb, MA – RaterDenise Stephens, L.M.F.T. – Rater and Clinical DirectorDalia R. Botros, M.B.B.S. – Director of OperationsAnne Cabral, M.A. – Study Coordinator SupervisorGeraldine Lucas, RN, CCRC – Study CoordinatorHanna Voltattorni, B.S. – Study CoordinatorMarilou Dichoso – Study Coordinator

Additional investigators, raters, and coordinators CVs upon request

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Sponsor Relations Team

Expedited feasibility and budget/contract negotiation handled by single point of contact with Sponsor Relations Team. Our team is responsible for handling the business development needs of the group, sponsor and CRO relations, facilitating the site selection process (CDAs, feasibility questionnaires, CVs, site capabilities information), budgets and contracts, keeping in regular contact for feedback and garnering new study opportunities so the site personnel can focus on their studies in process. There is no charge to sponsors or CROs for these services.

Jeanette Caruso Finance Manager

Bobbie TheodoreAlliance Director



Contact Information

Bobbie TheodoreAlliance Director(916) 939-6696

[email protected]


(916) [email protected]

For Inquiries contact:

mailto:[email protected]

mailto:[email protected]

CNS, LLC CLINICAL PHARMACOLOGY UNIT 2600 Redondo Avenue, Suite 500 Long Beach, CA 90806

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