TMU Call Minutes 06/10/2008
Present

Columbia: Marlene Carlson and Fred Jarskog

Duke: Rich Keefe and Joe McEvoy

MGH/BIDMC (Harvard): Don Goff and Lisa Raeke

MPRC: Bob Buchanan, Bernie Fischer, Bob McMahon, and Chris Wells

NIMH: Adam Haim and Ellen Stover

NKI: Rosemary Coslit, Jim Robinson, and Connie Shope

UCLA: Ayala Ofek

Wash. U.: Deanna Barch and Jim Galvin

Action Items

Merck

All sites – Submit polypharm amendment to IRBs. *Do not recruit with new criteria until after FDA approval (30days).

Allon

Nothing to report

Epix

Nothing to report

Novartis

Nothing to report

All Protocols

Nothing to report

Site Monitoring Visit

Nothing to report

Notes

Merck

NIMH DSMB

Merck was approved

1 to 2 2nd generation antipsychotics are acceptable

Amendment was submitted to FDA last week (S. Marder)

Sites should begin submittal process (Language sent out to site coordinators, P. Ball)

Do not recruit until after FDA approves (30 days)

No other issues reported

Allon

No study related issues reported

Contract ending in August

Budget roll-over discussed

Epix

Nothing to report

Novartis

fMRI

  • Novartis and D. Barch met on 06/09
  • Some tasks may be removed to reduce costs
  • CRO may be used for image QA

oThought that 3rd party analyst may relieve burdens for study personnel to focus on other aspects of study

oPlans was not deemed as cost effective

Protocol revisions

  • Currently includes phases 1 and 2, however study design may change

oInterim data set will be produced/analyzed before proceeding to phase 2

oPhases 1 and 2 may be submitted as separate protocols

oStudy may proceed as original fMRI protocol

  • Summary

oPhase 1 (single dose)  Phase 2 (Multi-dose)

oResults from phase one used to determine dosages used in phase 2

oCan be done if following are know: Half-life, absorption rate, metabolite kinetics

  • WTAR

oWill be used since 5th grade reading level required

  • Polypharmacy

oWe are O.K. with 2 or more second generation antipsychotics

  • Male birthcontrol

oNovartis requires use of two forms and up to 3 months after participating in study

oPropose change to…if subject agrees to use “adequate methods”…

  • Concomitant Medication

o3a4, 2d6, 1a2 inhibitors, SSRIs, low dose chronic anxiolytics, will be allowed

oanti-epileptics ok (Neurotonin, lithium < 0.8)

ono Pan-inducers (Dilantin, depakote)

oGalantamine and varenicline should not be allowed

oSee appendix 3 for drug list

  • Smoking

o3:1 ratio for population

oPropose expired CO to be used to determine smoking status (10ppm cut-off)

  • Pharmacological Kinetics

oAll day event

oSubjects should be compensated for extra time involved with testing

  • Phase 2

oDesigned to collect primarily for collection of safety data

oAssessment schedule reviewed

  • Inclusion/Exclusion Criteria (p.8/9)

oVitals ranges ok’d

oBody temp may be removed

oPulse rate may need adjustment

oBMI needs to be raised above 30

oOrthostatic hypotension measurement not necessary

oSGPT within normal range criterion too strict

NKI will conduct data collection

  • Protocol under review
  • AE and SAEs procedure will require further discussion
  • Novartis CRF will be used

All Protocols

Nothing to report

Site Monitoring Visit

Nothing to report

Next Coordinators call: June 17, 2008

Next TMU call: June 24, 2008