IMPAACT Pharmacology Laboratories

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IMPAACT Pharmacology Laboratories

• July 2006

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IMPAACT Pharmacology Lab Activities

• Assay development (5-20)
• Protocol development (10-20)
• Assay performance (20-50)
• Mini-repository
• PK analysis (10-65)
• Real time PK reports for protocols
• (e.g. P1020, P1021, P1026s, P1034, P1030, P1038,
  P1058)
• Intensive PK analyses
• Population PK analyses
• Other analyses (PD/adherence etc)

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Labs Performing Pharmacology Assays for IMPAACT
Studies

• Core
• UCSD
• J Hopkins - grand fathered for HPTN 046 / 057
• Specialty Labs -
• Colorado
• UAB
• UCSF
• UCSD
• St Judes (unfunded)
• International Labs-
• South Africa (P1041 -INH)
• Chang Mai (P1032, P1056)

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Pharmacology Lab- Colorado
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Pharmacology Lab- UAB
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Pharmacology Lab- UC San Diego
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Pharmacology Lab- UC San Francisco
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IMPAACT Studies with Pharmacology Components
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(No Transcript)
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Priority Specialty Assays

• New ARVs
• TPV (UCSD/UAB in development)
• TMC-278
• Merck Integrase Inhibitor
• Darunavir
• CCR5 antagonist
• Other Drugs
• Anti-TB?
• Anti-malarials?

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Priority Specialty Assays Intracellular NTRI-TP
assays

• Methodologies require large volumes
• Use in PACTG Studies
• P1012 (St Judes)
• P1052 (St Judes)
• Methods
• Colorado (ZDV-TP, 3TC-TP, TFV-DP-published )
• UC San Francisco?
• UAB?

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Priority Specialty Assays Non-plasma matrices

• Breast Milk
• UCSD (NVP, 3TC, ZDV) working on TFV
• UAB working on TFV
• Dried Blood Spots
• UCSD (NVP, 3TC, ZDV) working on TFV
• Amniotic Fluid / Vaginal Secretions
• UAB
• CSF-
• UCSD (LPV, ABC, ZDV, 3TC, IDV, NVP)
• UCSF
• Other Tissues
• UCSF

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Priority Specialty Assays Unbound Assays

• Populations where important
• Pregnancy
• Newborns
• Alpha1 acid-glycoprotein bound drug
• Protocols - P1026s, (P1030)
• Assays
• Ultrafiltration - UCSD (LPV)
• Equilibrium Dialysis -UCSF (NFV, LPV, APV)
• Alpha1 acid glycoprotein - UCSD

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Improved IMPAACT (Pharmacology) Lab Utilization

• Critical Review of RT assays
• RTV for boosting not need to be assayed in real
  time if combo assay only RTV count as batched
• Re-justify PK assays beyond 1 year of subject
  enrollment studies with assays out to 5 years
  costly and delays analysis/manuscript
• Develop realistic assay template for tracking
  responsibility of pharmacologist. OPS to provide
  access to study status including subjects on
  study and stage
• lt 8 wks/ 8wks 1yr / gt1yr
• Required time lines for analysis, presentation,
  publication based on protocol goals
• Incorporate fees into Industry agreements for
  use of IMPAACT PK data

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Reasonable Workload from Current Funding Level
One pharmacologists opinion what 110K/yr
supports

• Derive activity costs
• Mix and match
• Develop / validate 1 assay method in year for
  IMPAACT
• Oversight of Lab / IMPAACT participation
  (including meetings)
• 600 batched assays/year
• Weight RT at 3.3x or 4.2x for RT with report
• Weight Intracellular at 3x
• Weight unbound at 1.5x
• 1 cohort standard PK analysis for cohort/year
• Weight PopPK at 3x
• Participate in an active protocol / pharmacology
  plan
• Extra activities support through protocol funds