Phase I Research

Ensuring subject safety and efficiently capturing quality PK and PD data in phase 1 research is paramount for pharmaceutical and biotech companies in today’s drug development environment. The ability to make informed Go / No Go decisions on drug development candidates earlier in clinical development can save millions of dollars.

CRI Lifetree understands the importance around these aspects of early phase research. We partner with our clients to optimize the value that drug candidates bring to their pipelines.

Considerations in Phase 1

• Establish clear goals for phase 1 program and options to consider as real data is generated.
• Safety, tolerability, dose escalation, human PK
• Specific Stopping Criteria.
• Related to general safety and tox observations AND to intended pharmacology.
• Know your targets and shoot for them.
• Rushing into and through early phase 1 can leave critical gaps in a program.

Phase 1 Strategic Drug Development Guidelines (pdf)

PK Collections

PK collections of blood and urine are routinely performed as part of phase 1 research, but are anything but routine at CRI Lifetree. Our operations and quality teams utilize study specific tools to ensure adherence to the protocol specifics regarding collection, processing and the documentation thereof. PK and PD relationships add highly valuable data in early phase drug development. An increased emphasis on the study of these interactions reflects the current resurgence in biomarker research for disease modification agents. PK/PD relationships also provide insight regarding the pharmacological basis of unique, "first in class” therapeutics. While PD samples can be collected in the same PK, urine, and CSF samples noted above, CRI Lifetree also has additional unique tools to further explore PD in early phase drug research.

Academic Collaboration

Academic collaborations include the University of Utah’s Brain Institute. Through this collaboration we have used PET scanning, fMRI, and MRS to spatially assess brain levels of drugs, neurotransmitters, and products of altered brain activity (bold oxygen level detection). These techniques have also been coupled at our facility with PK/PD work on CFS and blood to provide comprehensive understanding of drug distribution, kinetics, etc., leading to exceedingly valuable data when making informed decisions on Phase 2 study designs or Go / No Go decisions.

Additional Information

Additional early phase clinical proof-of-concept tests at CRI Lifetree Salt Lake City include cold pressor for assessment of analgesia, typically valuable to assessment of CNS drug involving mechanism of action aspects which include opioid pathway.

Phase 1 Research Highlights:

• Healthy Volunteer
  • Healthy Volunteer
  • POC
  • SAD
  • MAD
  • MTD
  • DDI
  • Food Effect
  • Specialized Populations including recreational opioid users
  • Full PK and PD characterizations in plasma, urine, and CSF
  • Cardiac Safety (QTc) evaluation
  • PD characterization - Cognitive safety and efficacy assessments
  • PD characterization - Neuroimaging (fMRI, MRS, PET)
  • Sleep Architecture Assessments (Polysomnography in our sleep center)

  Specific fiber characterization of signaling of CNS compounds can be assessed using a neurometer which is also being developed at CRI Lifetree.

Phase 1 Metrics - Recent Case Study

• 36 Subjects
• Total CRFs = 23,364
• Total Data Points = 766,639
• No cGCP violations
• Total queries = 386
• 6 days from LPLV to database lock
• 14 days from LPLV to "QA’d PK Data and Draft PK Report Available" - Bioanalytical
  • Inter-cohort analysis
  • 1473 samples in 10 days total
    (two analyte assay, no run failures)