Day Two - 15th May 2008

07:30

Registration opens

08:00

Breakfast Briefing: Identification of human drug metabolites – how important and when?
Human ADME studies are often conducted at Phase II and sometimes even as late as Phase III in drug development. The result is that if human specific metabolites are found at these stages then much further work on identification and characterization needs to be performed with consequent time delays and increased costs. The US FDA has produced a draft guidance document on safety testing of metabolites which states that human ADME studies be
conducted early in the drug development process. They also stated that human metabolites need to be characterized that are 10% of either total drug equivalents or 10% of parent.
This briefing discussion will focus on the implications of the FDA’s recommendations and how they may be carried out using Enhanced Phase I approaches.
Facilitated by: Xceleron

09:00

Coffee

09:15

Opening remarks from the chair

09:30

Keynote address: Medical risk and the future of drug development in Europe
» Regulators stand proxy for the public in setting acceptable levels of risk in
reaching all regulatory decisions, from clinical trial authorisation through to post-market vigilance. In reality, the true concern is with risk-benefit as assessed at each point; this concept features little in public discourse
» We are hampered by lack of understanding of public attitudes and perceptions, since these are filtered through the mass media. The Agency has addressed this by commissioning population research.
» Any substantial modification to the existing developmental pathway will require public support, based on a better-informed debate on the key issues than currently exists.
Professor Kent Woods, Chief Executive, Medicines and Healthcare products Regulatory Agency (MHRA)

10:00

Outsourcing Phase I Trials: Sponsor perspective
» AstraZeneca’s Phase I Outsourcing Strategy
» Implementation and experience with service providers
» Overall benefits and lessons learnt
Dr Susan Kihlblom, Clinical Project Coordinator Director, AstraZeneca R&D

10:30

Tea

Stream One

11:00

Smarter Early Development : Human Microdosing and Enhanced Phase I strategies
Chairman: Professor Colin Garner, CEO, Xceleron

11:00

Opening remarks

11:15

Enhanced Phase I: obtaining iv kinetics using microtracers
» Reducing late stage attrition and enhancing pipeline value through smarter approaches in Phase I
» How to gain metabolite profiling, iv kinetics, absolute bioavailability and mass balance information in a Phase I setting
» Industry case studies
Professor Colin Garner, CEO, Xceleron

11:45

Use of microdosing approaches with Positron Emission Tomography in early drug development. Examples of recent advances and decision enabling studies
Dr. Svante Nyberg, Discovery Medicine Director, AstraZeneca, Sweden

12:15

Human Microdosing : Servier’s experiences
» What is human microdosing and how is it used?
» Benefits / Challenges of the approach
» Future perspectives on microdosing in early clinical development
Dr Richard J Weaver, Head of Metabolism & Pharmacokinetics, Servier R&D

12:45

Closing remarks

Stream Two

11:00

Creating a smooth transition between preclinical and first-in-man use.
This practical and interactive workshop will focus on minimizing risk in the design and conduct of Phase I FIM studies.
Facilitated by leading Early Phase practitioners and experts - this workshop provides delegates
with an overview of critical issues to aid decision making when transitioning from preclinical to the first use in man.

11.00

Opening remarks

11.10

Preclinical data review - investigator responsibilities
Access to experts

11.40

Study design and dosing strategies - optimizing safety
The role of safety - PK/PD assessments

12.00

Investigator suitability
Clinical Investigation sites - access to emergency & specialist care

12.20

Case Study: First use in Man - A sponsors perspective

12.50

Questions and closing remarks

Facilitated by:
Dr Elizabeth Allen, Director of Scientific Affairs, Quintiles GDRU
Dr Tim Mant, Senior Medical Advisor, Quintiles GDRU
Dr Darren Wilbraham, Associate Medical Director, Quintiles GDRU

14:00

Choosing the right dose
» Why is it difficult?
» Thinking in logarithms
» Past mistakes
» Stepwise approach to exposure
Dr John Warren, Senior Medical Assessor, MHRA

14:30

The use of biomarkers in early clinical development
» The coherent use of biomarkers from pre clinical into the early clinical phase
» The validation of biomarkers in early development and their preparation as surrogates
» The use of biomarkers to establish dose response
Steve Pascoe MD MSc, Global Head Respiratory/Dermatology Profiling, Exploratory Clinical Development, Novartis

15:00

Case study: Improving inclusion criteria for healthy volunteers in phase 1 trials
» Two-year survey at Antwerp SGS Clinic
» Vital signs and ECG parameters
» Key biochemical parameters?
Dr Steven Ramael, Medical Director, SGS Clinical Pharmacology Unit

15:30

QT assessment in early development and using Preclinical QT Data to Impact Clinical Study Design and Decision Making
The optimal approach to assessing QT in early development and the Thorough QT study will be discussed. Some pharmaceutical companies are stopping the development of investigational agents that have even very weak preclinical QT signals (e.g., hERG IC50 to therapeutic plasma concentration >1/300).
This lecture will also explore how the results of preclinical data- hERG, APD measurement, animal QT, and heart rate changes in dogs can be used to impact internal decision making in a thoughtful manner and, along with additional preclinical arrhythmia testing, can significantly impact the design of the early clinical studies.
Appropriately integrating the preclinical data into the early clinical studies’ design can provide early clinical data of QT risk or its absence, and thus significantly influence future development decisions.
Approaches to further clinically validate preclinical arrhythmia models will also be discussed.
Dr Philip Sager, Executive Director, AstraZeneca

16:00

The Relationship between pharmacokinetic exposure and QT prolongation in Cardiac Safety Trials
Dr Arne Ring, Phase I – IIa Statistics, Boehringer Ingelheim Pharma GmbH

16:30

Tea

16:45

Case study: Safe transition into first in human dose
» Effective use of preclinical data in the transition into man
» Study design
» Finding the right dose and dose escalation
» Maintaining patient safety
» Regulatory compliance
Dr Karin Kramer Nielson, Director of Clinical Pharmacology, Novo Nordisk

17:15

Case Study: Exploratory development of CNS product
» How to improve animal models from a clinical perspective
» Barriers in development organizations
» Challenges within the CNS indications
Dr Birgitte Soegaard, Head of Clinical Pharmacology & Pharmacokinetics, Lundbeck

17:45

Closing remarks

18:00

End of conference