Phase-0 / Microdosing Approaches

Safer, Accelerated, Human-Specific Translation in Drug Development

Join our 3rd International Phase-0/Microdosing Stakeholder Meeting

Friday, April 22, 2022, 8:00 am - 5:00 pm in Leiden, The Netherlands (and online)

See program below

Register at:  tburt@Phase-0Microdosing.org

Check our recent AAPS webinar on Phase-0 approaches:

Phase-0/Microdosing: Time for mainstream application in drug development

https://www.pathlms.com/aaps/events/2332/video_presentations/189322

And respective publication at: https://rdcu.be/cxlbW

Phase-0 Including Microdosing Approaches

Phase-0 drug development trials are clinical development approaches that include microdosing trials. These approaches are sometimes called ‘Exploratory Clinical Trials’ ‘Exploratory Investigational New Drug (eIND)’ applications. Phase-0 studies are aimed at providing human data to support selection of preclinical drug candidates prior to entering clinical development.
Read more...

Phase-0 approaches, also called 'Exploratory Clinical Trials', and 'exploratory Investigational New Drug' (eIND) applications:

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Regulatory Framework

The International Conference on Harmonization (ICH) M3 Guidelines outline the regulatory position on Phase-0 including Microdosing approaches. In addition, examples of 5 Phase-0 approaches are provided.

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Operational Factors

Phase-0 approaches offer many operational advantages over traditional Phase-1 approaches. These advantages enable arrival at meaningful developmental decisions in a safer, quicker, and cheaper manner than is possible with traditional Phase-1.

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Application Criteria

The Phase-0 application criteria are developmental scenarios in which Phase-0 may provide advantages over traditional Phase-1. These criteria are the product of Phase-0/Microdosing Network discussions and stakeholder meetings.

Meetings

Third International Phase-O/Microdosing Stakeholder Meeting: Safer, Accelerated, Human-Based Trnslation in Drug Development

In-person / online meeting

Friday, April 22, 2022 (8:00 am - 5:00 pm Central European Standard Time) 

Leiden, The Netherlands

Enabling Human-Based Translation in Drug Development

Enabling Human-Based Translation in Drug Development

In-person and online meeting

Friday, April 22, 2022

Organized by: Phase-0/Microdosing Network (phase-0microdosing.org) 

Chair: Tal Burt, MD - President, Phase-0/Microdosing Network and Burt Consultancy, LLC
Co-Chair: Saskia de Wildt, MD, PhD - Professor of Clinical Pharmacology and pediatric intensivist at Radboud University Medical Center.

Organizing Committee:

Organizing Committee:

Members:

Yuichi Sugiyama, PhD, - Special Professor Emeritus in Josai Interanational University.

Kirsten Anderson, - Vice President, Presage Bioscience.

Elizabeth Baker, Esq., - Pharmaceutical Policy Program Director for the Physicians Committee for Responsible Medicine (PCRM).

Oliver Langer, PhD, - Associate Professor at the Medical University of Vienna in Austria (Department of Clinical Pharmacology).

Esther van Duijn, PhD - Senior scientist at the Department of Metabolic Health Research within the Netherlands Organisation for Applied Scientific Research (TNO).

Safer, Accelerated, Human-Specific Translation in Drug Development

In-Person and Online Meeting

Friday, April 22, 2022, Leiden, The Netherlands

Organized by: Phase-0/Microdosing Network (phase-0microdosing.org) 

Chair: Tal Burt, MD - President, Phase-0/Microdosing Network and Burt Consultancy, LLC.
Co-Chair: Saskia de Wildt, MD, PhD - Professor of Clinical Pharmacology and pediatric intensivist at Radboud University Medical Center.

Organizing Committee:

Chair: Tal Burt, MD - President, Phase-0/Microdosing Network and Burt Consultancy, LLC
Co-Chair: Hiroshi Yamazaki, PhD - President of APDD and Professor, Showa Pharmaceutical University

Ichimaro Yamada, PhD., Vice President APDD and General Manager for R&D, TNAX Biopharma Corporation
Wooin Lee, PhD., Associate Professor, Laboratory of Molecular Pharmaceutics, College of Pharmacy, Seoul National University
Graeme Young, PhD., Director and GSK Fellow, DMPK, David Jack Centre for R&D, GSK
Koji Chiba, PhD., Professor, Laboratory of Clinical Pharmacology Yokohama University of Pharmacy

Goals:

  1. Formulate guidelines for the application of Phase-O/Microdosing approaches
  2. Establish recommendations for further research and development

Objectives:

  1. Provide update on validation, methodology, applications, and research
  2. Obtain input from stakeholders (regulatory, academia, industry, CROs) on the value, prospects, and challenges of these approaches
  3. Establish consensus statements on future directions in research and applications

AGENDA

9:30 - 12:45 : Plenary session:

TIME

SPEAKER

TITLE

8:00-8:25

Tal Burt

Overview of Phase-0 Approaches

8:25-8:50

Oliver Jonas

Intra-Target Microdosing (ITM)

8:50-9:15

Kirsten Anderson

Utility of Phase 0 Intratumoral Microdosing for Evaluation of MOA in Tumor Microenvironment (TME)

9:15-9:50

Yuichi Sugiyama & Yasunori Aoki

ITM Modeling and Simulations

9:50-10:05

Break

10:05-10:30

Elizabeth Baker

Phase-0 and Animal Research

10:30-10:55

Oliver Langer

PET-microdosing

10:55-11:20

Saskia de Wildt

Microdosing in Pediatric and Pregnancy Drug Development

11:20-11:45

Jan Willem van der Laan

EMA Regulatory Perspective of Phase-0


TimeSpeakerTitle
8:00-8:25Tal BurtOverview of Phase-0 Approaches
8:25-8:50Oliver JonasIntra-Target Microdosing (ITM)
8:50-9:15Kirsten AndersonUtility of Phase 0 intratumoral microdosing for evaluation of MOA in tumor microenvironment (TME)
9:15-9:50Yuichi Sugiyama + Yasunori AokiITM Modeling and Simulations
9:50-10:05Break
10:05-10:30Elizabeth BakerPhase-0 and Animal Research
10:30-10:55Saskia de WildtMicrodosing in Pediatric and Pregnancy Drug Development
10:55-11:20Oliver LangerPET-microdosing
11:20-11:45Jan Willem van der LaanEMA Regulatory Perspective of Phase-0

12:00 - 13:00 : Luncheon seminar (Lunch time talks by sponsors) and break
13:00 - 15:00 : Breakout Sessions:

TIME

Moderators

Group

Discussion item

13:00-15:00

Oliver Jonas

Yuichi Sugiyama

1

ITM

13:00-15:00

Saskia de Wildt

Bianca van Groen

2

Vulnerable populations

13:00-15:00

Ad Roffel

Kirsten Anderson

3

Strategy and execution

13:00-15:00

Oliver Langer

Esther van Duijn

4

Regulatory environment and Phase-0


TimeModeratorsGroupDiscussion item
13:00-15:00Oliver Jonas Yuichi Sugiyama1ITM
13:00-15:00Saskia de Wildt Bianca van Groen2Vulnerable populations
13:00-15:00Ad Roffel Kirsten Anderson3Strategy and execution
13:00-15:00Oliver Langer Esther van Duijn4Regulatory environment and Phase-0

15:00 - 15:15 : Break
Closeout session: 15:15 - 17:00 : Summary of breakout sessions, consensus statements, and action items (Chairs: Tal Burt & Saskia de Wildt)

Abstract

Drug development is associated with exponential increase in costs and only modest productivity. In addition, there are concerns about the risks of exposing humans and animals to novel chemical entities. These challenges have led to efforts to improve the drug development process. Such efforts include limited exposure clinical trials such as microdosing and other Phase-O approaches. These approaches are also called Exploratory Investigational New Drug (eIND) or exploratory clinical trials, are an alternative regulatory framework for First-in-Human (FIH) trials. 

Common to these approaches is the use and implied safety of limited exposure to the drug.

For example, with microdosing the dose is less than 100 µg or 1/100th of the anticipated therapeutic dose. The primary applications of Phase-0 approaches include study of drug pharmacokinetic (PK) and pharmacodynamic (PD) properties. Specific applications include use in target localization, drug-drug interactions (DDIs), effects in vulnerable populations (e.g., pediatric), and Intra-Target Microdosing (ITM). The sub-therapeutic doses in Phase-O/Microdose studies require the use of sensitive analytic tools such as Accelerator Mass Spectrometer (AMS), Positron Emission Tomography (PET) and Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS). These tools are used to study disposition, effects, and metabolites of the novel drug under study. 

When AMS, PET, and LC-MS/MS are used in combinations, they can increase the versatility of study design and the power of the data obtained.

Validation studies over the past decade have demonstrated the reliability of extrapolation of data from sub-therapeutic exposures to therapeutic-level exposures in more than 80% of cases. This constitutes an improvement over traditional allometric approaches. Nevertheless, utilization of Phase-O/Microdosing by drug developers remains modest, although growing in number and scope. The purpose of the meeting is to understand and address this under-utilization and formulate recommendations for future research, development, and applications of these approaches.

From Our Sponsors

Silver Sponsor

TNO image

TNO (https://www.tno.nl/en/) is a non-profit research organization with a focus on innovation and applied science, and owns the only biomedical AMS facility in Europe. TNO’s microdosing and microtracer technology offers the opportunity to generate human data early in drug development.

Silver Sponsor

GSK Logo

GSK is a science-led global healthcare company with a special purpose: to help people do more, feel better, live longer. www.gsk.com

Bronze Sponsor

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The Physicians Committee for Responsible Medicine (PCRM) is dedicated to saving and improving human and animal lives through plant-based diets and ethical and effective scientific research (https://www.pcrm.org/)

Bronze Sponsor

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Novartis Institutes for BioMedical Research, Inc.  Major discovery efforts at the frontiers of science www.novartis.com

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