Phase-0 / Microdosing Approaches

Safer, Accelerated, Targeted, and 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.
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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, Targeted, and Human-Specific Translation in Drug Development

In-person / online meeting

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

Leiden, The Netherlands

Safer, Accelerate, Targeted, and Human-Specific Translation in Drug Development

Safer, Accelerate, Targeted, and Human-Specific 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, Targeted, and 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: Saskia N. de Wildt, M.D., Ph.D. - Professor of Clinical Pharmacology, Pediatric intensivist; Radboud University, Nijmegen 

Kirsten Anderson - Senior Vice President, Presage Biosciences 

Esther van Duijn, Ph.D. - Senior Scientist/Study Director, TNO, The Netherlands

Elizabeth Baker, Esq. - Pharmaceutical Policy Program Director, Physicians Committee for Responsible Medicine 

Oliver Langer, Ph.D. - Medical University of Vienna, Department of Clinical Pharmacology 

Yuichi Sugiyama, Ph.D. - Special Professor Emeritus in Josai Interanational University, Yokohama, Japan

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

8:00-8:20

Tal Burt

Overview of Phase-0 Approaches

8:20-8:45

Go van Dam

Hitting the R&D Sweet Spot with Phase 0/Microdosing Trials

8:45-9:05

Elizabeth Baker

Employing Phase 0 to Reduce Animal Use in Research

9:05-9:40

Yuichi Sugiyama & Yasunori Aoki

Intra-Target Microdosing {ITM) Modeling and Simulations

9:40-9:55

Break

9:55-10:20

Oliver Langer

PET-Microdosing

10:20-10:45

Saskia de Wildt

Microdosing in Pediatric and Pregnancy Drug Development

10:45-11:10

Jan Willem van der Laan

European Regulatory Perspective of Phase-0

11:10-11:35

11:35-12:00

Oliver Jonas

Joseph DiMasi

Use of ITM to Measure Multiple Drug Responses in Cancer Patients

Economics of Phase-0 Approaches


TimeSpeakerTitle
8:00-8:20Tal BurtOverview of Phase-0 Approaches
8:20-8:45Go van DamHitting the R&D Sweet Spot with Phase 0/Microdosing Trials
8:45-9:05Elizabeth BakerEmploying Phase 0 to Reduce Animal Use in Research
9:05-9:40Yuichi Sugiyama + Yasunori AokiIntra-Target Microdosing (ITM) Modeling and Simulations
9:40-9:55Break
9:55-10:20Oliver LangerPET-Microdosing
10:20-10:45Saskia de WildtMicrodosing in Pediatric and Pregnancy Drug Development
10:45-11:10Jan Willem van der LaanEuropean Regulatory Perspective of Phase-0
11:10-11:35Oliver JonasUse of ITM to Measure Multiple Drug Responses in Cancer Patients
11:35-12:00Joseph DimasiEconomics of Phase-0 Approaches

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

Kev Dhaliwal

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 Kev Dhaliwal3Strategy 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 has been associated with increases in costs and duration and only modest increases in 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 by using limited exposure clinical trials such as microdosing and other Phase-O approaches that allow safer and earlier entry into human testing, and human-based selection from preclinical candidates. These approaches are also called Exploratory Investigational New Drug (eIND) applications and exploratory clinical trials and are regulated under the internationally harmonized ICH M3 guidance.  

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.

 

Recent research has advanced the validity and applicability of Phase-0 approaches.

The approaches can accelerate drug development timelines and reduce developmental attrition by increasing the quality of candidates entering clinical development and by reducing the time to ‘go-no-go’ decisions. This can be done by adding human data to preclinical candidate selection, and by applying methodological and operational advantages that Phase 0 have over traditional approaches. The limited, sub-therapeutic exposure to the test article, means a reduced risk to research volunteers, and reduced regulatory requirements, timelines, and costs of first-in-human (FIH) testing. While many operational aspects of Phase 0 approaches are similar to those of other early-phase clinical development programs, they have some unique strategic, regulatory, ethical, feasibility, economic, and cultural aspects. The meeting will engage participants in discussion of the recent advances, implementation challenges, and future directions in research 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.

Bronze Sponsor

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The Physicians Committee for Responsible Medicine is a non-profit organization working for more effective, efficient, and ethical medical research, product testing, and training. (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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