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:
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.
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.
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.
4th Annual Phase-0/Microdosing Stakeholder Meeting: Intra-Target Microdosing (ITM): Revolutionizing Clinical Pharmacology and Drug Development
In-person / online meeting
Monday, April 24, 2023 (8:00 am - 5:00 pm Eastern Standard Time)
Wyndham Boston Beacon Hill
Boston, MA, USA
Intra-Target Microdosing (ITM): Revolutionizing Clinical Pharmacology and Drug Development
In-person and online meeting
Monday, April 24, 2023
Organized by: Phase-0/Microdosing Network (phase-0microdosing.org)
Chair: Tal Burt, MD - President, Phase-0/Microdosing Network and Burt Consultancy, LLC
Organizing Committee:
Yuichi Sugiyama, PhD, - Special Professor Emeritus in Josai Interanational University.
Kirsten Anderson
Markus Weiss, PhD - Director in clinical pharmacokinetics, Novartis Institutes for Biomedical Research
Joseph DiMasi, PhD, - Director of Economic Analysis, Tufts Center for the Study of Drug Development, Tufts University
Kev Dhaliwal, MD, PhD - Professor of Molecular Imaging & Healthcare Technology, University of Edinburgh, UK
Go van Dam, MD, PhD - CEO & Co-Founder, TRACER
Intra-Target Microdosing (ITM): Revolutionizing Clinical Pharmacology and Drug Development
In-Person and Online Meeting
Monday, April 24, 2023, Boston, MA, USA
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
Yuichi Sugiyama, PhD, - Special Professor Emeritus in Josai Interanational University.
Kirsten Anderson
Markus Weiss, PhD - Director in clinical pharmacokinetics, Novartis Institutes for Biomedical Research
Joseph DiMasi, PhD, - Director of Economic Analysis, Tufts Center for the Study of Drug Development, Tufts University
Kev Dhaliwal, MD, PhD - Professor of Molecular Imaging & Healthcare Technology, University of Edinburgh, UK
Go van Dam, MD, PhD - CEO & Co-Founder, TRACER
Goals:
- Formulate guidelines for the application of ITM and other Phase-0/Microdosing
- Establish recommendations for further research and development
Objectives:
- Provide update on validation, methodology, applications, and
- Obtain input from stakeholders (regulatory, academia, industry, CROs, non-profit, patient advocacy) on the value, prospects, and challenges facing these approaches.
- Establish consensus statements on future directions in research and applications
AGENDA
8:00 - 12:00 : Plenary session:
TIME
SPEAKER
TITLE
8:00-8:25
Tal Burt, MD
Introduction to Intra-Target Microdosing (ITM)
8:25-8:50
Oliver Jonas, PhD
Lab-in-a-Patient Microdevices for Multiple Drug Screening in Oncology
8:50-9:15
Nathan Schauer, PhD
CIVO: Bridging the Translational Divide in Oncology
9:15-9:45
Yuichi Sugiyama, PhD & Yasunori Aoki, PhD
ITM Modeling and Simulations
9:45-10:00
Break
10:00-10:25
Kev Dhaliwal, MD, PhD
Pulmonary ITM
10:25-10:55
Technology panel
Technology Aspects of ITM and Other Phase-0 Approaches
10:55-11:35
Regulatory panel
Regulatory Aspects of ITM and Other Phase-0 Approaches
11:35-12:00
Joseph DiMasi, PhD
The Economics of Implementing Phase 0 Techniques – Methods for Measuring Financial Value
| Time | Speaker | Title |
|---|---|---|
| 8:00-8:25 | Tal Burt, MD | Introduction to Intra-Target Microdosing (ITM) |
| 8:25-8:50 | Oliver Jonas, PhD | Lab-in-a-Patient Microdevices for Multiple Drug Screening in Oncology |
| 8:50-9:15 | Nathan Schauer, PhD | CIVO: Bridging the Translational Divide in Oncology |
| 9:15-9:45 | Yuichi Sugiyama, PhD + Yasunori Aoki, PhD | ITM Modeling and Simulations |
| 9:45-10:00 | Break | |
| 10:00-10:25 | Kev Dhaliwal, MD, PhD | Pulmonary ITM |
| 10:25-10:55 | Technology Panel | Technology Aspects of ITM and Other Phase-0 Approaches |
| 10:55-11:35 | Regulatory Aspects of ITM and Other Phase-0 Approaches | Regulatory Panel |
| 11:35-12:00 | Joseph DiMasi, PhD | The Economics of Implementing Phase 0 Techniques – Methods for Measuring Financial Value |
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
Kev Dhaliwal, MD, PhD
1
ITM
13:00-15:00
Oliver Jonas, PhD
2
Technology
13:00-15:00
Tal Burt, MD
3
Regulatory
13:00-15:00
Nathan Schauer, PhD
4
Strategy and execution
| Time | Moderators | Group | Discussion item |
|---|---|---|---|
| 13:00-15:00 | Kev Dhaliwal, MD, PhD | 1 | ITM |
| 13:00-15:00 | Oliver Jonas, PhD | 2 | Technology |
| 13:00-15:00 | Tal Burt, MD | 3 | Regulatory |
| 13:00-15:00 | Nathan Schauer, PhD | 4 | Strategy and Execution |
15:00 - 15:15 : Break
15:15 - 17:00 : Colseout Session: Summary of breakout sessions, consensus statements, and action items (Chairs: Tal Burt & Kev Dhaliwal)
Abstract
Concerns about the costs and duration of drug development projects and the risks of exposing animals, in early work, and humans to novel chemical entities, have led to efforts to improve drug development with limited exposure studies using microdosing and other Phase-0 approaches. Common to these approaches is the implied safety of limited exposures to the investigational drug. For example, with microdosing the dose is less than 100 µg or 1/100th of the anticipated therapeutic dose. With Intra-Target Microdosing (ITM) the microdose is administered directly into an area about 1/100th of the body mass, momentarily generating therapeutic-level exposures. Such approaches 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.
Phase-0 approaches allow 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 ITM. The sub-therapeutic doses in Phase-0/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 microdosing and other 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. The meeting will engage participants in discussion of the recent advances, implementation challenges, and future directions in research and applications of these approaches.
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