Early Phase Clinical Research

When a new drug or device undergoes “first in human” experience, the primary focus is on participant safety. 

How will the drug or device interact with the human body? 

And will this interaction be safe?

To answer these two questions, regulatory authorities around the world require medical product manufacturers to conduct Phase I, also known as early phase clinical trials.

To learn more about the complexities in early phase clinical trials, I invited Dr. Oren Cohen, President of Clinical Pharmacology Services and Chief Medical Officer at Labcorp Drug Development on the show.

Dr. Cohen has more than 30 years of healthcare experience which includes his work on clinical development. 

Prior to joining Labcorp, Dr. Cohen served as the Chief Medical Officer at Viamet Pharmaceuticals. 

He has also held multiple leadership roles at Quintiles Inc. such as Senior Vice President, Global Head of Early Clinical Development and Precision Medicine, Senior Vice President, Clinical Research Strategies, Vice President and Senior Director, Medical and Scientific Services, among others.

Dr. Cohen received his MD from Duke University and completed his internship and residency at The New York Hospital, Cornell Medical Center in New York City. 

He completed his infectious diseases fellowship at the National Institute of Allergy and Infectious Diseases (NIAID) and stayed on to become an investigator in the Laboratory of Immunoregulation where he conducted basic and translational research under the supervision of Dr. Anthony Fauci. 

He also served on the national antiretroviral guidelines panel and ultimately served as Assistant Director for Medical Affairs for NIAID.

Dr. Cohen has published scientific papers in Science, The New England Journal of Medicine, The Lancet, The Journal of Clinical Investigation and Proceedings of the National Academy of Sciences, among others. 

He is a Fellow of the Infectious Diseases Society of America and a Consulting Professor of Medicine at Duke University Medical Center.

Please join me in welcoming Dr. Cohen to the Clinical Trial Podcast.


This podcast is brought to you by Calyx. Calyx is a trusted name in medical imaging, having delivered imaging services to meet the needs of global biopharmaceutical sponsors and clinical research organizations for over 25 years. To learn more, visit https://www.calyx.ai/

Rather than trying to get the whole Mississippi River in a Dixie cup, go back to the well after you’ve got the fundamentals of pharmacokinetics – Dr. Oren Cohen

Selected Links From The Episode:

Dr. Oren Cohen on LinkedIn

Labcorp Drug Development

Medicines & Healthcare products Regulatory Agency (MHRA)




TeGenero incident

Northwick Park Hospital

CAR T cell

Small interfering RNA

Physician Drug Reference (PDR)

COVID vaccine

ICH Good Clinical Practice (GCP) 

Dr. Jill Fisher

FDA draft guidance document on diversity in clinical trials 

Nucleus Network

Patient Recruitment in Phase I Studies with Dr. Graham Wood

Dr. Anthony Fauci


University of Pennsylvania

Show Notes:

[3:03] Dr. Cohen and his team are responsible for four (4) Phase I clinical pharmacology units, also known as Phase I units

[5:01] Phase I clinical trials are no longer exclusively conducted in healthy volunteers. These trials are now conducted:

  • At multiple Phase I units
  • In external sites
  • In patients at University/ specialized sites 

[6:10] Phase I clinical trials have become more complex

  • Pressure to accelerate results not only in terms of safety and pharmacokinetics but also pharmacodynamics
  • Hybrid protocol i.e. single ascending dose, multiple ascending dose, food effect, drug-drug interaction, Asian ethno-bridging, cohort of patients with the disease – all in one protocol 

[8:56] Although Phase I unit and clinical pharmacology unit are used interchangeably, not every Phase I unit is capable of doing clinical pharmacology i.e. safety surveillance and sampling of pharmacokinetics

[10:20] Have complex Phase I trial designs made us go faster? 

  • Sometimes trying to do too much in short amount of time can backfire 
  • Sometimes it can lead to tremendous acceleration, and elimination of “whitespace” – the  time between phases or between studies, where analysis was being done before the next phase of the study was initiated

[18:09] What can we learn and replicate from our experience conducting COVID vaccine clinical trials? 

  • Forming teams quickly
  • Efficient protocol writing process
  • Efficient project management process
  • Effective liaison with the regulatory authorities – real time guidance and conversations 

[20:46] Definition of Pharmacokinetics (PK) and Pharmacodynamics (PD)

  • PK – tracing out the drug levels in a relevant body compartment over time
    • For example, say a pill that gets swallowed and absorbed over a certain period of time from the small intestine, it achieves a certain plasma level over time, and achieves a maximum level, T-max, the time that the maximum level is achieved. Then there is a decay over time, the time at which half of the maximum concentration is present would be T-½, the the half life of elimination
    • Characterizes the roots of elimination
    • Looks at metabolites that may be present in the plasma and the fate of those metabolites
  • PD – Looks more at what the drug is doing to the body, rather than what the body is doing to the drug
    • Think about biomarkers – the drug is ingested, it’s achieving its certain levels. If it’s achieving what might be therapeutic levels, it may be interacting with its target receptor, which might be having some biological effect, if it’s intended to  
    • For example, if a drug is intended to dilate blood vessels and be an antihypertensive drug, then a pharmacodynamic effect might be measuring somebody’s blood pressure, that would be a pharmacodynamic effect

[24:39] PK sampling requirements/ methods vary based on the compound

  • refrigerated centrifugation
  • Separation of the plasma
  • Immediate freezing of the plasma
  • Shipping frozen plasma 
  • Temperature before and during shipping 

[27:08] Clinic vs. Clinical Pharmacology Unit (CPU)

  • A PK sample has to be drawn at a very precise time, it has to be drawn in the correct tube, it has to be drawn in the correctly labeled tube, it has to be then centrifuged, at the proper speed, at the proper temperature, etc. It cannot be repeated or replace 
  • The whole purpose of the clinical trial in large measure is to sketch out that pharmacokinetics curve. Precision is essential 

[29:13] Safety surveillance – a lot of it is routine, but sometimes unanticipated and unexpected issues can occur

  • Highly trained highly skilled doctors and nurses on the floor, ready to deal with any emergency
  • Crash carts
  • Have protocols for emergency transfer and emergency care during transfer that includes advanced life support
  • The most common emergency situation is an anaphylactic reaction. It’s rare, but it happens

[31:27] TeGenero incident at Northwick Park Hospital and lessons learned

[33:47] ***Sponsor Message***

Calyx is a trusted name in medical imaging. 

Calyx’s experience includes over 2,600 clinical trials and 270 FDA supported approvals and spans multiple therapeutic areas, with significant concentration in oncology and CNS-related drug development across all phases, geographic areas, and degrees of complexity.

To learn more about how Calyx can help you with your imaging needs, visit calyx.ai or contact your Calyx solutions specialist today.

[35:20] Complex aspects of early phase clinical trials

  • Oncology
  • Cell and gene therapy
  • Chimeric Antigen Receptor (CAR) T-Cell Therapy
  • Antibody and antibody like modalities in inflammation, fibrosis, cardiac disease

[41:14] Basic science is revealing and is the key driver in our progress 

  • As we understand more and more at a pinpoint granular level, the pathophysiology of disease reveals how to target a disease, how to create a therapeutic strategy, how to draw the disease
  • he tools we have available to probe biologic processes and understand diseases at the molecular level

[43:57] Bioanalysis and what does it entail

  • Liquid chromatography, mass spectroscopy based

[44:51] Medical imaging in phase 1 studies

  • MRI scans in patients with Parkinson’s disease, ALS, Alzheimer’s disease
  • PET scan

[46:51] Phase I study design 

  • Depends on molecule and potential indiciation 
  • Do not overcomplicate 
  • Combined protocols, Combined single ascending dose, Multiple ascending dose, Food Effects study can be helpful 
  • The Supreme Pizza which also includes the fate effect of age, gender, Asian Ethno, Bridging, drug-drug interaction and cohort in patients. This may be too much to include in the same protocol/ study
  • Intensive QT monitoring is also not recommended 
  • Driven by preclinical data 

[53:07] Endpoint design for Phase 1 studies

  • Primary endpoints are pharmacokinetics and safety
  • Secondary endpoints are exploratory, biomarker exploratory endpoints
  • The purpose is to delineate the pharmacokinetics and establish safety and tolerability 

[54:46] Site selection for Phase 1 units 

  • Highly professional trained staff – beyond ICH GCP, understands medical ethics 
  • Well trained and well drilled staff in advanced life support
  • A facility that is fit for purpose – central nursing station with monitoring that does not have bunk beds
  • Location – in close proximity to a hospital with an emergency department and intensive care unit (ICU) and there is a protocol for transfer 
  • Standard Operating Procedures – ex: dosing SOP involves redundancy 
  • Employ Failure Modes and Effects Analysis – ex: what might go wrong with this protocol, how do we prevent it from going wrong, can we do a simulation or dry run 

[59:30] Patient recruitment in a  Phase 1 healthy volunteer study 

  • Call centers 
  • Advertising
  • Multimedia
  • Social Media
  • Ability to bring a full cohort, including extra health volunteers in case there are screen failures 

[1:01:42] Challenges with getting full cohort due to the pandemic 

  • To be confined to the clinical pharmacology unit for various periods of time has been challenging 

[1:03:04] Overrepresentation of minorities in Phase 1 studies due to compensation 

  • Compensation is for inconvenience and time, nevertheless it is compensation
  • Feedback from volunteers

[1:09:35] Advice for healthy volunteers looking to participate in Phase 1 trials

  • Read the informed consent 

[1:11:36] Examples of Single Ascending Dose, Multiple Ascending Dose, Food Effects. For example, a cohort of eight people, six get the active dose and two get the placebo

  • Single Ascending Dose
    • Single ascending dose means one single dose that escalates with successive cohorts
    • For example, let’s say the first dose is going to be one milligram. The first cohort gets one milligram, the next cohort gets a single dose of two milligrams, and then the next cohort gets a single dose of four milligrams
  • Multiple Ascending Dose
    • The multiple ascending dose is multiple doses over a certain number of days that escalates with successive cohorts
    • For example, the first multiple ascending dose cohort is going to get a half a milligram twice a day for five days. Then the next cohort is going to get one milligram twice a day for five days 
  • Food Effects – Drug levels may get boosted when you administer the drug with food. Especially fatty foods have a tendency to boost drug levels, and it can sometimes be significant. It’s a simple experiment where you dose people with or without food

[1:15:21] Working with Dr. Anthony Fauci 

[1:19:02] ***Sponsor Message***

Calyx has been a trusted name in medical imaging for almost two decades. 

Kunal shares his own personal experience working at Perceptive Informatics (now Calyx). 

To learn more about how Calyx can help you with your imaging needs, visit calyx.ai or contact your Calyx solutions specialist today.

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