The Crucial Role of Phase I Clinical Trials in Advancing Medicine; by David Walling, PhD

The journey from a promising scientific discovery to a safe and effective medication available to the public is a complex and rigorous process. At the heart of this process are clinical trials, with Phase I clinical trials playing a pivotal role. These trials are the initial step in the long and arduous journey of drug development, serving as a crucial foundation for the advancement of medical science.  It is estimated that only one of every 10 drugs that enters into human trials will eventually be approved for use.   In this blog post, we will explore the importance of Phase I clinical trials and why they are essential for the development of new treatments and therapies.

What Are Phase I Clinical Trials?

Before delving into their significance, let’s understand what Phase I clinical trials are. Phase I trials are the first stage of clinical testing in humans after extensive laboratory and preclinical testing. These trials are typically conducted on a small group of healthy volunteers or, in some cases, patients with the condition the new drug or treatment is intended to address. The primary goals of Phase I clinical trials are to assess the safety, tolerability, and pharmacokinetics of the experimental treatment.  After the completion of initial Phase I studies, the drug will go on to larger Phase II and III trials to examine safety and efficacy in the disease states for which it is intended to be used.

Why Phase I Trials Matter

There are many types of Phase I trials that may be conducted.  Initial trials are quite small and often referred to as First in Human (FIH).  These studies are looking solely at the safety of the compound as the molecule under study is leaving pre-clinical (laboratory and animal testing) and entering the human phase of study.  Other studies look at how the drug is metabolized in the human body (PK studies) or how the potential therapy may impact the heart (QTc studies).  There are many other types of studies that may be conducted to make sure that the drug is safe prior to approval from a regulatory agency.

Safety Evaluation

Safety is paramount in medicine, and Phase I trials are designed to protect the public by making sure that the potential medication does not cause harm.   These trials are closely overseen by research teams (comprised of MD’s, Ph.D.’s, PA’s, RN’s and other medical professionals) that are trained to observe and document any possible adverse effects of the new medication.  Multiple laboratory tests, ECG’s and other more specialized procedures are a standard part of the monitoring that insures participant safety in a Phase I study.   If significant adverse events emerge, the trial may be stopped or the dosing lowered to prevent harm to participants.

Dose Determination

Phase I trials also help researchers establish the optimal dosage range for a new drug. By administering varying doses to participants and observing their responses, researchers can determine the most effective and safe dosage to carry forward into subsequent phases of testing.  Many times this is done through a multiple ascending dose (MAD) trial in which higher doses are given to volunteers so that potential adverse events can be observed and documented.  For Phase I trials, there is always built in stopping criteria so if significant events are observed, the study can be stopped.

Pharmacokinetics and Metabolism

Understanding how the body absorbs, distributes, metabolizes, and excretes a drug is vital for its development. Phase I trials provide valuable insights into a drug’s pharmacokinetics, helping researchers refine dosing schedules and assess potential drug-drug interactions.  Specific studies may be designed looking at the impact of food intake upon the absorption of the drug while others may look at certain medications and how those may interfere with the use of the proposed compound.

Early Identification of Efficacy

While the primary focus of Phase I trials is safety, they can also offer preliminary insights into a drug’s effectiveness. While it is possible that healthy volunteers can provide some insight into the efficacy of a compound, many sponsors tend to add cohorts of individuals who have the disease for which the drug is intended.  These patient cohorts can prove invaluable in moving a compound forward.   If positive responses are observed in early-phase trials, it can motivate researchers to move forward with confidence in subsequent phases.

Ethical Considerations

Phase I trials are generally conducted on healthy volunteers, which reduces the ethical concerns associated with exposing patients to unproven treatments. These trials are carefully designed to minimize risks to participants and adhere to strict ethical guidelines.  All studies, whether Phase I or later phase, are overseen by an Institutional Review Board (or Ethical Review Board).  The IRB reviews the study to make sure that participant safety is overseen and also to make sure that the research has a valid and sound scientific purpose.

Regulatory Approval

Data generated from Phase I trials are submitted to regulatory agencies like the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA). The Phase I data is usually submitted, and discussed with the regulatory agencies prior to proceeding with Phase II and III trials.  The initial safety signal of a compound is a crucial component of the final approval process.

Phase I clinical trials are the foundation upon which the development of new treatments and therapies is built. They provide essential data regarding safety, dosage, and pharmacokinetics, helping researchers make informed decisions about whether to proceed with further testing. Without Phase I trials, the process of bringing innovative drugs and therapies to the market would be far riskier and less effective. These trials not only protect the well-being of patients but also hold the potential to revolutionize medicine, offering hope to those in need of new treatments. So, the next time you hear about a groundbreaking medical discovery, remember that it likely began its journey with Phase I clinical trials, where the importance of safety and science converge.

If you’d like more information on how CenExel may support your Phase I clinical trials, please visit www.CenExel.com.

David Walling, PhD; Chief Clinical Officer, CenExel CNS