What Is a Phase 1 Clinical Trial? Safety, Dosing & First-in-Human Studies Explained

Clinical trials are a long process to ensure new medical treatments are not only effective but safe in their target populations. There are multiple phases in clinical trials intended to assess and review investigative products intended for use in humans. With multiple phases, each with a unique goal, it is important for anyone looking to conduct clinical research to understand all the phases form preclinical trials to Phase 4 trials. 

Clinical trials tart with pre-clinical studies. If successful they continue to Phase 1 clinical trials which represent the first time an investigational product is tested in humans Phase 1 studies are intended to evaluate safety of the investigative product and to determine appropriate dosing strategies in humans before larger studies begin.

While Phase 1 trials are often associated with specialized research centers that is not a rule. Understanding their purpose helps healthcare providers appreciate how treatments progress through the development pathway and allows them the opportunity to participate in these important trails. 

What Is a Phase 1 Clinical Trial?

Phase 1 clinical trials are commonly referred to as the "first-in-human" studies. This is when an investigational product (IP) is first tested in humans. The IP can be medications, medical devices, prosthetics, or other medical treatments to be used in humans. They follow pre-clinical studies where the IP was tested in animals.  

These trials are important as they are intended to evaluate the safety of the IP in humans. This includes determining the tolerability and/or different dose ranges of the IP for multiple reasons explained below. An important part of Phase 1 trials is also understanding the pharmacokinetics and the pharmacodynamics of the IP. This means understanding how a healthy individual’s body absorbs and processes the IP.

The primary objective of a phase 1 trial is not to prove that a treatment works. Instead, the primary goal is for researchers to understand how the human body responds to the IP.

Who Participates in Phase 1 Trials?

Most Phase 1 studies enroll healthy volunteers. This helps them understand how the IP will work in a healthy individual. In phase 1 trials there are usually between 20-100 participants that are closely monitored, sometimes in a closed environment. They are frequently assessed to monitor the actions of the investigational product. 

By starting trials in healthy individuals it allows researchers to evaluate the safety of the IP without the underlying influence of disease processes

It is important to note an important exception for Phase 1 trials in oncology. Investigational products intended as cancer therapies often involve patients with the disease instead of healthy volunteers. This is due to the significant risks and toxicities that many oncology treatments pose. 

Determining the Maximum Tolerated Dose (MTD)

One of the reasons Phase 1 trials are done in healthy individuals is to determine the Maximum Tolerated Dose (MTD) of their investigational product in humans. Initial safe doses are established in animal models but still need Rutherford evaluation. This evaluation is done in Phase1 trials to determine safe dosing ranges for which the IP can be used in humans. This also helps researchers recommend IP doses for future studies. 

While conducting a Phase 1 trials, researchers will gradually increase the IP dose while monitoring study participants. This is done to identify and monitor any side effects or adverse events that may occur as a result of the IP. This also helps identify any laboratory abnormalities that may have been present in previous studies. 

By conducting Phase 1 trials, researchers are able to determine the IP’s safe dosage ranges in humans. This also allows them to establish safe recommended dosages for future studies and Phase 2 trials.  

Understanding Adverse Events

An important part of Phase 1 trials i identifying and documenting adverse events. An adverse event is any unintended medical occurrence that was not intended or unfavorable as a result of a medical treatment, drug, or procedure. This can occur at improper dosing of an IP in human. 

Throughout Phase 1 trials, researchers carefully document any mild and serious adverse effects. They also identify and document any dose-limiting toxicities, earning a dose at which the IP is more detrimental than it is beneficial. These findings shape future study design and participant safety measures.

Why Phase 1 Trials Matter

Phase 1 studies are important as they provide researchers with key insights to move onto future trial stages. Phase 1 trials provide researchers with important information of the artery of the Ip in humans. It also helps them establish appropriate dosing ranges for the next phase of studies. Through pharmacokinetic and pharmacodynamic studies they are able to determine the pathways(s) of drug metabolism and how the body deals with the Ip. This also allows them to identify any potential toxicities the IP has in humans. 

Ultimately, Phase 1 provides the foundation for all subsequent clinical development.

How Clinical Research Sites Fit Into Phase 1 Trials and Transition to Phase 2 Trials

Once Phase 1 safety and dose information are established, promising investigational products advance to Phase 2 studies. In Phase 2 trials, researchers begin evaluating efficacy of the IP in the target patient population it is intended to treat. This makes managing Phase 2 trials much different than Phase 1 trials. 

While Phase 1 studies often require specialized infrastructure, an understanding of these trials helps researchers and those interested in clinical research participate and appreciate the development pathway that ultimately leads to Phase 2 and Phase 3 opportunities. Partnering with. Site Management Organizations such as TriStar Clinical Research Consulting can help drive a new research site or multiple trial studies.