A phase 1 clinical trial is the first time an experimental drug or treatment is tested in people. Its primary goal is safety: researchers want to find out what dose the human body can tolerate, what side effects occur, and how the drug behaves once it enters the bloodstream. These trials are small, typically enrolling 20 to 80 participants, and they last several months.
Before a phase 1 trial, a drug has only been tested in labs and animals. This stage is where it crosses into human biology for the first time, which is why the design is cautious, tightly regulated, and focused almost entirely on protecting participants rather than proving the drug works.
What a Phase 1 Trial Is Trying to Learn
The central question isn’t “Does this drug cure the disease?” That comes later, in phase 2 and phase 3 trials. Phase 1 is about establishing a safe and reliable dose that can be carried forward into those larger studies. Researchers track how the body absorbs, processes, and eliminates the drug, and they watch carefully for side effects at each dose level.
Specifically, researchers collect data on two things. First, what happens to the drug inside the body: how quickly blood levels rise after a dose, how high they peak, and how long the drug stays in the system. Second, what the drug does to the body: whether it hits its intended biological target, and whether it causes harmful effects. Regulatory agencies like the FDA require both of these profiles before a drug can advance.
A key concept is the “maximum tolerated dose,” the highest dose that causes acceptable side effects. Finding this ceiling is often the trial’s most important deliverable. In cancer drug development, researchers also look for early signs that the drug is affecting the tumor’s biology, though proving effectiveness isn’t required at this stage.
How Doses Are Tested
Phase 1 trials don’t give everyone the same dose. Instead, they use a staircase approach, starting extremely low and working up. The two most common designs are single ascending dose and multiple ascending dose studies, and many trials run both back to back.
In a single ascending dose stage, a small group receives one dose of the drug, and researchers monitor them before clearing the next group to receive a slightly higher dose. Once the single-dose safety profile is established, the trial moves into a multiple ascending dose stage, where participants take repeated doses over days or weeks. This reveals how the drug accumulates in the body with ongoing use, and it tends to surface more side effects simply because exposure is longer. In one published trial comparing the two stages, researchers observed 12 adverse events during the single-dose phase and 87 during the multiple-dose phase.
Sentinel Dosing: Protecting the First Participants
Because the drug has never been given to humans before, the very first dose carries the most uncertainty. To manage this, trials use a practice called sentinel dosing. Two participants are dosed hours or even a full day before anyone else in their group. One receives the real drug and the other a placebo, so neither the participants nor the researchers know which is which. If the first participant on the active drug develops a serious reaction, the rest of the group is never exposed.
This approach became standard after two high-profile disasters in early-phase trials, one involving a drug called TGN1412 in 2006 and another involving a drug from the company BIAL in 2016. European regulators now expect sentinel dosing in at least the first dose of the first group for any new drug, and the practice is widely used in trials globally.
Who Participates
Most phase 1 trials enroll healthy volunteers. These are people without the disease the drug is meant to treat. Using healthy participants makes it easier to isolate the drug’s effects on the body without the complications of an underlying illness.
Cancer drugs are the major exception. Because chemotherapy and many targeted therapies are inherently toxic, it would be unethical to give them to healthy people. Oncology phase 1 trials instead enroll patients who have already exhausted standard treatments. For these participants, the trial offers a chance to access a new therapy, though the primary purpose remains finding the right dose rather than treating their cancer.
Regulatory Requirements Before a Trial Can Start
No phase 1 trial can begin in the United States without an active Investigational New Drug (IND) application on file with the FDA. This submission includes all the preclinical data from lab and animal studies, a detailed plan for the trial, and information about how the drug is manufactured.
The FDA can place a trial on “clinical hold,” blocking it from starting or pausing it mid-course, if it determines that participants would face unreasonable risk or that the application doesn’t contain enough information to properly assess safety. Every trial also requires approval and ongoing oversight from an institutional review board, an independent committee that evaluates whether the study’s design adequately protects participants.
How Long It Takes and What Comes Next
A phase 1 trial typically runs for several months, though the exact timeline depends on how many dose levels are being tested and how long each group needs to be monitored before the next one begins. Some oncology trials take longer because participants continue receiving the drug as long as it appears to help them.
Completing phase 1 doesn’t guarantee a drug moves forward. Across all disease areas, roughly 66% of drugs that enter phase 1 successfully transition into phase 2, based on an analysis of industry-sponsored trials from 2000 to 2015. That means about one in three drugs is dropped after this stage, usually because the side effect profile is too severe or the drug doesn’t behave in the body the way researchers expected.
For the drugs that do advance, phase 2 trials test whether the treatment actually works against the disease in a larger group of patients. Phase 3 trials then compare it head to head against existing treatments in hundreds or thousands of people. The entire journey from phase 1 to an approved medication takes years, and many drugs that look promising early on fail at later stages. Phase 1 is simply the first filter, designed to answer the most basic question: can people take this drug safely?