Phase 1 Clinical Trial

Key facts

Defined in

21 CFR 312.21(a)

Typical size (FDA regulation)

Generally 20 to 80 subjects, varying with the drug

Participants

Healthy volunteers or patients, depending on the drug

Main questions

Safety, side effects at increasing doses, pharmacokinetics

Federal registration mandate

Not required under 42 CFR Part 11, which excludes Phase 1 drug trials

What is a Phase 1 clinical trial?

Phase 1 is the first time an investigational drug or biologic is given to people, after laboratory and animal studies support an Investigational New Drug Application (IND). FDA regulations describe Phase 1 studies as closely monitored studies designed to determine the metabolism and pharmacologic actions of the drug in humans and the side effects associated with increasing doses, and, if possible, to gain early evidence on effectiveness.

Many Phase 1 studies enroll healthy volunteers at specialized clinical pharmacology units. When a drug is too toxic to give to healthy people, as with many cancer therapies, Phase 1 enrolls patients who have the disease instead.

ClinicalTrials.gov also uses an Early Phase 1 label, formerly called Phase 0, for exploratory studies that give very small doses to a few people before a traditional Phase 1 trial.

How Phase 1 trials are designed

A Phase 1 program is usually a set of small studies rather than one trial. Common designs include:

• Single ascending dose (SAD): small groups each receive one dose, and the dose is raised group by group while safety is reviewed.
• Multiple ascending dose (MAD): groups receive repeated doses so researchers can study accumulation and steady-state exposure.
• Dose escalation in patients: common in oncology, aiming to find the maximum tolerated dose and a recommended Phase 2 dose.
• Clinical pharmacology studies: food effect, drug-drug interaction and bioavailability studies, some of which continue after later phases start.

Why Phase 1 trials matter

A Phase 1 start is the earliest sign that a company is moving a molecule into human testing, so pipeline trackers and business development teams treat new Phase 1 records as leads on emerging mechanisms and licensing targets.

Phase 1 activity also identifies experienced early-phase units and investigators, which matters for site selection in first-in-human and oncology dose-escalation work.

Because the federal registration requirement in 42 CFR Part 11 excludes Phase 1 drug trials, public coverage of this phase is incomplete. A missing ClinicalTrials.gov record does not prove that a program does not exist.