Have you been following along with our Drug Development 101 series? If so, you’ll remember that last month, we provided some insight into preclinical research – an early but vital stage of testing that enables researchers to obtain foundational data about an investigational therapy. Today, we’re excited to talk about what comes next – the Phase I clinical trial.
A Significant Step
Entering Phase I clinical trials is a significant step in the drug development process because it’s the first time an investigational therapy will be tested in people. Most drugs that undergo preclinical testing never actually make it to human trials, so reaching Phase I is a notable accomplishment. For a researcher, it’s almost like seeing your child enter a new grade at school. They have passed several tests and proven they’re ready to advance. However, you know there is still a lot more to learn.
The Overarching Objective
In Phase I trials, researchers gain initial information about how the investigational therapy interacts with the human body. A key objective is safety. Researchers evaluate each patient to see how they are responding to the therapy, carefully identifying any side effects that might arise as dosage levels increase. Another important goal of Phase 1 is to assess how the therapy is absorbed, metabolized, and excreted. The data from Phase 1 helps determine the best way to administer the therapy (e.g., an oral medication or injection) and provides initial information regarding the best dosage to minimize its risks and maximize the benefits.
Phase 1 Trials
While specific trial protocols vary, Phase I typically includes clinical pharmacokinetic measurements that assess what the body’s physiology does to the drug and how rapidly the drug is eliminated, as well as pharmacodynamic measurements that assess what the drug does to the body.
Since it is still early on in the drug development process, the number of participants in these trials is lower than subsequent phases of clinical testing. Phase I trials typically involve 20 – 100 study participants. Typically, some participants get placebo to help determine if any effects seen are truly related to the drug or incidental findings. The length of administration of the drug in Phase 1 is short. The first Phase 1 study often involves administration of a single dose or placebo to participants who are healthy volunteers. If safe, subsequent Phase 1 studies usually involve several weeks of drug administration, either to healthy volunteers or patients with a specific condition. For some drugs, the initial Phase 1 study can be in patients. In both the single dose studies and those involving several weeks of administration, doses are carefully increased between groups of study participants, monitoring the effects before deciding to proceed with dose-escalation to minimize the chance of causing any serious side effects.
The Phase 1 study participants should not expect to get any benefit from the drug in these short studies. The studies are designed to gain initial information on the drug safety and actions, in a cautious manner, before proceeding to larger and longer studies in patients.
A Positive Outlook
If all goes well in Phase I, the therapy will move on to Phase II. Fortunately, the odds of this happening are pretty good. In fact, the FDA reports that approximately 70% of drugs in Phase I move on to Phase II – something we will explore in more detail in our next Drug Development 101 post.
In the meantime, we hope you found this overview of Phase I clinical trials to be helpful. Overall, they are a critical step in the journey from molecule to medicine, with patient safety at heart.
Image Source: Sanofi.com – Ethics in R&D