Phase 1 Clinical Trials

The Safety Of A New Drug Compound Is Determined With A Phase 1 Trial

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A Phase 1 trial can include testing and observing patients to see how they respond to a new drug formulation. Image © Jan Friml

Before a medication can be approved by the Food and Drug Administration (FDA) and available to patients and physicians, it must go through a clinical trial process. The trial process has several steps, beginning with animal testing or computer modeling (called the preclinical phase), and eventually progressing to four phases of human trials. The first time a drug is given to humans, it is in what is called a Phase 1 (or Phase I) trial.

Before a Phase I trial can begin, the pharmaceutical or biochemical company that has created the drug must apply for a investigational new drug (IND) approval from the FDA. The FDA will look at the results of the preclinical testing, and determine if there is enough evidence to begin further testing the drug in humans.

Why Phase 1 Trials?

In the case of a brand new drug that is not currently available on the market, in most cases the first time it is being tried for use in a human would be in a Phase 1 trial. Because the drug is new and untested in people (although it has already been extensively tested in a laboratory models and/or in animals), the Phase 1 test group is often small, typically anywhere from 15 to 100 patients. The Phase 1 trial period for a drug is typically takes about one year, which is much shorter than other phases of the trial period. The short time period is because a Phase 1 trial is not used to see if the drug is effective, only that it is safe for humans to use.

Some of the questions researchers may be looking to answer about a drug with a Phase 1 trial include:

  • Does it cause any serious side effects?
  • Are patients able to tolerate the drug?
  • What's the safest route of administration (such as pill, injection, infusion)?
  • How is it metabolized by the body?
  • What's the highest dose that is tolerable to patients?

    How Patients Are Recruited

    For drugs being tested for use in treating inflammatory bowel disease (IBD), patients recruited to participate in the Phase 1 trial are actually healthy volunteers. One way this might be accomplished is through a research center. A research center recruits healthy people who are willing to take a new drug for a period of time. Other drugs (such as those for very severe conditions) might begin their clinical trial period in actual patients (in a Phase 0 trial, or in a compassionate use scenario), but this is typically not the case for IBD drugs.

    Volunteers are recruited to participate based on several factors that will be different for each particular trial. In general, patients asked to enroll in a Phase 1 trial would need to meet certain conditions. These conditions might be that they do not have any chronic illnesses and that they will be able to complete the course of medication and the monitoring necessary through the completion of the trial. Each Phase 1 trial is different, so there may be other conditions that are needed, and some volunteers might not be able to meet all of them.

    Phase 1 research may be conducted in only 1 or 2 physical locations, which is helpful to researchers who must closely monitor the volunteers for potential side effects.

    Cohorts In A Phase 1 Trial

    One aspect of developing a new drug is determining the dosage that should be recommended. Based on years of previous studies, researchers will already have a good idea of what the dosage for humans should be, but will generally try different dosages in different subsets of patients enrolled in a Phase 1 trial. In this way, the results of the trial will help show the dosages that might be best tolerated in patients. These subsets of volunteers are called cohorts, and the first cohort will receive a low dose. This first cohort will be studied to ensure that there are no serious side effects resulting from the initial low dose of the drug, or to what extent any side effects are troublesome or are tolerable to the volunteers.

    After the first cohort has passed through the initial testing, a second cohort of volunteers is chosen and given a higher dosage of the drug. The second cohort will be watched for side effects, just as the first one was. There may be more cohorts given increasing dosages of the new drug until the safety of these higher doses is established.

    It's estimated that about 2 out of 3 drugs will pass the Phase 1 trial and progress on to Phase 2 trials.

    Source:

    U. S. Food and Drug Administration. The FDA's Drug Review Process: Ensuring Drugs Are Safe and Effective." FDA.gov. 24 Apr 2014. 12 May 2014.

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