Phase I trials are usually the first step in testing a new drug or treatment on humans after successful laboratory and animal testing: sometimes called the first in human trial. They usually involve a small scale of healthy volunteers.
The trial often includes dose escalation studies to determine the optimal dosing regime of the treatment which will be only a fraction of those found to cause harm in pre-clinical studies. There are two types of dose escalation studies Single Ascending Dose and Multiple Ascending Dose studies.
Single Ascending Dose (SAD) studies gives small group of patients a low dose of the drug and observe them for specific period of time. If no adverse events occur a different group of patients will be given a slightly higher dose of the drug. This escalation of dosing continues until intolerable adverse events begin to occur. The final tolerated dose is the Maximal Tolerated Dose.
Multiple Ascending Dose (MAD) studies are designed to test the pharmacokinetics and pharmacodynamics of multiple dose of experimental drug. In this study a group of patients are initially given a low dose of the drug. Over time the dosage is increased within this group until a predetermined dosage has been reached. Various biological samples are collected over the time and studied to help understand how the drug is processed and how well it is tolerated by the body.
This step by step approach takes a long time. Hence to make drug development more efficient in time and direct cost, more creative strategies have evolved. This includes SAD/MAD designs as well as SAD/MAD designs with arms to test for food effects and drug-drug interactions. Recently, patient cohorts are being included in SAD/MAD combination studies with the goal of collecting more relevant safety and tolerability information as well as enhancing the chance of getting early signals of efficacy.