A clinical trial of a drug is conducted in order to test whether it is viable for use in humans, based mainly on its effectiveness and safety profile.
Drug development involves many stages and one of the most important is the phase 1 trial. Prior to this, the drug has to be studied extensively in animal models. Once the agent in question is deemed safe for use in animal models, a phase 1 clinical trial is performed to test the drug out in a small group of around 20 to 100 human subjects to identify a safe dosage range, examine the pharmacokinetics and assess the potential side effects of the drug.
Aims of a phase 1 clinical trial
The main reasons a phase 1 trial is conducted is to:
Determine the tolerability of different doses that are planned for use in future trials and to establish an accurate safety profile of the agent or agents being tested.
One of the main problems with phase 1 trials is dose escalation. If the dose of the drug is increased too quickly, the participants may be at risk of toxicity. On the other hand, does escalation that is not fast enough may delay or interrupt effective treatment.
The standard phase 1 design uses a set of "Fibonacci" dose levels that decrease in increments of 100%, 67%, 50%, 40%, and 33%. For example, the second dose level is 100% more than the first, the third is 67% more than the second and so on… Decisions about whether to increase to the next dose level or drop down to a lower dose depends on the toxicity information obtained.
Characterize the drug's pharmacokinetic parameters such as its absorption, distribution, metabolism, and excretion.
It is particularly important to understand how the drug is cleared and to be aware of any accumulation of drug metabolites, or potential interactions between drugs. The effects of food on drug bioavailability is also important. Pharmacokinetic information on how the drug behaves in subgroups such as those with impaired elimination due to renal disease, the elderly or ethnic subgroups should also be obtained.