An investigational drug is one that is under study and is not approved by the U.S. Food and Drug Administration (FDA) for sale in the United States. Medical research studies are conducted to evaluate the safety and effectiveness of an investigational drug. These research studies are also called clinical trials. Once an investigational drug has been proven safe and effective in clinical trials, FDA may approve the drug for sale in the United States.
PSI-5004 (also known as Racivir) is an investigational drug that is being studied for the treatment of HIV infection.
PSI-5004 belongs to a class (group) of HIV drugs called nucleoside reverse transcriptase inhibitors (NRTIs).2 NRTIs block an HIV enzyme called reverse transcriptase. (An enzyme is a protein that starts or increases the speed of a chemical reaction.) By blocking reverse transcriptase, NRTIs prevent HIV from multiplying and can reduce the amount of HIV in the body.
PSI-5004 is similar in chemical structure to the FDA-approved NRTIs lamivudine (brand name: Epivir) and emtricitabine (brand name: Emtriva).5
In vitro studies have shown that PSI-5004 is also active against hepatitis B virus (HBV).5 (In vitro studies are studies done in test tubes or other laboratory equipment and not on animals or humans.)
Clinical trials are conducted in phases. Each phase has a different purpose and helps researchers answer different questions.6
In most cases, an investigational drug must be proven safe and effective in a Phase III clinical trial to be considered for approval by FDA for sale in the United States. Some drugs go through FDA’s accelerated approval process and are approved before a Phase III clinical trial is complete. After a drug is approved by FDA and made available to the public, researchers track its safety in Phase IV trials to seek more information about the drug’s risks, benefits, and optimal use.6
PSI-5004 has been studied in Phase II clinical trials.2
In a Phase II study (known as Study 201), the safety and effectiveness of PSI-5004 was compared to the safety and effectiveness of lamivudine. The study included HIV-infected participants who were already taking HIV medicines before entering the study (also called treatment-experienced) and who had the M184V HIV mutation (a mutation associated with drug resistance to the HIV medicine lamivudine). Before starting the study, all participants were on a failing antiretroviral therapy (ART) regimen that included lamivudine. (A failing ART regimen is one that is not effective at controlling a person's HIV.) Study participants were randomly assigned to receive either PSI-5004 in place of lamivudine or to continue with lamivudine as part of their ART.7-9
In this study, PSI-5004 was shown to decrease viral load (the amount of HIV in a blood sample) in the treatment-experienced adults who had the M184V resistance mutation and who had fewer than three thymidine analog mutations (HIV mutations associated with NRTI drug resistance). In terms of safety, no severe drug-related side effects occurred in either the PSI-5004 treatment group or the lamivudine treatment group.8
In a 14-day Phase Ib/IIa study of various doses of PSI-5004, the most common side effects reported were mild to moderate dizziness and headache, both of which may have been related to PSI-5004. Some other side effects that occurred in the study and may have been because of PSI-5004 included the following: difficulty concentrating, nausea, fatigue, common cold, and eye discomfort. Heartburn and vomiting were also noted by participants and may have been associated with PSI-5004.10
In Study 201, the Phase II study discussed under the previous question, no severe side effects were reported after 28 days of treatment with PSI-5004.8
Because PSI-5004 is still being studied, information on possible side effects of the drug is not complete. As testing of PSI-5004 continues, additional information on possible side effects will be gathered.
More information about racivir-related research studies is available from the AIDSinfo database of ClinicalTrials.gov study summaries. Click on the title of any trial in the list to see the ClinicalTrials.gov trial summary and more information about the study.
Participating in a clinical trial can provide benefits. For example, a volunteer participant can benefit from new research treatments before they are widely available. Participants also receive regular and careful medical attention from a research team that includes doctors and other health professionals. However, clinical trials may also involve risks of varying degrees, such as unpleasant, serious, or even life-threatening side effects from the treatment being studied.6
Your health care provider can help you decide whether participating in a clinical trial is right for you. For more information, visit NIH Clinical Research Trials and You.
Last Reviewed: October 25, 2014
Last Updated: October 25, 2014