What is an investigational drug?
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.
What is PSI-5004?
PSI-5004 (also known as Racivir) is an investigational drug that has been 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.)
How are clinical trials of investigational drugs conducted?
Clinical trials are conducted in phases. Each phase has a different purpose and helps researchers answer different questions.6
- Phase I trials: Researchers test an investigational drug in a small group of people (20–80) for the first time. The purpose is to evaluate its safety and identify side effects.
- Phase II trials: The investigational drug is administered to a larger group of people (100–300) to determine its effectiveness and to further evaluate its safety.
- Phase III trials: The investigational drug is administered to large groups of people (1,000–3,000) to confirm its effectiveness, monitor side effects, compare it with standard or equivalent treatments, and collect information that will allow the investigational drug to be used safely.6
In most cases, an investigational drug must be proven effective and must show continued safety 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
In what phase of testing is PSI-5004?
PSI-5004 has been studied in Phase II clinical trials.2
What are some studies on PSI-5004?
Study Names: Study 201; NCT00121979
Location: United States, Argentina, Mexico, Panama
- HIV-infected adults who had taken HIV medicines before entering the study (also called treatment-experienced). Participants were taking an antiretroviral therapy (ART) regimen containing lamivudine.
- Participants were on a failing ART regimen. (A failing ART regimen is one that is not effective at controlling a person's HIV.)
- All participants had HIV that contained a mutation called M184V. (The M184V HIV mutation is known to cause lamivudine to not work well.)
Purpose: The purpose of this study was to compare the safety and effectiveness of PSI-5004 to the safety and effectiveness of lamivudine over 28 days.
Study Design: Participants were assigned to either 600 mg of PSI-5004 (in place of lamivudine) or to continue with lamivudine therapy. All participants also received the same background regimen that they were originally taking before entering the study. (A background regimen is a combination of drugs that are not being studied as the investigational drug[s] in the clinical trial, but are being given to help control a participant’s HIV infection.)
After 28 days, participants who were receiving PSI-5004 could continue with PSI-5004 treatment, with or without an optimized background regimen for an additional 20 weeks. (An optimized background regimen is a combination of drugs, chosen on the basis of a person’s resistance test results and treatment history, that are not being studied as the investigational drug[s] in the clinical trial, but are given to help control a participant’s HIV infection.)
- 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 HIV mutation and who had fewer than three thymidine analog mutations. (Thymidine analog mutations are 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.7-9
What side effects might PSI-5004 cause?
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.
Where can I get more information about clinical trials studying PSI-5004?
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.
I am interested in participating in a clinical trial of PSI-5004. How can I find more information about participating in a clinical trial?
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.
- United States National Library of Medicine. ChemIDplus Advanced. Available at: http://chem.sis.nlm.nih.gov/chemidplus/rn/143491-54-7. Last accessed on January 1, 2016.
- National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. Available at: http://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Last accessed on January 1, 2016.
- Hurwitz SJ, Otto MJ, Schinazi RF. Comparative pharmacokinetics of Racivir, (+/-)-beta-2',3'-dideoxy-5-fluoro-3'-thiacytidine in rats, rabbits, dogs, monkeys and HIV-infected humans. Antivir Chem Chemother. 2005;16(2):117-27. Available at: http://www.intmedpress.com/serveFile.cfm?sUID=48452b2e-7c1d-49c7-9e79-7d04bd125fc2. Last accessed on January 1, 2016.
- Gilead Sciences, Inc.: Press Release, dated November 21, 2011. Gilead Sciences to Acquire Pharmasset, Inc. for $11 Billion. Available at: http://www.gilead.com/news/press-releases/2011/11/gilead-sciences-to-acquire-pharmasset-inc-for-11-billion. Last accessed on January 1, 2016.
- Sen S, Mathur AG, Gupta RM, Kapila K, Chopra GS. Investigational Antiretroviral Drugs. Recent Pat Antiinfect Drug Discov. 2008 Nov;3(3):199-205. Available at: https://www.researchgate.net/profile/Sourav_Sen/publication/228361706_Investigational_Antiretroviral_Drugs/links/0fcfd50fd6511ebf44000000.pdf?origin=publication_list. Last accessed on January 1, 2016.
- National Institutes of Health (NIH). NIH Clinical Research Trials and You. Available at: http://www.nih.gov/health-information/nih-clinical-research-trials-you. Last accessed on January 1, 2016.
- Pharmasset. Randomized, Double-Blind, Placebo-Controlled, Multicenter Study Exploring the Safety, Tolerability, and Antiviral Effect of Substituting 600 mg Racivir for 3TC in HIV-Infected Subjects Who Have the M184V Mutation and Are Currently Failing on a HAART Regimen Containing Lamivudine. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 18, 2005. NLM Identifier: NCT00121979. Available at: http://www.clinicaltrials.gov/ct2/show/NCT00121979. Last accessed on January 1, 2016.
- Cahn P, Sosa N, Wiznia A, et al. Racivir Demonstrates Safety and Efficacy in Patients Harboring HIV with the M184V Mutation and <3 TAM. Abstract presented at: 14th Conference on Retroviruses and Opportunistic Infections (CROI); February 25-28, 2007; Los Angeles, CA. Abstract 488. Available at: http://www.retroconference.org/2007/Abstracts/30151.htm. Last accessed on May 29, 2013.
- Pharmasset, Inc: Press Release, dated September 17, 2008. Racivir – New HIV Drug. Available from National AIDS Treatment Advocacy Project (NATAP) at: http://www.natap.org/2008/HIV/091708_01.htm. Last accessed on January 1, 2016.
- Herzmann C, Arastèh K, Murphy RL, et al. Safety, pharmacokinetics, and efficacy of (+/-)-beta-2',3'-dideoxy-5-fluoro-3'-thiacytidine with efavirenz and stavudine in antiretroviral-naïve human immunodeficiency virus-infected patients. Antimicrob Agents Chemother. 2005 Jul;49(7):2828-33. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1168662/. Last accessed on January 1, 2016.
Last Reviewed: January 1, 2016