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 dexelvucitabine?
Dexelvucitabine is an investigational drug that has been studied for the treatment of HIV infection.
Dexelvucitabine 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.
Dexelvucitabine is a prodrug, which means that it is an inactive drug. Once taken, a prodrug does not work until the body converts it into an active form. In the body, dexelvucitabine is converted to DFC-5′-triphosphate (DFC-TP).5,6
In vitro studies have shown that dexelvucitabine may be effective against strains of HIV that are no longer affected by other NRTIs. (In vitro studies are studies done in test tubes or other laboratory equipment and not on animals or humans).5
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.7
- 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.7
In most cases, an investigational drug must be proven safe and effective in a Phase III clinical trial to be considered for approval by the FDA for sale in the United States. Some drugs go through the FDA’s accelerated approval process and are approved before a Phase III clinical trial is complete. After a drug is approved by the 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. 7
In what phase of testing is dexelvucitabine?
Dexelvucitabine has been studied in Phase II clinical trials.2
The clinical development of dexelvucitabine for the treatment of HIV infection was discontinued in April 2006 because of side effects.2,4
What have recent studies shown about dexelvucitabine?
In a Phase IIb study (known as Study 203), three different strengths of dexelvucitabine taken once daily were compared with placebo (an inactive drug that is identical in appearance to the active drug being studied). The study included HIV-infected participants who were already taking HIV medicines before entering the study (treatment-experienced). Participants had HIV mutations associated with drug resistance at the time they entered the study. For the first 2 weeks of the study, dexelvucitabine or placebo was added to a participant’s previous antiretroviral (ARV) therapy regimen. After 2 weeks, participants continued either dexelvucitabine or placebo and then also began an optimized background regimen. (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.) During the final 8 weeks of the study, participants who had been receiving placebo were allowed to take dexelvucitabine.8,9
In this study, dexelvucitabine taken at the highest dose reduced viral load. (Viral load is the amount of HIV in the blood.) The study also found that treatment with the highest dose of dexelvucitabine and without the FDA-approved NRTIs lamivudine (brand name: Epivir) or emtricitabine (brand name: Emtriva) was more effective in reducing viral load than treatment with placebo. However, some participants taking dexelvucitabine did develop severe hyperlipasemia, which is high levels of lipase (a protein released by the pancreas) and which may indicate a problem with the pancreas. The majority of participants who had severe hyperlipasemia were also taking the FDA-approved NRTI didanosine (brand name: Videx). Pancreatitis (inflammation of the pancreas) also occurred in several participants.8,9
In a long-term extension of the study described above, dexelvucitabine taken at the two higher doses was further examined. During this study (known as Study 901), it became apparent that too many severe cases of hyperlipasemia were occurring in participants taking dexelvucitabine at the highest dose. Because of this safety issue, study investigators decided to stop the clinical development of dexelvucitabine for the treatment of HIV infection.4
What side effects might dexelvucitabine cause?
In the Phase IIb study (Study 203) discussed under the previous question, most side effects were generally mild and included headache, fatigue, and gastrointestinal disorders. However, some participants (many of whom were also taking didanosine) developed severe hyperlipasemia and pancreatitis.8
Severe hyperlipasemia was also reported in Study 901, the long-term extension of Study 203.4
Information on possible side effects of the drug is not complete. If testing of dexelvucitabine continues, additional information on possible side effects will be gathered.
Where can I get more information about clinical trials studying dexelvucitabine?
More information about dexelvucitabine-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 dexelvucitabine. 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.7
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.
1. United States National Library of Medicine. ChemIDplus Advanced. Last accessed on November 30, 2013.
2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. Last accessed on November 30, 2013.
3. Incyte Corporation: Press Release. Incyte and Pharmasset Enter into a Collaborative Licensing Agreement for a Phase II HIV Drug. Last accessed on November 30, 2013.
4. Incyte Corporation: Press Release. Incyte to Discontinue Development of DFC as a Treatment for HIV; Conference Call Scheduled for 8:30 a.m. ET Today. Last accessed on November 30, 2013.
5. Schinazi RF, Mellors J, Bazmi H, et al. DPC 817: a cytidine nucleoside analog with activity against zidovudine- and lamivudine-resistant viral variants. Antimicrob Agents Chemother. 2002 May;46(5):1394-401. Last accessed on November 30, 2013.
6. Schinazi RF, Massud I, Rapp KL, et al. Selection and characterization of HIV-1 with a novel S68 deletion in reverse transcriptase. Antimicrob Agents Chemother. 2011 May;55(5):2054-60. Last accessed on November 30, 2013.
7. National Institutes of Health (NIH). NIH Clinical Research Trials and You. Last accessed on November 30, 2013.
8. Cohen C, Katlama C, Murphy R, et al. Antiretroviral Activity and Tolerability of Reverset (D-d4FC), a New Fluoro-cytidine Nucleoside Analog, When Used in Combination Therapy in Treatment-Experienced Patients: Results of Phase IIb Study RVT-203. Abstract presented at: 3rd International AIDS Society (IAS) Conference on HIV Pathogenesis and Treatment; July 24-27, 2005; Rio de Janeiro, Brazil. Abstract WeOaLB0103. Last accessed on November 30, 2013.
9. Erickson-Viitanen S, Hou K, Lloyd R Jr, et al. Baseline Genotype/Phenotype, Virological Response, and Lack of de novo Resistance Mutation Generation During Therapy With Dexelvucitabine (Formerly Reverset) In Study RVT-203. Abstract presented at: 13th Conference on Retroviruses and Opportunistic Infections (CROI); February 5-8, 2006; Denver, CO. Abstract 632. Last accessed on November 30, 2013.
Last Reviewed: November 30, 2013
Last Updated: November 30, 2013