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 amdoxovir?
Amdoxovir is an investigational drug that is being studied for the treatment of HIV infection.
Amdoxovir 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.
Amdoxovir 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, amdoxovir is converted to DXG-TP.4
In vitro studies have shown that amdoxovir may be an effective option for treating people for whom the NRTIs lamivudine, emtricitabine, zidovudine, and stavudine are not working. (In vitro studies are studies done in test tubes or other laboratory equipment and not on animals or humans.) However, it is possible for someone to develop drug resistance to amdoxovir and for amdoxovir to then not work in that person.5,6
In vitro studies have also shown that amdoxovir is active against hepatitis B virus (HBV).4
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 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.7
In what phase of testing is amdoxovir?
Amdoxovir is currently being studied in a Phase II clinical trial.2
What are some studies on amdoxovir?
In a Phase Ib/IIa study (known as RFS-AMDX-203), investigators looked at the safety and effectiveness of amdoxovir used alone and amdoxovir combined with two different doses of zidovudine (brand name: Retrovir) in HIV-infected adults. All treatments were compared with placebo. (A placebo is an inactive drug that is identical in appearance to the active drug being studied.) Some of the study participants had never taken HIV medicines before entering the study (also called treatment-naive), and others had taken HIV medicines previously (also called treatment-experienced). The treatment-experienced participants were required to be off HIV medicines for at least 3 months before starting the study. Participants were assigned to one of the following three treatment groups for 10 days:
- 500 mg of amdoxovir or placebo taken twice daily
- 500 mg of amdoxovir or placebo, each combined with a standard 300-mg dose of zidovudine, taken twice daily
- 500 mg of amdoxovir or placebo, each combined with a reduced 200-mg dose of zidovudine, taken twice daily.6,8,9
In this study, amdoxovir given in combination with either a standard dose or a reduced dose of zidovudine proved similarly effective in reducing viral load (the amount of HIV in a blood sample). Also, amdoxovir combined with the reduced dose of zidovudine was significantly more effective in reducing viral load than amdoxovir alone, suggesting a potentially beneficial drug synergism. (In this case, drug synergism of amdoxovir and zidovudine is when the drugs work well together, resulting in a greater decrease in viral load than amdoxovir alone.) However, longer studies will need to be undertaken to confirm these findings. In terms of safety, both amdoxovir and amdoxovir in combination with zidovudine appeared to be safe. Side effects were reported as being temporary and mild to moderate. No participants stopped the study because of abnormal laboratory values or adverse events.8
A currently ongoing Phase IIa study (known as RFSP-AMDX-2010) is looking at two different doses of twice-daily amdoxovir versus the FDA-approved NRTI tenofovir disoproxil fumarate (brand name: Viread) take once daily. The study includes treatment-experienced adults who have HIV that is prone to not being affected by NRTIs. Both amdoxovir and tenofovir disoproxil fumarate are being studied in combination with zidovudine plus a third drug. (The third drug will initially be an HIV medicine that is not working for the participant. Then after the 2nd week of the study, the third drug will be switched to the FDA-approved combination protease inhibitor lopinavir/ritonavir (brand name: Kaletra).10
What side effects might amdoxovir cause?
In the RFS-AMDX-203 study discussed under the previous question, amdoxovir alone and amdoxovir in combination with zidovudine appeared to be safe. Side effects were reported as being temporary and mild to moderate. The most common side effects reported among the group receiving amdoxovir combined with zidovudine were headache and nausea.8
Because amdoxovir is still being studied, information on possible side effects of the drug is not complete. As testing of amdoxovir continues, additional information on possible side effects will be gathered.
Where can I get more information about clinical trials studying amdoxovir?
More information about amdoxovir-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 amdoxovir. 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.
- United States National Library of Medicine. ChemIDplus Advanced. Available at: http://chem.sis.nlm.nih.gov/chemidplus/rn/145514-04-1. Last accessed on October 29, 2014.
- 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 October 29, 2014.
- RFS Pharma, LLC: Press Release, dated November 15, 2010. RFS Pharma Awarded Therapeutic Tax Credit and Announces the Approval by the U.S. FDA to Initiate a Phase 2 Study on the Anti-HIV drug Amdoxovir. Available at: http://www.rfspharma.com/images/Press_Release_RFSP_November_15_2010.pdf. Last accessed on October 29, 2014.
- Hurwitz SJ, Asif G, Fromentin E, Tharnish PM, Schinazi RF. Lack of Pharmacokinetic Interaction between Amdoxovir and Reduced- and Standard-Dose Zidovudine in HIV-1-Infected Individuals. Antimicrob Agents Chemother. 2010 Mar;54(3):1248-55. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2826005/. Last accessed on October 29, 2014.
- Pozniak AL. Investigational agents for salvage. Curr Opin HIV AIDS. 2009 Nov;4(6):524-30. National AIDS Treatment Advocacy Project (NATAP): HIV Articles; Investigational HIV agents for salvage. Available at: http://www.natap.org/2009/HIV/011110_02.htm. Last accessed on October 29, 2014.
- Murphy RL, Kivel NM, Zala C, et al. Antiviral activity and tolerability of amdoxovir with zidovudine in a randomized double-blind placebo-controlled study in HIV-1-infected individuals. Antivir Ther. 2010;15(2):185-92. Available at: http://www.intmedpress.com/serveFile.cfm?sUID=c012fd04-d7b4-4a7f-8c82-c772579b039a. Last accessed on October 29, 2014.
- 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 October 29, 2014.
- Murphy R, Zala C, Ochoa C, et al. Pharmacokinetics and Potent Anti-HIV-1 Activity of Amdoxovir Plus Zidovudine in a Randomized Double-blind Placebo-controlled Study. 15th Conference on Retroviruses and Opportunistic Infections (CROI); February 3-6, 2008; Boston, MA. Levin: Conference reports for National AIDS Treatment Advocacy Project (NATAP); 2008. Available at: http://www.natap.org/2008/CROI/croi_96.htm. Last accessed on October 29, 2014.
- RFS Pharma, LLC. A Randomized, Placebo-Controlled Study to Evaluate Safety, Tolerance, Pharmacokinetics and Antiviral Activity of Amdoxovir and Zidovudine in Untreated HIV-1 Infected Subjects Currently Untreated. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 5, 2007. NLM Identifier: NCT00432016. Available at: http://www.clinicaltrials.gov/ct2/show/NCT00432016. Last accessed on October 29, 2014.
- RFS Pharma, LLC. A Phase IIa, Randomized, Double-blind, Active-controlled, 12-week Study of Amdoxovir (Two Doses) Versus Tenofovir DF, in Combination With Zidovudine in HIV-1 Treatment-experienced Subjects With M184I/V Mutation in Addition to 0-2 Confirmed Thymidine Analog Mutations. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 27, 2012. NLM Identifier: NCT01737359. Available at: http://www.clinicaltrials.gov/ct2/show/NCT01737359. Last accessed on October 29, 2014.
Last Reviewed: October 29, 2014