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.
To learn more about investigational drugs, read the AIDSinfo What is an Investigational HIV Drug? fact sheet.
What is elvucitabine?
Elvucitabine is an investigational drug that is being studied for the treatment of HIV infection.
Elvucitabine 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.
Elvucitabine's chemical structure is similar to the structure of the FDA-approved NRTIs lamivudine (brand name: Epivir) and emtricitabine (brand name: Emtriva).5 However, in vitro studies have suggested that elvucitabine may work on certain HIV strains against which other NRTIs, such as lamivudine and emtricitabine, no longer work.6 (In vitro studies are studies done in test tubes or other laboratory equipment and not on animals or humans.)
Studies have also suggested that elvucitabine may be effective against hepatitis b virus (HBV) infection.6-8
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.9
- 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.9
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.9 (Some clinical trials are categorized as “a” or “b,” such as “Phase Ia” or “Phase IIb.” These different subphases typically mean that a study is researching certain types of information or using a certain type of participant population.)
In what phase of testing is elvucitabine?
Elvucitabine has been studied in Phase II clinical trials.2 The company developing elvucitabine reported that it is out-licensing elvucitabine and looking to work with partner companies to focus elvucitabine’s development in regions outside the United States. Through a partner company, elvucitabine is being developed in China, Hong Kong, and Taiwan.3,4
What are some studies on elvucitabine?
Study Names: (1) ACH443-015; NCT00350272 and (2) ACH443-904; NCT00675844
Sponsor: Achillion Pharmaceuticals
Location: United States and Puerto Rico
- Participants were HIV-infected adults who had never taken HIV medicines before entering the study. Participants did not have any of the serious illnesses associated with an AIDS diagnosis (called AIDS-defining illnesses) in the 3 months before the study began.
- Participants had viral load levels of at least 5,000 copies/mL. (Viral load is the amount of HIV in a blood sample.)
- All participants had CD4 cell counts of at least 200 cells/mm3 and less than 500 cells/mm3. (A CD4 count is a laboratory test that measures the number of CD4 cells—a type of immune cell— in a sample of blood and is an important indicator of immune function.)
- None of the participants had drug resistance mutations that would prevent them from taking elvucitabine, lamivudine (brand name: Epivir), emtricitabine (brand name: Emtriva), efavirenz (brand name: Sustiva), or tenofovir disoproxil fumarate (brand name: Viread).
: ACH443-015 was designed to compare the safety and effectiveness of elvucitabine with that of lamivudine
. ACH443-904 was a 48-week extension study that involved participants who had completed 96 weeks of treatment with elvucitabine and whose viral load levels were successfully controlled by the HIV medicines.10,11
Study Names: (1) ACH443-014A; NCT00312039, (2) ACH443-018; NCT00380159, and (3) ACH443-904; NCT00675844
Sponsor: Achillion Pharmaceuticals
Location: Dominican Republic, Germany, Spain, United States
- Participants were HIV-infected adults who had been taking an antiretroviral therapy (ART) regimen containing either lamivudine or emtricitabine for at least 4 weeks before the start of the study. (ART is the recommended treatment for HIV infection and involves using a combination of different antiretroviral [ARV] drugs to prevent HIV from replicating.)
- Participants were experiencing treatment failure at the start of the study. (Treatment failure is when an ART regimen is unable to control HIV infection.)
- All participants had HIV that contained a mutation called M184V. (The M184V HIV mutation is known to cause lamivudine and emtricitabine to not work well against HIV.)
- Participants had viral load levels between 2,000 and 150,000 copies/mL and had CD4 cell counts greater than 100 cells/mm3.
: ACH443-014A was designed to evaluate the safety and effectiveness of elvucitabine in adults with the M184V HIV mutation. The researchers compared elvucitabine to lamivudine
. ACH443-018 and ACH443-904 were extension studies that allowed participants who completed ACH443-014A to continue receiving elvucitabine.11-13
For more details on the studies listed above, see the Health Professional version.
What side effects might elvucitabine cause?
In the 96-week Phase II study (NCT00350272) discussed under the previous question, the number, types, and severity of side effects that occurred were similar between the elvucitabine and lamivudine groups. Some drug-related side effects that were reported included the following: nausea, dizziness, fatigue, diarrhea, vomiting, indigestion, and weakness.10,14,15
Because elvucitabine is still being studied, information on possible side effects of the drug is not complete. As testing of elvucitabine continues, additional information on possible side effects will be gathered.
Where can I get more information about clinical trials studying elvucitabine?
More information about elvucitabine-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.
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.9
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/181785-84-2. Last accessed on January 4, 2017.
- National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. Available at: https://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Last accessed on January 4, 2017.
- Achillion Pharmaceuticals. Achillion Pharmaceuticals 2009 Annual Report. Available at: http://files.shareholder.com/downloads/ACHN/3406700524x0x368900/1A85086D-BD5F-4384-B5F9-960A5E379C48/ACHL_09AR_4.26.10.pdf. Last accessed on January 4, 2017.
- Achillion Pharmaceuticals. Annual Report 2015. Available at: http://ir.achillion.com/common/download/download.cfm?companyid=ACHN&fileid=886891&filekey=15492205-1075-42CF-B4D3-7D81C2EF4B1E&filename=ACHN_2015_AR.pdf. Last accessed on January 4, 2017.
- Shi J, Mathew JS, Tharnish PM, et al. N4-acyl-modified D-2',3'-dideoxy-5-fluorocytidine nucleoside analogues with improved antiviral activity. Antivir Chem Chemother. 2003 Mar;14(2):81-90. Available at: http://www.ncbi.nlm.nih.gov/pubmed/12856919. Last accessed on January 4, 2017.
- Colucci P, Pottage JC, Robison H, Turgeon J, Ducharme MP. Effect of a Single Dose of Ritonavir on the Pharmacokinetic Behavior of Elvucitabine, a Nucleoside Reverse Transcriptase Inhibitor, Administered in Healthy Volunteers. Antimicrob Agents Chemother. 2009 Feb;53(2):646-50. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2630647/. Last accessed on January 4, 2017.
- Zhu YL, Dutschman DE, Liu SH, Bridges EG, Cheng YC. Anti-Hepatitis B Virus Activity and Metabolism of 2',3'-Dideoxy-2',3'-Didehydro-beta-L(-)-5-Fluorocytidine. Antimicrob Agents Chemother. 1998 Jul;42(7):1805-10. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC105687/. Last accessed on January 4, 2017.
- DeJesus E, Saple D, Morales-Ramirez J, et al. Elvucitabine Phase II 48 Week Interim Results Show Safety and Efficacy Profiles Similar to Lamivudine in Treatment Naive HIV-1 Infected Patients with a Unique Pharmacokinetic Profile. 48th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC)/46th Infectious Diseases Society of America (IDSA) Meeting; October 25-28. 2008; Washington DC. Levin: Conference reports for National AIDS Treatment Advocacy Project (NATAP); 2008. Available at: http://www.natap.org/2008/ICAAC/ICAAC_22.htm. Last accessed on January 4, 2017.
- 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 4, 2017.
- Achillion Pharmaceuticals. A Randomized, Blinded, 12-week Comparison of Elvucitabine/Efavirenz/Tenofovir Versus Lamivudine/Efavirenz/Tenofovir in HIV-1 Infected, Treatment Naive Subjects. There is a 36 Week, Open Label, Extension Phase for Eligible Subjects. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 6, 2006. NLM Identifier: NCT00350272. Available at: http://www.clinicaltrials.gov/ct2/show/NCT00350272. Last accessed on January 4, 2017.
- Achillion Pharmaceuticals. An Open Label Treatment Protocol to Provide Continued Elvucitabine Treatment for 48-Weeks in Subjects Who Have Completed 96 -Weeks of Elvucitabine Therapy in Protocol ACH443-015 or 48 Weeks of Therapy in Protocol ACH443-018. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 8, 2008. NLM Identifier: NCT00675844. Available at: http://www.clinicaltrials.gov/ct2/show/NCT00675844. Last accessed on January 4, 2017.
- Achillion Pharmaceuticals. A 14 Day Randomized, Double Blind, Study of Once Daily Elvucitabine Versus Lamivudine in Subjects With a Documented M184V Mutation. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on April 5, 2006. NLM Identifier: NCT00312039. Available at: http://www.clinicaltrials.gov/ct2/show/NCT00312039. Last accessed on January 4, 2017.
- Achillion Pharmaceuticals. An Open-Label,48 Week Extension Study of Elvucitabine Administered In Combination With Background Antiretroviral Agents in Subjects Who Have Completed 14 Days of Treatment in Protocol ACH443-014A. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on September 21, 2006. NLM Identifier: NCT00380159. Available at: http://www.clinicaltrials.gov/ct2/show/NCT00380159. Last accessed on January 4, 2017.
- Mascolini M. Elvucitabine Versus 3TC in First-Line Regimens for 96 Weeks - see slides from poster below. Conference Reports for National AIDS Treatment Advocacy Project (NATAP): 17th Conference on Retroviruses and Opportunistic Infections (CROI); February 16-19, 2010; San Francisco, CA. Available at: http://www.natap.org/2010/CROI/croi_60.htm. Last accessed on January 4, 2017.
- DeJesus E, Saple D, Morales-Ramirez J, et al. Elvucitabine vs Lamivudine with Tenofovir and Efavirenz in Antiretroviral-Treatment-Naïve HIV-1 Infected Patients: 96 Week Final Results. Poster presented at: 17th Conference on Retroviruses and Opportunistic Infections (CROI); February 16-19, 2010; San Francisco, CA. Paper 511. Available at: http://www.retroconference.org/2010/PDFs/511.pdf. Last accessed on May 29, 2013.
Last Reviewed: January 4, 2017