NOTE: The development of apricitabine for HIV treatment has been discontinued.
The study of apricitabine as an HIV medicine was discontinued in 2016. The company developing the drug decided to stop their clinical trials due to a lack of funding and a lack of interest in apricitabine’s early access program.3 (An early access program provides an investigational drug to patients outside of clinical trials and before a drug is sold for profit.)
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 apricitabine?
Apricitabine is an investigational drug that was being studied for the treatment of HIV infection.
Apricitabine 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.
In vitro studies have shown that apricitabine appears to work on certain HIV strains against which other FDA-approved NRTIs, such as lamivudine (brand name: Epivir), may no longer work.4 (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.5
- 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.5
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.5
(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 apricitabine?
A Phase III study on apricitabine was planned and registered, but the study was withdrawn before any participants enrolled. The overall study of apricitabine as an HIV medicine has been discontinued.2,3,6
What are some studies on apricitabine?
Study Names: Not available
Sponsor: Not available
Location: Argentina, South Africa, Thailand
- Participants were HIV-infected adults who had never taken HIV medicines before entering the study.
- Participants had viral load levels between 5,000 and 100,000 copies/mL. (Viral load is the amount of HIV in a blood sample.)
- Participants had CD4 counts of at least 250 cells/mm3. (A CD4 count is a laboratory test that measures the number of CD4 cells in a sample of blood and is an important indicator of immune function.)
: The purpose of this study was to look at the safety and effectiveness of different doses of apricitabine and to compare apricitabine to a placebo
. (A placebo is an inactive drug that is identical in appearance to the active drug being studied.) Apricitabine was given alone without any other HIV medicines (also called monotherapy
Study Names: (1) AVX-201; NCT00126880 and (2) AVX-201E; NCT00367952
Location: Argentina and Australia
Participants: (for AVX-201)
- Participants were HIV-infected adults who had previously taken HIV medicines from at least 2 different antiretroviral (ARV) drug classes.
- For at least 2 months before the study, participants were on the same 3-drug antiretroviral therapy (ART) regimen that contained either lamivudine (brand name: Epivir) or emtricitabine (brand name: Emtriva).
- Participants were experiencing treatment failure. (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.)
- Participants had viral load levels of at least 2,000 copies/mL and CD4 counts of at least 50 cells/mm3.
Purpose: The purpose of this study was to look at the safety and effectiveness of 2 different doses of apricitabine in adults who had HIV that contained the M184V mutation.
AVX-201E was an extension of the AVX-201 study. AVX-201E offered participants who completed AVX-201 the option to continue receiving apricitabine twice daily plus optimized background therapy for an additional 96 weeks. (Optimized background therapy 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 in the clinical trial, but are given to help control a participant’s HIV infection.)9-11
Study Names: AVX-301; NCT00612898
Location: Multiple countries, including United States
- Participants were HIV-infected adults who had taken ART before the start of the study.
- Participants were experiencing treatment failure on an ART regimen that contained either lamivudine or emtricitabine. Their viral load levels were greater than 2,000 copies/mL.
- All participants had HIV that contained either the M184V or M184I mutation (both known to cause drug resistance to lamivudine and emtricitabine).
Purpose: The purpose of this study was to look at the safety and effectiveness of apricitabine plus optimized background therapy in adults who had HIV that contained either the M184V or M184I mutation and were experiencing treatment failure.12,13
What side effects might apricitabine cause?
In the first Phase II study discussed under the previous question, headache was the most common side effect in apricitabine-treated participants. Nasal congestion occurred more frequently in apricitabine-treated participants than in placebo-treated participants.7
In the Phase IIb study AVX-201 (NCT00126880), the most common side effects at Week 24 across all study groups were diarrhea, nausea, high triglyceride levels, common colds, and infections of the upper respiratory tract. Some side effects that may have been related to apricitabine treatment included diarrhea, dizziness, nausea, heartburn, anorexia, weight loss, and digestive system problems.9,14
In the Phase IIb/III study AVX-301 (NCT00612898), treatment with apricitabine over 24 weeks appeared to be safe. Apricitabine appeared to have a safety profile similar to that of lamivudine.12,13
Because apricitabine is still being studied, information on possible side effects of the drug is not complete. As testing of apricitabine continues, additional information on possible side effects will be gathered.
Where can I get more information about clinical trials studying apricitabine?
More information about apricitabine-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.5
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/160707-69-7. Last accessed on January 6, 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 6, 2017.
- Avexa Limited. Annual Report 2016. Available at: http://www.asx.com.au/asxpdf/20161028/pdf/43cf167shmyq98.pdf. Last accessed on January 6, 2017.
- Cahn P, Wainberg MA. Resistance profile of the new nucleoside reverse transcriptase inhibitor apricitabine. J Antimicrob Chemother. 2010 Feb; 65(2):213-7. Available at: http://jac.oxfordjournals.org/content/65/2/213.full.pdf+html. Last accessed on January 6, 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 6, 2017.
- Avexa. A Phase 3, Open Label 96-week Extension Study of the Safety of Apricitabine in Treatment-experienced HIV-1 Infected Patients Who Have Completed Protocol AVX-301 or AVX-302 or Who Have Met the Criteria for Open-label Access to ATC Because of Virological Failure/Lack of Response. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 27, 2008. NLM Identifier: NCT00686270. Available at: https://www.clinicaltrials.gov/ct2/show/NCT00686270. Last accessed on January 9, 2017.
- Cahn P, Cassetti I, Wood, R, et al. Efficacy and tolerability of 10-day monotherapy with apricitabine in antiretroviral-naive, HIV-infected patients. AIDS. 2006 June; 20(9): 1261-1268. National AIDS Treatment Advocacy Project (NATAP): HIV Articles; Efficacy and tolerability of 10-day monotherapy with SPD574 (apricitabine) in antiretroviral-naive, HIV-infected patients. Available at: http://www.natap.org/2006/HIV/081106_07.htm. Last accessed on January 6, 2017.
- Cahn P, van Leeuwen R, Sawyer J, Shiveley L. Tolerability and Anti-HIV-1 Activity of SPD754 as 10 days’ Monotherapy in Treatment-Naïve Patients. Poster presented at: 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); September 14-17, 2003; Chicago, IL. Poster/Abstract A-3093. Available at: http://www.avexa.com.au/sites/default/files/news/Cahn%20A-3093%2043rd%20ICAAC%202003.pdf. Last accessed on December 1, 2015.
- Avexa. A Phase II, Randomised, Double-blind, Dose-ranging Study of AVX754 Versus Lamivudine in Treatment-experienced HIV-1 Infected Patients With the M184V Mutation in Reverse Transcriptase. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 3, 2005. NLM Identifier: NCT00126880. Available at: https://www.clinicaltrials.gov/ct2/show/NCT00126880. Last accessed on January 6, 2017.
- Avexa. An Open Label Long Term Safety Extension Study of Apricitabine in Treatment-experienced HIV-1 Infected Subjects. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 22, 2006. NLM Identifier: NCT00367952. Available at: https://www.clinicaltrials.gov/ct2/show/NCT00367952. Last accessed on January 6, 2017.
- Cahn P, Altclas J, Martins M, et al. Antiviral activity of apricitabine in treatment-experienced HIV-1-infected patients with M184V who are failing combination therapy. HIV Med. 2011 Jul; 12(6):334-42. Available at: http://onlinelibrary.wiley.com/doi/10.1111/j.1468-1293.2010.00887.x/pdf. Last accessed on January 6, 2017.
- Avexa. A Phase 2b/3, Randomized, Double Blind, Dose Confirming Study of the Safety, Efficacy and Tolerability of Apricitabine Versus Lamivudine in Treatment-experienced HIV-1 Infected Patients With the M184V/I Mutation in Reverse Transcriptase. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 30, 2008. NLM Identifier: NCT00612898. Available at: https://www.clinicaltrials.gov/ct2/show/NCT00612898. Last accessed on January 6, 2017.
- Avexa. ATC: Phase 3 data from the AVX-301 study. Slides presented at: 24th International Conference on Antiviral Research (ICAR); May 8-11, 2011; Sofia, Bulgaria. Available at: http://www.avexa.com.au/sites/default/files/news/ICAR%20Sofia%20Clin%20Symp%20May%202011.pdf. Last accessed on December 1, 2015.
- Cahn P, Altclas J, Martins M, et al. 24 Week Data from Study AVX-201: A Prospective, Randomised, Double-Blind, Dose-Ranging Phase 2b Study of Apricitabine in Treatment-Experienced Patients with M184V and NRTI Resistance. Poster presented at: 15th Conference on Retroviruses and Opportunistic Infections (CROI); February 3-6, 2008; Boston, MA. Poster 793. Available at: http://www.avexa.com.au/sites/default/files/news/CROI%20poster%20formatted%2024Jan2008.pdf. Last accessed on December 1, 2015.
Last Reviewed: January 6, 2017