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 censavudine?
Censavudine is an investigational drug that is being studied for the treatment of HIV infection.
Censavudine 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.
Censavudine is similar in chemical structure to the FDA-approved NRTI stavudine (brand name: Zerit). However, in vitro studies have shown that censavudine may be more effective than stavudine and may be less toxic than stavudine and other NRTIs.4-6 (In vitro studies are studies done in test tubes or other laboratory equipment and not on animals or humans.) Research in animals has shown that censavudine is not associated with kidney or bone toxicities.7
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.8
- 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.8
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.8 (Some clinical trials are categorized as “a” or “b,” such as “Phase Ia” or “Phase IIb.” These different sub-levels 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 censavudine?
Censavudine has been studied in a Phase IIb clinical trial.2
What are some studies on censavudine?
Study Name: EudraCT Number 2008-004810-29
Funding Organizations: Oncolys Pharma and Bristol-Myers Squibb
- Participants were HIV-infected adults who had taken HIV medicines before entering the study but who were off HIV medicines for at least 3 months.
- Participants had viral load levels of at least 5,000 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 antiviral
activity, safety, and drug properties of censavudine.9
: AI467003; NCT01489046
: Bristol-Myers Squibb
: Multiple countries, including United States
- Participants were HIV-infected adults who had never taken HIV medicines before or had taken HIV medicines for less than 1 week.
- Participants had viral load levels greater than 5,000 copies/mL and CD4 counts greater than 200 cells/mm3.
: The purpose of this study was to identify a safe and effective dose
of censavudine for when censavudine is used in combination with the FDA-approved HIV medicines efavirenz
(brand name: Sustiva
) and lamivudine
(brand name: Epivir
For more details on the studies listed above, see the Health Professional version
What side effects might censavudine cause?
In the 10-day Phase IIa study (EudraCT number 2008-004810-29) discussed under the previous question, the most common side effects that occurred in the censavudine groups were abdominal pain, swollen lymph nodes, nausea, headache, and fatigue.9
In the Phase IIb study (NCT01489046), participants in the censavudine groups had a smaller decline in bone mineral density than the participants in the group that did not receive censavudine. (Bone mineral density is a measurement of the amount of minerals, such as calcium, in an area of the bone.) There was a trend towards a build-up of limb and trunk fat with censavudine treatment, especially at the highest dose tested. Also, a slight increase in total cholesterol was seen with censavudine treatment.11
Because censavudine is still being studied, information on possible side effects of the drug is not complete. As testing of censavudine continues, additional information on possible side effects will be gathered.
Where can I get more information about clinical trials studying censavudine?
More information about censavudine-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 censavudine. 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.8
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. http://chem.sis.nlm.nih.gov/chemidplus/rn/634907-30-5. Last accessed on December 2, 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 December 2, 2016.
- Oncolys BioPharma website. OBP-601 (Censavudine). Available at: http://www.oncolys.com/en/pipeline/obp-601.html. Last accessed on December 2, 2016.
- Dutschman GE, Grill SP, Gullen EA, et al. Novel 4'-Substituted Stavudine Analog with Improved Anti-Human Immunodeficiency Virus Activity and Decreased Cytotoxicity. Antimicrob Agents Chemother. 2004 May;48(5):1640-6. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC400579/. Last accessed on December 2, 2016.
- Yang G, Dutschman GE, Wang CJ, et al. Highly selective action of triphosphate metabolite of 4'-ethynyl D4T: a novel anti-HIV compound against HIV-1 RT. Antiviral Res. 2007 Mar;73(3):185-91. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17109975. Last accessed on December 2, 2016.
- Wang F, Flint O. The HIV NRTI BMS-986001 does not degrade mitochondrial DNA in long term primary cultures of cells isolated from human kidney, muscle and subcutaneous fat. Abstract presented at: 19th International AIDS Conference; July 22-27, 2012; Washington, DC. Abstract TUPE042. Available at: http://pag.aids2012.org/abstracts.aspx?aid=17957. Last accessed on December 2, 2016.
- Guha M, Pilcher G, Moehlenkamp J, et al. Absence of renal and bone toxicity in non-clinical studies of BMS-986001, a nucleoside reverse transcriptase inhibitor (NRTI) of human immunodeficiency virus (HIV). Abstract presented at: 19th International AIDS Conference; July 22-27, 2012; Washington, DC. Abstract TUPE041. Available at: http://pag.aids2012.org/abstracts.aspx?aid=16832. Last accessed on December 2, 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 December 2, 2016.
- Cotte L, Dellamonica P, Raffi F, et al. Randomized Placebo-Controlled Study of the Safety, Tolerability, Antiviral Activity, and Pharmacokinetics of 10-day Monotherapy with BMS-986001, a Novel HIV NRTI, in Treatment-Experienced HIV-1-Infected Subjects. J Acquir Immune Defic Syndr. 2013 Jul 1;63(3):346-54. Available at: http://www.natap.org/2013/HIV/Randomized_Placebo_Controlled_Study_of_the_Safety,.13.pdf. Last accessed on December 2, 2016.
- Bristol-Myers Squibb. A Phase IIb Randomized, Controlled, Partially Blinded Clinical Trial to Investigate Safety, Efficacy and Dose-response of BMS-986001 in Treatment-naive HIV-1-infected Subjects, Followed by an Open-label Period on the Recommended Dose. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on December 7, 2011. NLM Identifier: NCT01489046. Available at: http://www.clinicaltrials.gov/ct2/show/NCT01489046. Last Accessed on December 2, 2016.
- McComsey GA, Gupta SK, Orrell C, et al. HIV NRTI BMS-986001 in Antiretroviral-Naïve Subjects: Evaluation of Bone and Metabolic Safety Data Through Week 48. 54th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); September 5-9, 2014; Washington, DC. Levin: Conference reports for National AIDS Treatment Advocacy Project (NATAP); 2014. Available at: http://www.natap.org/2014/ICAAC/ICAAC_29.htm. Last accessed on December 2, 2016.
Last Reviewed: December 2, 2016