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 OBP-601?
OBP-601 is an investigational drug that is being studied for the treatment of HIV infection.
OBP-601 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.
OBP-601 is similar in chemical structure to the FDA-approved NRTI stavudine (brand name: Zerit). However, in vitro studies have shown that OBP-601 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 OBP-601 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 safe and effective 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
In what phase of testing is OBP-601?
OBP-601 has been studied in a Phase IIb clinical trial.2
What are some studies on OBP-601?
In a 10-day Phase IIa study, four different strengths of OBP-601 taken once daily were compared with placebo in HIV-infected participants who had taken HIV medicines before entering the study (also called treatment-experienced) but who were off HIV medicines for at least 3 months. (A placebo is an inactive drug that is identical in appearance to the active drug being studied.) Study participants did not receive additional HIV medicines as part of a background regimen. (A background regimen is a combination of drugs that are not being studied as the investigational drug[s] in the clinical trial, but are being given to help control a participant’s HIV infection.)9-11
In this study, significant reductions in viral load (the amount of HIV in a blood sample) were seen after 10 days of treatment with each of the OBP-601 doses studied. In terms of safety, there were no serious side effects or study drop-outs caused by OBP-601 treatment. More participants taking OBP-601 had a moderate-to-severe side effect than participants taking placebo.9-11
A Phase IIb study focused on identifying a safe and effective dose of OBP-601 for when OBP-601 is used in combination with the FDA-approved HIV medicines efavirenz (brand name: Sustiva) and lamivudine (brand name: Epivir) in HIV-infected adults who had never taken HIV medicines before entering the study (also called treatment-naive). The FDA-approved nucleoside reverse transcriptase inhibitor (NRTI) medicine tenofovir disoproxil fumarate (brand name: Viread) was used as a comparison. This study was terminated.12
What side effects might OBP-601 cause?
In the 10-day Phase IIa study discussed under the previous question, the most common side effects that occurred in the OBP-601 groups were abdominal pain, swollen lymph nodes, nausea, headache, and fatigue.11
Because OBP-601 is still being studied, information on possible side effects of the drug is not complete. As testing of OBP-601 continues, additional information on possible side effects will be gathered.
Where can I get more information about clinical trials studying OBP-601?
More information about OBP-601-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 OBP-601. 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 October 1, 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 1, 2014.
- Clayden P, Collins S, Daniels C, et al. HIV i-BASE/Treatment Action Group. 2014 Pipeline Report. Benzacar A, ed. July 2014. Available at: http://www.pipelinereport.org/sites/g/files/g575521/f/201407/2014%20Pipeline%20Report%20Full_0.pdf. Last accessed on October 1, 2014.
- 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 October 1, 2014.
- 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 October 1, 2014.
- 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 October 1, 2014.
- 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 October 1, 2014.
- National Institutes of Health (NIH). NIH Clinical Research Trials and You. Available at: http://nih.gov/health/clinicaltrials/index.htm. Last accessed on October 1, 2014.
- Cotte L, Dellamonica P, Raffi F, et al. A Phase-Ib/IIa Dose-Escalation Study of OBP-601 (4’-ethynyl-d4T, Festinavir) in Treatment-Experienced, HIV-1-Infected Patients. Abstract presented at: 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); September 12-15, 2010; Boston, MA. Abstract H-933. Available at: http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=d89fb4da-4268-4d6b-88ee-4f4ebcd548de&cKey=74572456-29b9-410f-8a57-972c2b0676c3&mKey=%7b93AEED6A-54D4-4EF6-99BD-A9B3CE9FACD9%7d. Last accessed on October 1, 2014.
- Hwang C, Zhu L, Chan H, et al. Antiviral activity, exposure-response, and resistance analyses of monotherapy with the novel HIV NRTI BMS-986001 in ART-experienced subjects. Abstract presented at: 13th International Workshop on Clinical Pharamcology of HIV Therapy; March 16-18, 2012; Barcelona, Spain. Abstract O_06. Available at: http://regist2.virology-education.com/abstractbook/2012_3.pdf. Last accessed on October 1, 2014.
- 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 October 1, 2014.
- 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 October 1, 2014.
Last Reviewed: October 1, 2014