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.
KP-1461 is an investigational drug that has been studied for the treatment of HIV infection.
KP-1461 belongs to a class (group) of HIV drugs called nucleoside reverse transcriptase inhibitors (NRTIs).2 KP-1461, however, does not work like a typical NRTI. Typical NRTIs block an HIV enzyme called reverse transcriptase, which prevents HIV RNA from being converted to HIV DNA. (An enzyme is a protein that starts or increases the speed of a chemical reaction.) Preventing the RNA-to-DNA conversion step stops HIV from replicating.
With KP-1461, HIV RNA is still converted to HIV DNA. But while the HIV DNA is being formed, KP-1461 introduces mutations into the DNA. These mutations harm HIV rather than help it to survive. In theory, KP-1461 causes so many mutations to build up in HIV over time that the virus cannot continue to live and cannot multiply in the body. This process of stimulating mutations in HIV at a higher-than-normal rate to ultimately stop HIV from multiplying is called “viral decay acceleration.” And KP-1461 is known as a “viral decay accelerator.”3-6
KP-1461 is also 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, KP-1461 is first converted to KP-1212. Then, once KP-1212 is inside cells, it is converted to an active form called KP-1212-TP.5,6
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
KP-1461 has been studied in a Phase II clinical trial.2
Study Names: KP-1461-201; NCT00504452
Phase: IIa
Location: United States and Puerto Rico
Participants:
Purpose: The purpose of this study was to look at the safety and effectiveness of KP-1461.
Study Design: Participants took 1600 mg of KP-1461 orally and twice daily for 124 days. KP-1461 was given without any other HIV medicines (also known as monotherapy).
Results:
In the Phase IIa study (KP-1461-201) discussed under the previous question, the majority of participants reported at least one side effect. Most of the reported side effects were mild to moderate in severity. Half of participants experienced at least one side effect that was considered possibly related to KP-1461. The most frequently reported KP-1461-related side effects were gastrointestinal (GI) disorders and nervous system disorders. Nausea was the most common GI disorder. Dizziness and impaired taste were the most common nervous system disorders.4
Because KP-1461 is still being studied, information on possible side effects of the drug is not complete. As testing of KP-1461 continues, additional information on possible side effects will be gathered.
More information about KP-1461-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.
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.
Last Reviewed: January 14, 2016