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AIDSinfo Drug Database

AIDSinfo Drug Database

Drugs by class

FDA-approved

Investigational

Cabotegravir  Audio icon

Other Names: 744 LA, CAB, GSK-1265744, GSK1265744, GSK744, GSK744 LA, GSK744 LAP, S-265744, S/GSK1265744, cabotegravir LA, cabotegravir sodium
Drug Class: Integrase Inhibitors
Molecular Formula: C19 H17 F2 N3 O5
Registry Number: 1051375-10-0 (CAS)
Chemical Name: (3S,11aR)-N-((2,4-difluorophenyl)methyl)-6-hydroxy-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydrooxazolo(3,2-a)pyrido(1,2-d)pyrazine-8-carboxamide
Company: ViiV Healthcare
Phase of Development: IIb
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Chemical Image:
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cabotegravir
cabotegravir
Molecular Weight: 405.3553
(Compound details obtained from ChemIDplus Advanced,1 NIAID Therapeutics Database,2 and ViiV Healthcare website3)

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 cabotegravir?

Cabotegravir (also known as S/GSK1265744) is an investigational drug that is being studied for the treatment and prevention of HIV infection.4

Cabotegravir belongs to a class (group) of HIV drugs called integrase inhibitors.2 Integrase inhibitors block an HIV enzyme called integrase. (An enzyme is a protein that starts or increases the speed of a chemical reaction.) By blocking integrase, integrase inhibitors prevent HIV from multiplying and can reduce the amount of HIV in the body.

Cabotegravir does not require boosting with an additional drug. (Boosting involves the use of a second drug to increase the effectiveness of the main [first] drug.)5

Two forms of cabotegravir are being studied: tablets that are taken by mouth (known as oral cabotegravir or oral CAB) and a long-acting injectable form that is injected into the muscle (known as cabotegravir LA or CAB LA).6,7 (A long-acting drug formulation works over a long period of time. Using this type of drug might mean that the drug could be taken less often, making a treatment or prevention regimen simpler to take.)4

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

In what phase of testing is cabotegravir?

Cabotegravir is currently being studied in Phase IIb clinical trials.2,6,7

What are some studies on cabotegravir?

Study Name: LAI116482 (LATTE); NCT01641809
Phase: IIb
Location: United States and Canada
Participants: HIV-infected adults who had not taken HIV medicines before entering the study (also called treatment-naive).
Purpose: The purpose of this study was to find a safe and effective dose of oral cabotegravir, given as HIV maintenance therapy with the HIV oral medicine rilpivirine (brand name: Edurant). (Maintenance therapy is an ongoing treatment used to help an initial treatment succeed or to prevent a return of disease or infection.)
Study Design: All doses of oral cabotegravir were given once daily. This was a two-part study, with an option to continue treatment after the second part of the study.

Part 1:

During the first part of the study, which lasted 24 weeks, participants were assigned to one of the following four regimens to reduce their viral load (the amount of HIV in a blood sample):

  • 10 mg of oral cabotegravir plus two FDA-approved HIV medicines from the nucleoside reverse transcriptase inhibitor (NRTI) drug class.
  • 30 mg of oral cabotegravir plus two FDA-approved NRTIs.
  • 60 mg of oral cabotegravir plus two FDA-approved NRTIs.
  • 600 mg of efavirenz (brand name: Sustiva) plus two FDA-approved NRTIs.

Participants who were taking oral cabotegravir and who had successful viral suppression could continue to the second part of the study. (Viral suppression is when antiretroviral therapy [ART] reduces the amount of HIV in a person’s blood sample to an undetectable level.)

Part 2:
  • In the second part of the study, participants began their maintenance therapy regimen. Participants who were taking oral cabotegravir stopped their two NRTI medicines and added oral rilpivirine once daily. Participants in the efavirenz group continued taking efavirenz plus the two NRTIs. Part 2 continued through Week 96 of the study.
Option to continue treatment:
  • Participants who were taking oral cabotegravir plus oral rilpivirine in the second part of the study could enroll to continue treatment on this regimen beyond Week 96.

Results:
  • During Part 1 of the study, oral cabotegravir showed antiviral activity at all three dosing strengths studied. Week 24 results showed that viral load appeared to decline significantly faster in participants taking oral cabotegravir than in participants taking efavirenz.
  • Results from Week 96 showed that maintenance therapy with oral cabotegravir plus oral rilpivirine, when used in participants with viral suppression, was as effective at controlling viral load as efavirenz plus two NRTIs.
  • On the basis of safety and efficacy data, investigators selected the 30-mg dose of oral cabotegravir for future study.
  • In terms of safety, no serious adverse events related to oral cabotegravir treatment were reported. Fewer participants in the oral cabotegravir dosing groups dropped out of the study because of a side effect than in the efavirenz group.6,9-12


Study Name: LATTE 2; NCT02120352
Phase: IIb
Location: United States, Canada, France, Germany, Spain
Participants: HIV-infected, treatment-naive adults
Purpose:The purpose of this study is to look at the safety and effectiveness of using two investigational long-acting injectable medicines together as HIV maintenance therapy. The two medicines are cabotegravir LA and rilpivirine LA. LA stands for “long-acting.” (Rilpivirine LA is also known as TMC278 LA.)
Study Design: This study consists of three parts as follows:

Part 1:

Participants will receive 30 mg of oral cabotegravir and the HIV combination medicine Epzicom once daily for 20 weeks. In the last 4 weeks of Part 1, participants will also receive oral rilpivirine once daily. (Participants who meet certain criteria can continue to the second part of the study.)

Part 2:

In the second part of the study, participants will be randomly assigned to one of three groups for maintenance therapy. (All doses of cabotegravir LA and rilpivirine LA will be given as an intramuscular [IM] injection.)

  • Group 1: Participants will receive an initial dose of medicine (called a “loading dose”) on Day 1 of cabotegravir LA plus rilpivirine LA. Then, starting at Week 4, participants will receive 400 mg of cabotegravir LA plus 600 mg of rilpivirine LA every 4 weeks for 96 weeks.
  • Group 2: Participants will receive two loading doses, one on Day 1 (cabotegravir LA plus rilpivirine LA) and one at Week 4 (only cabotegravir LA). Then, starting at Week 8, participants will receive 600 mg of cabotegravir LA plus 900 mg of rilpivirine LA every 8 weeks for 96 weeks.
  • Group 3: Participants will receive 30 mg of oral cabotegravir plus Epzicom once daily for 96 weeks (or for 104 weeks if continuing to Part 3 of the study).
Part 3:

The purpose of the third part of the study is to collect long-term safety and effectiveness data about the study medicines.

Investigators also plan to do long-term follow-up on participants who drop out of the study but have already received at least one dose of cabotegravir LA or rilpivirine LA.



* LATTE 2 is currently ongoing, and results are not yet available.7,13

Cabotegravir LA is also being developed as a medicine for pre-exposure prophylaxis (PrEP) for adults at risk of acquiring HIV. PrEP means using a medicine before possible exposure to a virus or bacteria to reduce the risk of becoming infected with the virus or bacteria. Two Phase IIa studies will be looking at the safety and drug properties of cabotegravir LA. The first, called the ECLAIR study, will include HIV-uninfected men. The second, called HPTN 077, will include HIV-uninfected men and women.13-16 Also, another Phase II trial called CAPRISA 014 will look at the safety and acceptability of cabotegravir LA in women who are at risk of acquiring HIV.17

What side effects might cabotegravir cause?

In the Phase IIb LATTE study discussed under the previous question, headache that was mild to moderate in intensity was more common in participants taking oral cabotegravir than in participants taking efavirenz.11,18

Because cabotegravir is still being studied, information on possible side effects of the drug is not complete. As testing of cabotegraivr continues, additional information on possible side effects will be gathered.

Where can I get more information about clinical trials studying cabotegravir?

More information about cabotegravir-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 cabotegravir. 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.

References

  1. United States National Library of Medicine. ChemIDplus Advanced. Available at: http://chem.sis.nlm.nih.gov/chemidplus/rn/1051375-10-0. Last accessed on September 18, 2015.
  2. 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 September 18, 2015.
  3. ViiV Healthcare website. Medicines in development. Available at: https://www.viivhealthcare.com/our-medicines/medicines-in-development.aspx. Last accessed on September 18, 2015.
  4. Ford SL, Margolis D, Chen S, Gould E, Spreen W. Plasma and tissue GSK1265744 pharmacokinetics following long-acting parenteral administration in healthy male and female subjects. Abstract presented at: 14th International Workshop on Clinical Pharmacology of HIV Therapy; April 22-24, 2013; Amsterdam, The Netherlands. Abstract O_02. Available at: http://regist2.virology-education.com/abstractbook/2013_3.pdf. Last accessed on September 18, 2015.
  5. Ford SL, Gould E, Chen S, et al. Effects of Etravirine on the Pharmacokinetics of the Integrase Inhibitor S/GSK1265744. Antimicrob Agents Chemother. 2013 Jan;57(1):277-80. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3535890/. Last accessed on September 18, 2015.
  6. ViiV Healthcare. A Phase IIb, Dose Ranging Study of Oral GSK1265744 in Combination With Nucleoside Reverse Transcriptase Inhibitors for Induction of Human Immunodeficiency Virus -1 (HIV-1) Virologic Suppression Followed by an Evaluation of Maintenance of Virologic Suppression When Oral GSK1265744 is Combined With Oral Rilpivirine in HIV-1 Infected, Antiretroviral Therapy Naive Adult Subjects. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 28, 2012. NLM Identifier: NCT01641809. Available at: http://www.clinicaltrials.gov/ct2/show/NCT01641809. Last accessed on September 18, 2015.
  7. ViiV Healthcare. A Phase IIb Study Evaluating a Long-Acting Intramuscular Regimen of GSK1265744 Plus TMC278 For The Maintenance of Virologic Suppression Following an Induction of Virologic Suppression on an Oral Regimen of GSK1265744 Plus Abacavir/Lamivudine in HIV-1 Infected, Antiretroviral Therapy-Naive Adult Subjects. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on April 17, 2014. NLM Identifier: NCT02120352. Available at: http://www.clinicaltrials.gov/ct2/show/NCT02120352. Last accessed on September 18, 2015.
  8. 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 September 18, 2015.
  9. Margolis D, Brinson C, Eron J, et al. 744 and Rilpivirine as Two-Drug Oral Maintenance Therapy: LAI116482 (LATTE) Week 48 Results. Abstract presented at: 21st Conference on Retroviruses and Opportunistic Infections (CROI); March 3-6, 2014; Boston, MA. Abstract 91LB. Available at: http://croi2014.org/sites/default/files/uploads/CROI2014_Final_Abstracts.pdf. Last accessed on September 18, 2015.
  10. Margolis D, Bhatti L, Smith G, et al. Once-daily Oral GSK1265744 (GSK744) as Part of Combination Therapy in Antiretroviral Naïve Adults: 24-week Safety and Efficacy Results from the LATTE Study (LAI116482). Abstract presented at: 14th European AIDS Conference; October 16-19, 2013; Brussels, Belgium. Abstract PS7/1. Available at: http://www.professionalabstracts.com/eacs2013/planner/index.php?go=abstract&action=abstract_iplanner&print=0&lprID=148&highlight=GSK1265744&PSID=IVXPCJJQVIXZCSVVMQWX. Last accessed on September 18, 2015.
  11. Margolis DA, Brinson CC, Smith GHR, et al. Cabotegravir and Rilpivirine As Two-Drug Oral Maintenance Therapy: LATTE Week 96 Results. Poster presented at: 22nd Conference on Retroviruses and Opportunistic Infections (CROI); February 23-26, 2015; Seattle, WA. Poster 554LB. Available at: http://www.croiconference.org/sites/default/files/posters-2015/554LB.pdf. Last accessed on September 18, 2015.
  12. Margolis DA, Brinson CC, Smith GH, et al. Cabotegravir and Rilpivirine As 2-Drug Oral Maintenance Therapy: LATTE W96 Results. Abstract presented at: 22nd Conference on Retroviruses and Opportunistic Infections (CROI); February 23-26, 2015; Seattle, WA. Abstract 554LB. Available at: http://www.croiconference.org/sessions/cabotegravir-and-rilpivirine-2-drug-oral-maintenance-therapy-latte-w96-results. Last accessed on September 18, 2015.
  13. Spreen B. Nanoformulations: Update from ViiV Healthcare. Slides presented at: 16th International Workshop on Clinical Pharmacology of HIV and Hepatitis Therapy; May 26-28, 2015; Washington, DC. Available at: http://regist2.virology-education.com/2015/16HIVHEP/10_Spreen.pdf. Last accessed on September 18, 2015.
  14. ViiV Healthcare. A Phase IIa Study to Evaluate the Safety, Tolerability and Acceptability of Long Acting Injections of the HIV Integrase Inhibitor, GSK1265744, in HIV Uninfected Men (ECLAIR). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 27, 2014. NLM Identifier: NCT02076178. Available at: http://www.clinicaltrials.gov/ct2/show/NCT02076178. Last accessed on September 18, 2015.
  15. National Institute of Allergy and Infectious Diseases (NIAID). A Phase IIa Study to Evaluate the Safety, Tolerability and Pharmacokinetics of the Investigational Injectable HIV Integrase Inhibitor, GSK1265744, in HIV-uninfected Men and Women. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 27, 2014. NLM Identifier: NCT02178800. Available at: http://www.clinicaltrials.gov/ct2/show/NCT02178800. Last accessed on September 18, 2015.
  16. Hankins C. Pre-Exposure Prophylaxis: state-of-the-art and roll-out. Slides presented at: 8th International Workshop on HIV Treatment, Pathogenesis and Prevention Research in Resource-Poor Settings (INTEREST); May 5-9, 2014; Lusaka, Zambia. Available at: http://regist2.virology-education.com/2014/8INTEREST/16_Hankins.pdf. Last accessed on September 18, 2015.
  17. Centre for the AIDS Programme of Research in South Africa. Phase II Trial to Assess the Safety and Acceptability of the Long-acting Injectable HIV Integrase Inhibitor, Cabotegravir (GSK1265744), in HIV Uninfected Women in KwaZulu-Natal, South Africa. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 27, 2015. NLM Identifier: NCT02462772. Available at: https://clinicaltrials.gov/ct2/show/NCT02462772. Last accessed on September 18, 2015.
  18. Margolis DA, Brinson CC, Eron JJ, et al. 744 and Rilpivirine as Two Drug Oral Maintenance Therapy: LAI116482 (LATTE) Week 48 Results. 21st Conference on Retroviruses and Opportunistic Infections (CROI); March 3-6, 2014; Boston, MA. Levin: Conference Reports for National AIDS Treatment Advocacy Project (NATAP); 2014. Available at: http://www.natap.org/2014/CROI/croi_27.htm. Last accessed on September 18, 2015.


Last Reviewed: October 1, 2015

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