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AIDSinfo Drug Database

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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?

Cabotegravir for HIV Treatment

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 was 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.) On the basis of results from this study, investigators also plan to choose a dosing regimen to be used in Phase III studies.
Study Design: This study consists of three parts as follows:

Part 1:

Participants received 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 also received oral rilpivirine once daily. (Participants who demonstrated control of their viral load continued to the second part of the study.)

Part 2:

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

  • Group 1: Participants received an initial dose of medicine (called a “loading dose”) on Day 1 of cabotegravir LA plus rilpivirine LA. Then, starting at Week 4, participants received 400 mg of cabotegravir LA plus 600 mg of rilpivirine LA every 4 weeks until Week 32. Treatment will continue to Week 96 (or longer for participants who continue to Part 3 of the study).
  • Group 2: Participants received 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 received 600 mg of cabotegravir LA plus 900 mg of rilpivirine LA every 8 weeks until Week 32. Treatment will continue to Week 96 (or longer for participants who continue to Part 3 of the study).
  • Group 3: Participants received 30 mg of oral cabotegravir plus Epzicom once daily until Week 32. Treatment will continue to Week 96 (or longer for participants who elect to receive IM medication in Part 3 of the study).

Part 3:

The purpose of the third part of the study (the extension phase) is to collect long-term safety and effectiveness data about cabotegravir LA plus rilpivirine LA.

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.

Results:

  • As maintenance therapy, both IM dosing regimens of cabotegravir LA plus rilpivirine LA (Groups 1 and 2) had similar effectiveness in controlling participants’ viral loads as daily oral cabotegravir plus Epzicom through 32 weeks.
  • Investigators will be analyzing Week 48 data to select a cabotegravir LA plus rilpivirine LA dosing regimen to be used in future studies.
  • In terms of safety, no drug-related serious side effects were reported. Nine participants dropped out of the study because of a side effect during maintenance therapy: eight participants were receiving cabotegravir LA plus rilpivirine LA; one participant was receiving oral cabotegravir.7,13-15

Cabotegravir for HIV Prevention

Study Name: ECLAIR; NCT02076178
Phase: IIa
Location: United States
Participants: HIV-uninfected adult males
Purpose: The purpose of this study was to look at the safety, tolerability, and acceptability of cabotegravir LA.
Study Design:

  • Oral Phase: Participants initially received 30 mg of oral cabotegravir or placebo once daily for 4 weeks.
  • Injection Phase: Participants received 800 mg of cabotegravir LA or placebo, given by IM injection once every 12 weeks for 3 injection cycles.

Participants will continue to be followed for 40 weeks after the last injection cycle.

Results:

  • Analysis at Week 41 found that the majority of participants receiving cabotegravir LA were satisfied with the treatment injections. In terms of convenience, flexibility, and lifestyle, participants reported being more satisfied with cabotegravir LA than with oral cabotegravir.
  • Reactions occurring at the location where the injection was given (also known as injection site reactions) occurred in 93% of participants receiving cabotegravir LA and in 57% of participants receiving placebo. Most of these injection site reactions were mild to moderate in severity.
  • The most common injection site reaction experienced by both cabotegravir LA and placebo participants was pain at the location of the injection, which occurred in 92% of cabotegravir LA participants and in 27% of placebo participants.
  • Four percent of participants receiving cabotegravir LA dropped out of the study because of “injection intolerability.” During the Oral Phase, 7% of cabotegravir participants dropped out of the study because of a side effect.16-19

Another Phase IIa study, called HPTN 077, will be evaluating the safety, tolerability, and drug properties of cabotegravir LA in HIV-uninfected men and women.20 Also, a 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.21

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.11,22

In the LATTE-2 study, the most common injection site reactions were pain at the location of the injection, swelling, and nodules. Most injection site reactions were mild to moderate in severity. Other side effects occurring during maintenance therapy in participants receiving either oral treatment or injectable treatment were common cold (nasopharyngitis), headache, and diarrhea.13-15

In the ECLAIR study, a common side effect related to cabotegravir LA was mild to moderate pain at the location of the injection. Some other injection site reactions that occurred in participants receiving cabotegravir LA included itching, swelling, and nodules.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 March 28, 2016.
  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 March 28, 2016.
  3. ViiV Healthcare website. Medicines in development. Available at: https://www.viivhealthcare.com/our-medicines/medicines-in-development.aspx. Last accessed on March 28, 2016.
  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 March 28, 2016.
  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 March 28, 2016.
  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 March 28, 2016.
  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 March 28, 2016.
  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 March 28, 2016.
  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 March 28, 2016.
  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 March 28, 2016.
  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 March 28, 2016.
  13. Gonzalez-Garcia J, Stellbrink H-J, Eron JJ, et al. Cabotegravir + Rilpivirine as Long-Acting Maintenance Therapy: LATTE-2 Week 32 Results. 23rd Conference on Retroviruses and Opportunistic Infections (CROI); February 22-25, 2016; Boston, MA. Levin: Conference reports for National AIDS Treatment Advocacy Project (NATAP); 2016. Available at: http://www.natap.org/2016/CROI/croi_06.htm. Last accessed on March 28, 2016.
  14. Margolis DA, González-García J, Stellbrink H-J, et al. Cabotegravir+Rilpivirine as Long-Acting Maintenance Therapy: LATTE-2 Week 32 Results. Abstract presented at: 23rd Conference on Retroviruses and Opportunistic Infections (CROI); February 22-25, 2016; Boston, MA. Abstract 31LB. Available at: http://www.croiconference.org/sessions/cabotegravirrilpivirine-long-acting-maintenance-therapy-latte-2-week-32-results. Last accessed on March 28, 2016.
  15. ViiV Healthcare: Press Release, dated February 23, 2016. ViiV Healthcare announces phase II study results for first two drug, long-acting injectable regimen for HIV-1 treatment. Available at: https://www.viivhealthcare.com/media/press-releases/2016/february/viiv-healthcare-announces-phase-ii-study-results-for-first-two-drug-long-acting-injectable-regimen-for-hiv-1-treatment.aspx. Last accessed on March 28, 2016.
  16. 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 March 28, 2016.
  17. Markowitz M, Frank I, Grant R, et al. ÉCLAIR: Phase 2A Safety and PK Study of Cabotegravir LA in HIV-Uninfected Men. Abstract presented at: 23rd Conference on Retroviruses and Opportunistic Infections (CROI); February 22-25, 2016; Boston, MA. Abstract 106. Available at: http://www.croiconference.org/sessions/%C3%A9clair-phase-2a-safety-and-pk-study-cabotegravir-la-hiv-uninfected-men. Last accessed on March 28, 2016.
  18. Murray M, Markowitz M, Frank I, et al. Tolerability and Acceptability of Cabotegravir LA Injection: Results From the ECLAIR Study. Poster presented at: 23rd Conference on Retroviruses and Opportunistic Infections (CROI); February 22-25, 2016; Boston, MA. Poster 471. Available at: http://www.croiconference.org/sites/default/files/posters-2016/471.pdf. Last accessed on March 28, 2016.
  19. Meyers K, Rodriguez K, Markowitz M, Golub SA. Understanding Pain and Anxiety Experienced Around Long-Acting Injectable PrEP. Abstract presented at: 23rd Conference on Retroviruses and Opportunistic Infections (CROI); February 22-25, 2016; Boston, MA. Abstract 881. Available at: http://www.croiconference.org/sessions/understanding-pain-and-anxiety-experienced-around-long-acting-injectable-prep. Last accessed on March 28, 2016.
  20. 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 March 28, 2016.
  21. 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 March 28, 2016.
  22. 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 March 28, 2016.


Last Reviewed: March 28, 2016

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