Drug Description

Cobicistat (COBI), also known as GS-9350, is a specific, potent, mechanism-based inhibitor of cytochrome P450 3A (CYP3A) enzymes that lacks antiretroviral activity.[1][2]

References

[1] Gilead Sciences, Inc. – Newsroom: Press Releases. Gilead Initiates Phase III Clinical Program Evaluating Single-Tablet, Once-Daily “Quad” Regimen for HIV [press release], April 12, 2010. Available at: http://www.gilead.com/pr_1411934. Accessed 10/2/2010.

[2] Conf Retroviruses Opportunistic Infect 16th, 2009. Abstract 40.

HIV/AIDS-Related Uses

Cobicistat is an investigational compound being developed as a pharmacoenhancing agent (booster) to increase blood levels and allow once-daily dosing for certain antiviral drugs. [1] Cobicistat is being studied as part of an integrase-based fixed-dose regimen. In addition, cobicistat’s stand-alone role in boosting currently available HIV protease inhibitors is being examined. [2]

Two Phase III clinical trials evaluating a fixed-dose, single-tablet “Quad” regimen of elvitegravir (EVG), an investigational integrase inhibitor; cobicistat; emtricitabine (FTC); and tenofovir disoproxil fumarate (TDF) have been initiated. [3][4][5] A separate Phase III study investigating the safety and efficacy of GS-9350-boosted atazanavir (ATV) versus ritonavir (RTV)-boosted ATV, each administered with FTC/TDF (Truvada), is under way. [6]

References

[1] Gilead Sciences, Inc. – Newsroom: Press Releases. Gilead Announces Data Demonstrating Pharmacokinetic Boosting Activity of GS 9350 [press release], February 9, 2009. Available at: http://www.gilead.com/pr_1254580. Accessed 10/2/2010.

[2] Gilead Sciences, Inc. – Newsroom: Press Releases. Gilead Initiates Phase III Clinical Program Evaluating Single-Tablet, Once-Daily “Quad” Regimen for HIV [press release], April 12, 2010. Available at: http://www.gilead.com/pr_1411934. Accessed 10/2/2010.

[3] Gilead Sciences, Inc. – Newsroom: Press Releases. Gilead Initiates Phase III Clinical Program Evaluating Single-Tablet, Once-Daily “Quad” Regimen for HIV [press release], April 12, 2010. Available at: http://www.gilead.com/pr_1411934. Accessed 10/2/2010.

[4] ClinicalTrials.gov – Phase 3, Randomized, Double Blind Study to Evaluate the Safety and Efficacy of Elvitegravir/Emtricitabine/Tenofovir Disoproxil Fumarate/GS-9350 Versus Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate in HIV-1 Infected, Antiretroviral Treatment-Naïve Adults. Available at: http://www.clinicaltrials.gov/ct2/show/NCT01095796?term=GS9350&rank=3. Accessed 10/2/2010.

[5] ClinicalTrials.gov – Study to Evaluate the Safety and Efficacy of Elvitegravir/Emtricitabine/Tenofovir Disoproxil Fumarate/GS-9350 Versus Ritonavir-Boosted Atazanavir Plus Emtricitabine/Tenofovir Disoproxil Fumarate in HIV-1 Infected, Antiretroviral Treatment-Naïve Adults. Available at: http://www.clinicaltrials.gov/ct2/show/NCT01106586?term=GS9350&rank=5. Accessed 10/2/2010.

[6] ClinicalTrials.gov – Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of GS-9350-boosted Atazanavir Versus Ritonavir-boosted Atazanavir Each Administered With Emtricitabine/Tenofovir Disoproxil Fumarate in HIV-1 infected, Antiretroviral Treatment-Naïve Adults. Available at: http://www.clinicaltrials.gov/ct2/show?term=GS9350&rank=2. Accessed 10/2/2010.

Dosing Information

Oral. [1]

Dosage Form

GS-9350 has been studied as a tablet in doses of 50, 100, 150, and 200 mg. [2]

GS-9350 is also being studied as part of a single tablet containing EVG 150 mg, cobicistat 150 mg, FTC 200 mg, and TDF 300 mg. [3]

Cobicistat is currently being evaluated in treatment-naïve adults in two Phase III trials as part of a once-daily “Quad” tablet, administered by mouth. [4][5]

A separate Phase III trial of treatment-naïve adults is evaluating GS-9350 150 mg-boosted ATV 300 mg + FTC 200 mg/TDF 300 mg, administered by mouth. [6]
 

Storage

GS-9350 is being developed to be stable at room temperature. [7]

References

[1] Gilead Sciences, Inc. – Newsroom: Press Releases. Gilead Announces Data Demonstrating Pharmacokinetic Boosting Activity of GS 9350 [press release], February 9, 2009. Available at: http://www.gilead.com/pr_1254580. Accessed 10/2/2010.

[2] Gilead Sciences, Inc. – Newsroom: Press Releases. Gilead Announces Data Demonstrating Pharmacokinetic Boosting Activity of GS 9350 [press release], February 9, 2009. Available at: http://www.gilead.com/pr_1254580. Accessed 10/2/2010.

[3] ClinicalTrials.gov – Study to Evaluate the Safety and Efficacy of Elvitegravir/Emtricitabine/Tenofovir Disoproxil Fumarate/GS-9350 Versus Ritonavir-Boosted Atazanavir Plus Emtricitabine/Tenofovir Disoproxil Fumarate in HIV-1 Infected, Antiretroviral Treatment-Naïve Adults. Available at: http://www.clinicaltrials.gov/ct2/show/NCT01106586?term=GS9350&rank=5. Accessed 10/2/2010.

[4] ClinicalTrials.gov – Phase 3, Randomized, Double Blind Study to Evaluate the Safety and Efficacy of Elvitegravir/Emtricitabine/Tenofovir Disoproxil Fumarate/GS-9350 Versus Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate in HIV-1 Infected, Antiretroviral Treatment-Naïve Adults. Available at: http://www.clinicaltrials.gov/ct2/show/NCT01095796?term=GS9350&rank=3. Accessed 10/2/2010.

[5] Gilead Sciences, Inc. – Newsroom: Press Releases. Gilead Initiates Phase III Clinical Program Evaluating Single-Tablet, Once-Daily “Quad” Regimen for HIV [press release], April 12, 2010. Available at: http://www.gilead.com/pr_1411934. Accessed 10/2/2010.

[6] ClinicalTrials.gov – Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of GS-9350-boosted Atazanavir Versus Ritonavir-boosted Atazanavir Each Administered With Emtricitabine/Tenofovir Disoproxil Fumarate in HIV-1 infected, Antiretroviral Treatment-Naïve Adults. Available at: http://www.clinicaltrials.gov/ct2/show?term=GS9350&rank=2. Accessed 10/2/2010.

[7] Gilead Sciences, Inc. – Newsroom: Press Releases. Gilead Announces Data Demonstrating Pharmacokinetic Boosting Activity of GS 9350 [press release], February 9, 2009. Available at: http://www.gilead.com/pr_1254580. Accessed 10/2/2010.

Pharmacology

Cobicistat, GS-9350, is a potent, mechanism-based inhibitor of human CYP3A isoforms. As a pharmacoenhancer, cobicistat is used to increase the blood levels and increase the systemic exposure of certain coadministered antiretroviral agents that are metabolized by CYP3A enzymes. Unlike ritonavir (RTV), which is in current clinical use as a boosting agent for HIV therapy, GS-9350 does not have anti-HIV activity. In vitro, preclinical data showed that GS-9350 has no antiviral activity at concentrations up to 90 microM. [1][2][3]

A Phase I study evaluating the safety, tolerability, pharmacokinetics and boosting capacity of GS-9350 compared to RTV found that GS-9350 is a potent (Ki<1 microM) human CYP3A inhibitor; two-step enzyme inactivation studies found that GS-9350 was a potent mechanism-based human CYP3A inhibitor (kinact 0.44 min^-1, Ki 0.94 microM). GS-9350 did not activate the human aryl hydrocarbon receptor and was a weak agonist (median effective concentration [EC₅₀]>30 microM) of the human pregnane X receptor, which is responsible for induction of drug metabolism and transport.  In humans, GS-9350 exhibited non-linear pharmacokinetics with respect to dose and time. GS-9350 doses of 100 mg and 200 mg inhibited the clearance of midazolam, the CYP3A probe substrate, by 92% and 95%, respectively, similar in effect to RTV 100 mg. [4][5][6]

Furthermore, GS-9350 showed no inhibition of lipid accumulation in adipocytes at 30 microM and <10% inhibition of insulin-stimulated glucose uptake at 10 microM. [7][8]

Pharmacokinetics data from a Phase I trial of 42 HIV-uninfected volunteers receiving ATV 300 mg coadministered with either GS-9350 100 mg, GS-9350 150 mg, or RTV 100 mg for three 10-day periods with a 4-day washout between each period demonstrate that ATV levels were bioequivalent in participants receiving RTV 100 mg and GS-9350 150 mg. The ATV area under the plasma concentration-time curve for a dosing-interval (AUC_tau), peak plasma concentration (C_max), time to maximum concentration (T_max) and half-life (T _1/2) were 55,200, 45,100, and 55,900 ng(h)/mL; 5270, 4420, and 4880 ng/mL; 3.0, 3.5, and 3.0 h; and 15.7, 9.7, and 16.7 h for ritonavir 100 mg, GS-9350 100 mg, and GS-9350 150 mg, respectively. [9][10]

A Phase I open-label, partially randomized study evaluating two versions of a fixed-dose single tablet regimen containing either COBI 100 mg or COBI 150 mg, each with EVG, FTC, and TDF versus RTV 100 mg-boosted EVG, FTC/TDF found that the 150-mg GS-9350 dose resulted in maintenance of targeted high EVG trough concentrations (C_tau) based on RTV boosting. Additionally, the fixed-dose combination tablet containing GS-9350 150 mg resulted in clinically equivalent tenofovir and FTC exposures compared to FTC/TDF administered individually. Relative to RTV-boosted EVG, the geometric least-squares means ratios (GMR) (90% confidence interval [CI]) for EVG AUC_tau, C_max, and trough concentration (C_tau) were 118 (110 to 126), 108 (100 to 116), and 110 (95.3 to 127), respectively, with EVG/COBI 150mg/FTC/TDF. Relative to FTC + TDF, FTC GMR (90% CI) were 127 (115 to 140) for AUC_tau, 121 (107 to 137) for C_max, and 126 (118 to 136) for C_tau; TDF GMR (90% CI) were 118 (114 to 122) for AUC_tau, 130 (122 to 138) for C_max, and 124 (119 to 129) for C_tau, with EVG/COBI 150 mg/FTC/TDF. [11][12]

Study 236-0104, an ongoing double-blind, randomized, active-controlled Phase II trial evaluating the safety and efficacy of a fixed-dose single-tablet “Quad” regimen (EVG/GS-9350/FTC/TDF) (n = 48) versus efavirenz/FTC/TDF (Atripla) (n = 23) among HIV-infected treatment-naïve adults, demonstrated that, at 24 weeks, 90% of patients in the “Quad” arm and 83% of patients in the Atripla arm achieved viral load <50 copies/mL. At 24 weeks, patients in the “Quad” arm experienced a median increase in CD4 cell count of 123 cells/mm³, compared to a median increase of 124 cells/mm³ in the Atripla arm. At Week 48, 90% patients in the “Quad” arm and 83% of patients in the Atripla arm achieved the study’s primary objective of HIV-1 RNA levels of less than 50 copies/mL, using an analysis where missing equals failure. When using an analysis where missing values were excluded, 96% and 95% of patients in the “Quad” and Atripla groups, respectively, achieved HIV-1 RNA levels of less than 50 copies/mL. Patients taking the “Quad” versus patients taking Atripla experienced a mean increase in CD4 cell counts of 240 cells/mm³ compared to 162 cells/mm³, respectively, at 48 weeks. [13][14][15][16]

A separate Phase II trial, study 216-0105, is an ongoing double-blind, randomized, active-controlled trial examining the safety and efficacy of cobicistat-boosted ATV (n = 50) compared to RTV-boosted ATV (n = 29), each in combination with FTC/TDF, in HIV-infected treatment naïve adults. Data at 24 weeks found that 84% of patients in the cobicistat group and 86% of those in the RTV-boosted ATV group achieved viral load <50 copies/mL, the primary outcome measure.  Patients taking a cobicistat-boosted regimen experienced a median increase in CD4 cell count of 206 cells/mm³, compared with 190 cells/mm³ among patients in the RTV-boosted group. At 48 weeks, 82% and 86% of patients in the cobicistat and ritonavir groups, respectively, met the primary objective of achieving HIV RNA levels of less than 50 copies/mL, using an analysis where missing equals failure. When using an analysis where missing values are excluded, 91% of patients in the cobicistat arm and 96% of those in the ritonavir arm achieved HIV RNA levels of less than 50 copies/mL. In addition, at Week 48, patients taking a cobicistat-boosted regimen experienced a mean increase in CD4 cell count of 230 cells/mm³, compared to a mean increase of 206 cells/mm³ among patients taking a ritonavir-boosted regimen. [17][18][19][20]

References

[1] Clin Pharmacol Ther. 2010 Mar;87(3):322-9.

[2] Conf Retroviruses Opportunistic Infect 16th, 2009. Abstract 40.

[3] Gilead Sciences, Inc. – Newsroom: Press Releases. Gilead Announces Data Demonstrating Pharmacokinetic Boosting Activity of GS 9350 [press release], February 9, 2009. Available at: http://www.gilead.com/pr_1254580. Accessed 10/2/2010.

[4] Clin Pharmacol Ther. 2010 Mar;87(3):322-9.

[5] Conf Retroviruses Opportunistic Infect 16th, 2009. Abstract 40.

[6] Gilead Sciences, Inc. – Newsroom: Press Releases. Gilead Announces Data Demonstrating Pharmacokinetic Boosting Activity of GS 9350 [press release], February 9, 2009. Available at: http://www.gilead.com/pr_1254580. Accessed 10/2/2010.

[7] Gilead Sciences, Inc. – Newsroom: Press Releases. Gilead Announces Data Demonstrating Pharmacokinetic Boosting Activity of GS 9350 [press release], February 9, 2009. Available at: http://www.gilead.com/pr_1254580. Accessed 10/2/2010.

[8] Conf Retroviruses Opportunistic Infect 16th, 2009. Abstract 40.

[9] HIV and Hepatitis.com – Investigational Pharmaco-enhancer GS-9350 Equals Ritonavir (Norvir) as a Booster for Atazanavir (Reyataz). Coverage of the 49th Interscience Conference on Antimicrobia Agents and Chemotherapy, September 12-15, 2009. Available at: http://www.hivandhepatitis.com/2009icr/icaac/docs/092909_a.html. Accessed 10/2/2010.

[10] 49th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), 2009. Poster A1-1301. Available at: http://www.hivandhepatitis.com/2009icr/icaac/pdfs/2_Ramanathan.pdf. Accessed 10/2/2010.

[11] J Acquir Immune Defic Syndr. 2010 Jul 30. [Published ahead of print]. Available at: http://journals.lww.com/jaids/Abstract/publishahead/Pharmacokinetics_and_Bioavailability_of_an.98945.aspx. Accessed 10/2/2010.

[12] Gilead Sciences, Inc. – Newsroom: Press Releases. Gilead Announces Data Demonstrating Pharmacokinetic Boosting Activity of GS 9350 [press release], February 9, 2009. Available at: http://www.gilead.com/pr_1254580. Accessed 10/2/2010.

[13] Gilead Sciences, Inc. – Newsroom: Press Releases. Gilead’s Single-Tablet “Quad” Regimen for HIV Achieves a High Rate of Virologic Suprression in Phase II Study [press release], February 17, 2010. Available at: http://www.gilead.com/pr_1391910. Accessed 10/2/2010.

[14] HIV and Hepatitis.com – Gilead’s Quad Pill Matches Atripla, New Booster Cobicistat (GS 9350) Looks Good with Atazanavir (Reyataz). Coverage of the 17th Conference on Retroviruses and Opportunistic Infections, February 16-19, 2010. Available at: http://www.hivandhepatitis.com/2010_conference/croi/docs/0219_2010_c.html. Accessed 10/2/2010.

[15] Conf Retroviruses Opportunistic Infect 17th, 2010. Paper 58LB.

[16] Gilead Sciences Press Release Archive: Gilead’s Single-Tablet “Quad” HIV Regimen Maintains High Viral Suppression Through 48 Weeks in Phase II Study [press release], September 13, 2010. Available at: http://www.gilead.com/pr_1470367. Accessed 10/2/2010.

[17] Gilead Sciences, Inc. – Newsroom: Press Releases. Gilead’s Single-Tablet “Quad” Regimen for HIV Achieves a High Rate of Virologic Suprression in Phase II Study [press release], February 17, 2010. Available at: http://www.gilead.com/pr_1391910. Accessed 10/2/2010.

[18] HIV and Hepatitis.com – Gilead’s Quad Pill Matches Atripla, New Booster Cobicistat (GS 9350) Looks Good with Atazanavir (Reyataz). Coverage of the 17th Conference on Retroviruses and Opportunistic Infections, February 16-19, 2010. Available at: http://www.hivandhepatitis.com/2010_conference/croi/docs/0219_2010_c.html. Accessed 10/2/2010.

[19] Conf Retroviruses Opportunistic Infect 17th, 2010. Paper 58LB.

[20] Gilead Sciences Press Release Archive: Gilead’s Single-Tablet “Quad” HIV Regimen Maintains High Viral Suppression Through 48 Weeks in Phase II Study [press release], September 13, 2010. Available at: http://www.gilead.com/pr_1470367. Accessed 10/2/2010.

Adverse Events/Toxicity

In a Phase I crossover trial (n = 42) comparing ATV 300 mg with either GS-9350 100 mg, GS-9350 150 mg, or RTV 100 mg, reported adverse events were mild to moderate and resolved on treatment. Three participants taking ATV/GS-9350 (n = 2 at 100 mg, n = 1 at 150 mg) discontinued treatment due to skin rash. Neither Grade 3/4 laboratory abnormalities nor serious adverse events, including liver toxicity or clinically relevant heart rhythm (ECG) changes, were seen. [1][2]

In a separate Phase I 14-day multiple-dose escalation study, one drug-related Grade 3 adverse event (discoordination) occurred in a single trial participant during multiple dose administration of GS-9350 100 mg.  No participants developed drug-related Grade 3/4 laboratory abnormalities or Grade 4 adverse events. [3][4]

Safety data from study 236-0104 demonstrated a similar discontinuation rate and adverse event profile for both arms of the trial. Three patients discontinued treatment in each arm of the study. In the “Quad” group, no patients discontinued due to an adverse event, compared to one subject who stopped treatment in the Atripla group. Adverse event rates were reported as similar between treatment arms, although fewer CNS events were observed among “Quad” patients. The most commonly observed treatment-emergent adverse events occurring in greater than 5% of patients in either treatment arm were abnormal dreams/nightmares, fatigue, dizziness, diarrhea, somnolence, headache, anxiety, nausea, abdominal distension, and rash. Two Grade 3/4 adverse events were observed among “Quad” patients (pneumonia and anogenital warts); two Grade 3/4 adverse events were reported among Atripla patients (B-cell lymphoma with lymphadenopathy and neutropenia). There was a similar incidence of laboratory abnormalities (Grades 2–4) across both arms of the study. Laboratory abnormalities occurring in greater than 5% of patients in either treatment arm included hyperamylasemia, hypercholesterolemia, creatine kinase, neutropenia, and proteinuria. Mean changes in cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglycerides were reported as small and similar in both arms of the study.  [5][6][7]

In study 216-0105, discontinuation rates were similar between the cobicistat and RTV arms. Two cobicistat patients discontinued treatment due to adverse events (vomiting and rash), as did one RTV patient (scleral icterus). The most commonly observed treatment-emergent adverse events occurring in greater than 5% of patients in either treatment arm were diarrhea, nausea, fatigue, and flatulence. There were two Grade 3/4 adverse events among cobicistat-treated patients ( hyperbilirubinemia and rash). The incidence of laboratory abnormalities (Grades 2–4) was similar across both arms. Grades 2–4 laboratory abnormalities occurring in greater than 5% of patients in either treatment arm included hyperbilirubinemia, hyperamylasemia, hypercholesterolemia, creatine kinase, hypophosphotemia and hematuria. Mean changes in cholesterol, LDL, HDL, and triglycerides were reported as similar in both treatment arms.  [8][9][10]

In both study 236-0104 and 216-0105, small increases in serum creatinine with resulting decreases in estimated creatinine clearance (by Cockroft-Gault) were observed by Week 24. In study 236-0104, participants receiving GS-9350 experienced a slightly greater increase in serum creatinine (+0.14 mg/dL vs. +0.04 mg/dL in the Atripla arm). At 24 weeks, mean estimated glomerular filtration (eGFR) rate was lower in the “Quad” arm compared with the Atripla arm (111 vs. 126 mL/min, respectively). In study 216-0105, at Week 24, serum creatinine was slightly elevated in patients taking cobicistat (+0.18 mg/dL) compared with the RTV arm (+0.14 mg/dL). Mean eGFR for patients taking cobicistat and RTV was 102 and 111 mL/min, respectively. Results from a separate renal study in healthy volunteers indicate that cobicistat does not affect actual glomerular filtration rates (GFR) as assessed by iohexol clearance. Reportedly, the increase in serum creatinine with cobicistat occurs within days of drug initiation and is reversible with values returning to baseline within days after cessation of cobicistat. Study investigators also report that in study 216-0105, increases in serum creatinine with resulting decreases in estimated creatinine clearance stabilized through Week 48 and were comparable in both treatment arms. [11][12][13]
 

References

[1] HIV and Hepatitis.com – Investigational Pharmaco-enhancer GS-9350 Equals Ritonavir (Norvir) as a Booster for Atazanavir (Reyataz). Coverage of the 49th Interscience Conference on Antimicrobia Agents and Chemotherapy, September 12-15, 2009. Available at: http://www.hivandhepatitis.com/2009icr/icaac/docs/092909_a.html. Accessed 10/2/2010.

[2] 49th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), 2009. Poster A1-1301. Available at: http://www.hivandhepatitis.com/2009icr/icaac/pdfs/2_Ramanathan.pdf. Accessed 10/2/2010.

[3] Gilead Sciences, Inc. – Newsroom: Press Releases. Gilead Announces Data Demonstrating Pharmacokinetic Boosting Activity of GS 9350 [press release], February 9, 2009. Available at: http://www.gilead.com/pr_1254580. Accessed 10/2/2010.

[4] Conf Retroviruses Opportunistic Infect 16th, 2009. Abstract 40.

[5] HIV and Hepatitis.com – Gilead’s Quad Pill Matches Atripla, New Booster Cobicistat (GS 9350) Looks Good with Atazanavir (Reyataz). Coverage of the 17th Conference on Retroviruses and Opportunistic Infections, February 16-19, 2010. Available at: http://www.hivandhepatitis.com/2010_conference/croi/docs/0219_2010_c.html. Accessed 10/2/2010.

[6] Gilead Sciences, Inc. – Newsroom: Press Releases. Gilead’s Single-Tablet “Quad” Regimen for HIV Achieves a High Rate of Virologic Suprression in Phase II Study [press release], February 17, 2010. Available at: http://www.gilead.com/pr_1391910. Accessed 10/2/2010.

[7] Gilead Sciences Press Release Archive: Gilead’s Single-Tablet “Quad” HIV Regimen Maintains High Viral Suppression Through 48 Weeks in Phase II Study [press release], September 13, 2010. Available at: http://www.gilead.com/pr_1470367. Accessed 10/2/2010.

[8] Gilead Sciences, Inc. – Newsroom: Press Releases. Gilead’s Single-Tablet “Quad” Regimen for HIV Achieves a High Rate of Virologic Suprression in Phase II Study [press release], February 17, 2010. Available at: http://www.gilead.com/pr_1391910. Accessed 10/2/2010.

[9] HIV and Hepatitis.com – Gilead’s Quad Pill Matches Atripla, New Booster Cobicistat (GS 9350) Looks Good with Atazanavir (Reyataz). Coverage of the 17th Conference on Retroviruses and Opportunistic Infections, February 16-19, 2010. Available at: http://www.hivandhepatitis.com/2010_conference/croi/docs/0219_2010_c.html. Accessed 10/2/2010.

[10] Gilead Sciences Press Release Archive: Gilead’s Single-Tablet “Quad” HIV Regimen Maintains High Viral Suppression Through 48 Weeks in Phase II Study [press release], September 13, 2010. Available at: http://www.gilead.com/pr_1470367. Accessed 10/2/2010.

[11] Gilead Sciences, Inc. – Newsroom: Press Releases. Gilead’s Single-Tablet “Quad” Regimen for HIV Achieves a High Rate of Virologic Suprression in Phase II Study [press release], February 17, 2010. Available at: http://www.gilead.com/pr_1391910. Accessed 10/2/2010.

[12] HIV and Hepatitis.com – Gilead’s Quad Pill Matches Atripla, New Booster Cobicistat (GS 9350) Looks Good with Atazanavir (Reyataz). Coverage of the 17th Conference on Retroviruses and Opportunistic Infections, February 16-19, 2010. Available at: http://www.hivandhepatitis.com/2010_conference/croi/docs/0219_2010_c.html. Accessed 10/2/2010.

[13] Gilead Sciences Press Release Archive: Gilead’s Single-Tablet “Quad” HIV Regimen Maintains High Viral Suppression Through 48 Weeks in Phase II Study [press release], September 13, 2010. Available at: http://www.gilead.com/pr_1470367. Accessed 10/2/2010.

Drug and Food Interactions

In a 14-day multiple-dose escalation study, results indicated that GS-9350 doses of 100 mg and 200 mg inhibited the clearance of midazolam, the study's CYP3A probe substrate, by 92% and 95%, respectively, similar in effect to RTV 100 mg. [1]

References

[1] Conf Retroviruses Opportunistic Infect 16th, 2009. Abstract 40.

Clinical Trials

Click here to search ClinicalTrials.gov for trials that use .

Chemistry

Molecular Formula

C40-H53-N7-O5-S2 [1]

References

[1] ChemIDplus Available at: http://chem.sis.nlm.nih.gov/chemidplus/chemidlite.jsp. Accessed 10/2/2010.

Further Reading

Gilead Sciences, Inc. – Newsroom: Press Releases. Gilead Announces Data Demonstrating Pharmacokinetic Boosting Activity of GS 9350 [press release], February 9, 2009. Available at: http://www.gilead.com/pr_1254580. Accessed 10/02/2010.

Gilead Sciences, Inc. – Newsroom: Press Releases. Gilead Initiates Phase III Clinical Program Evaluating Single-Tablet, Once-Daily “Quad” Regimen for HIV [press release], April 12, 2010. Available at: http://www.gilead.com/pr_1411934. Accessed 10/02/2010.

Conf Retroviruses Opportunistic Infect 16th, 2009. Abstract 40.
 

Manufacturer Information

Cobicistat

Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
Phone: (650) 574-3000
Fax: (650) 578-9264