Delving into the Latest Updates on Atazanavir Sulfate/Ritonavir with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

ATZ/RTV

Target

HIV-1 pol

Action

inhibitors

Mechanism

HIV-1 pol inhibitors(Human immunodeficiency virus type 1 protease inhibitors)

Therapeutic Areas

Immune System DiseasesInfectious DiseasesUrogenital Diseases

Active Indication

HIV Infections

Inactive Indication-

Originator Organization

Matrix Laboratories BV (Belgium)

Active Organization

Mylan Laboratories Ltd.

Matrix Labs LLC

Emcure Pharmaceuticals Ltd.

Inactive Organization-

Drug Highest PhaseNDA/BLA

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC38H54N6O11S

InChIKeyDQSGVVGOPRWTKI-QVFAWCHISA-N

CAS Registry229975-97-7

View All Structures (2)

Since the outbreak of the novel coronavirus disease in 2019 (COVID-19), an unprecedented global search for potential therapeutics and vaccines is ongoing. In this study, a combination of two drugs that have been shown to be effective against the germ that causes COVID-19 in the laboratory will be tested in patients diagnosed with moderate to severe COVID-19. One of the drugs is called nitazoxanide and the second is atazanavir/ritonavir. Nitazoxanide has been used for the treatment of diarrhea since 2004 while atazanavir/ritonavir was approved for HIV treatment in 2003. They are known to be safe in humans.
In this pilot study, 98 COVID-19 patients will be recruited into two groups. The 49 patients in group 1 will receive the standard of care determined by their primary care providers while the 49 patients in group 2 will receive both the standard of care combined with the two study drugs. Patients in group 2 will receive the study drugs for 14 days and all patients will be monitored for a total of 28 days.
The time it takes for the germ that causes COVID-19 to be completely removed from the body (in nasal secretions) and the time to clinical improvement will be monitored in all patients and compared between the two groups.

Start Date09 Oct 2020

Sponsor / Collaborator

Obafemi Awolowo University

[+3]

NCT04022967

/ Active, not recruitingPhase 3IIT

Randomized, Non-inferiority Trial Comparing a Dual Maintenance Therapy Strategy With Dolutegravir + Lamivudine (DTG/3TC) or Atazanavir/Ritonavir + Lamivudine (ATV/r+3TC) Versus the Standard WHO First Line Triple Therapy Tenofovir + Lamivudine + Efavirenz (TDF+3TC+EFV) or Dolutegravir + Lamivudine + Tenofovir (DTG+3TC+TDF) in West and Central African HIV-1 Infected Patients

MODERATO is a phase III, open-label, randomized, multicenter, non-inferiority trial conducted in West and Central Africa (Cameroon, Côte d'Ivoire, Burkina Faso).
HIV-1 infected adults receiving first line ART with TDF+XTC+EFV or DTG+XTC+TDF virologically suppressed will be recruited and followed during 100 weeks.
The objective is to assess the non-inferiority of a strategy consisting of switching to a dual maintenance therapy (DTG+3TC or ATV/r+3TC), comparing to WHO standard first line regimen (TDF+3TC+EFV or DTG+3TC+TDF), in terms of virological success at 96 weeks

Start Date21 Sep 2020

Sponsor / Collaborator

ANRS, Emerging Infectious Diseases

[+1]

100 Clinical Results associated with Atazanavir Sulfate/Ritonavir

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100 Translational Medicine associated with Atazanavir Sulfate/Ritonavir

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100 Patents (Medical) associated with Atazanavir Sulfate/Ritonavir

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5

Literatures (Medical) associated with Atazanavir Sulfate/Ritonavir

01 Jul 2015·The Lancet Infectious DiseasesQ1 · MEDICINE

Dual treatment with atazanavir–ritonavir plus lamivudine versus triple treatment with atazanavir–ritonavir plus two nucleos(t)ides in virologically stable patients with HIV-1 (SALT): 48 week results from a randomised, open-label, non-inferiority trial

Q1 · MEDICINE

Article

Author: Estébanez, Miriam ; Navarro, José ; Antela, Antonio ; Esteban, Herminia ; Sanz-Moreno, José ; Moreno, Santiago ; Pasquau, Juan ; Rivero, Antonio ; Santos, Jesús ; Troya, Jesús ; Perez-Molina, José A ; Navarro, Jordi ; Riera, Melcior ; Suárez-Lozano, Ignacio ; Mariño, Ana ; Rubio, Rafael

BACKGROUNDProblems associated with lifelong antiretroviral therapy, such as need for strict adherence, drug-related toxic effects, difficulties with treatment schedules, and cost, mean that simplification strategies should be sought. We aimed to explore the efficacy and safety of dual treatment with atazanavir-ritonavir plus lamivudine as an option to switch to from standard combination antiretroviral therapy in patients with an HIV-1 infection who are virologically suppressed.METHODSIn this randomised, open-label, non-inferiority trial, we recruited patients aged 18 years and older with chronic HIV-1 infection and no previous treatment failure or resistance, and with HIV-1 RNA of less than 50 copies per mL for at least 6 months, negative hepatitis B virus surface antigen, and good general health, from 30 hospitals in Spain. Exclusion criteria were switch in antiretroviral therapy during the previous 4 months, previous virological failure, pregnancy or breastfeeding, Gilbert's syndrome, use of contraindicated drugs, grade 4 laboratory abnormalities, and previous intolerance to any of the study drugs. We randomly assigned patients (1:1; stratified by active hepatitis C virus infection and previous treatment; computer-generated random number sequence) to dual treatment with oral atazanavir (300 mg once daily) and ritonavir (100 mg once daily) plus lamivudine (300 mg once daily) or triple treatment with oral atazanavir (300 mg once daily) and ritonavir (100 mg once daily) plus two nucleos(t)ide reverse transcriptase inhibitors at the discretion of the investigators. The primary endpoint was virological response, defined as HIV-1 RNA of less than 50 copies per mL at week 48, in the per-protocol population, with a non-inferiority margin of 12%. We included patients who received at least one dose of the study drug in the safety analysis. This study is registered at ClinicalTrials.gov, number NCT01307488.FINDINGSBetween Sept 29, 2011, and May 2, 2013, we randomly assigned 286 patients (143 [50%] to each group). At week 48 in the per-protocol population, 112 (84%) of 133 patients had virological response in the dual-treatment group versus 105 (78%) of 135 in the triple-treatment group (difference 6% [95% CI -5 to 16%), showing non-inferiority at the prespecified level. 14 (5%) patients developed severe adverse events (dual treatment six [4%]; triple treatment eight [6%]), none of which we deemed related to the study drug. Grade 3-4 adverse events were similar between groups (dual treatment 77 [55%] of 140; triple treatment 78 [55%] of 141). Treatment discontinuations were less frequent in the dual-treatment group (three [2%]) than in the triple-treatment group (ten [7%]; p=0·047).INTERPRETATIONIn our trial, dual treatment was effective, safe, and non-inferior to triple treatment in patients with an HIV-1 infection who are virologically suppressed who switch antiretroviral therapy because of toxic effects, intolerance, or simplification. This combination has the potential to suppress some of the long-term toxic effects associated with nucleos(t)ide reverse transcriptase inhibitors, preserve future treatment options, and reduce the cost of antiretroviral therapy.FUNDINGBristol Myers-Squibb and Fundación SEIMC-GESIDA.

01 Jun 2015·JAIDS Journal of Acquired Immune Deficiency SyndromesQ3 · MEDICINE

Final 48-Week Results (The Advanz-3 Trial)

Q3 · MEDICINE

Article

Author: Miro, Jose M. ; Curran, Adrian ; Manzardo, Christian ; Ferrer, Elena ; Cruceta, Anna ; Gatell, Jose M. ; Perez, Inaki ; Plana, Montserrat ; Lozano, Francisco ; Domingo, Pere ; Clotet, Bonaventura ; Guardo, Alberto C. ; Podzamczer, Daniel ; Lonca, Montserrat

BACKGROUNDFew randomized clinical trials have investigated antiretroviral regimens in very advanced HIV-1-infected patients. The objective was to study the immune reconstitution in very immunosuppressed antiretroviral-naive, HIV-1-infected individuals by comparing an efavirenz-based regimen with 2 ritonavir-boosted protease inhibitor regimens.METHODSRandomized, controlled, open-label, multicenter clinical trial. Eighty-nine HIV-1-infected antiretroviral-naive patients with <100 CD4 cells per cubic millimeter were randomly assigned in a 1:1:1 ratio to efavirenz (n = 29), atazanavir/ritonavir (n = 30), or lopinavir/ritonavir (n = 30) combined with tenofovir plus emtricitabine. The primary outcome was median increase in CD4 cell count at week 48. Secondary end points were the proportion of patients with HIV-1 RNA <50 copies per milliliter, adverse events, disease progression, and death.RESULTSIn the on-treatment analysis, the median (interquartile range) increase in the CD4 count after 48 weeks was +193 (129-349) cells per microliter in the efavirenz arm, +197 (146-238) cells per microliter in the ritonavir-boosted atazanavir arm, and +205 (178-327) cells per microliter in the ritonavir-boosted lopinavir arm (P = 0.73). The percentage of patients achieving viral suppression was similar in all 3 treatment arms at 48 weeks {efavirenz, 85.71% [95% confidence interval (CI): 68.5 to 94.3]; atazanavir, 80% [95% CI: 62.7 to 90.5]; and lopinavir, 82.8% [95% CI: 65.5 to 92.4]; P = 0.88}. Bacterial translocation, inflammation, immune activation, and apoptotic markers, but not D-dimer, declined significantly and similarly in the 3 treatment arms. Adverse events had a similar incidence in all 3 antiretroviral regimens. No patients died.CONCLUSIONSThe immune reconstitution induced by an efavirenz-based regimen in very advanced HIV-1-infected patients was similar to that induced by a ritonavir-boosted protease inhibitor-based regimen (ClinicalTrials.gov registration number: NCT00532168).

01 Dec 2014·Pediatric Infectious Disease JournalQ4 · MEDICINE

Pharmacokinetics of Atazanavir/Ritonavir Among HIV-infected Thai Children Concomitantly Taking Tenofovir Disoproxil Fumarate

Q4 · MEDICINE

Article

Author: Thaintip Sahakijpicharn ; Wasana Prasitsuebsai ; Jintanat Ananworanich ; Siriwan Keadpudsa ; Chonnamet Techasaensiri ; Thanyawee Puthanakit ; Torsak Bunupuradah ; Narukjaporn Thammajaruk ; Amornrat Srimuan

BACKGROUNDAtazanavir/ritonavir (ATV/r) is a recommended once-daily protease inhibitor. Tenofovir disoproxil fumarate (TDF) can reduce ATV exposure. The authors studied ATV pharmacokinetic (PK) parameters among children who received atazanavir/ritonavir co-administered with TDF.METHODSHIV-infected children aged 6-18 years with a body weight of 25-50 kg were eligible. Branded ATV 200 mg/capsule was taken with generic ritonavir 100 mg/tablet once daily plus TDF and lamivudine. A 24-hour PK study was performed at week 4 at t = 0 (pre-dose), 2, 4, 6, 8, 10, 12 and 24 hours. PK parameters were calculated using non-compartmental methods with WinNonlin software. Targeted ATV AUC 0-24 was 15 mg h/L and C trough was 0.15 mg/L. Comparisons of geometric means of ATV PK parameters between different weight bands were made using regression models.RESULTSEighteen HIV-infected children with a median (IQR) age of 13 (11-14) years were enrolled. Median (range) body weight and body surface area were 35 (25-42) kg and 1.21 (0.96-1.35) m2, respectively. Median (IQR) CD4 cell count was 735 (540-1233) cells/mm3. Median (range) of ATV was 164 (145-209) mg/m2. Geometric mean (SD) ATV AUC 0-24 was 35.05 (1.06) mg h/L, and ATV C trough was 0.31 (1.13) mg/L. No child had ATV AUC 0-24 or C trough below target levels. There were no significant differences in PK parameters among weight bands.CONCLUSIONAtazanavir/ritonavir 200/100 mg dosing provided adequate ATV AUC 0-24 when used with TDF in HIV-infected Thai children weighing between 25 and 50 kg.

100 Deals associated with Atazanavir Sulfate/Ritonavir

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
HIV Infections	NDA/BLA	United States	Matrix Labs LLC	-
HIV Infections	NDA/BLA	United States	Emcure Pharmaceuticals Ltd.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ARIA study (IAS2020)	Not Applicable	-	495	DTG/ABC/3TC	(pwpdiqoynj) = ddylbxjjls quretuiwhb (cbeqozshih ) View more	-	01 Jan 2020
				Atazanavir/ritonavir + tenofovir disoproxil + emtricitabine	(pwpdiqoynj) = juyfmromvo quretuiwhb (cbeqozshih ) View more
NCT01194856 (CTgov)	Phase 4	Mitochondrial Diseases \| Lipodystrophy \| HIV Infections	1	Efavirenz (Efavirenz 600 mg)	pkwvhmcjsm(esuxgwvosx) = txhgvugktu wugddjolhe (mzezyegshy, ukeozyxqqj - ozwywlpnca) View more	-	11 Aug 2017
				Atazanavir/ritonavir (Arm B - Atazanavir/Ritonavir)	pkwvhmcjsm(esuxgwvosx) = xhdpwubmru wugddjolhe (mzezyegshy, kliyzkufpf - luuhzcufcm) View more
NCT01307488 (SALT, Pubmed \| J Antimicrob Chemother) Manual	Phase 3	HIV Infections	286	lamivudine+Atazanavir/Ritonavir	kwcacraivt(qmepvjiwxw) = tiymkumrxv nxsmtpeoon (wfscbhydhm ) View more	Non-inferior	01 Jan 2017
				2NUCs+Atazanavir/Ritonavir	kwcacraivt(qmepvjiwxw) = ozpipdfqcn nxsmtpeoon (wfscbhydhm ) View more
PHACS Adolescent Master Protocol Study (IAS2017)	Not Applicable	HIV Infections	47	Atazanavir/ritonavir	(xonygnfjzm) = vacygsmart akegxdjjea (ofjbgblgvm )	-	01 Jan 2017
				Older PI-based ART	(xonygnfjzm) = yccggdraec akegxdjjea (ofjbgblgvm )
WAVES Study (IAS2015)	Not Applicable	HIV Infections	575	Elvitegravir (EVG) / cobicistat (COBI) / emtricitabine (FTC)/ tenofovir disoproxil fumarate (TDF)	(xmojdjbgcy) = ylqpcwjrvc oblhnbxcyo (evzsvldeaw )	Positive	01 Jan 2015
				ritonavir (RTV) boosted atazanavir (ATV) plus FTC/TDF	(xmojdjbgcy) = hpnxfofzib oblhnbxcyo (evzsvldeaw )
ACTG 5202 (IAS2014)	Not Applicable	HIV Infections First line	-	Tenofovir/emtricitabine+Efavirenz	hhgkoemleo(nnzwsyotnk) = ygbkgmpufo sdgwzwpkol (sawfdjvykk )	-	01 Jan 2014
				Tenofovir/emtricitabine+Atazanavir/ritonavir	hhgkoemleo(nnzwsyotnk) = otxolbsgkn sdgwzwpkol (sawfdjvykk )
IAS2013	Not Applicable	First line	2,167	ritonavir-boosted atazanavir (ATV/r)	weefrusntb(senaieumzg) = isuccemqsi jdheywbwcw (urrhuxcpjy ) View more	-	01 Jan 2013
				efavirenz (EFV)	weefrusntb(senaieumzg) = ypoowtzenh jdheywbwcw (urrhuxcpjy ) View more
A5202 (IAS2012)	Not Applicable	Acquired Immunodeficiency Syndrome	929	Efavirenz	porllkebtm(aauvwgnbhs) = egcbcppncn keocqzyjgc (dtpipsuvtu )	-	01 Jan 2012
				Atazanavir/Ritonavir	porllkebtm(aauvwgnbhs) = qfvbdltvxv keocqzyjgc (dtpipsuvtu )
IAS2010	Not Applicable	-	-	Atazanavir 300mg/ Ritonavir 100mg	lchtfdsqfa(atjancqltl) = xyyovlboci fzbbucjfle (xfjkicxslm, 271 - 581) View more	-	01 Jan 2010
				Atazanavir 400mg/ Ritonavir 100mg	lchtfdsqfa(atjancqltl) = lacjljyafh fzbbucjfle (xfjkicxslm, 307 - 854) View more
BMS AI424182 (IAS2008)	Not Applicable	HIV Seropositivity	-	Atazanavir 300 mg QD/ritonavir 100 mg (ATV/r) QD + ZDV/3TC	(vwoxvtjpxr) = ktmxjaxqlk qbkvqepeor (djpjkdozaq, (43)) View more	-	01 Jan 2008