LONDON, May 6, 2015 /PRNewswire/ --
First programme to evaluate dual HIV maintenance therapy with dolutegravir and rilpivirine
ViiV Healthcare today announced the start of a Phase III clinical trial programme to evaluate the safety and efficacy of dolutegravir (Tivicay(R)) and rilpivirine (Edurant(R)[1]) as maintenance therapy for adult patients with HIV. The Phase III programme comprises two replicate studies evaluating 48 week viral suppression with a two drug regimen combining an integrase inhibitor (dolutegravir) and a non-nucleoside reverse transcriptase inhibitor (rilpivirine) in patients with HIV who have already achieved viral suppression with a three drug regimen.
"As HIV care becomes an increasingly long term consideration, patients and clinicians are seeking to balance efficacy and side effects of treatment. We are able to attain initial viral suppression with a standard three drug regimen and the question is whether we can maintain viral suppression with two drugs instead of three." said Dr John Pottage, Chief Scientific and Medical Officer, ViiV Healthcare. "An interesting part of this Phase III programme is the inclusion of measures of the patient experience -- we're looking at health-related quality of life and adherence to treatment, in addition to the primary efficacy and safety endpoints."
In June 2014, ViiV Healthcare and Janssen Sciences Ireland UC, one of the Janssen Pharmaceutical Companies of Johnson & Johnson announced a partnership to investigate the potential of combining dolutegravir and rilpivirine in a single-tablet in order to expand the treatment options available to people living with HIV (ViiV Healthcare announces new collaboration with Janssen [http://www.viivhealthcare.com/media/press-releases/2014/june... ] ).
About the Phase III programme
The Phase III programme will evaluate the efficacy, safety, and tolerability of switching to dolutegravir plus rilpivirine from current INI-,NNRTI-, or PI-based antiretroviral regimen in HIV-1-infected adults who are virologically suppressed. In the clinical trials, dolutegravir and rilpivirine will be provided as individual tablets; development of the single-tablet formulation will be concurrent with conduct of the trials.
SWORD-1 (NCT02429791) and SWORD-2 (NCT02422797) are replicate 148-week, randomised, open-label, non-inferiority studies to assess the antiviral activity and safety of a two-drug regimen of DTG + RPV compared with current antiretroviral therapy. Each study seeks to enrol approximately 500 patients across 13 countries and aims to enrol meaningful numbers of patients from groups underrepresented in HIV clinical studies, such as women and people over 50 years of age.
The primary endpoint is proportion of patients with plasma HIV-1 RNA <50 copies per milliliter (c/mL) at Week 48. Key secondary endpoints include evaluation of the development of viral resistance, measurements of safety and tolerability, and changes in renal, bone and cardiovascular biomarkers. The study will also include exploratory measures to assess change in health-related quality of life, willingness to switch, and adherence to treatment regimens.
For more information on the trials please visit: http://www.clinicaltrials.gov
Important Information about Tivicay(R) (dolutegravir) in the US
FDA Indication and Usage: TIVICAY is a human immunodeficiency virus type 1 (HIV-1) integrase strand transfer inhibitor (INSTI) indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection.
Use of TIVICAY in INSTI-experienced patients should be guided by the number and type of baseline INSTI substitutions. The efficacy of TIVICAY 50 mg twice daily is reduced in patients with an INSTI-resistance Q148 substitution plus 2 or more additional INSTI-resistance substitutions including T66A, L74I/M, E138A/K/T, G140S/A/C, Y143R/C/H, E157Q, G163S/E/K/Q, or G193E/R.
Important Safety Information for Tivicay(R) (dolutegravir)
Contraindication: TIVICAY is contraindicated (1) in patients with previous hypersensitivity reaction to dolutegravir, and (2) in patients receiving dofetilide (antiarrhythmic) due to the potential for increased dofetilide plasma concentrations and the risk for serious and/or life-threatening events.
Hypersensitivity Reactions: Hypersensitivity reactions have been reported and were characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury. The events were reported in 1% or fewer subjects receiving TIVICAY in Phase 3 clinical trials. Discontinue TIVICAY and other suspect agents immediately if signs or symptoms of hypersensitivity reaction develop, (including but not limited to, severe rash or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters or peeling of the skin, oral blisters or lesions, conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema, difficulty breathing.) Monitor clinical status, including liver aminotransferases, and initiate appropriate therapy. Delay in stopping treatment with TIVICAY or other suspect agents after the onset of hypersensitivity may result in a life-threatening reaction. TIVICAY is contraindicated in patients who have experienced a hypersensitivity reaction to dolutegravir.
Effects on Serum Liver Biochemistries in Patients with Hepatitis B or C Coinfection: Patients with underlying hepatitis B or C may be at increased risk for worsening or development of transaminase elevations with use of TIVICAY. In some cases the elevations in transaminases were consistent with immune reconstitution syndrome or hepatitis B reactivation particularly in the setting where anti-hepatitis therapy was withdrawn. Appropriate laboratory testing prior to initiating therapy and monitoring for hepatotoxicity during therapy with TIVICAY are recommended in patients with underlying hepatic disease such as hepatitis B or C.
Fat Redistribution: Redistribution/accumulation of body fat has been observed in patients receiving antiretroviral therapy.
Immune Reconstitution Syndrome: During the initial phase of treatment, immune reconstitution syndrome can occur, which may necessitate further evaluation and treatment. Autoimmune disorders have been reported to occur in the setting of immune reconstitution; the time to onset is more variable and can occur many months after initiation of treatment.
Adverse Reactions: The most commonly reported (greater than or equal to2%) adverse reactions of moderate to severe intensity in treatment naive adult subjects in any one trial receiving TIVICAY in a combination regimen were insomnia (3%), fatigue (2%), and headache (2%).
Drug Interactions: Co-administration of TIVICAY with drugs that are strong inducers of UGT1A1 and/or CYP3A4 may result in reduced plasma concentrations of dolutegravir and require dose adjustments of TIVICAY.
-- TIVICAY should be taken2 hours before or 6 hours after taking cation-containing antacids or laxatives, sucralfate, oral iron supplements, oral calcium supplements, or buffered medications.
-- Consult the full Prescribing Information for TIVICAY for more information on potentially significant drug interactions, including clinical comments.
Pregnancy: Pregnancy category B. TIVICAY should be used during pregnancy only if the potential benefit justifies the potential risk. An Antiretroviral Pregnancy Registry has been established.
Breastfeeding: Breastfeeding is NOT recommended due to the potential for HIV transmission and the potential for adverse reactions in nursing infants.
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