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®) and rilpivirine (Edurant®[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).
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® (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®
(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 (≥2%)
adverse reactions of moderate to severe intensity in treatment
naïve 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.
Paediatric Patients: Safety and efficacy of TIVICAY has
not been established in children younger than 12 years old, or
weighing <40 kg, or in INSTI-experienced paediatric patients
with documented or clinically suspected INSTI resistance.
Please visit the following link for the full US prescribing and
patient information:
https://www.viivhealthcare.com/media/58599/us_tivicay.pdf.
How TIVICAY Works
TIVICAY belongs to a class of HIV medicines called integrase
inhibitors. Integrase inhibitors block HIV replication by
preventing the viral DNA from integrating into the genetic material
of human immune cells (T-cells). This step is essential in the HIV
replication cycle and is also responsible for establishing chronic
infection.
About ViiV Healthcare
ViiV Healthcare is a global specialist HIV company established in
November 2009 by GlaxoSmithKline
(LSE: GSK) and Pfizer (NYSE: PFE) dedicated to delivering advances
in treatment and care for people living with HIV. Shionogi joined
as a 10% shareholder in October 2012.
The company's aim is to take a deeper and broader interest in
HIV/AIDS than any company has done before and take a new approach
to deliver effective and new HIV medicines, as well as support
communities affected by HIV. For more information on the company,
its management, portfolio, pipeline and commitment, please
visit http://www.viivhealthcare.com.
Important Information
about EDURANT®(rilpivirine)
EDURANT® (rilpivirine) is a prescription HIV
medicine that is used with other antiretroviral medicines to treat
Human Immunodeficiency Virus-1 (HIV-1)
in adults:
- Who have never taken HIV medicines
before and
- Who have an amount of HIV in their blood (called "viral
load") that is no more than 100,000 copies/mL. Your healthcare
professional will measure your viral load
EDURANT® should be taken in combination with
other HIV medicines. Your healthcare professional will work with
you to find the right combination of HIV medicines
It is important that you remain under the care of your
healthcare professional during treatment with
EDURANT®
EDURANT® is not recommended for patients less
than 18 years of age
EDURANT® does not cure HIV
infection or AIDS. You should remain on your HIV medications
without stopping to ensure that you control your HIV
infection and decrease the risk of HIV-related
illnesses. Ask your healthcare professional about how to prevent
passing HIV to other people.
Important Safety Information for
EDURANT® (rilpivirine)
Can EDURANT® betaken
withother medicines?
EDURANT® may affect the way other medicines work and other
medicines may affect how EDURANT® works and may cause serious side
effects. If you take certain medicines with EDURANT®, the amount of
EDURANT® in your body may be too low and it may not work to help
control your HIV infection, and the HIV virus in your body may
become resistant to EDURANT® or other HIV medicines that are like
it. To help get the right amount of medicine in your body, you
should always take EDURANT® with a meal. A protein drink alone does
not replace a meal.
Do not take
EDURANT® if:
- Your HIV infection has been previously treated with HIV
medicines
- You are taking any of the following medicines:
- Anti-seizure medicines: carbamazepine (Carbatrol®, Equetro®,
Tegretol®, Tegretol-XR®, Teril®, Epitol®), oxcarbazepine
(Trileptal®), phenobarbital (Luminal®), phenytoin (Dilantin®,
Dilantin-125®, Phenytek®)
- Anti-tuberculosis (anti-TB) medicines: rifampin (Rifater®,
Rifamate®, Rimactane®, Rifadin®), rifapentine (Priftin®)
- Proton pump inhibitor (PPI) medicine for certain stomach or
intestinal problems: esomeprazole (Nexium®, Vimovo®), lansoprazole
(Prevacid®), omeprazole (Prilosec®, Zegerid®), pantoprazole sodium
(Protonix®), rabeprazole (Aciphex®)
- More than 1 dose of the steroid medicine dexamethasone or
dexamethasone sodium phosphate
- St. John's wort (Hypericum
perforatum)
Especially
tell your doctor if you take:
- Rifabutin (Mycobutin®, a medicine to treat some bacterial
infections). Talk to your doctor or pharmacist about the
right amount of EDURANT you should take if you also take rifabutin.
- Medicines used to treat HIV
- An antacid medicine that contains aluminum, magnesium
hydroxide, or calcium carbonate. Take antacids at least 2 hours
before or at least 4 hours after you take EDURANT®
- Medicines to block acid in your stomach, including
cimetidine (Tagamet®), famotidine (Pepcid®), nizatidine (Axid®), or
ranitidine hydrochloride (Zantac®). Take these medicines at
least 12 hours before or at least 4 hours after you take
EDURANT®
This is not a
complete
list of medicines. Before
starting EDURANT®,
be sure
to tell your healthcare
professional about all the
medicines you are taking or
plan to take,
including prescription and nonprescription
medicines, vitamins, and herbal supplements.
Before taking EDURANT®, also tell your healthcare professional
if you have had or currently have liver problems (including
hepatitis B or C), have ever had a mental health problem, are
pregnant or planning to become pregnant, or breastfeeding. It is
not known if EDURANT® will harm your unborn baby. You and your
healthcare professional will need to decide if taking EDURANT® is
right for you.
- Do not breastfeed if you are taking EDURANT®. You should
not breastfeed if you have HIV because of the chance of passing HIV
to your baby
What are the
possible side effects
of EDURANT®?
EDURANT® can cause serious
side effects including:
- Depression or mood changes. Tell your doctor right away
if you have any of the following symptoms: feeling sad or hopeless,
feeling anxious or restless, have thoughts of hurting yourself
(suicide), or have tried to hurt yourself
- Liver problems. People with a history of hepatitis B or
C virus infection or who have certain liver function test changes
may have an increased risk of developing new or worsening liver
problems during treatment. Liver problems were also reported during
treatment in some people without a history of liver disease. Your
healthcare professional may need to do tests to check liver
function before and during treatment
- Changes in body shape or
body fat have been seen in some patients
taking HIV medicines. The exact cause and long-term health effects
of these conditions are not known
- Changes
in your immune system
(immune reconstitution syndrome).
Your immune system may get stronger and begin to fight infections.
Tell your healthcare professional right away if you start having
any new symptoms of infection.
Other common side effects of EDURANT® include depression,
headache, trouble sleeping (insomnia), and rash.
This is not a complete list of all side effects. If you
experience these or other symptoms, contact your healthcare
professional right away. Do not stop taking EDURANT® or any other
medications without first talking to your healthcare
professional.
You are
encouraged to report negative
side effects
of prescription drugs to
the FDA. Visit
http://www.fda.gov/medwatch, or
call1-800-FDA-1088.
Please see full Product Information for more
details: http://www.edurant.com/sites/default/files/EDURANT-PI.pdf
About Edurant® (rilpivirine)
Rilpivirine was developed by Janssen Sciences Ireland UC, one of
the Janssen Pharmaceutical Companies of Johnson & Johnson.
Rilpivirine is a tablet dosed at 25mg taken once a day in
combination with other antiviral agents. The overall safety profile
of rilpivirine is based on Phase III clinical studies. In the
rilpivirine arm, the most frequently reported adverse drug
reactions (≥ 2%) that were at least of moderate intensity were
depression (3.5%), insomnia (2.9%), headache (2.6%) and rash
(2.2%).
Rilpivirine is available in the United
States (US) and the European Union as part of a once daily
fixed dose antiretroviral combination with Gilead Sciences Inc.'s
tenofovir and emtricitabine. This combination, known as COMPLERA®
(US) or EVIPLERA®, was granted marketing authorisation from the
Food and Drug Administration in August
2011, with Gilead Sciences Inc. being the marketing
authorisation holder in the US, and from the European Commission in
November 2011, with Gilead Sciences
International Ltd. being the marketing authorisation holder in
Europe, Middle East and Africa.
Cautionary statement regarding forward-looking
statements
GSK cautions investors that any forward-looking statements or
projections made by GSK, including those made in this announcement,
are subject to risks and uncertainties that may cause actual
results to differ materially from those projected. Such factors
include, but are not limited to, those described under Item 3.D
'Risk factors' in the company's Annual Report on Form 20-F for
2014.
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1. Edurant® is a registered trademark of Janssen Janssen
Sciences Ireland UC.
SOURCE ViiV Healthcare