The primary objective of this study is:To evaluate the efficacy of a regimen containing GS 9350-boosted Atazanavir versus ritonavir-boosted atazanavir each administered with emtricitabine/tenofovir disoproxil fumarate in HIV 1 infected,…
ID
Source
Brief title
Condition
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Efficacy: The primary efficacy endpoint is the proportion of subjects that
achieve HIV 1 RNA < 50 copies/mL at Week 48 as defined by the Food and Drug
Administration (FDA) snapshot analysis.
Secondary outcome
The proportion of subjects with HIV 1 RNA < 50 copies/mL at Week 96, 144 and
192 as defined by the FDA snapshot analysis
The change from baseline in CD4+ cell count at Weeks 48, 96, 144 and 192.
Safety: Adverse events and clinical laboratory tests to evaluate the safety and
tolerability of the treatment regimens.
Background summary
Approximately 33.2 million people are infected with HIV worldwide.
Standard-care for the treatment of HIV involves the use of a combination of
antiretroviral drugs to suppress viral replication and delay disease
progression. While combination ARV therapy has been largely successful in
reducing the morbidity and mortality associated with HIV disease, a significant
proportion of subjects eventually experience loss of virologic, immunologic or
clinical benefit from their current regimens.
Ritonavir, a potent HIV protease inhibitor, is an extremely efficient
inhibitor. The combination of a low, antiviral dose of Ritonavir with other HIV
drugs, results in a significant boosting of plasma concentration of the
co-administered drug. The majority of HIV drugs are prescribed in combination
with low-dose Ritonavir.
GS-9350 has been developed as a pharmacoenhancer, is devoid of anti-HIV
activity and may have less adverse biochemical effects relative to Ritonavir.
GS-9350 can therefore be a good alternative to Ritonavir in combination with
HIV inhibitors.
Study objective
The primary objective of this study is:
To evaluate the efficacy of a regimen containing GS 9350-boosted Atazanavir
versus ritonavir-boosted atazanavir each administered with
emtricitabine/tenofovir disoproxil fumarate in HIV 1 infected, antiretroviral
treatment-naïve adult subjects as determined by the achievement of HIV 1 RNA <
50 copies/mL at Week 48
The secondary objectives of this study are:
To evaluate the efficacy, safety and tolerability of the two treatment regimens
through 96 weeks of treatment.
To evaluate the durability of the efficacy, safety and tolerability results of
the two treatment regimens observed through 192 weeks of treatment
Study design
Randomized, double-blind, multicenter, active-controlled. Subjects will be
randomized in a 1:1 ratio to one of the two treatment arms. Randomization will
be stratified by HIV 1 RNA level (* 100,000 copies/mL or * 100,000 copies/mL)
at screening.
Intervention
Treatment group 1: active GS-9350 + ritonavir-placebo + 300 mg atazanavir +
Truvada.
Treatment group 2: 100 mg active ritonavir + GS-9350-placebo + 300 mg
atazanavir + Truvada.
Study burden and risks
In case of an average of 2 visites after week 96:
7 x comlete physical exam
12 x physical exam as needed
4 x ECG
1 x length
19 x weight
8 x fasten glucose- and lipid panel
FTC; Emtriva® SIDE EFFECTS
(Emtricitabine)
Headache, diarrhea, nausea, rash, dizziness, changes in skin color, weakness,
difficulty sleeping, abnormal dreams, pain, vomiting, stomach pain, problems
with digestion, increased triglycerides (fatty acid), increased bilirubin in
the blood, increased glucose in the blood, allergic reaction, hives, adverse
effects on the function of the liver and pancreas, low white blood cell count,
increased creatine kinase in the blood, actic acidosis, and liver problems with
enlargement of the liver and fat in the liver, including fatal cases.
TDF; Viread® SIDE EFFECTS
(Tenofovir DF)
Diarrhea, nausea, vomiting, flatulence (intestinal gas), dizziness, weakness,
abdominal pain, allergic reaction including potentially serious swelling of the
face, lips, and/or tongue, with or without rash, pancreatitis (inflammation of
the pancreas), high levels of amylase in the blood, shortness of breath, rash,
abnormalities of tests that measure hepatic (liver) function, hepatitis
(inflammation of liver), lactic acidosis, liver problems including fatal cases,
kidney problems, bone toxicity, worsening of hepatitis B.
GS-9350; SIDE EFFECTS
Yellowing of the whites of the eye (ocular icterus), yellowing of skin
(jaundice), increased bilirubin concentration in blood (hyperbilirubinemia) and
mild decreases in estimated kidney function.
Lakeside Drive 333
Foster City CA 94404
US
Lakeside Drive 333
Foster City CA 94404
US
Listed location countries
Age
Inclusion criteria
* Plasma HIV-1 RNA levels * 5,000 copies/mL at screening
* No prior use of any approved or investigational antiretroviral drug for any length of time
* Screening genotype report provided by Gilead Sciences must show sensitivity to FTC,
TDF and ATV
* Adequate renal function: Estimated glomerular filtration rate * 70 mL/min according to the Cockcroft-Gault formula.
* Hepatic transaminases (AST and ALT) * 5 × upper limit of normal (ULN)
* Total bilirubin * 1.5 mg/dL, or normal direct bilirubin
* Adequate hematologic function (absolute neutrophil count * 1,000/mm3; platelets
* 50,000/mm3; hemoglobin * 8.5 g/dL)
* Serum amylase * 5 × ULN (subjects with serum amylase > 5 × ULN will remain eligible
if serum lipase is * 5 × ULN)
* Age * 18 years
* Life expectancy * 1 year
Exclusion criteria
* A new AIDS-defining condition (excluding CD4 cell count and percentage criteria) diagnosed within the 30 days prior to screening
* Subjects receiving drug treatment for Hepatitis C, or subjects who are anticipated to
receive treatment for Hepatitis C during the course of the study.
* Subjects experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, etc.)
* Have an implanted defibrillator or pacemaker
* Have an ECG PR interval * 220 msec
* Current alcohol or substance use judged by the Investigator to potentially interfere with
subject study compliance.
* A history of malignancy within the past 5 years (prior to screening) or ongoing
malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or
resected, non-invasive cutaneous squamous carcinoma. Subjects with cutaneous KS are
eligible, but must not have received any systemic therapy for KS within 30 days of
Baseline and must not be anticipated to require systemic therapy during the study.
* Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or
antifungal therapy within 30 days prior to Baseline.
* Subjects receiving ongoing therapy with any of the medications as listed in the protocol v 15Mar2010.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-016759-22-NL |
| CCMO | NL32249.100.10 |