BMS-Reyataz Study in Treatment in Naive Subjects to Compare the Efficacy and Safety Between Boosted Reyataz and Kaletra When in Combination With Fixed Dose Truvada

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT00272779
• Date of registration: 05/01/2006
• Primary sponsor: Bristol-Myers Squibb
• Public title: BMS-Reyataz Study in Treatment in Naive Subjects to Compare the Efficacy and Safety Between Boosted Reyataz and Kaletra When in Combination With Fixed Dose Truvada
• Scientific title: A 96 Week Study Comparing the Antiviral Efficacy and Safety of Atazanavir/Ritonavir With Lopinavir/Ritonavir, Each in Combination With Fixed Dose Tenofovir-Emtricitabine in HIV-1 Infected Treatment in Naive Subjects
• Date of first enrolment: November 2005
• Target sample size: 1057
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00272779
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, Colombia, Costa Rica, Denmark, Dominican Republic, France, Germany, Guatemala, Hong Kong, Indonesia, Italy, Mexico, Netherlands, Panama, Peru, Portugal, Puerto Rico, Singapore, South Africa, Spain, Taiwan, Thailand, United Kingdom, United States

Contacts

• Name: Bristol-Myers Squibb
• Affiliation: Bristol-Myers Squibb

Key inclusion & exclusion criteria

Inclusion Criteria:

- HIV RNA =5000 c/ml

Exclusion Criteria:

- Any antiretroviral therapy within 30 days prior to screening;

- Women of Childbearing potential (WOCBP) unwilling or unable to use an acceptable
method to avoid pregnancy for the entire study and for up to 8 weeks after the study;

- WOCBP using a prohibited contraceptive method

- WOCBP who are pregnant or breastfeeding;

- Women with a positive pregnancy test on enrollment or prior to study drug
administration;

- Presence of a newly diagnosed HIV-Related opportunistic infection or any medical
condition requiring acute therapy at the time of enrollment;

- Suspected primary (acute) HIV infection;

- Prior antiviral therapy (>30 days of NRTI and/or >7 days of non-nucleoside reverse
transcriptase inhibitor (NNRTI) or PI therapies) or any antiretroviral therapy within
30 days prior to screening; some exceptions are allowed for ARV therapy in use for
Mother-to-child transmission;

- Participants with Cushing's syndrome;

- Untreated hypothyroidism or hyperthyroidism. A participant who is euthyroid on a
stable replacement dose of thyroid hormone is acceptable provided the thyroid
stimulating hormone (TSH) performed within 30 days of screening is within normal drug
range;

- Recent therapy with agents with significant systemic myelosuppressive, neurotoxic,
pancreatotoxic, hepatotoxic or cytotoxic potential within 3 months of study start or
expected need for such therapy at the time of enrollment; or therapy with methadone
or ribavirin/interferons or treatment with neurotoxic drugs or drugs that affect
CYP3A4;

- Participants with obstructive liver disease;

- Active alcohol or substance use sufficient, in the Investigator's opinion, to prevent
adequate compliance with study therapy or to increase the risk of developing
pancreatitis or chemical hepatitis;

- Proven or suspected acute hepatitis in the 30 days prior to study entry;

- Intractable diarrhea (=6 loose stools/day for at least 7 consecutive days) within 30
days prior to study entry;

- Inability to swallow capsules;

- Active peripheral neuropathy;

- Presence of cardiomyopathy (due to any cause) or any significant cardiovascular
disease, such as unstable ischemic heart disease;

- Known, clinically significant cardiac conduction system disease.

- Baseline laboratory values measured within 2 weeks prior to initiating study drugs as
follows:

1. calculated creatine clearance <60 mL/min as estimated by the Cockcroft-Gault
equation;

2. total serum lipase = 1.4 times the upper limit of normal;

3. liver enzymes (AST, ALT) = 5 times the upper limit of normal;

4. total serum bilirubin = 1.5 times the upper limit of normal.

- Hypersensitivity to any component of the formulation of study drug;

- Prohibited therapies;

- Any other clinical conditions or prior therapy that, in the opinion of the
Investigator, would make the participant unsuitable for study or unable to comply
with the dosing requirements;

- Prisoners or participants who are compulsorily detained (involuntarily incarcerated)
for treatment of either a psychiatric or physical (e.g., infectious disease) illness
must not be enrolled into this study.



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

HIV Infections

Intervention(s)

Drug: ATV

Drug: LPV

Drug: RTV

Drug: Tenofovi-Emtricitabine (TDF/FTC) tablet

Primary Outcome(s)

Area Under the Concentration-time Curve, in One Dosing Interval [AUC(TAU)] of ATV/RTV and LPV/RTV in the Presence of an ARV Regimen Including TDF at Week 4 [Time Frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 Hrs post dosing with ATV/RTV and TDF all given QD and at predose, 1, 2, 3, 4, 6, 8, 12 Hrs post dosing with LPV/RTV given BID and TDF given QD.]

AUC (0-24) of RTV at Week 4 [Time Frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 Hrs post dosing with ATV/RTV and TDF all given QD and at predose, 1, 2, 3, 4, 6, 8, 12 Hrs post dosing with LPV/RTV given BID and TDF given QD.]

AUC (TAU) of Tenofovir at Week 4 [Time Frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 Hrs post dosing with ATV/RTV and TDF all given QD and at predose, 1, 2, 3, 4, 6, 8, 12 Hrs post dosing with LPV/RTV given BID and TDF given QD.]

Cmax of RTV at Week 4 [Time Frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 Hrs post dosing with ATV/RTV and TDF all given QD and at predose, 1, 2, 3, 4, 6, 8, 12 Hrs post dosing with LPV/RTV given BID and TDF given QD.]

Cmax of Tenofovir at Week 4 [Time Frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 Hrs post dosing with ATV/RTV and TDF all given QD and at predose, 1, 2, 3, 4, 6, 8, 12 Hrs post dosing with LPV/RTV given BID and TDF given QD.]

Cmin of RTV at Week 4 [Time Frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 Hrs post dosing with ATV/RTV and TDF all given QD and at predose, 1, 2, 3, 4, 6, 8, 12 Hrs post dosing with LPV/RTV given BID and TDF given QD.]

Cmin of Tenofovir at Week 4 [Time Frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 Hrs post dosing with ATV/RTV and TDF all given QD and at predose, 1, 2, 3, 4, 6, 8, 12 Hrs post dosing with LPV/RTV given BID and TDF given QD.]

Inhibitory Quotient (IQ) of ATV and LPV When Dosed With RTV at Week 4 [Time Frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 Hrs post dosing with ATV/RTV and TDF all given QD and at predose, 1, 2, 3, 4, 6, 8, 12 Hrs post dosing with LPV/RTV given BID and TDF given QD.]

Maximum Plasma Concentration (Cmax) of ATV/RTV and LPV/RTV in the Presence of an Antiretroviral (ARV) Regimen Including TDF at Week 4 [Time Frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 Hrs post dosing with ATV/RTV and TDF all given every day (QD) and at predose, 1, 2, 3, 4, 6, 8, 12 Hrs post dosing with LPV/RTV given twice daily (BID) and TDF given QD.]

Mean Change From Baseline in Fasting Non-High Density Lipoprotein (HDL) Cholesterol Associated With RETN_097 [Time Frame: Baseline (Day 1), Week 48, and Week 96.]

Mean Change From Baseline in Fasting Plasminogen Activator Inhibitor (PAI)-1 Associated With APOE_R176C [Time Frame: Baseline (Day 1), Week 48, and Week 96.]

Mean Change From Baseline in Fasting Triglycerides Associated With APOE_C130R [Time Frame: Baseline (Day 1), Week 48, and Week 96.]

Mean Change From Baseline in Fasting Triglycerides Associated With RETN_097 [Time Frame: Baseline (Day 1), Week 48, and Week 96.]

Mean Change From Baseline in Fasting Triglycerides Associated With RETN_2265 [Time Frame: Baseline (Day 1), Week 48, and Week 96.]

Mean Change From Baseline in Fasting Triglycerides Associated With RETN_598 [Time Frame: Baseline (Day 1), Week 48, and Week 96.]

Mean Change From Baseline in Fasting Triglycerides Associated With RETN_734 [Time Frame: Baseline (Day 1), Week 48, and Week 96.]

Mean Change From Baseline in Fasting Tumor Necrosis Factor (TNF)-Alpha Associated With IL6_5309 [Time Frame: Baseline (Day 1), Week 48, and Week 96.]

Mean Change From Baseline in Fasting Tumor Necrosis Factor (TNF)-Alpha Asssociated With RS11030679 [Time Frame: Baseline (Day 1), Week 48, and Week 96.]

Mean Change From Baseline in Subcutaneous Adipose Tissue (SAT)-To-Trunk Adipose Tissue (TAT) Ratio Associated With CCDC122_5980 [Time Frame: Baseline (Day 1), Week 48, and Week 96.]

Mean Change From Baseline in Trunk-to-Limb Fat Ratio as Measured by Dual Energy X-ray Absorptiometry (DEXA) at Week 96 [Time Frame: Baseline (Day 1) and Week 96.]

Mean Change From Baseline in VAT Associated With RETN_730 [Time Frame: Baseline (Day 1), Week 48, and Week 96.]

Mean Change From Baseline in VAT-to-TAT Ratio Associated With CCDA122_5980 [Time Frame: Baseline (Day 1), Week 48, and Week 96.]

Mean Change From Baseline in Visceral Adipose Tissue (VAT) Associated With BRUNOL_1842 [Time Frame: Baseline (Day 1), Week 48, and Week 96.]

Minimum Plasma Concentration (Cmin) of ATV/RTV and LPV/RTV in the Presence of an ARV Regimen Including TDF at Week 4 [Time Frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 Hrs post dosing with ATV/RTV and TDF all given QD and at predose, 1, 2, 3, 4, 6, 8, 12 Hrs post dosing with LPV/RTV given BID and TDF given QD.]

Number of Participants With Human-immunodeficiency Virus- Ribonucleic Acid (HIV-RNA) < 50 Copies (c)/mL at Week 48 [Time Frame: Baseline (Day 1) and Week 48]

Number of Participants With Single Nucleotide Polymorphisms (SNPs) Included in Genotype-Phenotype Analysis [Time Frame: Baseline visit]

Protein Binding Adjusted Effective Concentration (EC-90) of ATV and LPV When Dosed With RTV at Week 4 [Time Frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 Hrs post dosing with ATV/RTV and TDF all given QD and at predose, 1, 2, 3, 4, 6, 8, 12 Hrs post dosing with LPV/RTV given BID and TDF given QD.]

Terminal Elimination Half-life (T-half) of ATV/RTV and LPV/RTV in the Presence of an ARV Regimen Including TDF at Week 4 [Time Frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 Hrs post dosing with ATV/RTV and TDF all given QD and at predose, 1, 2, 3, 4, 6, 8, 12 Hrs post dosing with LPV/RTV given BID and TDF given QD.]

Time to Reach Maximum Observed Plasma Concentration (Tmax) of ATV/RTV and LPV/RTV in the Presence of an ARV Regimen Including TDF at Week 4 [Time Frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 Hrs post dosing with ATV/RTV and TDF all given QD and at predose, 1, 2, 3, 4, 6, 8, 12 Hrs post dosing with LPV/RTV given BID and TDF given QD.]

Secondary Outcome(s)

Mean Change From Baseline (BL) in Quality of Life as Measured by the Impact of Gastro-intestinal Toxicity at Week 4 (IBS-QoL) [Time Frame: IBS-QoL is administered at baseline (Day 1) and Week 4.]

Mean Change From Baseline in BMI at Week 48 [Time Frame: Baseline (Day 1) and Week 48.]

Mean Change From Baseline in BMI at Week 96 [Time Frame: Baseline (Day 1) and Week 96]

Mean Change From Baseline in Body Weight at Week 48 [Time Frame: Baseline (Day 1) and Week 48]

Mean Change From Baseline in Body Weight at Week 96 [Time Frame: Baseline (Day 1) and Week 96]

Mean Change From Baseline in CD4 Cell Count at Week 96 [Time Frame: Baseline (Day 1) and Week 96]

Mean Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Count at Week 48 [Time Frame: Baseline (Day 1) and Week 48.]

Mean Change From Baseline in Quality of Life as Measured by the Impact of Gastro-intestinal Toxicity at Week 12 (IBS-QoL) [Time Frame: IBS-QoL is administered at baseline (Day 1) and Week 12.]

Mean Change From Baseline in Quality of Life as Measured by the Impact of Gastro-intestinal Toxicity at Week 24 Using the Irritable Bowel Syndrome Quality of Life (IBS-QoL) [Time Frame: Baseline (Day 1) and Week 24]

Mean Change From Baseline in Quality of Life as Measured by the Medical Outcomes Survey - Human Immunodeficiency Virus (MOS-HIV) at Week 24 [Time Frame: Baseline (Day 1) and Week 24.]

Mean Change From Baseline in Quality of Life as Measured by the Medical Outcomes Survey - Human Immunodeficiency Virus (MOS-HIV) at Week 48 [Time Frame: Baseline (Day 1) and Week 48]

Mean Change From Baseline in Trunk-to-limb Fat Ratio Measured by DEXA at Week 48 [Time Frame: DEXA scans were taken at Baseline (Day 1) and at Weeks 48.]

Mean Change From Baseline in Waist Circumference at Week 48 [Time Frame: Baseline (Day 1) and Week 48]

Mean Change From Baseline in Waist Circumference at Week 96 [Time Frame: Baseline (Day 1) and Week 96.]

Mean Change From Baseline in Waist-to-hip-ratio at Week 48 [Time Frame: Baseline (Day 1) and Week 48]

Mean Change From Baseline in Waist-to-hip-ratio at Week 96 [Time Frame: Baseline (Day 1) and Week 96]

Mean Change in Body Mass Index (BMI) in Participants at Week 48 [Time Frame: Baseline (Day 1) and Week 48]

Mean Change in Fasting Glucose at Week 48 [Time Frame: Baseline (Day 1) and Week 48.]

Mean Change in Fasting Insulin at Week 48 [Time Frame: Baseline (Day 1) and Week 48.]

Mean Change in Fasting Lipid at Week 48 [Time Frame: Baseline (Day 1) and Week 48.]

Mean Change in Weight From Baseline at Week 48 [Time Frame: Baseline (Day 1) and Week 48]

Mean Changes From Baseline in Body Weight at Week 96 [Time Frame: Physical examination was performed at Baseline (Day 1) and Weeks 48 and 96.]

Mean Changes in Fasting Glucose at Week 96 [Time Frame: Baseline (Day 1) and Week 96]

Mean Changes in Fasting Insulin at Week 96 [Time Frame: Baseline (Day 1) and Week 96.]

Mean Changes in Fasting Lipids at Week 96 [Time Frame: At screening (Day -30), baseline (Day 1), Week 4, 12, 24, 36, 48, 60, 72, 84 and 96.]

Mean Percent Changes From Baseline in BMD Measured by DEXA at Week 96 [Time Frame: Baseline (Day 1) and Week 96]

Mean Percent Changes From Baseline in Bone Mineral Density (BMD) Measured by DEXA at Week 48 [Time Frame: DEXA scans were taken at Baseline (Day 1) and Week 48.]

Mean Percent Changes From Baseline in Limb, Trunk and Total Body Fat Measured by DEXA at Week 48 [Time Frame: DEXA scans were performed at baseline (within 30 days of starting study treatment), and at Weeks 48.]

Mean Percent Changes From Baseline in Limb, Trunk and Total Body Fat Measured by DEXA at Week 96 [Time Frame: Baseline (Day 1) and Week 96.]

Median Changes From Baseline at Week 96 in VAT-to-TAT, VAT-to-SAT and, Trunk-to-limb Fat Ratio Measured by Computed Tomography (CT)/DEXA [Time Frame: Baseline (Day 1) and Week 96.]

Number of Participants Who Adhered to Regimen as Measured by Multicenter AIDS Cohort Study Adherence Questionnaire (MACS) at Week 48 [Time Frame: Week 48]

Number of Participants Who Died, Experienced Other Serious Adverse Events (SAEs), Experienced Adverse Events (AEs) and Experienced AEs Leading to Discontinuation Through Week 48 [Time Frame: From baseline (Day 1) to Week 48.]

Number of Participants Who Died, Experienced Other Serious Adverse Events (SAEs), Experienced Adverse Events (AEs) and Experienced Events Leading to Discontinuation Through Week 96 [Time Frame: From Day 1 through Week 96]

Number of Participants With Confirmed Plasma HIV RNA < 400 c/mL at Week 48 (Defined by the Food and Drug Administration [FDA] Time to Loss of Virologic Response [TLOVR] Algorithm) [Time Frame: Baseline (Day 1) and Week 48]

Number of Participants With HIV RNA < 400 c/mL at Week 48 [Time Frame: Baseline (Day 1) and Week 48]

Number of Participants With HIV RNA < 400 c/mL) at Week 96 [Time Frame: Baseline (Day 1) and Week 96]

Number of Participants With HIV RNA < 50 c/mL) at Week 96 [Time Frame: Baseline (Day 1) and Week 96]

Number of Participants With Laboratory Abnormalities in Electrolytes Level Through Week 96 [Time Frame: At screening (Day -30), baseline (Day 1), Week 4, 12, 24, 36, 48, 60, 72, 84 and 96.]

Number of Participants With Laboratory Abnormalities in Electrolytes Through Week 48 [Time Frame: At Screening (Day -30), Baseline (Day 1), Week 4, 12, 24, 36, and 48.]

Number of Participants With Laboratory Abnormalities in Fasting Glucose Levels Through Week 96 [Time Frame: At screening (Day -30), baseline (Day 1), Week 4, 12, 24, 36, 48, 60, 72, 84 and 96.]

Number of Participants With Laboratory Abnormalities in Fasting Glucose Through Week 48 [Time Frame: At Screening (Day -30), Baseline (Day 1), Week 4, 12, 24, 36, and 48.]

Number of Participants With Laboratory Abnormalities in Fasting Lipids Level Through Week 96 [Time Frame: At screening (Day -30), baseline (Day 1), Week 4, 12, 24, 36, 48, 60, 72, 84 and 96.]

Number of Participants With Laboratory Abnormalities in Fasting Lipids Through Week 48 [Time Frame: At Screening (Day -30), Baseline (Day 1), Week 4, 12, 24, 36, and 48.]

Number of Participants With Laboratory Abnormalities in Hematology Through Week 48: Hemoglobin, Hematocrit, Platelet Count, International Normalized Ratio (INR), Neutrophils, Prothrombin Time (PT) and White Blood Cells (WBC) [Time Frame: At Screening (Day -30), Baseline (Day 1), Week 4, 12, 24, 36, and 48.]

Number of Participants With Laboratory Abnormalities in Hematology: Hemoglobin, Hematocrit, Platelet Count, INR, Neutrophils, PT and WBC Through Week 96 [Time Frame: At screening (Day -30), baseline (Day 1), Week 4, 12, 24, 36, 48, 60, 72, 84 and 96.]

Number of Participants With Laboratory Abnormalities in Liver Function Test Through Week 48 [Time Frame: At Screening (Day -30), Baseline (Day 1), Week 4, 12, 24, 36, and 48.]

Number of Participants With Laboratory Abnormalities in Liver Function Test Through Week 96 [Time Frame: At screening (Day -30), baseline (Day 1), Week 4, 12, 24, 36, 48, 60, 72, 84 and 96.]

Number of Participants With Laboratory Abnormalities in Renal Function Test Through Week 48 [Time Frame: At screening (Day -30), baseline (Day 1), Week 4, 12, 24, 36, and 48.]

Number of Participants With Laboratory Abnormalities in Renal Function Test Through Week 96 [Time Frame: At screening (Day -30), baseline (Day 1), Week 4, 12, 24, 36, 48, 60, 72, 84 and 96.]

Number of Participants With Laboratory Abnormalities in Serum Enzyme Levels Through Week 96 [Time Frame: At screening (Day -30), baseline (Day 1), Week 4, 12, 24, 36, 48, 60, 72, 84 and 96.]

Number of Participants With Laboratory Abnormalities in Serum Enzymes Levels Through Week 48 [Time Frame: At Screening (Day -30), Baseline (Day 1), Week 4, 12, 24, 36, and 48.]

Number of Participants With Laboratory Abnormalities in Urinalysis Through Week 48 [Time Frame: At Screening (Day -30), Baseline (Day 1), Week 4, 12, 24, 36, and 48.]

Number of Participants With Laboratory Abnormalities in Urinalysis Through Week 96 [Time Frame: At screening (Day -30), baseline (Day 1), Week 4, 12, 24, 36, 48, 60, 72, 84 and 96.]

Number of Participants With Virologic Failure Showing Treatment Emergent Resistance Through Week 96 [Time Frame: Baseline (Day 1) and Week 96.]

Percentage of Participants With Lipoatrophy at Week 96 [Time Frame: Baseline (Day 1) and Week 96]

Reduction of log10 HIV RNA Levels From Baseline at Week 96 [Time Frame: Baseline (Day 1) and Week 96]

Reduction of log10 HIV RNA Levels From Baseline to Week 48 [Time Frame: Baseline (Day 1) and Week 48]

Treatment Emergent Resistance in Isolates From Participants With Virologic Failure at Week 48 [Time Frame: Baseline (Day 1) and Week 48]

Secondary ID(s)

AI424-138

Source(s) of Monetary Support

Please refer to primary and secondary sponsors