Clinical trial NCT00711009: Study Comparing Lopinavir/Ritonavir (LPV/r) + Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) With a Nucleoside Sparing Regimen Consisting of Lopinavir/Ritonavir + Raltegravir (RAL)
Official title: A Randomized, Open-label Study of Lopinavir/Ritonavir 400/100 mg Tablet Twice Daily + Co-formulated Emtricitabine/Tenofovir Disoproxil Fumarate 200/300 mg Once Daily Versus Lopinavir/Ritonavir 400/100 mg Tablet Twice Daily + Raltegravir 400 mg Twice Daily in Antiretroviral Naive, HIV-1 Infected Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Human Immunodeficiency Virus Infection
Keywords: Human Immunodeficiency Virus infection
Lead sponsor: Abbott
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2008-07-08
Enrollment: 206
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the safety, tolerability, and antiviral activity of the lopinavir/ritonavir tablet when administered in combination with reverse transcriptase inhibitors to lopinavir/ritonavir tablets when administered in combination with a human immunodeficiency virus type 1 ( HIV-1) integrase inhibitor in antiretroviral naive HIV-1 infected subjects.


Eligibility criteria: Inclusion Criteria:

* Participants must provide written, voluntary informed consent to participate in the study.
* Participants must be naive to antiretroviral treatment with HIV RNA greater than or equal to 1,000 copies/mL at screening, and in the investigator's opinion, require antiretroviral therapy.
* Participant's vital signs, physical examination, and laboratory results must not exhibit evidence of acute illness.
* Participant has not been treated for an active acquired immune deficiency syndrome (AIDS)-defining opportunistic infection within 45 days of initiating study drug. Participants who are on stable maintenance therapy for an opportunistic infection may be enrolled after consultation with the Sponsor.
* Participant does not require and agrees not to take any drugs that are contraindicated or have significant pharmacokinetic interactions with study drugs during the course of the study. Participant agrees not to take any medication during the study, including over-the-counter medicines, vitamins, minerals, herbal preparations, alcohol, or recreational drugs without the knowledge and permission of the principal investigator.
* Female participants must be either postmenopausal for at least one year, surgically sterile, or must use a non-hormonal method of birth control that is acceptable to both the participant and investigator. All female participants must have a urine pregnancy test performed at screening visit and on Day minus 1/baseline, and results of both tests must be negative. Female participants may not be breastfeeding.
* Participants have received no prior treatment with an HIV-1 integrase inhibitor.

Exclusion Criteria:

* Participants must not have history of an allergic reaction or significant sensitivity to the study drugs.
* Participants may not have an ongoing history of substance abuse or psychiatric illness that could preclude protocol adherence.
* Participant cannot have resistance to lopinavir/ritonavir, tenofovir, or emtricitabine based on the HIV-1 drug resistance genotypic test results at the screening visit.
* Participant may not have significant medical history of concomitant illness or disease that would adversely affect his/her participating in the study.
* Participants may not have received any investigational drug or investigational vaccine within 30 days prior to study drug administration.
* Participants may not have any of the following abnormal screening results: Hemoglobin \<= 8.0 grams/deciliter, absolute neutrophil count \<= 750 cells/microliter, Platelet count \<= 50,000 per milliliter, alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase \[SGPT\]) or aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) \>= 3.0 x upper limit of normal (ULN), calculated creatinine clearance \< 50 milliliter/minute, hepatitis B surface antigen (HBsAg) is positive.
* The investigator considers the participant to be an unsuitable candidate for the study.

Primary outcomes:
measure: Percentage of Participants Responding (Plasma HIV-1 Ribonucleic Acid [RNA] Levels Less Than 40 Copies/Milliliter [mL]) at Week 48 Based on the Food and Drug Administration (FDA) Time to Loss of Virologic Response (TLOVR) Algorithm
timeFrame: Baseline to Week 48
measure: Percentage of Participants With Moderate or Severe Treatment-emergent, Drug-related Adverse Events
timeFrame: Week 96
measure: Primary Outcome: Percentage of Participants With Potentially Clinically Significant Laboratory Values
timeFrame: Baseline to Week 96
Secondary outcomes:
measure: Percentage of Participants Responding (Plasma HIV-1 RNA Levels Below 40 Copies/Milliliter [mL]) at Each Visit Based on the FDA Time to Loss of Virologic Response (TLOVR) Algorithm
timeFrame: Baseline to Week 96
measure: Mean Change in CD4+ T-Cell Counts From Baseline to Each Visit
timeFrame: Baseline to Week 96
measure: Time to Loss of Virologic Response - Percentage of Participants Still Categorized as Responders at Day 672
timeFrame: Baseline to Week 96
measure: Number of Participants Who Developed Resistance to Each Drug in the Study Regimen, as Defined by the International AIDS Society-USA (IAS-USA) Panel.
timeFrame: Baseline to Week 96
measure: Number of Participants Who Developed Resistance, Defined Conservatively, to Lopinavir
timeFrame: Baseline to Week 96
measure: Change From Baseline on Physical Component Score of the Medical Outcomes Study HIV Health Survey
timeFrame: Baseline to Week 96
measure: Change From Baseline on Mental Component of Medical Outcomes Study HIV Health Survey
timeFrame: Baseline to Week 96
measure: Score on Effectiveness Scale of Treatment Satisfaction Questionnaire for Medication (TSQM)
timeFrame: Week 96
measure: Score on Side Effects Scale of Treatment Satisfaction Questionnaire for Medication
timeFrame: Week 96
measure: Score on Global Satisfaction Scale of Treatment Satisfaction Questionnaire for Medication
timeFrame: Week 96
measure: Mean Change From Baseline in Hemoglobin (Grams/Liter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Hematocrit (Fraction)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Red Blood Cell Count (x 10^12/Liter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Platelet Count (x 10^9/Liter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in White Blood Cell Count (x 10^9/Liter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Neutrophils (x 10^9/Liter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Lymphocytes (x 10^9/Liter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Monocytes (x 10^9/Liter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Eosinophils (x 10^9/Liter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Basophils (x 10^9/Liter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Alanine Aminotransferase (Units/Liter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Aspartate Aminotransferase (Units/Liter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Alkaline Phosphatase (Units/Liter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Creatine Phosphokinase (Units/Liter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Total Bilirubin (Micromoles/Liter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Creatinine (Micromoles/Liter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Blood Urea Nitrogen (Micromoles/Liter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Uric Acid (Micromoles/Liter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Inorganic Phosphate (Micromoles/Liter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Calcium (Micromoles/Liter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Sodium (Micromoles/Liter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Potassium (Micromoles/Liter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Chloride (Micromoles/Liter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Bicarbonate (Micromoles/Liter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Albumin (Grams/Liter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Total Protein (Grams/Liter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Cholesterol (Micromoles/Liter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in High Density Lipoprotein Cholesterol (HDL) (Micromoles/Liter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Low Density Lipoprotein (LDL) (Micromoles/Liter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Low Density Lipoprotein (LDL): High Density Lipoprotein (HDL) Ratio (Ratio)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Triglycerides (Micromoles/Liter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Calculated Creatinine Clearance (Milliliters/Second)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Fasting Glucose (Millimoles/Liter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Lactate Dehydrogenase (Units/Liter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Lipase (Units/Liter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Magnesium (Millimoles/Liter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Adiponectin (Micrograms/Milliliter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Interleukin-6 (Nanograms/Liter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Lactate (Millimoles/Liter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Soluble Tumor Necrosis Factor Receptor-1 (Picograms/Milliliter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Soluble Tumor Necrosis Factor Receptor-2 (Picograms/Milliliter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Leptin (Nanograms/Milliliter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Insulin (Picomoles/Liter)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Urine Specific Gravity
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Urine pH
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Sitting Systolic Blood Pressure (mm Hg)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Sitting Diastolic Blood Pressure (mm Hg)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Sitting Heart Rate (Beats Per Minute)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Weight (kg)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Temperature (°F)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Chest Measurement (cm)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Waist Measurement (cm)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Mid-Arm Measurement (cm)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Hips Measurement (cm)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Mid-Thigh Measurement (cm)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Upper Extremity Fat (Grams)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Upper Extremity Lean Mass (Grams)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Upper Extremity Total Mass (Grams)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Lower Extremity Fat (Grams)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in DEXA Scan of Lower Extremity Lean Mass (Grams)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Lower Extremity Total Mass (Grams)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Trunk Fat (Grams)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Trunk Lean Mass (Grams)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Trunk Mass (Grams)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Total Body Fat (Grams)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Total Body Lean Mass (Grams)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Total Body Mass (Grams)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Bone Mineral Content (Grams)
timeFrame: Baseline to Week 96
measure: Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Bone Mineral Density (Grams/cm^2)
timeFrame: Baseline to Week 96
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Site Reference ID/Investigator# 8431
state: Arizona
city: Beverly Hills
country: United States
facility: Site Reference ID/Investigator# 8432
state: California
city: Atlantis
country: United States
facility: Site Reference ID/Investigator# 8394
state: Florida
city: Fort Pierce
country: United States
facility: Site Reference ID/Investigator# 8393
state: Florida
city: Orlando
country: United States
facility: Site Reference ID/Investigator# 8425
state: Florida
city: Tampa
country: United States
facility: Site Reference ID/Investigator# 8402
state: Florida
city: Vero Beach
country: United States
facility: Site Reference ID/Investigator# 8396
state: Florida
city: Atlanta
country: United States
facility: Site Reference ID/Investigator# 8395
state: Georgia
city: Decatur
country: United States
facility: Site Reference ID/Investigator# 8429
state: Georgia
city: Boston
country: United States
facility: Site Reference ID/Investigator# 8424
state: Massachusetts
city: Charlotte
country: United States
facility: Site Reference ID/Investigator# 8426
state: North Carolina
city: Huntersville
country: United States
facility: Site Reference ID/Investigator# 11461
state: North Carolina
city: Dallas
country: United States
facility: Site Reference ID/Investigator# 8403
state: Texas
city: Houston
country: United States
facility: Site Reference ID/Investigator# 8433
state: Texas
city: Ottawa
country: Canada
facility: Site Reference ID/Investigator# 7963
state: Ontario
city: Toronto
country: Canada
facility: Site Reference ID/Investigator# 7831
state: Ontario
city: Toronto
country: Canada
facility: Site Reference ID/Investigator# 7959
state: Ontario
city: Montreal
country: Canada
facility: Site Reference ID/Investigator# 8099
state: Quebec
city: Lyon Cedex 04
country: France
facility: Site Reference ID/Investigator# 7695
city: Montpellier Cedex 5
country: France
facility: Site Reference ID/Investigator# 7960
city: Paris
country: France
facility: Site Reference ID/Investigator# 8063
city: Paris
country: France
facility: Site Reference ID/Investigator# 7821
city: Genoa
country: Italy
facility: Site Reference ID/Investigator# 8052
city: Milan
country: Italy
facility: Site Reference ID/Investigator# 7789
city: Perugia
country: Italy
facility: Site Reference ID/Investigator# 8051
city: Rome
country: Italy
facility: Site Reference ID/Investigator# 8050
city: Wroclaw
country: Poland
facility: Site Reference ID/Investigator# 8221
city: Bayamon
country: Puerto Rico
facility: Site Reference ID/Investigator# 7713
city: Ponce
country: Puerto Rico
facility: Site Reference ID/Investigator# 7700
city: Barcelona
country: Spain
facility: Site Reference ID/Investigator# 11102
city: Barcelona
country: Spain
facility: Site Reference ID/Investigator# 7697
city: Barcelona
country: Spain
facility: Site Reference ID/Investigator# 7689
city: L'Hospitalet de Llobregat
country: Spain
facility: Site Reference ID/Investigator# 7692
city: Madrid
country: Spain
facility: Site Reference ID/Investigator# 7698
city: Madrid
country: Spain
facility: Site Reference ID/Investigator# 7693
city: Madrid
country: Spain
facility: Site Reference ID/Investigator# 7691
city: Seville
country: Spain
facility: Site Reference ID/Investigator# 7690
Study officials:
affiliation: Abbott
name: Thomas J Podsadecki, MD
role: STUDY_DIRECTOR
References:
citation: Reynes J, Trinh R, Pulido F, Soto-Malave R, Gathe J, Qaqish R, Tian M, Fredrick L, Podsadecki T, Norton M, Nilius A. Lopinavir/ritonavir combined with raltegravir or tenofovir/emtricitabine in antiretroviral-naive subjects: 96-week results of the PROGRESS study. AIDS Res Hum Retroviruses. 2013 Feb;29(2):256-65. doi: 10.1089/aid.2011.0275. Epub 2012 Aug 3.
citation: Reynes J, Lawal A, Pulido F, Soto-Malave R, Gathe J, Tian M, Fredrick LM, Podsadecki TJ, Nilius AM. Examination of noninferiority, safety, and tolerability of lopinavir/ritonavir and raltegravir compared with lopinavir/ritonavir and tenofovir/ emtricitabine in antiretroviral-naive subjects: the progress study, 48-week results. HIV Clin Trials. 2011 Sep-Oct;12(5):255-67. doi: 10.1310/hct1205-255.