Phase 3
Completed N=206
Study Comparing Lopinavir/Ritonavir (LPV/r) + Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) With a Nucleoside Sparing Regimen Consisting of Lopinavir/Ritonavir + Raltegravir (RAL)
Source: ClinicalTrials.gov NCT00711009 ↗Enrolled (actual)
206
Serious AEs
12.6%
Results posted
Feb 2011
Primary outcomePrimary: 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 — 84.8; 83.2 Percentage of Participants — p=0.850
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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 |
84.8; 83.2 | 0.850 |
| PRIMARY Percentage of Participants With Moderate or Severe Treatment-emergent, Drug-related Adverse Events |
34.3; 30.7; 16.2; 7.9; 4.8; 8.9 | — |
| PRIMARY Primary Outcome: Percentage of Participants With Potentially Clinically Significant Laboratory Values |
2.9; 5.0; 2.9; 5.0; 8.7; 19.8 | — |
| SECONDARY 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 |
7.6; 33.7; 17.1; 63.4; 36.2; 75.2 | — |
| SECONDARY Mean Change in CD4+ T-Cell Counts From Baseline to Each Visit |
97.2; 113.4; 107.9; 124.5; 158.7; 141.6 | — |
| SECONDARY Time to Loss of Virologic Response - Percentage of Participants Still Categorized as Responders at Day 672 |
79.1; 77.8 | — |
| SECONDARY Number of Participants Who Developed Resistance to Each Drug in the Study Regimen, as Defined by the International AIDS Society-USA (IAS-USA) Panel. |
0; 0; 1; 0; 0; 0 | — |
| SECONDARY Number of Participants Who Developed Resistance, Defined Conservatively, to Lopinavir |
0; 1 | — |
| SECONDARY Change From Baseline on Physical Component Score of the Medical Outcomes Study HIV Health Survey |
-1.0; -1.1 | — |
| SECONDARY Change From Baseline on Mental Component of Medical Outcomes Study HIV Health Survey |
1.3; 1.3 | — |
| SECONDARY Score on Effectiveness Scale of Treatment Satisfaction Questionnaire for Medication (TSQM) |
75.5; 76.0 | — |
| SECONDARY Score on Side Effects Scale of Treatment Satisfaction Questionnaire for Medication |
84.6; 86.2 | — |
| SECONDARY Score on Global Satisfaction Scale of Treatment Satisfaction Questionnaire for Medication |
82.5; 85.5 | — |
| SECONDARY Mean Change From Baseline in Hemoglobin (Grams/Liter) |
5.4; 5.1 | — |
| SECONDARY Mean Change From Baseline in Hematocrit (Fraction) |
0.038; 0.036 | — |
| SECONDARY Mean Change From Baseline in Red Blood Cell Count (x 10^12/Liter) |
0.12; 0.16 | — |
| SECONDARY Mean Change From Baseline in Platelet Count (x 10^9/Liter) |
46.8; 34.2 | — |
| SECONDARY Mean Change From Baseline in White Blood Cell Count (x 10^9/Liter) |
0.90; 1.20 | — |
| SECONDARY Mean Change From Baseline in Neutrophils (x 10^9/Liter) |
0.509; 0.705 | — |
| SECONDARY Mean Change From Baseline in Lymphocytes (x 10^9/Liter) |
0.332; 0.368 | — |
| SECONDARY Mean Change From Baseline in Monocytes (x 10^9/Liter) |
0.065; 0.112 | — |
| SECONDARY Mean Change From Baseline in Eosinophils (x 10^9/Liter) |
-0.012; 0.015 | — |
| SECONDARY Mean Change From Baseline in Basophils (x 10^9/Liter) |
0.005; 0.003 | — |
| SECONDARY Mean Change From Baseline in Alanine Aminotransferase (Units/Liter) |
-6.1; -13.4 | — |
| SECONDARY Mean Change From Baseline in Aspartate Aminotransferase (Units/Liter) |
-0.8; -9.6 | — |
| SECONDARY Mean Change From Baseline in Alkaline Phosphatase (Units/Liter) |
14.5; 1.7 | — |
| SECONDARY Mean Change From Baseline in Creatine Phosphokinase (Units/Liter) |
398.9; 157.2 | — |
| SECONDARY Mean Change From Baseline in Total Bilirubin (Micromoles/Liter) |
0.9; 1.9 | — |
| SECONDARY Mean Change From Baseline in Creatinine (Micromoles/Liter) |
5.7; 1.6 | — |
| SECONDARY Mean Change From Baseline in Blood Urea Nitrogen (Micromoles/Liter) |
0.00; 0.37 | — |
| SECONDARY Mean Change From Baseline in Uric Acid (Micromoles/Liter) |
-29.0; -6.1 | — |
| SECONDARY Mean Change From Baseline in Inorganic Phosphate (Micromoles/Liter) |
-0.046; -0.028 | — |
| SECONDARY Mean Change From Baseline in Calcium (Micromoles/Liter) |
-0.040; -0.016 | — |
| SECONDARY Mean Change From Baseline in Sodium (Micromoles/Liter) |
0.1; 0.7 | — |
| SECONDARY Mean Change From Baseline in Potassium (Micromoles/Liter) |
0.13; 0.03 | — |
| SECONDARY Mean Change From Baseline in Chloride (Micromoles/Liter) |
-0.4; 0.2 | — |
| SECONDARY Mean Change From Baseline in Bicarbonate (Micromoles/Liter) |
-0.5; -0.8 | — |
| SECONDARY Mean Change From Baseline in Albumin (Grams/Liter) |
1.4; 1.3 | — |
| SECONDARY Mean Change From Baseline in Total Protein (Grams/Liter) |
-6.3; -7.2 | — |
| SECONDARY Mean Change From Baseline in Cholesterol (Micromoles/Liter) |
0.808; 1.113 | — |
| SECONDARY Mean Change From Baseline in High Density Lipoprotein Cholesterol (HDL) (Micromoles/Liter) |
0.257; 0.346 | — |
| SECONDARY Mean Change From Baseline in Low Density Lipoprotein (LDL) (Micromoles/Liter) |
0.535; 0.715 | — |
| SECONDARY Mean Change From Baseline in Low Density Lipoprotein (LDL): High Density Lipoprotein (HDL) Ratio (Ratio) |
-0.056; -0.040 | — |
| SECONDARY Mean Change From Baseline in Triglycerides (Micromoles/Liter) |
0.846; 1.103 | — |
| SECONDARY Mean Change From Baseline in Calculated Creatinine Clearance (Milliliters/Second) |
-0.122; -0.024 | — |
| SECONDARY Mean Change From Baseline in Fasting Glucose (Millimoles/Liter) |
-0.011; 0.109 | — |
| SECONDARY Mean Change From Baseline in Lactate Dehydrogenase (Units/Liter) |
-21.157; -28.926 | — |
| SECONDARY Mean Change From Baseline in Lipase (Units/Liter) |
4.674; -1.898 | — |
| SECONDARY Mean Change From Baseline in Magnesium (Millimoles/Liter) |
0.019; -0.009 | — |
| SECONDARY Mean Change From Baseline in Adiponectin (Micrograms/Milliliter) |
2.112; 2.064 | — |
| SECONDARY Mean Change From Baseline in Interleukin-6 (Nanograms/Liter) |
-1.584; -53.286 | — |
| SECONDARY Mean Change From Baseline in Lactate (Millimoles/Liter) |
0.281; 0.444 | — |
| SECONDARY Mean Change From Baseline in Soluble Tumor Necrosis Factor Receptor-1 (Picograms/Milliliter) |
-138.602; -166.403 | — |
| SECONDARY Mean Change From Baseline in Soluble Tumor Necrosis Factor Receptor-2 (Picograms/Milliliter) |
-1257.9; -1594.7 | — |
| SECONDARY Mean Change From Baseline in Leptin (Nanograms/Milliliter) |
3.623; 2.927 | — |
| SECONDARY Mean Change From Baseline in Insulin (Picomoles/Liter) |
-6.724; 4.441 | — |
| SECONDARY Mean Change From Baseline in Urine Specific Gravity |
0.0042; 0.0052 | — |
| SECONDARY Mean Change From Baseline in Urine pH |
0.00; 0.03 | — |
| SECONDARY Mean Change From Baseline in Sitting Systolic Blood Pressure (mm Hg) |
-0.7; -2.4 | — |
| SECONDARY Mean Change From Baseline in Sitting Diastolic Blood Pressure (mm Hg) |
-2.4; -1.8 | — |
| SECONDARY Mean Change From Baseline in Sitting Heart Rate (Beats Per Minute) |
-4.6; -6.3 | — |
| SECONDARY Mean Change From Baseline in Weight (kg) |
1.83; 3.77 | — |
| SECONDARY Mean Change From Baseline in Temperature (°F) |
-0.152; -0.183 | — |
| SECONDARY Mean Change From Baseline in Chest Measurement (cm) |
1.13; 4.06 | — |
| SECONDARY Mean Change From Baseline in Waist Measurement (cm) |
1.88; 4.93 | — |
| SECONDARY Mean Change From Baseline in Mid-Arm Measurement (cm) |
1.76; 4.71 | — |
| SECONDARY Mean Change From Baseline in Hips Measurement (cm) |
2.45; 4.70 | — |
| SECONDARY Mean Change From Baseline in Mid-Thigh Measurement (cm) |
2.09; 5.13 | — |
| SECONDARY Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Upper Extremity Fat (Grams) |
7.28; 21.53 | — |
| SECONDARY Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Upper Extremity Lean Mass (Grams) |
-1.49; -1.25 | — |
| SECONDARY Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Upper Extremity Total Mass (Grams) |
-0.33; 1.52 | — |
| SECONDARY Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Lower Extremity Fat (Grams) |
15.32; 28.82 | — |
| SECONDARY Mean Change From Baseline in DEXA Scan of Lower Extremity Lean Mass (Grams) |
1.97; 2.27 | — |
| SECONDARY Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Lower Extremity Total Mass (Grams) |
4.32; 6.96 | — |
| SECONDARY Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Trunk Fat (Grams) |
13.75; 27.01 | — |
| SECONDARY Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Trunk Lean Mass (Grams) |
1.67; 2.56 | — |
| SECONDARY Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Trunk Mass (Grams) |
3.48; 6.34 | — |
| SECONDARY Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Total Body Fat (Grams) |
12.71; 25.31 | — |
| SECONDARY Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Total Body Lean Mass (Grams) |
1.08; 1.56 | — |
| SECONDARY Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Total Body Mass (Grams) |
2.9; 5.4 | — |
| SECONDARY Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Bone Mineral Content (Grams) |
-3.69; 0.52 | — |
| SECONDARY Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Bone Mineral Density (Grams/cm^2) |
-2.48; 0.68 | — |
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 = 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.
Data sourced from ClinicalTrials.gov (NCT00711009). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.