Study of Lopinavir/Ritonavir Tablets Comparing Once-Daily Versus Twice-Daily Administration When Coadministered With Nucleoside/Nucleotide Reverse Transcriptase Inhibitors in Antiretroviral-Experienced Human Immunodeficiency Virus Type 1 Infected Subjects

A Phase 3, Randomized, Open-Label Study of Lopinavir/Ritonavir (LPV/r) Tablets 800/200 Milligram (mg) Once-Daily (QD) Versus 400/100 mg Twice-Daily (BID) When Coadministered With Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs) in Antiretroviral-Experienced, Human Immunodeficiency Virus Type 1 (HIV-1) Infected Subjects

The purpose of this study was to compare the safety, tolerability, and antiviral activity of once-daily (QD) and twice-daily (BID) dosing of the lopinavir/ritonavir (LPV/r) tablet formulation in combination with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) in antiretroviral-experienced human immunodeficiency virus type 1 infected subjects with detectable viral load while receiving their current antiretroviral therapy.

Study Overview

• Status: Completed
• Conditions: Human Immunodeficiency Virus Infections
• Intervention / Treatment: Drug: lopinavir/ritonavir (LPV/r) tablet with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs); Drug: lopinavir/ritonavir (LPV/r) tablet with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)

• Study Type: Interventional
• Enrollment (Actual): 599
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Abbott Park, Illinois, United States, 60064
      • Medical Information - Abbott (1-800-633-9110)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects were human immunodeficiency virus type 1 (HIV-1) positive, antiretroviral-experienced adults at least 18 years of age currently receiving an antiretroviral regimen which had not changed for at least 12 weeks.
• Subjects had plasma HIV-1 ribonucleic acid (RNA) levels > 1,000 copies/mL at screening and were not acutely ill.
• Subject was currently failing his/her antiretroviral regimen with the most recent 2 consecutive prestudy plasma HIV-1 RNA levels > 400 copies/mL with the most recent being > 1000 copies/mL, and in the investigator's opinion, should change therapy
• Female subjects were nonpregnant and nonlactating.

Exclusion Criteria:

• Subjects were excluded if screening laboratory analyses showed hemoglobin <= 8.0 grams per deciliter.
• Subjects were excluded if screening laboratory analyses showed absolute neutrophil count <= 750 cells/microliter.
• Subjects were excluded if screening laboratory analyses showed platelet count <= 50,000 per cubic millimeter.
• Subjects were excluded if screening laboratory analyses showed alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >= 5.0 x upper limit of normal (ULN).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LPV/r 800/200 mg QD Tablet	Drug: lopinavir/ritonavir (LPV/r) tablet with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs); LPV/r 800/200 mg once-daily (QD) tablet; Other Names: Kaletra; ABT-378; lopinavir/ritonavir; Drug: lopinavir/ritonavir (LPV/r) tablet with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs); LPV/r 400/100 mg twice-daily (BID) tablet; Other Names: Kaletra; ABT-378; lopinavir/ritonavir
Active Comparator: LPV/r 400/100 mg BID Tablet	Drug: lopinavir/ritonavir (LPV/r) tablet with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs); LPV/r 800/200 mg once-daily (QD) tablet; Other Names: Kaletra; ABT-378; lopinavir/ritonavir; Drug: lopinavir/ritonavir (LPV/r) tablet with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs); LPV/r 400/100 mg twice-daily (BID) tablet; Other Names: Kaletra; ABT-378; lopinavir/ritonavir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Responding at Week 48 Based on the Food and Drug Administration (FDA) Time to Loss of Virologic Response (TLOVR) Algorithm	A participant was classified as a responder at the first of 2 consecutive human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) levels <50 copies/mL. The participant continued to be a responder until 2 consecutive values >=50 copies/mL were reached, until the final value if that value was >=50 copies/mL, or until discontinuation or death.	Week 48 (End of Study)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Levels < 50 Copies/Milliliter (mL) at Week 48		Week 48 (End of Study)
Mean Change From Baseline to Week 48 in Cluster of Differentiation 4 Single-Positive Thymocyte (CD4+ T) Cell Counts		Week 48 (End of Study)
Virologic Response (HIV-1 RNA <50 Copies/mL) at Week 48 for Participants With 0-2 Protease Inhibitor Substitutions at Baseline Associated With Reduced Response to Lopinavir/Ritonavir	Substitutions considered in the analysis were L10F/I/R/V, K20M/N/R, L24I, L33F, M36I, I47V, G48V, I54L/T/V, V82A/C/F/S/T, and I84V as defined in the proposed United States Package Insert.	Week 48 (End of Study)
Percentage of Participants With New Primary Protease Mutations at Week 48	Emergence of new primary protease inhibitor mutations (i.e., mutations at codons 30, 32, 48, 50, 82, 84, and 90 that were not present at baseline).	Week 48 (End of Study)

Collaborators and Investigators

• Sponsor: Abbott
• Investigators: Study Director: Thomas J Podsadecki, MD, Abbott

Study record dates

Study Major Dates

• Study Start: August 1, 2006
• Primary Completion (Actual): November 1, 2008
• Study Completion (Actual): November 1, 2008

Study Registration Dates

• First Submitted: July 28, 2006
• First Submitted That Met QC Criteria: July 28, 2006
• First Posted (Estimate): August 1, 2006

Study Record Updates

• Last Update Posted (Estimate): April 11, 2011
• Last Update Submitted That Met QC Criteria: April 7, 2011
• Last Verified: April 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir; Lopinavir; Reverse Transcriptase Inhibitors
• Other Study ID Numbers: M06-802