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

Human Immunodeficiency Virus Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00358917
• Other study ID #: M06-802
• Status: Completed
• Phase: Phase 3
• First received: July 28, 2006
• Last updated: April 7, 2011
• Start date: August 2006
• Est. completion date: November 2008

Study information

• Verified date: April 2011
• Source: Abbott
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 599
• Est. completion date: November 2008
• Est. primary completion date: November 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Human Immunodeficiency Virus Infections
• Immunologic Deficiency Syndromes
• Virus Diseases

Intervention

Drug:
• lopinavir/ritonavir (LPV/r) tablet with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)
LPV/r 800/200 mg once-daily (QD) tablet
• lopinavir/ritonavir (LPV/r) tablet with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)
LPV/r 400/100 mg twice-daily (BID) tablet

Locations

Country	Name	City	State
United States	Medical Information - Abbott (1-800-633-9110)	Abbott Park	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Abbott

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	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)	No
Secondary	Mean Change From Baseline to Week 48 in Cluster of Differentiation 4 Single-Positive Thymocyte (CD4+ T) Cell Counts		Week 48 (End of Study)	No
Secondary	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)	No
Secondary	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)	No