Study Comparing Lopinavir/Ritonavir (LPV/r) + Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) With a Nucleoside Sparing Regimen Consisting of Lopinavir/Ritonavir + Raltegravir (RAL)

NCT00711009 | Completed Phase 3 Results

• 2 other identifiers: M10-3362008-000881-22
• Study Type: interventional
• Target: 206
• Locations: 7 countries
• Sites: 37

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.

Conditions

Human Immunodeficiency Virus Infection

Keywords

Human Immunodeficiency Virus infection

Outcome Measures

Primary Outcomes (3)

• 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

  A participant was classified as a responder at the first of 2 consecutive visits with plasma HIV-1 RNA levels below 40 copies/mL. The participant continued to be a responder until one of the following: the participant had 2 consecutive values greater than or equal to 40 copies/mL; the final measurement, if the final measurement was the first one documenting an increase in plasma HIV-1 RNA level to greater than or equal to 40 copies/mL; the participant discontinued participation in the study or died.

  Baseline to Week 48

• Percentage of Participants With Moderate or Severe Treatment-emergent, Drug-related Adverse Events

  Treatment-emergent adverse events were defined as those occurring after study drug initiation and within 30 days after the last dose of study drug. Treatment-emergent, moderate or severe drug-related adverse events that occurred in at least 2% of participants in either treatment arm are presented.

  Week 96

• Primary Outcome: Percentage of Participants With Potentially Clinically Significant Laboratory Values

  Potentially clinically significant laboratory values that occurred in at least 2% of participants in either treatment arm are presented.

  Baseline to Week 96

Secondary Outcomes (79)

• 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

  Baseline to Week 96

• Mean Change in CD4+ T-Cell Counts From Baseline to Each Visit

  Baseline to Week 96

• Time to Loss of Virologic Response - Percentage of Participants Still Categorized as Responders at Day 672

  Baseline to Week 96

• Number of Participants Who Developed Resistance to Each Drug in the Study Regimen, as Defined by the International AIDS Society-USA (IAS-USA) Panel.

  Baseline to Week 96

• Number of Participants Who Developed Resistance, Defined Conservatively, to Lopinavir

  Baseline to Week 96

Study Arms (2)

LPV/r + FTC/TDF

ACTIVE COMPARATOR

lopinavir/ritonavir 400/100 milligram (mg) tablet twice-daily + co-formulated emtricitabine/tenofovir disoproxil fumarate 200/300 mg once-daily

Drug: lopinavir/ritonavir (LPV/r); Drug: emtricitabine/tenofovir disoproxil fumarate (FTC/TDF)

LPV/r + RAL

EXPERIMENTAL

lopinavir/ritonavir 400/100 mg tablet twice-daily + raltegravir 400 mg twice-daily

Drug: lopinavir/ritonavir (LPV/r); Drug: raltegravir (RAL)

Interventions

lopinavir/ritonavir (LPV/r) DRUG

LPV/r 400/100 mg BID

Also known as: ABT-378, lopinavir/ritonavir, LPV/r, Kaletra

LPV/r + FTC/TDF; LPV/r + RAL

emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) DRUG

FTC/TDF 200/300 mg QD

Also known as: emtricitabine/tenofovir disoproxil fumarate, FTC/TDF, Truvada

LPV/r + FTC/TDF

raltegravir (RAL) DRUG

RAL 400 mg BID

Also known as: raltegravir, RAL, Isentress, MK-0518

LPV/r + RAL

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Abbott: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (37)

Site Reference ID/Investigator# 8431

Phoenix, Arizona, 85006, United States

Location

Site Reference ID/Investigator# 8432

Beverly Hills, California, 90211, United States

Location

Site Reference ID/Investigator# 8394

Atlantis, Florida, 33462, United States

Location

Site Reference ID/Investigator# 8393

Ft. Pierce, Florida, 34982, United States

Location

Site Reference ID/Investigator# 8425

Orlando, Florida, 32803, United States

Location

Site Reference ID/Investigator# 8402

Tampa, Florida, 33614, United States

Location

Site Reference ID/Investigator# 8396

Vero Beach, Florida, 32960, United States

Location

Site Reference ID/Investigator# 8395

Atlanta, Georgia, 30303, United States

Location

Site Reference ID/Investigator# 8429

Decatur, Georgia, 30033, United States

Location

Site Reference ID/Investigator# 8424

Boston, Massachusetts, 02215, United States

Location

Site Reference ID/Investigator# 8426

Charlotte, North Carolina, 28209, United States

Location

Site Reference ID/Investigator# 11461

Huntersville, North Carolina, 28078, United States

Location

Site Reference ID/Investigator# 8403

Dallas, Texas, 75246, United States

Location

Site Reference ID/Investigator# 8433

Houston, Texas, 77004, United States

Location

Site Reference ID/Investigator# 7963

Ottawa, Ontario, K1H 8L6, Canada

Location

Site Reference ID/Investigator# 7831

Toronto, Ontario, M4N 3M5, Canada

Location

Site Reference ID/Investigator# 7959

Toronto, Ontario, M5B 1L6, Canada

Location

Site Reference ID/Investigator# 8099

Montreal, Quebec, H2L 5B1, Canada

Location

Site Reference ID/Investigator# 7695

Lyon, 69317, France

Location

Site Reference ID/Investigator# 7960

Montpellier, 34295, France

Location

Site Reference ID/Investigator# 8063

Paris, 75012, France

Location

Site Reference ID/Investigator# 7821

Paris, 75014, France

Location

Site Reference ID/Investigator# 8052

Genoa, 16132, Italy

Location

Site Reference ID/Investigator# 7789

Milan, 20127, Italy

Location

Site Reference ID/Investigator# 8051

Perugia, 06156, Italy

Location

Site Reference ID/Investigator# 8050

Rome, 00184, Italy

Location

Site Reference ID/Investigator# 8221

Wroclaw, 50-220, Poland

Location

Site Reference ID/Investigator# 7713

Bayamón, 00959, Puerto Rico

Location

Site Reference ID/Investigator# 7700

Ponce, 00717-1563, Puerto Rico

Location

Site Reference ID/Investigator# 11102

Barcelona, 08041, Spain

Location

Site Reference ID/Investigator# 7697

Barcelona, 08916, Spain

Location

Site Reference ID/Investigator# 7689

Barcelona, 8036, Spain

Location

Site Reference ID/Investigator# 7692

L'Hospitalet de Llobregat, 08907, Spain

Location

Site Reference ID/Investigator# 7698

Madrid, 28006, Spain

Location

Site Reference ID/Investigator# 7693

Madrid, 28041, Spain

Location

Site Reference ID/Investigator# 7691

Madrid, 28046, Spain

Location

Site Reference ID/Investigator# 7690

Seville, 41013, Spain

Location

Related Publications (2)

• 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.

  PMID: 22730929 DERIVED

• 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.

  PMID: 22180523 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Lopinavir; lopinavir-ritonavir drug combination; Emtricitabine; Tenofovir; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Raltegravir Potassium

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Drug Combinations; Pharmaceutical Preparations; Pyrrolidinones; Pyrrolidines

Results Point of Contact

• Title: Global Medical Services
• Organization: Abbott

800-633-9110

Study Officials

• Thomas J Podsadecki, MD

  Abbott

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2008
• First Posted: July 8, 2008
• Study Start: July 1, 2008
• Primary Completion: November 1, 2009
• Study Completion: October 1, 2010
• Last Updated: February 14, 2012
• Results First Posted: February 2, 2011

Record last verified: 2012-02

Locations

ES (8); FR (4); US (14); CA (4); IT (4); PL (1); PR (2)