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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LPV/r 800/200 mg QD Tablet | Experimental |
| |
| LPV/r 400/100 mg BID Tablet | Active Comparator |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| lopinavir/ritonavir (LPV/r) tablet with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) | Drug | LPV/r 800/200 mg once-daily (QD) tablet |
|
| 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) |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Thomas J Podsadecki, MD | Abbott | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medical Information - Abbott (1-800-633-9110) | Abbott Park | Illinois | 60064 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | LPV/r 800/200 mg QD Tablet | lopinavir/ritonavir 800/200 milligram (mg) once daily (QD) tablet |
| FG001 | LPV/r 400/100 mg BID Tablet | lopinavir/ritonavir 400/100 milligram (mg) twice daily (BID) tablet |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| lopinavir/ritonavir (LPV/r) tablet with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) | Drug | LPV/r 400/100 mg twice-daily (BID) tablet |
|
|
| 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) |
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| ID | Title | Description |
|---|---|---|
| BG000 | LPV/r 800/200 mg QD Tablet | lopinavir/ritonavir 800/200 mg once daily (QD) tablet |
| BG001 | LPV/r 400/100 mg BID Tablet | lopinavir/ritonavir 400/100 mg twice daily (BID) tablet |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Received Prior Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI) | Number | participants |
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| Received Prior Nucleoside/nucleotide Reverse Transcriptase Inhibitor (NRTI) | Number | participants |
| ||||||||||||||||
| Received Prior Protease Inhibitor (PI) | Number | participants |
| ||||||||||||||||
| Cluster of Differentiation 4 Single-Positive Thymocyte (CD4+ T) Cell Count | Mean | Standard Deviation | cells/microliter |
| |||||||||||||||
| Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Level | Mean | Standard Deviation | log10 copies/milliliter (mL) |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Intention to treat analysis of all randomized participants who received at least 1 dose of study drug. | Posted | Number | Percentage of Participants | Week 48 (End of Study) |
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| Secondary | Percentage of Participants With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Levels < 50 Copies/Milliliter (mL) at Week 48 | Observed data analysis using all available Week 48 data from all randomized participants who received at least 1 dose of study drug. | Posted | Number | Percentage of Participants | Week 48 (End of Study) |
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| Secondary | Mean Change From Baseline to Week 48 in Cluster of Differentiation 4 Single-Positive Thymocyte (CD4+ T) Cell Counts | All randomized participants who received at least 1 dose of study drug and who had CD4+ T cell counts at both the Baseline Visit and Week 48. | Posted | Mean | Standard Error | cells/microliter | Week 48 (End of Study) |
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| 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. | Dropouts-as-censored: participants were responders if they had HIV-1 RNA <50 copies/mL at Week 48. Participants who discontinued (d/c'd) while suppressed or w/o post baseline (BL) levels were excluded. Those d/c'd <Day 85 were excluded unless they had >=1 post BL level & didn't achieve a decrease >=1.0 log10 copies/mL, then they were nonresponders. | Posted | Number | Percentage of Participants | Week 48 (End of Study) |
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| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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). | All randomized participants who received at least 1 dose of study drug and had post baseline genotypic resistance assay results. | Posted | Number | Percentage of Participants | Week 48 (End of Study) |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | LPV/r 800/200 mg QD Tablet | lopinavir/ritonavir 800/200 mg once daily (QD) tablet | 27 | 300 | 201 | 300 | ||
| EG001 | LPV/r 400/100 mg BID Tablet | lopinavir/ritonavir 400/100 mg twice daily (BID) tablet | 37 | 299 | 180 | 299 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 11.1 | Systematic Assessment |
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| Leukocytosis | Blood and lymphatic system disorders | MedDRA (11.1) | Systematic Assessment |
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| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA (11.1) | Systematic Assessment |
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| Angina pectoris | Cardiac disorders | MedDRA (11.1) | Systematic Assessment |
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| Cardiac failure congestive | Cardiac disorders | MedDRA (11.1) | Systematic Assessment |
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| Cardiogenic shock | Cardiac disorders | MedDRA (11.1) | Systematic Assessment |
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| Tricuspid valve incompetence | Cardiac disorders | MedDRA 11.1 | Systematic Assessment |
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| Abdominal distension | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
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| Gastritis | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
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| Inguinal hernia | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
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| Asthenia | General disorders | MedDRA 11.1 | Systematic Assessment |
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| Chest pain | General disorders | MedDRA 11.1 | Systematic Assessment |
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| Chills | General disorders | MedDRA 11.1 | Systematic Assessment |
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| Death | General disorders | MedDRA 11.1 | Systematic Assessment |
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| Oedema peripheral | General disorders | MedDRA 11.1 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 11.1 | Systematic Assessment |
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| Unevaluable event | General disorders | MedDRA 11.1 | Systematic Assessment |
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| Cholecystitis | Hepatobiliary disorders | MedDRA 11.1 | Systematic Assessment |
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| Cholecystitis chronic | Hepatobiliary disorders | MedDRA 11.1 | Systematic Assessment |
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| Jaundice | Hepatobiliary disorders | MedDRA 11.1 | Systematic Assessment |
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| Drug hypersensitivity | Immune system disorders | MedDRA 11.1 | Systematic Assessment |
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| Abscess limb | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| Appendicitis | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| Bacterial disease carrier | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| Bronchitis | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| Cellulitis | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| Cerebral toxoplasmosis | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| Cryptococcosis | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| Dengue fever | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| Disseminated tuberculosis | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| Helicobacter infection | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| Herpes zoster | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| Meningitis | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| Meningitis tuberculous | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| Oral candidiasis | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| Sepsis | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| Staphylococcal bacteraemia | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| Staphylococcal infection | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| Staphylococcal skin infection | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| Syphilis | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| Tuberculosis | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| Clavicle fracture | Injury, poisoning and procedural complications | MedDRA 11.1 | Systematic Assessment |
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| Head injury | Injury, poisoning and procedural complications | MedDRA 11.1 | Systematic Assessment |
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| Hip fracture | Injury, poisoning and procedural complications | MedDRA 11.1 | Systematic Assessment |
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| Injury | Injury, poisoning and procedural complications | MedDRA 11.1 | Systematic Assessment |
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| Lung injury | Injury, poisoning and procedural complications | MedDRA 11.1 | Systematic Assessment |
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| Rib fracture | Injury, poisoning and procedural complications | MedDRA 11.1 | Systematic Assessment |
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| Road traffic accident | Injury, poisoning and procedural complications | MedDRA 11.1 | Systematic Assessment |
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| Scapula fracture | Injury, poisoning and procedural complications | MedDRA 11.1 | Systematic Assessment |
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| Skin laceration | Injury, poisoning and procedural complications | MedDRA 11.1 | Systematic Assessment |
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| Upper limb fracture | Injury, poisoning and procedural complications | MedDRA 11.1 | Systematic Assessment |
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| Haemoglobin decreased | Investigations | MedDRA 11.1 | Systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | MedDRA 11.1 | Systematic Assessment |
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| Gout | Metabolism and nutrition disorders | MedDRA 11.1 | Systematic Assessment |
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| Hyperlactacidaemia | Metabolism and nutrition disorders | MedDRA 11.1 | Systematic Assessment |
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| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Systematic Assessment |
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| Foot deformity | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Systematic Assessment |
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| Lumbar spinal stenosis | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Systematic Assessment |
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| Ocular neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 11.1 | Systematic Assessment |
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| Cerebral haemorrhage | Nervous system disorders | MedDRA 11.1 | Systematic Assessment |
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| Cerebral infarction | Nervous system disorders | MedDRA 11.1 | Systematic Assessment |
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| Cerebrovascular accident | Nervous system disorders | MedDRA 11.1 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 11.1 | Systematic Assessment |
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| Encephalitis | Nervous system disorders | MedDRA 11.1 | Systematic Assessment |
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| Mononeuritis | Nervous system disorders | MedDRA 11.1 | Systematic Assessment |
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| Paraesthesia | Nervous system disorders | MedDRA 11.1 | Systematic Assessment |
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| Abortion spontaneous | Pregnancy, puerperium and perinatal conditions | MedDRA 11.1 | Systematic Assessment |
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| Ectopic pregnancy | Pregnancy, puerperium and perinatal conditions | MedDRA 11.1 | Systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA 11.1 | Systematic Assessment |
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| Major depression | Psychiatric disorders | MedDRA 11.1 | Systematic Assessment |
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| Personality disorder | Psychiatric disorders | MedDRA 11.1 | Systematic Assessment |
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| Acute prerenal failure | Renal and urinary disorders | MedDRA 11.1 | Systematic Assessment |
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| Choluria | Renal and urinary disorders | MedDRA 11.1 | Systematic Assessment |
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| Renal failure | Renal and urinary disorders | MedDRA 11.1 | Systematic Assessment |
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| Renal failure acute | Renal and urinary disorders | MedDRA 11.1 | Systematic Assessment |
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| Cervical dysplasia | Reproductive system and breast disorders | MedDRA 11.1 | Systematic Assessment |
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| Epididymitis | Reproductive system and breast disorders | MedDRA 11.1 | Systematic Assessment |
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| Metrorrhagia | Reproductive system and breast disorders | MedDRA 11.1 | Systematic Assessment |
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| Vaginal dysplasia | Reproductive system and breast disorders | MedDRA 11.1 | Systematic Assessment |
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| Vaginal haemorrhage | Reproductive system and breast disorders | MedDRA 11.1 | Systematic Assessment |
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| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
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| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
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| Haemothorax | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
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| Lung disorder | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
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| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
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| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
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| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
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| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
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| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 11.1 | Systematic Assessment |
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| Stevens-Johnson syndrome | Skin and subcutaneous tissue disorders | MedDRA 11.1 | Systematic Assessment |
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| Arteriosclerosis | Vascular disorders | MedDRA 11.1 | Systematic Assessment |
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| Deep vein thrombosis | Vascular disorders | MedDRA 11.1 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 11.1 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
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This study has varying agreements that have been negotiated individually; however, it appears that the most restrictive of the agreements states that following the first publication/presentation of the study by Abbott (or twelve [12] months after the completion of the study at all sites, whichever occurs first), the Principal Investigator (PI) shall, during a period of twelve (12) months, have the right to publish/present the results of the site.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Information Specialist | Abbott | 800-633-9110 |
| ID | Term |
|---|---|
| D061466 | Lopinavir |
| D019438 | Ritonavir |
| D013607 | Tablets |
| C558899 | lopinavir-ritonavir drug combination |
| ID | Term |
|---|---|
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D001393 | Azoles |
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |
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| Male |
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| Did Not Receive Prior NNRTI |
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| Did Not Receive Prior NRTI |
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| Did Not Receive Prior PI |
|
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| Counts |
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| Participants |
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