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Study of Lopinavir/Ritonavir Tablets Versus Soft Gel Capsules and Once Daily Versus Twice Daily Administration, When Coadministered With Nucleoside Reverse Transcriptase Inhibitors in Antiretroviral Naive Human Immunodeficiency Virus Type 1 Infected Subjects

Sponsor
Abbott (Industry)
Overall Status
Completed
CT.gov ID
NCT00262522
Collaborator
(none)
664
Enrollment
129
Locations
4
Arms
32
Duration (Months)
5.1
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study was to compare the safety and tolerability of the to-be-marketed lopinavir/ritonavir (LPV/r) tablet formulation with the marketed soft gel capsule (SGC) formulation and to compare the safety, tolerability, and antiviral activity of once daily (QD) and twice daily (BID) dosing of the LPV/r tablet formulation in combination with select nucleoside reverse transcriptase inhibitors (NRTIs) in patients who have not previously received antiretroviral treatment.

Condition or Disease Intervention/Treatment Phase
  • Drug: lopinavir/ritonavir (LPV/r) (tablet or capsule) with nucleoside reverse transcriptase inhibitors (NRTIs)
  • Drug: lopinavir/ritonavir (LPV/r) (tablet or capsule) with nucleoside reverse transcriptase inhibitors (NRTIs)
  • Drug: lopinavir/ritonavir (LPV/r) (tablet or capsule) with nucleoside reverse transcriptase inhibitors (NRTIs)
  • Drug: lopinavir/ritonavir (LPV/r) (tablet or capsule) with nucleoside reverse transcriptase inhibitors (NRTIs)
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
664 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Randomized, Open-label, Study of Lopinavir/Ritonavir Tablets Versus Soft Gel Capsules and Once Daily Versus Twice Daily Administration, When Coadministered With NRTIs in Antiretroviral Naive HIV-1 Infected Subjects
Study Start Date :
Nov 1, 2005
Actual Primary Completion Date :
Jul 1, 2008
Actual Study Completion Date :
Jul 1, 2008

Arms and Interventions

Arm Intervention/Treatment
Experimental: LPV/r 800/200 mg QD Tablet

Drug: lopinavir/ritonavir (LPV/r) (tablet or capsule) with nucleoside reverse transcriptase inhibitors (NRTIs)
LPV/r 800/200 mg once daily (QD) tablet + emtricitabine (FTC) 200 mg QD + tenofovir disoproxil fumarate (TDF) 300 mg QD
Other Names:
  • ABT-378, Kaletra, lopinavir/ritonavir

    		•
    Experimental: LPV/r 800/200 mg QD SGC (Through Week 8)

    Drug: lopinavir/ritonavir (LPV/r) (tablet or capsule) with nucleoside reverse transcriptase inhibitors (NRTIs)
    LPV/r 800/200 mg QD soft gel capsule (SGC) + FTC 200 mg QD + TDF 300 mg QD (8 weeks) followed by LPV/r 800/200 mg QD Tablet + FTC 200 mg QD + TDF 300 mg QD
    Other Names:
  • ABT-378, Kaletra, lopinavir/ritonavir

    		•
    Active Comparator: LPV/r 400/100 mg BID Tablet

    Drug: lopinavir/ritonavir (LPV/r) (tablet or capsule) with nucleoside reverse transcriptase inhibitors (NRTIs)
    LPV/r 400/100 mg twice daily (BID) tablet + FTC 200 mg QD + TDF 300 mg QD
    Other Names:
  • ABT-378, Kaletra, lopinavir/ritonavir

    		•
    Active Comparator: LPV/r 400/100 mg BID SGC (Through Week 8)

    Drug: lopinavir/ritonavir (LPV/r) (tablet or capsule) with nucleoside reverse transcriptase inhibitors (NRTIs)
    LPV/r 400/100 mg BID SGC + FTC 200 mg QD + TDF 300 mg QD (8 weeks) followed by LPV/r 400/100 mg BID Tablet + FTC 200 mg QD + TDF 300 mg QD
    Other Names:
  • ABT-378, Kaletra, lopinavir/ritonavir

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Subjects With Adverse Events of Diarrhea During the First 8 Weeks [Week 8]

    2. Percentage of Subjects With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Levels < 50 Copies/mL at Week 48 [Week 48]

    Secondary Outcome Measures

    1. Percentage of Subjects With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Levels < 50 Copies/mL at Week 96 [Week 96 (End of Study)]

    2. Mean Change From Baseline to Week 96 in CD4+ T Cell Counts [Week 96 (End of Study)]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes

    Inclusion Criteria

    • Subjects were human immunodeficiency virus type 1 (HIV-1) positive, antiretroviral naïve adults at least 18 years of age with < 7 days of prior antiretroviral therapy.

    • Subjects had plasma HIV-1 ribonucleic acid (RNA) levels >= 1,000 copies/mL at screening and were not acutely ill.

    • Female subjects were nonpregnant and nonlactating.

    Exclusion Criteria

    • Subjects were excluded if screening laboratory analyses showed any of the following abnormal laboratory results:

    • Presence of hepatitis B surface antigen (HBsAg)

    • Hemoglobin <= 8.0 g/dL

    • Absolute neutrophil count <= 750 cells/microliter

    • Platelet count <= 50,000 per mL

    • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >= 3.0 x Upper Limit of Normal (ULN)

    • Calculated creatinine clearance < 50 mL/min

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Site Reference ID/Investigator# 823 Phoenix Arizona United States 85006
    2 Site Reference ID/Investigator# 846 Phoenix Arizona United States 85012
    3 Site Reference ID/Investigator# 851 Beverly Hills California United States 90211
    4 Site Reference ID/Investigator# 872 Fountain Valley California United States 92708
    5 Site Reference ID/Investigator# 826 Long Beach California United States 90813
    6 Site Reference ID/Investigator# 876 Newport Beach California United States 92663
    7 Site Reference ID/Investigator# 875 Washington District of Columbia United States 20037
    8 Site Reference ID/Investigator# 870 Atlantis Florida United States 33462
    9 Site Reference ID/Investigator# 844 Fort Lauderdale Florida United States 33311
    10 Site Reference ID/Investigator# 874 Miami Florida United States 33136
    11 Site Reference ID/Investigator# 1153 Orlando Florida United States 32803
    12 Site Reference ID/Investigator# 827 Orlando Florida United States 32803
    13 Site Reference ID/Investigator# 783 Plantation Florida United States 33317
    14 Site Reference ID/Investigator# 877 Port Saint Lucie Florida United States 34952
    15 Site Reference ID/Investigator# 845 Safety Harbor Florida United States 34695
    16 Site Reference ID/Investigator# 849 Sarasota Florida United States 34243
    17 Site Reference ID/Investigator# 825 Tampa Florida United States 33614
    18 Site Reference ID/Investigator# 848 Atlanta Georgia United States 30309
    19 Site Reference ID/Investigator# 873 Macon Georgia United States 31201
    20 Site Reference ID/Investigator# 1154 Chicago Illinois United States 60612
    21 Site Reference ID/Investigator# 824 Chicago Illinois United States 60613
    22 Site Reference ID/Investigator# 792 Wichita Kansas United States 67214
    23 Site Reference ID/Investigator# 1157 Minneapolis Minnesota United States 55404
    24 Site Reference ID/Investigator# 871 St. Louis Missouri United States 63108
    25 Site Reference ID/Investigator# 2450 Rochester New York United States 14620
    26 Site Reference ID/Investigator# 784 Charlotte North Carolina United States 28209
    27 Site Reference ID/Investigator# 1155 Dallas Texas United States 75208
    28 Site Reference ID/Investigator# 850 Dallas Texas United States 75246
    29 Site Reference ID/Investigator# 843 Houston Texas United States 77004
    30 Site Reference ID/Investigator# 1156 Hampton Virginia United States 23666
    31 Site Reference ID/Investigator# 244 Darlinghurst Australia 2010
    32 Site Reference ID/Investigator# 245 Melbourne Australia 3004
    33 Site Reference ID/Investigator# 246 South Yarra Australia 3141
    34 Site Reference ID/Investigator# 234 Antwerp Belgium 2000
    35 Site Reference ID/Investigator# 235 Brussels Belgium 1200
    36 Site Reference ID/Investigator# 233 Ghent Belgium 9000
    37 Site Reference ID/Investigator# 236 Leuven Belgium 3000
    38 Site Reference ID/Investigator# 225 Liege 1 Belgium 4000
    39 Site Reference ID/Investigator# 175 Calgary Canada T2R 0X7
    40 Site Reference ID/Investigator# 184 Hamilton Canada L8N 3Z5
    41 Site Reference ID/Investigator# 177 Montreal Canada H2L 4P9
    42 Site Reference ID/Investigator# 176 Montreal Canada H2L 5B1
    43 Site Reference ID/Investigator# 179 Montreal Canada H2X 2P4
    44 Site Reference ID/Investigator# 181 Ottawa Canada K1H 8L6
    45 Site Reference ID/Investigator# 173 Ottawa Canada K1N 6N5
    46 Site Reference ID/Investigator# 178 Ste-Foy Canada G1V 4G2
    47 Site Reference ID/Investigator# 180 Toronto Canada M4N 3M5
    48 Site Reference ID/Investigator# 182 Toronto Canada M5B 1L6
    49 Site Reference ID/Investigator# 174 Toronto Canada M5G 2C4
    50 Site Reference ID/Investigator# 183 Vancouver Canada V6Z 2C7
    51 Site Reference ID/Investigator# 172 Vancouver Canada V6Z 2T1
    52 Site Reference ID/Investigator# 294 Brno Czech Republic 639 00
    53 Site Reference ID/Investigator# 296 Plzen Czech Republic 305 99
    54 Site Reference ID/Investigator# 286 Aix en Provence France 13616
    55 Site Reference ID/Investigator# 275 Besancon France 25030
    56 Site Reference ID/Investigator# 256 Lyon France 69288
    57 Site Reference ID/Investigator# 278 Montpellier Cedex 5 France 34295
    58 Site Reference ID/Investigator# 257 Paris France 75012
    59 Site Reference ID/Investigator# 281 Paris France 75014
    60 Site Reference ID/Investigator# 280 Paris France 75475
    61 Site Reference ID/Investigator# 279 Paris France 75877
    62 Site Reference ID/Investigator# 284 Paris France 75970
    63 Site Reference ID/Investigator# 274 Rennes France 35033
    64 Site Reference ID/Investigator# 282 Vandoeuvre les Nancy France 54511
    65 Site Reference ID/Investigator# 265 Berlin Germany 13353
    66 Site Reference ID/Investigator# 270 Berlin Germany D-10243
    67 Site Reference ID/Investigator# 262 Bochum Germany D-44791
    68 Site Reference ID/Investigator# 268 Bonn Germany 53127
    69 Site Reference ID/Investigator# 271 Cologne Germany 50931
    70 Site Reference ID/Investigator# 266 Frankfurt Germany 60590
    71 Site Reference ID/Investigator# 264 Fuerth Germany D-90762
    72 Site Reference ID/Investigator# 273 Hamburg Germany 20146
    73 Site Reference ID/Investigator# 267 Hamburg Germany D-20099
    74 Site Reference ID/Investigator# 263 Hannover Germany 30159
    75 Site Reference ID/Investigator# 211 Athens Greece 115 26
    76 Site Reference ID/Investigator# 207 Thessaloniki Greece 54636
    77 Site Reference ID/Investigator# 249 Dublin 7 Ireland
    78 Site Reference ID/Investigator# 237 Dublin 8 Ireland
    79 Site Reference ID/Investigator# 203 Brescia Italy 25123
    80 Site Reference ID/Investigator# 192 Florence Italy 50011
    81 Site Reference ID/Investigator# 195 Genoa Italy 16132
    82 Site Reference ID/Investigator# 201 Milan Italy 20127
    83 Site Reference ID/Investigator# 198 Milan Italy 20157
    84 Site Reference ID/Investigator# 199 Pavia Italy 27100
    85 Site Reference ID/Investigator# 200 Rome Italy 00149
    86 Site Reference ID/Investigator# 196 Rome Italy 00161
    87 Site Reference ID/Investigator# 194 Rome Italy 00184
    88 Site Reference ID/Investigator# 193 Turin Italy 10149
    89 Site Reference ID/Investigator# 290 Zwolle Netherlands 8025 AB
    90 Site Reference ID/Investigator# 298 Chorzow Poland 41-500
    91 Site Reference ID/Investigator# 299 Warsaw Poland 01-201
    92 Site Reference ID/Investigator# 297 Wroclaw Poland 51-149
    93 Site Reference ID/Investigator# 185 Ponce Puerto Rico 00717-1563
    94 Site Reference ID/Investigator# 208 Ponce Puerto Rico 00731
    95 Site Reference ID/Investigator# 206 San Juan Puerto Rico 00936-5067
    96 Site Reference ID/Investigator# 186 Moscow Russian Federation 105275
    97 Site Reference ID/Investigator# 189 Moscow Russian Federation 105275
    98 Site Reference ID/Investigator# 188 St. Petersburg Russian Federation 190020
    99 Site Reference ID/Investigator# 5163 Singapore Singapore 308433
    100 Site Reference ID/Investigator# 221 A Coruna Spain 15006
    101 Site Reference ID/Investigator# 210 Alicante Spain 03010
    102 Site Reference ID/Investigator# 190 Barakaldo Spain 48903
    103 Site Reference ID/Investigator# 214 Barcelona Spain 08035
    104 Site Reference ID/Investigator# 216 Barcelona Spain 08041
    105 Site Reference ID/Investigator# 222 Barcelona Spain 08916
    106 Site Reference ID/Investigator# 224 Barcelona Spain 8036
    107 Site Reference ID/Investigator# 218 Barcelona Spain 8907
    108 Site Reference ID/Investigator# 292 Madrid Spain 28007
    109 Site Reference ID/Investigator# 205 Madrid Spain 28029
    110 Site Reference ID/Investigator# 191 Madrid Spain 28034
    111 Site Reference ID/Investigator# 219 Madrid Spain 28040
    112 Site Reference ID/Investigator# 209 Madrid Spain 28041
    113 Site Reference ID/Investigator# 223 Madrid Spain 28046
    114 Site Reference ID/Investigator# 213 Santander Spain 39008
    115 Site Reference ID/Investigator# 217 Santiago de Compostela Spain 15705
    116 Site Reference ID/Investigator# 220 Seville Spain 41013
    117 Site Reference ID/Investigator# 215 Valencia Spain 46009
    118 Site Reference ID/Investigator# 288 Basel Switzerland 4031
    119 Site Reference ID/Investigator# 289 Geneva 14 Switzerland 1211
    120 Site Reference ID/Investigator# 243 Lausanne Switzerland 1011
    121 Site Reference ID/Investigator# 254 St. Gallen Switzerland 9007
    122 Site Reference ID/Investigator# 241 Taipei City Taiwan 10016
    123 Site Reference ID/Investigator# 238 Birmingham United Kingdom B9 5SS
    124 Site Reference ID/Investigator# 232 Brighton United Kingdom BN2 1ES
    125 Site Reference ID/Investigator# 226 London United Kingdom N18 1QX
    126 Site Reference ID/Investigator# 231 London United Kingdom NW3 2QG
    127 Site Reference ID/Investigator# 227 London United Kingdom SW17 0QT
    128 Site Reference ID/Investigator# 228 London United Kingdom W2 1NY
    129 Site Reference ID/Investigator# 229 Manchester United Kingdom M8 5RB

    Sponsors and Collaborators

    • Abbott

    Investigators

    • Study Director: Daniel E Cohen, MD, Abbott

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Abbott
    ClinicalTrials.gov Identifier:
    NCT00262522
    Other Study ID Numbers:
    • M05-730
    • 2005-001430-32
    First Posted:
    Dec 7, 2005
    Last Update Posted:
    Feb 6, 2012
    Last Verified:
    Feb 1, 2012
    Keywords provided by Abbott
    Human Immunodeficiency Virus Infections
    Additional relevant MeSH terms:
    Virus Diseases
    Acquired Immunodeficiency Syndrome
    HIV Infections
    Immunologic Deficiency Syndromes
    Ritonavir
    Lopinavir
    Reverse Transcriptase Inhibitors

    Study Results

    Participant Flow

    Recruitment Details Subjects were enrolled at 131 sites in 19 countries.
    Pre-assignment Detail Of the 672 subjects randomized, 8 discontinued from the study prior to receiving study drug due to withdrawal of consent (3), acute illness (2), lost to follow-up (1), other (1), and required prohibited medication (1).
    Arm/Group Title LPV/r 800/200 mg QD Tablet LPV/r 800/200 mg QD SGC (Through Week 8) LPV/r 400/100 mg BID Tablet LPV/r 400/100 mg BID SGC (Through Week 8)
    Arm/Group Description lopinavir/ritonavir 800/200 mg once daily (QD) tablet lopinavir/ritonavir 800/200 mg once daily (QD) soft gel capsule (SGC) lopinavir/ritonavir 400/100 mg twice daily (BID) tablet lopinavir/ritonavir 400/100 mg twice daily (BID) soft gel capsule (SGC)
    Period Title: Study Start Through 8 Weeks
    STARTED 167 166 166 165
    COMPLETED 163 161 155 160
    NOT COMPLETED 4 5 11 5
    Period Title: Study Start Through 8 Weeks
    STARTED 333 0 331 0
    COMPLETED 284 0 276 0
    NOT COMPLETED 49 0 55 0
    Period Title: Study Start Through 8 Weeks
    STARTED 333 0 331 0
    COMPLETED 256 0 254 0
    NOT COMPLETED 77 0 77 0

    Baseline Characteristics

    Arm/Group Title LPV/r 800/200 mg QD Tablet LPV/r 800/200 mg QD SGC (Through Week 8) LPV/r 400/100 mg BID Tablet LPV/r 400/100 mg BID SGC (Through Week 8) Total
    Arm/Group Description lopinavir/ritonavir 800/200 mg once daily (QD) tablet lopinavir/ritonavir 800/200 mg once daily (QD) soft gel capsule (SGC) lopinavir/ritonavir 400/100 mg twice daily (BID) tablet lopinavir/ritonavir 400/100 mg twice daily (BID) soft gel capsule (SGC) Total of all reporting groups
    Overall Participants 167 166 166 165 664
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    38.7
    (9.80)
    38.2
    (9.63)
    38.3
    (9.69)
    39.5
    (10.31)
    38.7
    (9.85)
    Sex: Female, Male (Count of Participants)
    Female
    36
    21.6%
    31
    18.7%
    39
    23.5%
    38
    23%
    144
    21.7%
    Male
    131
    78.4%
    135
    81.3%
    127
    76.5%
    127
    77%
    520
    78.3%
    CD4+ T Cell Count (cells/mm3) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [cells/mm3]
    209.9
    (125.10)
    222.6
    (127.37)
    226.4
    (136.64)
    202.9
    (139.57)
    215.5
    (132.34)
    Plasma HIV-1 RNA Level (log10 copies/mL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [log10 copies/mL]
    4.92
    (0.64)
    4.94
    (0.67)
    5.04
    (0.68)
    5.06
    (0.64)
    4.99
    (0.66)

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Subjects With Adverse Events of Diarrhea During the First 8 Weeks
    Description
    Time Frame Week 8

    Outcome Measure Data

    Analysis Population Description
    All randomized subjects who received at least 1 dose of study drug.
    Arm/Group Title LPV/r 800/200 mg QD Tablet LPV/r 800/200 mg QD SGC (Through Week 8) LPV/r 400/100 mg BID Tablet LPV/r 400/100 mg BID SGC (Through Week 8)
    Arm/Group Description lopinavir/ritonavir 800/200 mg once daily (QD) tablet lopinavir/ritonavir 800/200 mg once daily (QD) soft gel capsule (SGC) lopinavir/ritonavir 400/100 mg twice daily (BID) tablet lopinavir/ritonavir 400/100 mg twice daily (BID) soft gel capsule (SGC)
    Measure Participants 167 166 166 165
    Number [Percentage of Subjects]
    49.1
    54.8
    44.6
    49.7
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection LPV/r 800/200 mg QD Tablet, LPV/r 800/200 mg QD SGC (Through Week 8), LPV/r 400/100 mg BID Tablet, LPV/r 400/100 mg BID SGC (Through Week 8)
    Comments Cochran-Mantel-Haenszel (CMH) test stratified by dosing regimen was used to assess the null hypothesis of no difference between the tablet and soft gel capsule (SGC). Sample size was 600 subjects (150 each in the 4 groups). Based on a projected 48% reporting treatment-emergent diarrhea in the QD arm and 32% in the BID arm within the SGC group, with a 12% reduction in the corresponding tablet groups, this sample size provided 80% power to determine a difference between the tablet and SGC.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value >0.100
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    2. Primary Outcome
    Title Percentage of Subjects With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Levels < 50 Copies/mL at Week 48
    Description
    Time Frame Week 48

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat noncompleters considered failures (ITT, NC=F); all randomized subjects who received at least 1 dose of study drug.
    Arm/Group Title LPV/r 800/200 mg QD Tablet LPV/r 800/200 mg QD SGC (Through Week 8) LPV/r 400/100 mg BID Tablet LPV/r 400/100 mg BID SGC (Through Week 8)
    Arm/Group Description lopinavir/ritonavir 800/200 mg once daily (QD) tablet lopinavir/ritonavir 800/200 mg once daily (QD) soft gel capsule (SGC) lopinavir/ritonavir 400/100 mg twice daily (BID) tablet lopinavir/ritonavir 400/100 mg twice daily (BID) soft gel capsule (SGC)
    Measure Participants 333 0 331 0
    Number [Percentage of Subjects]
    77.2
    75.8
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection LPV/r 800/200 mg QD Tablet, LPV/r 400/100 mg BID Tablet
    Comments The null hypothesis was that the response rate for the once daily (QD) regimen was more than 12% lower than the response rate for the twice daily (BID) regimen. The planned sample size of 600 subjects (300 subjects in each of the QD and BID treatment regimens) provided over 90% power to reject the null hypothesis, i.e., to determine noninferiority based on the 12% margin.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments The 95% confidence interval for the difference in response rates (QD minus BID, based on the normal approximation to the binomial distribution) was used to assess noninferiority. The QD regimen was considered noninferior to the BID regimen if the lower limit of the confidence interval remained above -12%.
    Statistical Test of Hypothesis p-Value 0.715
    Comments
    Method normal approx. to the binomial distr.
    Comments
    Method of Estimation Estimation Parameter percentage of subjects responding
    Estimated Value 1.3
    Confidence Interval () 95%
    -5.1 to 7.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Percentage of Subjects With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Levels < 50 Copies/mL at Week 96
    Description
    Time Frame Week 96 (End of Study)

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat noncompleters considered failures (ITT, NC=F); all randomized subjects who received at least 1 dose of study drug.
    Arm/Group Title LPV/r 800/200 mg QD Tablet LPV/r 800/200 mg QD SGC (Through Week 8) LPV/r 400/100 mg BID Tablet LPV/r 400/100 mg BID SGC (Through Week 8)
    Arm/Group Description lopinavir/ritonavir 800/200 mg once daily (QD) tablet lopinavir/ritonavir 800/200 mg once daily (QD) soft gel capsule (SGC) lopinavir/ritonavir 400/100 mg twice daily (BID) tablet lopinavir/ritonavir 400/100 mg twice daily (BID) soft gel capsule (SGC)
    Measure Participants 333 0 331 0
    Number [Percentage of Subjects]
    64.9
    69.2
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection LPV/r 800/200 mg QD Tablet, LPV/r 400/100 mg BID Tablet
    Comments The null hypothesis was that the response rate for the once daily (QD) regimen was more than 12% lower than the response rate for the twice daily (BID) regimen. The planned sample size of 600 subjects (300 subjects in each of the QD and BID treatment regimens) provided over 90% power to reject the null hypothesis, i.e., to determine noninferiority based on the 12% margin.
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments The 95% confidence interval for the difference in response rates (QD minus BID, based on the normal approximation to the binomial distribution) was used to assess noninferiority. The QD regimen was considered noninferior to the BID regimen if the lower limit of the confidence interval remained above -12%.
    Statistical Test of Hypothesis p-Value 0.249
    Comments
    Method normal approx. to the binomial distr.
    Comments
    Method of Estimation Estimation Parameter percentage of subjects responding
    Estimated Value -4.3
    Confidence Interval () 95%
    -11.5 to 2.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Mean Change From Baseline to Week 96 in CD4+ T Cell Counts
    Description
    Time Frame Week 96 (End of Study)

    Outcome Measure Data

    Analysis Population Description
    All randomized subjects who received at least 1 dose of study drug and who had CD4+ T cell counts available at both the Baseline Visit and Week 96.
    Arm/Group Title LPV/r 800/200 mg QD Tablet LPV/r 800/200 mg QD SGC (Through Week 8) LPV/r 400/100 mg BID Tablet LPV/r 400/100 mg BID SGC (Through Week 8)
    Arm/Group Description lopinavir/ritonavir 800/200 mg once daily (QD) tablet lopinavir/ritonavir 800/200 mg once daily (QD) soft gel capsule (SGC) lopinavir/ritonavir 400/100 mg twice daily (BID) tablet lopinavir/ritonavir 400/100 mg twice daily (BID) soft gel capsule (SGC)
    Measure Participants 333 0 331 0
    Mean (Standard Error) [cells/microliter]
    238.4
    (10.02)
    254.0
    (10.00)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection LPV/r 800/200 mg QD Tablet, LPV/r 400/100 mg BID Tablet
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.269
    Comments
    Method ANOVA
    Comments

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title LPV/r 800/200 mg QD Tablet LPV/r 400/100 mg BID Tablet
    Arm/Group Description lopinavir/ritonavir 800/200 mg once daily (QD) tablet lopinavir/ritonavir 400/100 mg twice daily (BID) tablet
    All Cause Mortality
    LPV/r 800/200 mg QD Tablet LPV/r 400/100 mg BID Tablet
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    LPV/r 800/200 mg QD Tablet LPV/r 400/100 mg BID Tablet
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 37/333 (11.1%) 50/331 (15.1%)
    Blood and lymphatic system disorders
    Anemia 1/333 (0.3%) 0/331 (0%)
    Febrile neutropenia 0/333 (0%) 1/331 (0.3%)
    Lymphadenopathy 0/333 (0%) 1/331 (0.3%)
    Lymphatic disorder 1/333 (0.3%) 0/331 (0%)
    Neutropenia 0/333 (0%) 2/331 (0.6%)
    Cardiac disorders
    Atrioventricular block 0/333 (0%) 1/331 (0.3%)
    Cardiac failure 0/333 (0%) 1/331 (0.3%)
    Palpitations 1/333 (0.3%) 0/331 (0%)
    Endocrine disorders
    Cushing's syndrome 1/333 (0.3%) 0/331 (0%)
    Hypothyroidism 1/333 (0.3%) 0/331 (0%)
    Gastrointestinal disorders
    Abdominal discomfort 0/333 (0%) 1/331 (0.3%)
    Abdominal pain 0/333 (0%) 2/331 (0.6%)
    Appendicitis perforated 1/333 (0.3%) 0/331 (0%)
    Diarrhea 0/333 (0%) 1/331 (0.3%)
    Enterocolitis 1/333 (0.3%) 1/331 (0.3%)
    Food poisoning 0/333 (0%) 1/331 (0.3%)
    Gastrointestinal obstruction 0/333 (0%) 1/331 (0.3%)
    Inguinal hernia 1/333 (0.3%) 0/331 (0%)
    Intestinal obstruction 0/333 (0%) 1/331 (0.3%)
    Nausea 0/333 (0%) 2/331 (0.6%)
    Esophagitis 1/333 (0.3%) 0/331 (0%)
    Peritonitis 1/333 (0.3%) 0/331 (0%)
    Small intestinal obstruction 1/333 (0.3%) 0/331 (0%)
    Umbilical hernia 0/333 (0%) 1/331 (0.3%)
    General disorders
    Chills 0/333 (0%) 1/331 (0.3%)
    Death 0/333 (0%) 2/331 (0.6%)
    Malaise 0/333 (0%) 1/331 (0.3%)
    Pyrexia 2/333 (0.6%) 6/331 (1.8%)
    Hepatobiliary disorders
    Cholangitis 0/333 (0%) 1/331 (0.3%)
    Cholelithiasis 0/333 (0%) 1/331 (0.3%)
    Cytolytic hepatitis 1/333 (0.3%) 0/331 (0%)
    Immune system disorders
    Hypersensitivity 1/333 (0.3%) 0/331 (0%)
    Immune reconstitution syndrome 0/333 (0%) 1/331 (0.3%)
    Infections and infestations
    Abdominal infection 1/333 (0.3%) 0/331 (0%)
    Anogenital warts 0/333 (0%) 1/331 (0.3%)
    Appendicitis 1/333 (0.3%) 1/331 (0.3%)
    Bronchopneumonia 0/333 (0%) 1/331 (0.3%)
    Cellulitis 1/333 (0.3%) 1/331 (0.3%)
    Clostridium difficile colitis 0/333 (0%) 1/331 (0.3%)
    Gangrene 0/333 (0%) 1/331 (0.3%)
    Gastroenteritis 1/333 (0.3%) 1/331 (0.3%)
    Infected skin ulcer 0/333 (0%) 1/331 (0.3%)
    Influenza 1/333 (0.3%) 0/331 (0%)
    Lower respiratory tract infection 1/333 (0.3%) 0/331 (0%)
    Malaria 0/333 (0%) 1/331 (0.3%)
    Meningitis 1/333 (0.3%) 0/331 (0%)
    Meningitis tuberculous 1/333 (0.3%) 0/331 (0%)
    Perichondritis 1/333 (0.3%) 0/331 (0%)
    Pneumonia 2/333 (0.6%) 1/331 (0.3%)
    Pneumonia bacterial 0/333 (0%) 1/331 (0.3%)
    Pyelonephritis 0/333 (0%) 2/331 (0.6%)
    Rectal abscess 1/333 (0.3%) 0/331 (0%)
    Respiratory tract infection 2/333 (0.6%) 1/331 (0.3%)
    Sepsis 0/333 (0%) 1/331 (0.3%)
    Sinusitis 1/333 (0.3%) 0/331 (0%)
    Syphilis 1/333 (0.3%) 2/331 (0.6%)
    Typhoid fever 0/333 (0%) 1/331 (0.3%)
    Viral infection 0/333 (0%) 1/331 (0.3%)
    Injury, poisoning and procedural complications
    Anastomotic ulcer 0/333 (0%) 1/331 (0.3%)
    Back injury 0/333 (0%) 1/331 (0.3%)
    Facial bones fracture 1/333 (0.3%) 0/331 (0%)
    Meniscus lesion 0/333 (0%) 1/331 (0.3%)
    Traumatic fracture 1/333 (0.3%) 0/331 (0%)
    Investigations
    Blood urine present 0/333 (0%) 1/331 (0.3%)
    Creatinine renal clearance decreased 1/333 (0.3%) 0/331 (0%)
    Neutrophil count decreased 1/333 (0.3%) 0/331 (0%)
    Metabolism and nutrition disorders
    Anorexia 1/333 (0.3%) 0/331 (0%)
    Dehydration 1/333 (0.3%) 2/331 (0.6%)
    Hypokalemia 0/333 (0%) 1/331 (0.3%)
    Musculoskeletal and connective tissue disorders
    Intervertebral disc degeneration 1/333 (0.3%) 0/331 (0%)
    Myalgia 0/333 (0%) 1/331 (0.3%)
    Rhabdomyolysis 0/333 (0%) 2/331 (0.6%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Hepatic adenoma 0/333 (0%) 1/331 (0.3%)
    Non-Hodgkin's lymphoma 1/333 (0.3%) 0/331 (0%)
    Non-Hodgkin's lymphoma recurrent 1/333 (0.3%) 0/331 (0%)
    Squamous cell carcinoma 0/333 (0%) 1/331 (0.3%)
    Uterine leiomyoma 0/333 (0%) 1/331 (0.3%)
    Nervous system disorders
    Convulsion 1/333 (0.3%) 0/331 (0%)
    Dizziness 1/333 (0.3%) 1/331 (0.3%)
    Grand mal convulsion 0/333 (0%) 1/331 (0.3%)
    Loss of consciousness 0/333 (0%) 1/331 (0.3%)
    Reversible ischemic neurological deficit 0/333 (0%) 1/331 (0.3%)
    Subarachnoid hemorrhage 0/333 (0%) 1/331 (0.3%)
    Panic attack 0/333 (0%) 1/331 (0.3%)
    Psychotic disorder 0/333 (0%) 1/331 (0.3%)
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous 0/333 (0%) 2/331 (0.6%)
    Blighted ovum 1/333 (0.3%) 0/331 (0%)
    Premature separation of placenta 0/333 (0%) 1/331 (0.3%)
    Depression 1/333 (0.3%) 1/331 (0.3%)
    Psychiatric disorders
    Drug dependence 1/333 (0.3%) 0/331 (0%)
    Suicide attempt 0/333 (0%) 1/331 (0.3%)
    Renal and urinary disorders
    Calculus ureteric 1/333 (0.3%) 0/331 (0%)
    Hydronephrosis 1/333 (0.3%) 0/331 (0%)
    Renal failure 0/333 (0%) 1/331 (0.3%)
    Renal failure acute 1/333 (0.3%) 0/331 (0%)
    Respiratory, thoracic and mediastinal disorders
    Asthma 1/333 (0.3%) 0/331 (0%)
    Dyspnea 1/333 (0.3%) 0/331 (0%)
    Pleuritic pain 1/333 (0.3%) 0/331 (0%)
    Pulmonary embolism 1/333 (0.3%) 1/331 (0.3%)
    Sinus congestion 1/333 (0.3%) 0/331 (0%)
    Skin and subcutaneous tissue disorders
    Dermatitis allergic 0/333 (0%) 1/331 (0.3%)
    Erythema multiform 1/333 (0.3%) 0/331 (0%)
    Granuloma skin 1/333 (0.3%) 0/331 (0%)
    Hyperhidrosis 0/333 (0%) 1/331 (0.3%)
    Idiopathic capillaritis 0/333 (0%) 1/331 (0.3%)
    Surgical and medical procedures
    Abortion induced 2/333 (0.6%) 4/331 (1.2%)
    Vascular disorders
    Deep vein thrombosis 0/333 (0%) 1/331 (0.3%)
    Hypotension 0/333 (0%) 1/331 (0.3%)
    Jugular vein thrombosis 0/333 (0%) 1/331 (0.3%)
    Subclavian vein thrombosis 0/333 (0%) 1/331 (0.3%)
    Other (Not Including Serious) Adverse Events
    LPV/r 800/200 mg QD Tablet LPV/r 400/100 mg BID Tablet
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 292/333 (87.7%) 287/331 (86.7%)
    Gastrointestinal disorders
    Abdominal pain 26/333 (7.8%) 28/331 (8.5%)
    Abdominal pain upper 22/333 (6.6%) 16/331 (4.8%)
    Diarrhea 210/333 (63.1%) 197/331 (59.5%)
    Dyspepsia 21/333 (6.3%) 9/331 (2.7%)
    Flatulence 17/333 (5.1%) 27/331 (8.2%)
    Nausea 105/333 (31.5%) 84/331 (25.4%)
    Vomiting 46/333 (13.8%) 46/331 (13.9%)
    General disorders
    Asthenia 25/333 (7.5%) 18/331 (5.4%)
    Fatigue 45/333 (13.5%) 37/331 (11.2%)
    Influenza like illness 9/333 (2.7%) 19/331 (5.7%)
    Pyrexia 28/333 (8.4%) 29/331 (8.8%)
    Infections and infestations
    Bronchitis 29/333 (8.7%) 26/331 (7.9%)
    Gastroenteritis 9/333 (2.7%) 19/331 (5.7%)
    Influenza 28/333 (8.4%) 24/331 (7.3%)
    Nasopharyngitis 58/333 (17.4%) 61/331 (18.4%)
    Sinusitis 19/333 (5.7%) 17/331 (5.1%)
    Upper respiratory tract infection 29/333 (8.7%) 25/331 (7.6%)
    Metabolism and nutrition disorders
    Hypercholesterolemia 18/333 (5.4%) 19/331 (5.7%)
    Hypertriglyceridemia 18/333 (5.4%) 23/331 (6.9%)
    Musculoskeletal and connective tissue disorders
    Back pain 21/333 (6.3%) 15/331 (4.5%)
    Nervous system disorders
    Dizziness 16/333 (4.8%) 17/331 (5.1%)
    Headache 44/333 (13.2%) 33/331 (10%)
    Psychiatric disorders
    Anxiety 13/333 (3.9%) 18/331 (5.4%)
    Depression 18/333 (5.4%) 19/331 (5.7%)
    Insomnia 24/333 (7.2%) 27/331 (8.2%)
    Respiratory, thoracic and mediastinal disorders
    Cough 32/333 (9.6%) 36/331 (10.9%)
    Pharyngolaryngeal pain 14/333 (4.2%) 21/331 (6.3%)
    Skin and subcutaneous tissue disorders
    Pruritus 18/333 (5.4%) 14/331 (4.2%)
    Rash 27/333 (8.1%) 32/331 (9.7%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Provide ABBOTT at least thirty (30) days prior to submission for review, ABBOTT shall return comments within thirty (30) days of receipt of draft. Proposed draft shall be delayed an additional sixty (60) days in addition to the Review Period

    Results Point of Contact

    Name/Title Global Medical Services
    Organization Abbott
    Phone 800-633-9110
    Email
    Responsible Party:
    Abbott
    ClinicalTrials.gov Identifier:
    NCT00262522
    Other Study ID Numbers:
    • M05-730
    • 2005-001430-32
    First Posted:
    Dec 7, 2005
    Last Update Posted:
    Feb 6, 2012
    Last Verified:
    Feb 1, 2012