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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Abbott
ClinicalTrials.gov Identifier:
NCT00262522
First received: December 5, 2005
Last updated: February 3, 2012
Last verified: February 2012
Results First Received: July 9, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Human Immunodeficiency Virus Infections
Intervention: Drug: lopinavir/ritonavir (LPV/r) (tablet or capsule) with nucleoside reverse transcriptase inhibitors (NRTIs)

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Subjects were enrolled at 131 sites in 19 countries.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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).

Reporting Groups
  Description
LPV/r 800/200 mg QD Tablet lopinavir/ritonavir 800/200 mg once daily (QD) tablet
LPV/r 800/200 mg QD SGC (Through Week 8) lopinavir/ritonavir 800/200 mg once daily (QD) soft gel capsule (SGC)
LPV/r 400/100 mg BID Tablet lopinavir/ritonavir 400/100 mg twice daily (BID) tablet
LPV/r 400/100 mg BID SGC (Through Week 8) lopinavir/ritonavir 400/100 mg twice daily (BID) soft gel capsule (SGC)

Participant Flow for 3 periods

Period 1:   Study Start Through 8 Weeks
    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)  
STARTED     167     166     166     165  
COMPLETED     163     161     155     160  
NOT COMPLETED     4     5     11     5  
Adverse Event                 1                 2                 3                 1  
Withdrawal by Subject                 1                 1                 3                 0  
Lost to Follow-up                 1                 2                 3                 2  
Noncompliance                 0                 0                 2                 2  
Death                 1                 0                 0                 0  

Period 2:   Study Start Through 48 Weeks
    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)  
STARTED     333 [1]   0 [2]   331 [1]   0 [3]
COMPLETED     284     0     276     0  
NOT COMPLETED     49     0     55     0  
Adverse Event                 16                 0                 10                 0  
Withdrawal by Subject                 10                 0                 11                 0  
Lost to Follow-up                 8                 0                 14                 0  
Noncompliance                 3                 0                 8                 0  
Death                 2                 0                 1                 0  
Virologic failure                 2                 0                 4                 0  
Relocated, Needed to take twice daily                 8                 0                 7                 0  
[1] Number of subjects who started the study, not the number who completed the first 8 weeks.
[2] After Week 8, these subjects received the tablet formulation once daily through the end of study.
[3] After Week 8, these subjects received the tablet formulation twice daily through the end of study.

Period 3:   Study Start Through 96 Weeks
    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)  
STARTED     333 [1]   0 [2]   331 [1]   0 [3]
COMPLETED     256     0     254     0  
NOT COMPLETED     77     0     77     0  
Adverse Event                 20                 0                 16                 0  
Withdrawal by Subject                 15                 0                 13                 0  
Lost to Follow-up                 19                 0                 18                 0  
Noncompliance                 6                 0                 11                 0  
Death                 2                 0                 2                 0  
Virologic failure                 5                 0                 8                 0  
Relocated, Needed to take twice daily                 10                 0                 9                 0  
[1] Number of subjects who started the study, not the number who completed the first 48 weeks.
[2] After Week 8, these subjects received the tablet formulation once daily through the end of study.
[3] After Week 8, these subjects received the tablet formulation twice daily through the end of study.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
LPV/r 800/200 mg QD Tablet lopinavir/ritonavir 800/200 mg once daily (QD) tablet
LPV/r 800/200 mg QD SGC (Through Week 8) lopinavir/ritonavir 800/200 mg once daily (QD) soft gel capsule (SGC)
LPV/r 400/100 mg BID Tablet lopinavir/ritonavir 400/100 mg twice daily (BID) tablet
LPV/r 400/100 mg BID SGC (Through Week 8) lopinavir/ritonavir 400/100 mg twice daily (BID) soft gel capsule (SGC)
Total Total of all reporting groups

Baseline Measures
    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  
Number of Participants  
[units: participants]
  167     166     166     165     664  
Age  
[units: years]
Mean ± Standard Deviation
  38.7  ± 9.80     38.2  ± 9.63     38.3  ± 9.69     39.5  ± 10.31     38.7  ± 9.85  
Gender  
[units: participants]
         
Female     36     31     39     38     144  
Male     131     135     127     127     520  
CD4+ T Cell Count [1]
[units: cells/mm3]
Mean ± Standard Deviation
  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  
[units: log10┬ácopies/mL]
Mean ± Standard Deviation
  4.92  ± 0.64     4.94  ± 0.67     5.04  ± 0.68     5.06  ± 0.64     4.99  ± 0.66  
[1] For once daily (QD) soft gel capsule (SGC), N=165.



  Outcome Measures
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1.  Primary:   Percentage of Subjects With Adverse Events of Diarrhea During the First 8 Weeks   [ Time Frame: Week 8 ]

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

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

4.  Secondary:   Mean Change From Baseline to Week 96 in CD4+ T Cell Counts   [ Time Frame: Week 96 (End of Study) ]


  Serious Adverse Events


  Other Adverse Events
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Time Frame No text entered.
Additional Description No text entered.

Frequency Threshold
Threshold above which other adverse events are reported   4.9%  

Reporting Groups
  Description
LPV/r 800/200 mg QD Tablet lopinavir/ritonavir 800/200 mg once daily (QD) tablet
LPV/r 400/100 mg BID Tablet lopinavir/ritonavir 400/100 mg twice daily (BID) tablet

Other Adverse Events
    LPV/r 800/200 mg QD Tablet     LPV/r 400/100 mg BID Tablet  
Total, other (not including serious) adverse events      
# participants affected / at risk     292/333     287/331  
Gastrointestinal disorders      
Abdominal pain † 1    
# participants affected / at risk     26/333 (7.81%)     28/331 (8.46%)  
Abdominal pain upper † 1    
# participants affected / at risk     22/333 (6.61%)     16/331 (4.83%)  
Diarrhea † 1    
# participants affected / at risk     210/333 (63.06%)     197/331 (59.52%)  
Dyspepsia † 1    
# participants affected / at risk     21/333 (6.31%)     9/331 (2.72%)  
Flatulence † 1    
# participants affected / at risk     17/333 (5.11%)     27/331 (8.16%)  
Nausea † 1    
# participants affected / at risk     105/333 (31.53%)     84/331 (25.38%)  
Vomiting † 1    
# participants affected / at risk     46/333 (13.81%)     46/331 (13.90%)  
General disorders      
Asthenia † 1    
# participants affected / at risk     25/333 (7.51%)     18/331 (5.44%)  
Fatigue † 1    
# participants affected / at risk     45/333 (13.51%)     37/331 (11.18%)  
Influenza like illness † 1    
# participants affected / at risk     9/333 (2.70%)     19/331 (5.74%)  
Pyrexia † 1    
# participants affected / at risk     28/333 (8.41%)     29/331 (8.76%)  
Infections and infestations      
Bronchitis † 1    
# participants affected / at risk     29/333 (8.71%)     26/331 (7.85%)  
Gastroenteritis † 1    
# participants affected / at risk     9/333 (2.70%)     19/331 (5.74%)  
Influenza † 1    
# participants affected / at risk     28/333 (8.41%)     24/331 (7.25%)  
Nasopharyngitis † 1    
# participants affected / at risk     58/333 (17.42%)     61/331 (18.43%)  
Sinusitis † 1    
# participants affected / at risk     19/333 (5.71%)     17/331 (5.14%)  
Upper respiratory tract infection † 1    
# participants affected / at risk     29/333 (8.71%)     25/331 (7.55%)  
Metabolism and nutrition disorders      
Hypercholesterolemia † 1    
# participants affected / at risk     18/333 (5.41%)     19/331 (5.74%)  
Hypertriglyceridemia † 1    
# participants affected / at risk     18/333 (5.41%)     23/331 (6.95%)  
Musculoskeletal and connective tissue disorders      
Back pain † 1    
# participants affected / at risk     21/333 (6.31%)     15/331 (4.53%)  
Nervous system disorders      
Dizziness † 1    
# participants affected / at risk     16/333 (4.80%)     17/331 (5.14%)  
Headache † 1    
# participants affected / at risk     44/333 (13.21%)     33/331 (9.97%)  
Psychiatric disorders      
Anxiety † 1    
# participants affected / at risk     13/333 (3.90%)     18/331 (5.44%)  
Depression † 1    
# participants affected / at risk     18/333 (5.41%)     19/331 (5.74%)  
Insomnia † 1    
# participants affected / at risk     24/333 (7.21%)     27/331 (8.16%)  
Respiratory, thoracic and mediastinal disorders      
Cough † 1    
# participants affected / at risk     32/333 (9.61%)     36/331 (10.88%)  
Pharyngolaryngeal pain † 1    
# participants affected / at risk     14/333 (4.20%)     21/331 (6.34%)  
Skin and subcutaneous tissue disorders      
Pruritus † 1    
# participants affected / at risk     18/333 (5.41%)     14/331 (4.23%)  
Rash † 1    
# participants affected / at risk     27/333 (8.11%)     32/331 (9.67%)  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 11.0



  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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