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 copies/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 ]
  Hide Outcome Measure 2

Measure Type Primary
Measure Title Percentage of Subjects With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Levels < 50 Copies/mL at Week 48
Measure Description No text entered.
Time Frame Week 48  
Safety Issue No  

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.
Intent-to-treat noncompleters considered failures (ITT, NC=F); all randomized subjects who received at least 1 dose of study drug.

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)

Measured Values
    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)  
Number of Participants Analyzed  
[units: participants]
  333     0     331     0  
Percentage of Subjects With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Levels < 50 Copies/mL at Week 48  
[units: Percentage of Subjects]
  77.2         75.8      


Statistical Analysis 1 for Percentage of Subjects With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Levels < 50 Copies/mL at Week 48
Groups [1] LPV/r 800/200 mg QD Tablet vs. LPV/r 400/100 mg BID Tablet
Non-Inferiority/Equivalence Test [2] Yes
Method [3] normal approx. to the binomial distr.
P Value [4] 0.715
percentage of subjects responding [5] 1.3
95% Confidence Interval ( -5.1 to 7.8 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  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%.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.



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


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
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
No text entered.  


Results Point of Contact:  
Name/Title: Global Medical Services
Organization: Abbott
phone: 800-633-9110


No publications provided


Responsible Party: Abbott
ClinicalTrials.gov Identifier: NCT00262522     History of Changes
Other Study ID Numbers: M05-730, 2005-001430-32
Study First Received: December 5, 2005
Results First Received: July 9, 2009
Last Updated: February 3, 2012
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
Belgium: Ministry of Social Affairs, Public Health and the Environment
Canada: Health Canada
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Greece: National Organization of Medicines
Ireland: Irish Medicines Board
Italy: The Italian Medicines Agency
Netherlands: Medicines Evaluation Board (MEB)
Poland: Ministry of Health
Russia: Ministry of Health of the Russian Federation
Singapore: Health Sciences Authority
Spain: Spanish Agency of Medicines
Switzerland: Swissmedic
Taiwan : Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration