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Pharmacokinetics of Lopinavir/Ritonavir at Three Different Doses. (ENCORE3)

This study has been completed.
Sponsor:
Information provided by:
Kirby Institute
ClinicalTrials.gov Identifier:
NCT00985543
First received: September 25, 2009
Last updated: March 2, 2011
Last verified: March 2011
Results First Received: February 4, 2011  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Pharmacokinetics Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Acquired Immunodeficiency Syndrome
Intervention: Drug: lopinavir/ritonavir

  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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
All Study Participants All participants were given three sequential doses of lopinavir/ritonavir: lopinavir/ritonavir 400/100mg twice daily (2 heat-stable 200/50mg tablets BID), lopinavir/ritonavir 200/150mg twice daily (1 heat-stable 200/50mg tablet BID plus 1 ritonavir 100mg capsule BID), lopinavir/ritonavir 200/50mg twice daily (1 heat-stable 200/50mg tablet BID). Each dosing phase lasted for 7 days and each phase was separated by a 7-day wash-out period. Pharmacokinetic evaluations were made over a 12-hour interval at the end of each dosing phase.

Participant Flow:   Overall Study
    All Study Participants  
STARTED     22  
COMPLETED     22  
NOT COMPLETED     0  



  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
All Study Participants All participants were given three sequential doses of lopinavir/ritonavir: lopinavir/ritonavir 400/100mg twice daily (2 heat-stable 200/50mg tablets BID), lopinavir/ritonavir 200/150mg twice daily (1 heat-stable 200/50mg tablet BID plus 1 ritonavir 100mg capsule BID), lopinavir/ritonavir 200/50mg twice daily (1 heat-stable 200/50mg tablet BID). Each dosing phase lasted for 7 days and each phase was separated by a 7-day wash-out period. Pharmacokinetic evaluations were made over a 12-hour interval at the end of each dosing phase.

Baseline Measures
    All Study Participants  
Number of Participants  
[units: participants]
  22  
Age  
[units: participants]
 
<=18 years     0  
Between 18 and 65 years     22  
>=65 years     0  
Age  
[units: years]
Mean ± Standard Deviation
  36  ± 9.49  
Gender  
[units: participants]
 
Female     8  
Male     14  
Region of Enrollment  
[units: participants]
 
United Kingdom     22  



  Outcome Measures
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1.  Primary:   Plasma Lopinavir/Ritonavir Concentrations as Measured by the Area Under the Curve (AUC 0-12h).   [ Time Frame: at the end of each 7-day dosing phase ]

Measure Type Primary
Measure Title Plasma Lopinavir/Ritonavir Concentrations as Measured by the Area Under the Curve (AUC 0-12h).
Measure Description Pharmacokinetics of plasma lopinavir/ritonavir over a 12-hour dosing interval following administration of lopinavir/ritonavir 400/100mg, 200/150mg and 200/50mg twice daily.
Time Frame at the end of each 7-day dosing phase  
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.
22 participants completed the three sequential dosing phases and pharmacokinetic evaluations as per protocol. The same 22 participants are in the analysis population for each lopinavir/ritonavir dose (arm).

Reporting Groups
  Description
LPV/r 400/100 mg Lopinavir/ritonavir 400/100 mg twice daily (2 heat-stable 200/50 mg tablets twice daily (BID))
LPV/r 200/150 mg Lopinavir/ritonavir 200/150 mg twice daily (1 heat-stable 200/50 mg tablet BID plus 1 ritonavir 100 mg capsule BID)
LPV/r 200/50 mg Lopinavir/ritonavir 200/50 mg twice daily (1 heat-stable 200/50 mg tablet BID)

Measured Values
    LPV/r 400/100 mg     LPV/r 200/150 mg     LPV/r 200/50 mg  
Number of Participants Analyzed  
[units: participants]
  22     22     22  
Plasma Lopinavir/Ritonavir Concentrations as Measured by the Area Under the Curve (AUC 0-12h).  
[units: ng.h/mL]
Geometric Mean ( 90% Confidence Interval )
  99599  
  ( 87180 to 113787 )  
  73603  
  ( 65121 to 83191 )  
  45146  
  ( 39251 to 51927 )  


Statistical Analysis 1 for Plasma Lopinavir/Ritonavir Concentrations as Measured by the Area Under the Curve (AUC 0-12h).
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Method [3] maximum likelihood regression
P Value [4] <0.05
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Dosing regimens lopinavir/ritonavir 200/150mg BID (Phase 2) and lopinavir/ritonavir 200/50mg BID (Phase 3) will be considered equivalent to lopinavir/ritonavir 400/100mg BID (Phase 1) if the 90% confidence interval (CI) for the mean AUC0–12h ratio and maximum concentration (Cmax) ratio lie between 0.80 and 1.25.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Results are considered statistically significant at p<0.05 or when 90% confidence intervals do not cross the value 1. No adjustments are made for multiple comparisons.
[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.



2.  Secondary:   Adverse Events   [ Time Frame: Up to 11 weeks from screening to final study visit ]

Measure Type Secondary
Measure Title Adverse Events
Measure Description Number of reported adverse events, severity of adverse events and relationship to study drug was assessed by questions, physical examination and laboratory parameters. Adverse event data was used to assess the safety and tolerability of low lopinavir/ritonavir doses.
Time Frame Up to 11 weeks from screening to final study visit  
Safety Issue Yes  

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.
22 participants completed the three sequential dosing phases and pharmacokinetic evaluations as per protocol. The same 22 participants are in the analysis population for each lopinavir/ritonavir dose (arm).

Reporting Groups
  Description
LPV/r 400/100 mg Lopinavir/ritonavir 400/100 mg twice daily (2 heat-stable 200/50 mg tablets twice daily (BID))
LPV/r 200/150 mg Lopinavir/ritonavir 200/150 mg twice daily (1 heat-stable 200/50 mg tablet BID plus 1 ritonavir 100 mg capsule BID)
LPV/r 200/50 mg Lopinavir/ritonavir 200/50 mg twice daily (1 heat-stable 200/50 mg tablet BID)

Measured Values
    LPV/r 400/100 mg     LPV/r 200/150 mg     LPV/r 200/50 mg  
Number of Participants Analyzed  
[units: participants]
  22     22     22  
Adverse Events  
[units: number of adverse events]
  27     2     4  

No statistical analysis provided for Adverse Events




  Serious Adverse Events


  Other Adverse Events


  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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  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.


Results Point of Contact:  
Name/Title: Dr Marta Boffito
Organization: St Stephens Centre, Chelsea and Westminster Hospital
phone: +44 2088 466 507
e-mail: marta.boffito@chelwest.nhs.uk


No publications provided by Kirby Institute

Publications automatically indexed to this study:

Responsible Party: Marta Boffito, Chelsea and Westminster Hospital
ClinicalTrials.gov Identifier: NCT00985543     History of Changes
Other Study ID Numbers: NCHECR-ENCORE3
Study First Received: September 25, 2009
Results First Received: February 4, 2011
Last Updated: March 2, 2011
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee