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
  Purpose

The purpose of this study is to assess the pharmacokinetics of plasma lopinavir/ritonavir over a 12-hour dosing interval, following administration to male and female HIV−negative healthy volunteers of:

  1. Lopinavir/ritonavir 400/100 mg twice daily
  2. Lopinavir/ritonavir 200/150 mg twice daily
  3. Lopinavir/ritonavir 200/50 mg twice daily

Condition Intervention Phase
Acquired Immunodeficiency Syndrome
Drug: lopinavir/ritonavir
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pharmacokinetics of Plasma Lopinavir/Ritonavir Over a 12 Hour Dosing Interval Following Administration of 400/100, 200/150, and 200/50 mg Twice Daily to HIV-negative Healthy Volunteers

Resource links provided by NLM:


Further study details as provided by Kirby Institute:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Adverse Events [ Time Frame: Up to 11 weeks from screening to final study visit ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 22
Study Start Date: October 2009
Study Completion Date: January 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: LPV/r 400/100 mg
Lopinavir/ritonavir 400/100 mg twice daily (2 heat-stable 200/50 mg tablets twice daily (BID))
Drug: lopinavir/ritonavir
Each participant received three sequential doses of lopinavir/ritonavir: 400/100 mg twice daily (2 heat-stable 200/50 mg tablets BID), 200/150 mg twice daily (1 heat-stable 200/50 mg tablet BID plus 1 ritonavir 100 mg capsule BID), and 200/50 mg twice daily (1 heat-stable 200/50 mg tablet BID). Each dosing phase lasted for 7 days and each phase was separated by a 7-day wash-out period.
Other Names:
  • Meltrex
  • Ritonavir
Experimental: 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)
Drug: lopinavir/ritonavir
Each participant received three sequential doses of lopinavir/ritonavir: 400/100 mg twice daily (2 heat-stable 200/50 mg tablets BID), 200/150 mg twice daily (1 heat-stable 200/50 mg tablet BID plus 1 ritonavir 100 mg capsule BID), and 200/50 mg twice daily (1 heat-stable 200/50 mg tablet BID). Each dosing phase lasted for 7 days and each phase was separated by a 7-day wash-out period.
Other Names:
  • Meltrex
  • Ritonavir
Experimental: LPV/r 200/50 mg
Lopinavir/ritonavir 200/50 mg twice daily (1 heat-stable 200/50 mg tablet BID)
Drug: lopinavir/ritonavir
Each participant received three sequential doses of lopinavir/ritonavir: 400/100 mg twice daily (2 heat-stable 200/50 mg tablets BID), 200/150 mg twice daily (1 heat-stable 200/50 mg tablet BID plus 1 ritonavir 100 mg capsule BID), and 200/50 mg twice daily (1 heat-stable 200/50 mg tablet BID). Each dosing phase lasted for 7 days and each phase was separated by a 7-day wash-out period.
Other Names:
  • Meltrex
  • Ritonavir

Detailed Description:

Data during the development of lopinavir/ritonavir showed that lower drug doses had similar efficacy to the standard dose of 400/100mg twice daily. Lower drug doses are also associated with limited toxicity and cost.

The purpose of this study is to assess the pharmacokinetics of plasma lopinavir/ritonavir following administration to male and female HIV−negative volunteers of 400/100mg, 200/150mg and 200/50mg lopinavir/ritonavir twice daily. Each dosing phase will last for 7 days and each phase will be separated by a 7-day wash-out period. Pharmacokinetic evaluations will be made over a 12-hour interval at the end of each dosing phase.

Healthy subjects as determined by their medical history and physical examinations will be eligible to participate in the study. HIV−positive subjects will not be recruited as there is a risk that HIV−resistant mutations will be selected by an experimentally reduced dose of lopinavir/ritonavir. There is no reason to presume that there is any meaningful difference in the metabolic processing of lopinavir/ritonavir between HIV−infected and HIV−uninfected people.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subjects must meet all of the following inclusion criteria within 28 days prior to the baseline visit:

    1. The ability to understand and sign a written informed consent form, prior to participation in any screening procedures and must be willing to comply with all study requirements
    2. Male or non-pregnant, non-lactating females
    3. Between 18 to 65 years, inclusive
    4. Body Mass Index (BMI) of 18 to 35 kg/m2, inclusive.
    5. Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for a period of at least 1 month after the study

Exclusion Criteria:

  1. Any significant acute or chronic medical illness
  2. Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations
  3. Positive blood screen for hepatitis B core and/or C antibodies and/or hepatitis B surface antigen
  4. Positive blood screen for HIV-1 and/or 2 antibodies
  5. Current or recent (within 3 months) gastrointestinal disease
  6. Clinically relevant alcohol or drug use (positive urine drug screen) or history of alcohol or drug use considered by the Investigator to be sufficient to hinder compliance with treatment, follow-up procedures or evaluation of adverse events. Smoking is permitted, but tobacco intake should remain consistent throughout the study
  7. Exposure to any investigational drug or placebo within 3 months of first dose of study drug
  8. Consumption of grapefruit, or Seville oranges or any grapefruit or Seville orange containing product within one week of first dose of study drug and for the duration of the study
  9. Use of any other drugs, including over-the-counter medications and herbal preparations, within two weeks prior to first dose of study drug, unless approved/prescribed by the Principal Investigator as known not to interact with study drugs.
  10. Females of childbearing potential without the use of effective non-hormonal birth control methods, or not willing to continue practising these birth control methods for at least 30 days after the end of the treatment period
  11. Previous allergy to any of the constituents of the pharmaceuticals administered in this trial
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00985543

Locations
United Kingdom
St Stephen's Centre, Chelsea and Westminster Hospital
London, United Kingdom, SW10 9TH
Sponsors and Collaborators
Kirby Institute
Investigators
Principal Investigator: Marta Boffito, MD PhD Chelsea and Westminster Hospital
  More Information

No publications provided by Kirby Institute

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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

Keywords provided by Kirby Institute:
HIV
ART
HAART
Pharmacokinetics
Lopinavir/ritonavir
Lower dose selection

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immune System Diseases
Ritonavir
Lopinavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 29, 2014