Kaletra Sex/Gender Pharmacokinetics (PK) Study (LPVGenderPK)

This study has been completed.
Sponsor:
Collaborator:
Abbott
Information provided by (Responsible Party):
Ighovwerha Ofotokun, Emory University
ClinicalTrials.gov Identifier:
NCT00148759
First received: September 6, 2005
Last updated: November 8, 2013
Last verified: November 2013
  Purpose

The levels of lopinavir achieved in the blood following oral ingestion of standard doses of Kaletra (lopinavir/ritonavir) in HIV-infected men was compared with those achieved in HIV-infected women receiving the same dose of the drug.


Condition Intervention Phase
HIV Infections
Drug: LPV/r
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Switch From Twice Daily to Once Daily Lopinavir/Ritonavir: A 24-hour Pharmacokinetic Profile to Evaluate Sex Differences

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • 24-hr LPV AUC [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    Steady state(2 weeks after therapy change)


Secondary Outcome Measures:
  • 24-hr LPV Cmax [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    LPV Cmax at Steady State


Enrollment: 23
Study Start Date: June 2005
Study Completion Date: January 2007
Primary Completion Date: January 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: adult male subjects
LPV/r 800/200 mg once daily
Drug: LPV/r
LPV/r 800/200 mg once daily
Other Names:
  • Daily LPV/r
  • Kaletra
Experimental: Adult female subjects
LPV/r 800/200 mg once daily
Drug: LPV/r
LPV/r 800/200 mg once daily
Other Names:
  • Daily LPV/r
  • Kaletra

Detailed Description:

The association between patient sex and the tolerability of antiretroviral drugs (ARVs) is increasingly being recognized. Several lines of evidence suggest that women are more likely than men to develop side effects to ARVs. On the other hand, it has been generally accepted that the efficacies of the ARVs are similar in both sexes. However, recent studies suggest that this may not always be the case. In addition to these observed sex-related differences in the effects of ARVs, there is growing evidence that the pharmacokinetic profile of some of these drugs may be different among male and female HIV infected patients.

The fact that female sex is a risk factor for enhanced antiretroviral effects (including toxicities) has an important implication, particularly from a global health perspective as women now represent the fastest growing segment of the HIV/AIDS epidemic. Therefore, an understanding of the magnitude, clinical significance, and the mechanisms underlying this phenomenon deserves further study. Knowledge acquired from such studies will likely contribute to improved survival among female HIV-infected patients, through optimization of antiretroviral therapeutic regimens in manners that minimize serious adverse effects and improve adherence.

Similarly, the influence of race on the pharmacological effects of ARVs deserves further investigation. Although, there is no reason to believe based on available evidence that racial differences exist in the pharmacological effects of ARVs, the need however exists to explore the influence of race on ARVs pharmacokinetics and treatment outcomes. This is so because data on race related differences on ARV effects is limited, and in addition, people of ethnic minority have been disproportionately under represented in clinical trials involving these drugs in spite of the fact that they bear a larger burden of the HIV epidemic.

Our study will examine the influence of race and sex on the 24-hr pharmacokinetics of lopinavir/ritonavir (an antiretroviral agent commonly used in naïve patients) following a switch from LPV/r 400/100 mg twice daily to 800/200 mg once daily dosing. Tolerability (measured by toxicity grade of diarrhea) and change in quality of life following switch from twice daily to once daily dosing will also be assessed using appropriate validated measurement tools.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age greater or equal to 18 years
  • Diagnosis of HIV infection as previously established by HIV Enzyme-Linked Immunosorbent Assay (ELISA) test and confirmed by Western blot analysis.
  • Must have been taking LPV/r as part of an antiretroviral regimen at a dose of 400/100 mg orally twice per day for at least 3 months.
  • Recent (within last 90 days) HIV-RNA copies must be less than 400 copies/ml

Exclusion Criteria:

  • Hepatic abnormality: alanine-aminotransferase (ALT), aspartate-aminotransferase (AST) or total bilirubin (TBR) ≥ 3 x upper limit of normal
  • Renal insufficiency: serum creatinine ≥ 2 mg/dl
  • Co-infection with hepatitis B and/or C viruses
  • Pregnant or breastfeeding
  • Use of concurrent medications known to affect lopinavir or ritonavir concentrations significantly.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00148759

Locations
United States, Georgia
Grady Infectious Diseases Program
Atlanta, Georgia, United States, 30308
Sponsors and Collaborators
Emory University
Abbott
Investigators
Principal Investigator: Igho Ofotokun, MD, MSc Emory University
  More Information

Publications:
Responsible Party: Ighovwerha Ofotokun, Associate Professor of Medicine, Emory University
ClinicalTrials.gov Identifier: NCT00148759     History of Changes
Other Study ID Numbers: IRB00002448, UPN 04092824, GCRC0605G
Study First Received: September 6, 2005
Results First Received: November 24, 2009
Last Updated: November 8, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Emory University:
Sex differences
Pharmacokinetic
Lopinavir/ritonavir
Treatment Experienced
HIV-infection

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
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 April 22, 2014