Kaletra Sex/Gender Pharmacokinetics (PK) Study

NCT ID: NCT00148759

Last Updated: 2013-12-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-06-30
• Study Completion Date: 2007-01-31

Brief Summary

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.

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.

Conditions

HIV Infections

Keywords

Sex differences; Pharmacokinetic; Lopinavir/ritonavir; Treatment Experienced; HIV-infection

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

adult male subjects

LPV/r 800/200 mg once daily

Group Type: ACTIVE_COMPARATOR

LPV/r

Intervention Type: DRUG

LPV/r 800/200 mg once daily

Adult female subjects

LPV/r 800/200 mg once daily

Group Type: EXPERIMENTAL

LPV/r

Intervention Type: DRUG

LPV/r 800/200 mg once daily

Interventions

LPV/r

LPV/r 800/200 mg once daily

Intervention Type: DRUG

Other Intervention Names

Daily LPV/r; Kaletra

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Abbott

INDUSTRY

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Ighovwerha Ofotokun

Associate Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Igho Ofotokun, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Grady Infectious Diseases Program

Atlanta, Georgia, United States

Countries

United States

References

Ofotokun I, Chuck SK, Binongo JN, Palau M, Lennox JL, Acosta EP. Lopinavir/Ritonavir pharmacokinetic profile: impact of sex and other covariates following a change from twice-daily to once-daily therapy. J Clin Pharmacol. 2007 Aug;47(8):970-7. doi: 10.1177/0091270007302564. Epub 2007 Jul 5.

Reference Type: RESULT

PMID: 17615254 (View on PubMed)

Other Identifiers

UPN 04092824

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

GCRC0605G

Identifier Type: OTHER

Identifier Source: secondary_id

IRB00002448

Identifier Type: -

Identifier Source: org_study_id