Clinical trial NCT00148759: Kaletra Sex/Gender Pharmacokinetics (PK) Study
Official title: A Switch From Twice Daily to Once Daily Lopinavir/Ritonavir: A 24-hour Pharmacokinetic Profile to Evaluate Sex Differences
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Infections
Keywords: Sex differences
Pharmacokinetic
Lopinavir/ritonavir
Treatment Experienced
HIV-infection
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: Abbott
First posted: 2005-09-08
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: 24-hr LPV AUC
timeFrame: 24 hours
Secondary outcomes:
measure: 24-hr LPV Cmax
timeFrame: 24 hours
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Grady Infectious Diseases Program
state: Georgia
Study officials:
affiliation: Emory University
name: Igho Ofotokun, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.