Clinical trial NCT00102986: Differences in Blood Levels of Lopinavir/Ritonavir in HIV Infected Men and Women
Official title: Sex Differences in Lopinavir/Ritonavir Pharmacokinetics Among HIV-1-Infected Men and Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV Infections
Keywords: Kaletra
Treatment Experienced
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
First posted: 2005-02-07
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Men's and women's bodies may process anti-HIV drugs differently. The purpose of this study is to determine the differences in blood levels of soft gel capsules and tablets of lopinavir/ritonavir (LPV/r) in HIV infected men and women.

Detailed description: It is estimated that 50% of people living with HIV/AIDS worldwide are women. HIV infected women face different psychosocial issues than men, and their bodies may react differently to HIV treatment. However, most of the data on the safety and efficacy of antiretrovirals (ARVs) used in the treatment of HIV infection are from studies conducted primarily in men. LPV/r in tablet form was approved by the FDA in October 2005. This study will determine the differences in pharmacokinetics (PK) in men and women taking a soft gel capsule and a tablet formulation of LPV/r.

No ARVs will be provided by this study. In Step 1, participants will receive soft gel capsules of LPV/r. All Step 1 participants will be asked to join Step 2 of the study upon completion of Step 1. In Step 2, participants will receive tablets of LPV/r. During the study, participants in both Step 1 and 2 will take a treatment regimen of LPV/r twice daily and one or more of the following: a nucleoside reverse transcriptase inhibitor (NRTI), tenofovir disoproxil fumarate, or enfuvirtide. Medical and medication history, blood collection, and clinical assessments will occur at study screening for both Steps 1 and 2. Participants in both steps will be asked to complete a medication diary from study entry to the day of the PK visit. The PK visit will occur within 30 days of study screening; blood collection for PK analysis will also occur at this visit.

Eligibility criteria: Note: Step 1 enrollment ended as of 06/28/06.

Inclusion Criteria

* HIV infected
* Have taken twice-daily LPV/r (soft gel formulation for Step 1 participants and tablet formulation for Step 2 participants) for at least 14 days immediately prior to step screening and are willing to continue taking LPV/r until the PK visit of that step
* Have taken LPV/r in combination with at least one of the following for at least 14 days immediately prior to study step screening: zidovudine, lamivudine, emtricitabine, stavudine, abacavir sulfate, didanosine, zalcitabine, tenofovir disoproxil fumarate, enfuvirtide, AND are willing to continue taking them until the PK visit of that step
* Body weight of more than 50 kg (110 lbs) for Step 1 participants only

Exclusion Criteria:

* Non-nucleoside reverse transcriptase inhibitor or dual protease inhibitor regimen within 30 days prior to study entry
* Require certain medications
* Current drug or alcohol abuse that, in the investigator's opinion, may interfere with the study
* Serious illness requiring systemic treatment or hospitalization within 30 days of study screening
* Acute AIDS-related opportunistic infection within 90 days of study entry

Primary outcomes:
measure: Lopinavir (LPV) area under the concentration-time curve (AUC) for 0 to 12 hours
Secondary outcomes:
measure: LPV maximum concentration (Cmax), concentration at 12 hours (C12h), and apparent oral clearance (CL/F)
measure: LPV AUC for 0 to 12 hours, Cmax, C12h, CL/F, and participant's race and ethnicity
measure: LPV AUC for 0 to 12 hours, Cmax, C12h, CL/F, participant's age, weight, and body mass index (BMI), and coadministration of TDF
measure: LPV AUC for 0 to 12 hours, Cmax, C12h, CL/F, and graded signs and symptoms
measure: LPV AUC for 0 to 12 hours, Cmax, C12h, CL/F, and graded gastrointestinal signs and symptoms (defined as nausea, vomiting, diarrhea, abdominal pain, and bloating)
measure: ritonavir (RTV) AUC for 0 to 12 hours, Cmax, C12h, and CL/F
measure: LPV/r AUC for 0 to 12 hours, Cmax, C12h, CL/F for both the soft gel capsule and tablet formulations
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California CRS
state: California
city: Los Angeles
country: United States
facility: UCLA CARE Center CRS
state: California
city: Palo Alto
country: United States
facility: Stanford AIDS Clinical Trials Unit CRS
state: California
city: San Diego
country: United States
facility: UCSD Antiviral Research Center CRS
state: California
city: Torrance
country: United States
facility: Harbor-UCLA CRS
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital CRS
state: Colorado
city: Washington
country: United States
facility: Georgetown University CRS (GU CRS)
state: District of Columbia
city: Miami
country: United States
facility: The University of Miami AIDS Clinical Research Unit (ACRU) CRS
state: Florida
city: Honolulu
country: United States
facility: Univ. of Hawaii at Manoa, Leahi Hosp.
state: Hawaii
city: Chicago
country: United States
facility: Cook County Hosp. CORE Ctr.
state: Illinois
city: Chicago
country: United States
facility: Rush University CRS
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Univ. School of Medicine, Infectious Disease Research Clinic
state: Indiana
city: Baltimore
country: United States
facility: Johns Hopkins University CRS
state: Maryland
city: Boston
country: United States
facility: Bmc Actg Crs
state: Massachusetts
city: St. Louis
country: United States
facility: Washington University Therapeutics (WT) CRS
state: Missouri
city: New York
country: United States
facility: Beth Israel Med. Ctr., ACTU
state: New York
city: New York
country: United States
facility: NY Univ. HIV/AIDS CRS
state: New York
city: New York
country: United States
facility: Columbia P&S CRS
state: New York
city: Rochester
country: United States
facility: Univ. of Rochester ACTG CRS
state: New York
city: Chapel Hill
country: United States
facility: Chapel Hill CRS
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati CRS
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth CRS
state: Ohio
city: Columbus
country: United States
facility: Ohio State University CRS
state: Ohio
city: Philadelphia
country: United States
facility: Penn Therapeutics, CRS
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh CRS
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt Therapeutics (VT) CRS
state: Tennessee
city: Galveston
country: United States
facility: Univ. of Texas Medical Branch, ACTU
state: Texas
city: Seattle
country: United States
facility: University of Washington AIDS CRS
state: Washington
city: San Juan
country: Puerto Rico
facility: Puerto Rico AIDS Clinical Trials Unit CRS
Study officials:
affiliation: Center for AIDS Research and Education, University of California, Los Angeles
name: Judith S. Currier, MD, MSc
role: STUDY_CHAIR
References:
citation: Umeh OC, Currier JS. Sex Differences in HIV: Natural History, Pharmacokinetics, and Drug Toxicity. Curr Infect Dis Rep. 2005 Jan;7(1):73-78. doi: 10.1007/s11908-005-0026-9.