Clinical trial NCT00043966: Study of Lopinavir, Ritonavir, Tenofovir and Emtricitabine in HIV-Infected Antiretroviral Naïve Subjects
Official title: A Randomized, Open-Label Study of 800 Mg Lopinavir/200 Mg Ritonavir QD in Combination With Tenofovir and Emtricitabine Vs. 400 Mg Lopinavir /100 Mg Ritonavir BID in Combination With Tenofovir and Emtricitabine in HIV-Infected Antiretroviral Naïve Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
Keywords: treatment naive
Lead sponsor: Abbott
Sponsor class: INDUSTRY
First posted: 2002-08-19
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the safety, tolerability and antiviral activity between once-daily (QD) and twice-daily (BID) dosing of lopinavir/ritonavir and to further characterize the pharmacokinetics of once-daily dosing of lopinavir/ritonavir.


Eligibility criteria: Inclusion Criteria:

* Subject is at least 18 years of age.
* If female, subject is not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy), or is of childbearing potential and practicing one of the following methods of birth control: \*condoms, sponge, foams, jellies, diaphragm or intrauterine device (IUD) \*contraceptives (oral or parenteral) for three months prior to study drug administration) \*a vasectomized partner \*total abstinence from sexual intercourse
* If female, the results of a urine pregnancy test performed at screening (urine specimen obtained no earlier than 28 days prior to study drug administration) and a urine pregnancy test performed on Study Day -1 are both negative and the subject agrees to use a barrier method of contraception throughout the study.
* Subject is not breast-feeding.
* Vital signs, physical examination and laboratory results do not exhibit evidence of acute illness.
* Subject has no significant history of cardiac, renal, neurologic, psychiatric, oncologic, endocrinologic, metabolic or hepatic disease that would adversely affect his/her participating in this study.
* Subject does not require and agrees not to take any of the following medications for the duration of the study: midazolam, triazolam, terfenadine, astemizole, cisapride, pimozide, propafenone, flecainide, certain ergot derivatives (ergotamine, dihydroergotamine, ergonovine, and methylergonovine), rifampin, lovastatin, simvastatin, and St. John's wort.
* Subject agrees not to take any medication during the study, including over-the-counter medicine, herbal medications, alcohol or recreational drugs without the knowledge and permission of the principal investigator.
* Subject has a Karnofsky Score greater than or equal to 70
* Subject has not been treated for an active AIDS-defining opportunistic infection within 30 days of screening. Subjects who are on stable maintenance therapy for an opportunistic infection may be enrolled after consultation with Abbott.
* Subject is naive to antiretroviral treatment (\< 7 days ARV treatment).
* Subject has a plasma HIV RNA level of greater than 1,000 copies/mL at screening.
* Subject agrees to take all doses of the lopinavir/ritonavir from the bottles provided by the sponsor (rather than take doses from a personal "dosette" box).
* Subject has voluntarily signed and dated an informed consent form, approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC), after the nature of the study has been explained and the subject has had the opportunity to ask questions. The informed consent must be signed before any study-specific procedures are performed.

Exclusion Criteria:

* Subject has a history of an allergic reaction or significant sensitivity to lopinavir/ritonavir, tenofovir or emtricitabine or to drugs similar to study drug.
* Subject has a recent (within the past 6 months) history of drug and/or alcohol abuse.
* Subject has a positive result on the screening tests for drugs of abuse.
* Subject has a history of substance abuse or psychiatric illness that could preclude adherence with the protocol.
* Screening laboratory analyses show any of the following abnormal laboratory results: \*Hemoglobin ≤ 8.0 g/dL \*Absolute neutrophil count ≤ 750 cells/µL \*Platelet count ≤ 50,000 per mL \*ALT or AST ≥ 3.0 x Upper Limit of Normal (ULN) \*Creatinine ≥ 1.5 x Upper Limit of Normal (ULN)
* Subject has received any investigational drug within 30 days prior to study drug administration.
* For any reason, subject is considered by the investigator to be an unsuitable candidate for the study.

Primary outcomes:
measure: Proportion of subjects with plasma HIV RNA level below 50 copies/mL at week 48
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix,
country: United States
facility: Phoenix Body Positive
state: Arizona
city: Beverly Hills
country: United States
facility: Pacific Oaks Research
state: California
city: Fountain Valley
country: United States
facility: Orange County Center for Special Immunology
state: California
city: Long Beach
country: United States
facility: Living Hope Clinical Foundation
state: California
city: Los Angeles
country: United States
facility: AIDS Healthcare Foundation Research Center
state: California
city: Altamonte Springs
country: United States
facility: IDS Research Initiative
state: Florida
city: Atlantis
country: United States
facility: South Florida Clinical Research
state: Florida
city: Fort Myers
country: United States
facility: Associates in Research
state: Florida
city: Ft. Lauderdale,
country: United States
facility: Gary J. Richmond, MD
state: Florida
city: Ft. Lauderdale
country: United States
facility: Comprehensive Care Center
state: Florida
city: Plantation
country: United States
facility: Morris, Sklaver, Mestre & Denney, M.D., PA
state: Florida
city: Safety Harbor
country: United States
facility: Health Positive
state: Florida
city: Tampa
country: United States
facility: Infectious Disease Research Institute, Inc.
state: Florida
city: Vero Beach
country: United States
facility: Treasure Coast Infectious Disease Consultants
state: Florida
city: Atlanta
country: United States
facility: AIDS Research Consortium of Atlanta Inc.
state: Georgia
city: Wichita,
country: United States
facility: Donna E. Sweet, MD
state: Kansas
city: New Orleans
country: United States
facility: Drs. Combs and Lutz
state: Louisiana
city: Newark
country: United States
facility: St. Michael's Medical Center
state: New Jersey
city: New York
country: United States
facility: Polari Medical Group
state: New York
city: Winston-Salem,
country: United States
facility: Wake Forest University School of Medicine
state: North Carolina
city: Akron
country: United States
facility: Akron Infectious Disease, Inc.
state: Ohio
city: Tulsa
country: United States
facility: Associates in Medical and Mental Health, P.C.
state: Oklahoma
city: Portland
country: United States
facility: The Research & Education Group
state: Oregon
city: Philadelphia,
country: United States
facility: Philadelphia FIGHT
state: Pennsylvania
city: Philadelphia
country: United States
facility: Triangle Medical
state: Pennsylvania
city: Austin
country: United States
facility: Central Texas Clinical Research
state: Texas
city: Houston
country: United States
facility: Joseph C. Gathe, Jr, MD
state: Texas
city: Houston
country: United States
facility: Southampton Medical Group
state: Texas
city: Hampton
country: United States
facility: Hampton Roads Medical Specialists
state: Virginia
city: Darlinghurst
country: Australia
facility: Ground Zero Medical Centre / AIDS Research Initiative
state: New South Wales
city: Darlinghurst
country: Australia
facility: Holdsworth House General Practice
state: New South Wales
city: Paris
country: France
facility: Hopital Saint Louis
state: Cedex 10
city: Paris
country: France
facility: Hopital Saint Antoine
state: Cedex 12
city: Paris
country: France
facility: Hopital Tenon
state: Cedex 20
city: Le Kremlin Bicetre
country: France
facility: CHU Kremlin Bicetre
city: Nice
country: France
facility: Hopital l'Archet
city: Paris
country: France
facility: Hopital Bichat
city: Frankfurt
country: Germany
facility: Klinikum J.W. Goethe Universitat
city: Koln
country: Germany
facility: Klinik I fur Innere Medizin der Universitat zu Koln
city: Tan Tock Seng
country: Singapore
facility: Tan Tock Seng Hospital
city: Badalona
country: Spain
facility: Hospital Germans Trias I Pujol
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Vall D'Hebron
city: Barcelona
country: Spain
facility: L'Hospitalet de Llobregat
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Madrid
country: Spain
facility: Hospital La Paz
city: Madrid
country: Spain
facility: Hospital de Mostolesi
city: E. Sussex
country: United Kingdom
facility: Brighton General Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: The Caldecot Centre King's Healthcare NHS Trust
city: London
country: United Kingdom
facility: St. Stephen's Centre Chelsea & Westminster Hospital
city: London
country: United Kingdom
facility: St. Mary Hospital
Study officials:
affiliation: Global Project Head, Antiviral Global Project Team
name: Scott Brun, M.D.
role: STUDY_DIRECTOR
References:
citation: Podsadecki TJ, Vrijens BC, Tousset EP, Rode RA, Hanna GJ. Decreased adherence to antiretroviral therapy observed prior to transient human immunodeficiency virus type 1 viremia. J Infect Dis. 2007 Dec 15;196(12):1773-8. doi: 10.1086/523704.