A Multicenter Study to Assess the Tolerability of Once Daily Lopinavir/Ritonavir (LPV/r) Liquid Versus Capsules

Condition(s) targeted: HIV Infection

Intervention: Different formulations of once-daily lopinavir/ritonavir (Drug)

Phase: Phase 4

Status: Not yet recruiting

Sponsored by: California Collaborative Treatment Group

Official(s) and/or principal investigator(s):
Eric Daar, MD, Principal Investigator, Affiliation: University of California, Los Angeles

Guidelines have continued to list lopinavir/ritonavir as a preferred protease inhibitor-containing regimen for HIV-infected individuals. There has recently been increasing interest in once daily therapy. While lopinavir/ritonavir has recently been approved as a once daily therapy it was associated with considerable diarrhea in those treated with soft gel capsules. It is the hope that alternative formulations of lopinavir/ritonavir may provide similar pharmacokinetics with improved tolerability. This includes the possibility of using liquid or newly released tablets. This study will treat people tolerating their current regimen with up to four weeks of each formulation with several assessments of pharmacokinetics and tolerability for each.

Official title: A Phase IV, Randomized, Open-Label Study of the Tolerability of Once Daily Lopinavir/Ritonavir (LPV/r) Liquid Versus Capsules

Study design: Treatment, Randomized, Open Label, Active Control, Crossover Assignment, Safety/Efficacy Study

Primary outcome: The primary outcome of the study is to compare the tolerability of once daily LPV/r (800/200 mg) as 10 ml liquid vs. 6 soft gel capsules.

Secondary outcome:

-To compare at week 4, or at the time therapy is discontinued, for each of the initial formulations (liquid versus soft gel capsules) of lopinavir/ritonavir:

--Maximum severity of diarrhea

--Maximum severity of nausea

--Use of antimotility or antiemetic therapy

--Development of adverse events (AEs) other than nausea and diarrhea

--Development of laboratory abnormalities, e.g. lipids, transaminases

--Development of treatment-limiting toxicity

--Plasma HIV-1 RNA suppression to <50 copies/mL

--Level of symptoms distress

Additional secondary measures will include:

-To compare the pharmacokinetics of once daily liquid and capsules of LPV/r after 2 weeks of therapy

-The above parameters after four weeks of the receiving the new tablet formulation of lopinavir/ritonavir

-The rates of plasma HIV-1 RNA <50 copies/mL at the end of up to 48 weeks of study.

Detailed description: This study is designed to assess the tolerability of different forms (liquid, capsules or tablets) of lopinavir/ritonavir given once-daily as part of combination therapy for HIV infection. Study subjects will be those tolerating a stable regimen of HIV medications with undetectable levels of HIV in their blood. They will be assigned by chance to receive once daily liquid or soft gel capsules of lopinavir/ritonavir for up to four weeks. At that time they will receive the alternative formulation for up to four weeks. They will then be given once daily lopinavir/ritonavir in the recently released tablet formulation. After up to four weeks of each of these formulations several assessments will be made of the overall tolerability of the drug. After four weeks of tablets they will be allowed to take whatever regimen they want and will be followed for an additional 36 weeks for a total duration of study of up to 48 weeks. The pharmacokinetics of each formulation of lopinavir/ritonavir given once daily will also be assessed in a subset of study subjects.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Ability and willingness of subject or legal guardian/representative to give written

informed consent.

- HIV-1 infected.

- At least 18 years of age

- Have the last two HIV-1 RNA measurements performed prior to screening be <50 or 75

copies/mL within the last 180 days, as well as at the time of screening.

- No evidence of primary PI mutations (defined by IAS-USA) documented on previous

resistance testing, if ever performed and available, or suggested to be present by previous treatment history.

- Laboratory values:

- Absolute neutrophil count (ANC) >500/mm3.

- -Hemoglobin >7. 0 g/dL.

- platelet count >50,000/mm3.

- AST (SGOT), ALT (SGPT), and alkaline phosphatase <5 X ULN.

- Total bilirubin <2. 5 x ULN, unless on IDV or ATV in which case must be <1. 5 x

ULN of direct bilirubin.

- Calculated creatinine clearance >50 mL/min as estimated by the Cockcroft-Gault

equation

- For women of reproductive potential, negative serum or urine pregnancy test within 7

days prior to initiating study medications. If participating in sexual activity that could lead to pregnancy, female study subjects must use two forms of contraception, one of which must be a barrier method. All subjects must continue to use contraception for 6 weeks after stopping the study medications.

- Willingness to take an alcohol containing product.

- Karnofsky performance score >70.

Exclusion Criteria:

- Pregnancy or breast-feeding

- Greater than Grade 1 diarrhea or nausea (as defined by protocol)

- Use of a NNRTI within 12 weeks of screening

- Use of antimotility or antiemetics during the 14 days prior to screening

- Use of any of the prohibited medications (defined by protocol) within 30 days of study

entry.

- Need to continue the use of prohibited or select precautionary medications (defined by

protocol)

- Known hypersensitivity to lopinavir/ritonavir

- Active drug or alcohol use or dependence which, in the Investigator’s opinion, may

interfere with adherence to study requirements or endanger subject’s health while on the study

- Serious illness requiring systemic treatment and/or hospitalization until subject

either completes therapy or is clinically stable on therapy, in the opinion of the investigator, for at least 30 days prior to study entry.

- Acute therapy for serious infection or other serious medical illnesses (in the

judgment of the site investigator) requiring systemic treatment and/or hospitalization within 14 days prior to study entry.

- Use of immunomodulators (e. g., interleukins, interferons, cyclosporine), HIV-1

vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to study entry

UCSD, San Diego, California 92103, United States

UCI, Irvine, California 92668, United States

Harbor-UCLA Medical Center, Torrance, California 90502, United States

USC, Los Angeles, California 90033, United States

Santa Clara Valley Medical Center, San Jose, California 95128, United States

Ending date: August 2007
Last updated: March 17, 2006