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

This study has been completed.
Sponsor:
Collaborator:
Abbott
Information provided by (Responsible Party):
California Collaborative Treatment Group
ClinicalTrials.gov Identifier:
NCT00281606
First received: January 23, 2006
Last updated: September 10, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
HIV Infection
Drug: Different formulations of once-daily lopinavir/ritonavir
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase IV, Randomized, Open-label Study of the Tolerability of Once Daily Lopinavir/Ritonavir (LPV/r) Liquid Versus Capsules

Resource links provided by NLM:


Further study details as provided by California Collaborative Treatment Group:

Primary Outcome Measures:
  • To compare the tolerability of once daily LPV/r (800/200 mg) as 10 ml liquid vs. 6 soft gel capsules. [ Time Frame: Baseline to week 48 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To compare between formulations severity of diarrhea, nausea, use of antidiarrheals, proportion with viral suppression and pharmacokinetics. [ Time Frame: Baseline to week 4 ] [ Designated as safety issue: No ]

Enrollment: 65
Study Start Date: February 2006
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: LPV/r (800/200 mg) 10 ml liquid
Once daily Lopinovir/ritonavir (800/200 mg) taken as a 10 ml liquid
Drug: Different formulations of once-daily lopinavir/ritonavir
CCTG585 is a randomized, open-label, two arm cross-over study to compare the tolerability of once daily LPV/r liquid versus capsules
Active Comparator: LPV/r (800/200 mg) 6 gel capsules
Once daily Lopinavir/ritonavir (800/200 mg) as 6 gel capsules
Drug: Different formulations of once-daily lopinavir/ritonavir
CCTG585 is a randomized, open-label, two arm cross-over study to compare the tolerability of once daily LPV/r liquid versus capsules

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00281606

Locations
United States, California
UCI
Irvine, California, United States, 92668
USC
Los Angeles, California, United States, 90033
UCSD
San Diego, California, United States, 92103
Santa Clara Valley Medical Center
San Jose, California, United States, 95128
Harbor-UCLA Medical Center
Torrance, California, United States, 90502
Sponsors and Collaborators
California Collaborative Treatment Group
Abbott
Investigators
Principal Investigator: Eric Daar, MD University of California, Los Angeles
  More Information

No publications provided

Responsible Party: California Collaborative Treatment Group
ClinicalTrials.gov Identifier: NCT00281606     History of Changes
Other Study ID Numbers: CCTG 585
Study First Received: January 23, 2006
Last Updated: September 10, 2013
Health Authority: United States: Food and Drug Administration (IND Exempted)

Keywords provided by California Collaborative Treatment Group:
Lopinavir
antiretroviral therapy
cross-over
tolerability

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Ritonavir
Lopinavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 19, 2014