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

NCT00281606 | Completed Phase 4

• 1 other identifier: CCTG 585
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

HIV Infection

Keywords

Lopinavir; antiretroviral therapy; cross-over; tolerability

Outcome Measures

Primary Outcomes (1)

• Measuring whether the subject has severity of diarrhea grade 2 or higher or exhibits treatment-limiting toxicity when treated with once daily Lopinavir/ritonavir [LPV/r] (800/200 mg) as 10 ml liquid vs. 6 soft gel capsules.

  To assess the comparative tolerability of once daily Lopinavir/ritonavir \[LPV/r\] (800/200 mg) as 10 ml liquid vs. 6 soft gel capsules by measuring incidence rates as assessed by the CTCAE v4.0 in each arm of: a) grade 2 or higher diarrhea plus b) dose limiting toxicity of any kind.

  Baseline to week 48

Secondary Outcomes (11)

• Incidence Measures of Treatment-limiting toxicity

  Baseline to week 48

• Incidence Measures of Drug-related diarrhea

  Baseline to week 48

• Incidence Measures of the Use of antiemetic and/or antimotility therapy

  Baseline to week 48

• Incidence Measures of Adverse events other than nausea and diarrhea

  Baseline to week 48

• Incidence Measures of Laboratory abnormalities, e.g. lipids, liver enzymes

  Baseline to week 48

Other Outcomes (9)

• Direct inspection of Pre-dose concentrations (Cpre-dose) for Lopinavir/ritonavir (LPV/r)

  Baseline and 12 weeks

• Direct inspection of trough concentrations (Ctrough) for Lopinavir/ritonavir (LPV/r)

  Baseline and 12 weeks

• Direct inspection of 24-hour post-dose concentrations (C24) for Lopinavir/ritonavir (LPV/r)

  Baseline and 12 weeks

Study Arms (2)

LPV/r (800/200 mg) 10 ml liquid

ACTIVE COMPARATOR

Once daily Lopinovir/ritonavir (800/200 mg) taken as a 10 ml liquid

Drug: Different formulations of once-daily lopinavir/ritonavir

LPV/r (800/200 mg) 6 gel capsules

ACTIVE COMPARATOR

Once daily Lopinavir/ritonavir (800/200 mg) as 6 gel capsules

Drug: Different formulations of once-daily lopinavir/ritonavir

Interventions

Different formulations of once-daily lopinavir/ritonavir DRUG

CCTG585 is a randomized, open-label, two arm cross-over study to compare the tolerability of once daily LPV/r liquid versus capsules

Also known as: Lopinavir/Ritonavir (LPV/r)

LPV/r (800/200 mg) 10 ml liquid; LPV/r (800/200 mg) 6 gel capsules

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Diego: lead
• Abbott: collaborator

Study Sites (5)

UCI

Irvine, California, 92668, United States

Location

USC

Los Angeles, California, 90033, United States

Location

UCSD

San Diego, California, 92103, United States

Location

Santa Clara Valley Medical Center

San Jose, California, 95128, United States

Location

Harbor-UCLA Medical Center

Torrance, California, 90502, United States

Location

Related Publications (1)

• 1. Best B, Rieg G, Sun S, Jain S, Kemper C, Diamond C, Hermes A, Haubrich R, Daar E, and California Collaborative Treatment Group (CCTG) 585 Team. Increased lopinavir concentrations on once-daily tablets as compared with capsules and liquid formulations. 15th Conference on Retroviruses and Opportunistic Infections; February 3-6, 2008; Boston, MA. Abstract 766a. 2. CDB088 Abstract Switching to once-daily (QD) lopinavir/ritonavir (LPV/r) liquid (Liq), capsules (caps) and tablets (tabs): a randomized, ppen label, cross-over study (CCTG 585). 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention; Cape Town 2009 G. Rieg1, S. Jain2, S. Sun2, R. Larsen3, C. Kemper4, C. Diamond5, S. Schneider6, D. Shamblaw7, A. Hermes8, R. Haubrich9, E. Daar10, California Collaborative Treatment Group (CCTG)

  RESULT

MeSH Terms

Conditions

HIV Infections

Interventions

Ritonavir; Lopinavir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidinones; Pyrimidines

Study Officials

• Eric Daar, MD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof Emeritus

Study Record Dates

• First Submitted: January 23, 2006
• First Posted: January 25, 2006
• Study Start: February 14, 2006
• Primary Completion: October 16, 2007
• Study Completion: June 13, 2012
• Last Updated: June 30, 2020

Record last verified: 2020-06

Locations

US (5)