HIV InfectionPhase 4NCT00281606
A Multicenter Study to Assess the Tolerability of Once Daily Lopinavir/Ritonavir (LPV/r) Liquid Versus Capsules
A Phase 4 study testing Different formulations of once-daily lopinavir/ritonavir in people with HIV Infection, run by University of California, San Diego at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infection
- What is being tested?
- Different formulations of once-daily lopinavir/ritonavir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 65 participants
- Where
- 5 sitesUnited States
- Study dates
- 14 Feb 2006to 13 Jun 2012
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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)
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- 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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
UCI
Irvine, California, 92668
USC
Los Angeles, California, 90033
UCSD
San Diego, California, 92103
Santa Clara Valley Medical Center
San Jose, California, 95128
Harbor-UCLA Medical Center
Torrance, California, 90502
About this study
Official title: A Phase IV, Randomized, Open-label Study of the Tolerability of Once Daily Lopinavir/Ritonavir (LPV/r) Liquid Versus Capsules
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.
Read the 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.
- Conditions
- HIV Infection
- Being tested
- Different formulations of once-daily lopinavir/ritonavir
- Keywords
- Lopinavir, antiretroviral therapy, cross-over, tolerability
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Different formulations of once-daily lopinavir/ritonavirDrug
Also called Lopinavir/Ritonavir (LPV/r)
CCTG585 is a randomized, open-label, two arm cross-over study to compare the tolerability of once daily LPV/r liquid versus capsules
| Study group | Role | What they receive |
|---|---|---|
| LPV/r (800/200 mg) 10 ml liquid | Active comparator | Once daily Lopinovir/ritonavir (800/200 mg) taken as a 10 ml liquid Receives: 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 Receives: Drug: Different formulations of once-daily lopinavir/ritonavir |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to week 48
Secondary outcomes (11)
Incidence Measures of Treatment-limiting toxicity
Separately evaluating at the end of week 4 or at the time therapy is discontinued for treatment-limiting toxicity of the two 4 week phases of the cross-over trial (Steps 1 and 2).
Measured: Baseline to week 48
Incidence Measures of Drug-related diarrhea
Separately evaluating at the end of week 4 or at the time therapy is discontinued for drug-related diarrhea of the two 4 week phases of the cross-over trial (Steps 1 and 2).
Measured: Baseline to week 48
Incidence Measures of the Use of antiemetic and/or antimotility therapy
Separately evaluating at the end of week 4 or at the time therapy is discontinued for antiemetic and/or antimotility therapy of the two 4 week phases of the cross-over trial (Steps 1 and 2).
Measured: Baseline to week 48
Incidence Measures of Adverse events other than nausea and diarrhea
Separately evaluating at the end of week 4 or at the time therapy is discontinued for adverse events other than nausea and diarrhea of the two 4 week phases of the cross-over trial (Steps 1 and 2).
Measured: Baseline to week 48
Incidence Measures of Laboratory abnormalities, e.g. lipids, liver enzymes
Separately evaluating at the end of week 4 or at the time therapy is discontinued for laboratory abnormalities of the two 4 week phases of the cross-over trial (Steps 1 and 2).
Measured: Baseline to week 48
Incidence Measures of HIV RNA suppression to <50 copies/ml
Separately evaluating at the end of week 4 or at the time therapy is discontinued for HIV RNA suppression to <50 copies/ml of the two 4 week phases of the cross-over trial (Steps 1 and 2).
Measured: Baseline to week 48
Preference for Lopinavir/ritonavir liquid, capsules or tablets, and the degree of like or dislike of each
The stated preference for LPV/r liquid, capsules or tablets, and the degree of like or dislike of each in those who choose an option other than once daily LPV/r tablets at start of Step 4
Measured: Week 8 and week 48
Evaluating the proportion of screened individuals who choose not to be randomized after the liquid Lopinavir/ritonavir taste test
Evaluating the proportion of screened individuals who choose not to be randomized after the liquid LPV/r taste test at the time of enrollment into the study
Measured: Baseline
Evaluating the severity of diarrhea
Measuring sum of days with diarrhea weighted for highest level of severity (sum of event severity numbers = 1-5) on that day via the Division of AIDS Table for Grading Adult Adverse Experiences that can be found on the ROC Web site: http://rcc.tech-res-intl.com/
Measured: Week 4, week 8 and week 48
Evaluating the severity of nausea
Measuring days of nausea weighted for the highest level of severity (sum of event severity numbers = 1-5) on that day via the Division of AIDS Table for Grading Adult Adverse Experiences that can be found on the ROC Web site: http://rcc.tech-res-intl.com/
Measured: Week 4, week 8 and week 48
Evaluating proportion with plasma HIV RNA <50 copies/mL at the end of Step 4
Evaluating the proportion of participants with plasma HIV RNA <50 copies/mL at the end of Step 4
Measured: Week 4, week 8 and week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2006 (estimated)
- Study start14 Feb 2006
- Primary completion16 Oct 2007
- Study completion13 Jun 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionStudies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Collaborators
- Abbott
- Responsible party
- Principal investigator, J Allen McCutchan, University of California, San Diego
- Investigators
- Eric Daar, MD, Principal investigator, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00281606
- Sponsor's protocol ID
- CCTG 585
- Status last verified
- Jun 2020
- First submitted
- 23 Jan 2006
- Last updated
- 30 Jun 2020
- Results posted
- No
Publications
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)
Study at a glance
From the registry record, last updated by the sponsor on 30 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IV, Randomized, Open-label Study of the Tolerability of Once Daily Lopinavir/Ritonavir (LPV/r) Liquid Versus Capsules
- ClinicalTrials.gov ID
- NCT00281606
- Acronym / sponsor ID
- CCTG 585
- Conditions
- HIV Infection
- Keywords
- Lopinavir, antiretroviral therapy, cross-over, tolerability
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 65 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Collaborators
- Abbott
- Study start
- 14 Feb 2006 (actual)
- Primary completion
- 16 Oct 2007 (actual)
- Study completion
- 13 Jun 2012 (actual)
- First posted
- 25 Jan 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LPV/r (800/200 mg) 10 ml liquid | Active comparator | Drug: Different formulations of once-daily lopinavir/ritonavirOnce daily Lopinovir/ritonavir (800/200 mg) taken as a 10 ml liquid |
| LPV/r (800/200 mg) 6 gel capsules | Active comparator | Drug: Different formulations of once-daily lopinavir/ritonavirOnce daily Lopinavir/ritonavir (800/200 mg) as 6 gel capsules |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Different formulations of once-daily lopinavir/ritonavirAlso: Lopinavir/Ritonavir (LPV/r)CCTG585 is a randomized, open-label, two arm cross-over study to compare the tolerability of once daily LPV/r liquid versus capsules | Drug | LPV/r (800/200 mg) 10 ml liquid, LPV/r (800/200 mg) 6 gel capsules |
Primary outcome
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.
Time frame: Baseline to week 48
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.
11 secondary outcomes
Incidence Measures of Treatment-limiting toxicity
Time frame: Baseline to week 48
Incidence Measures of Drug-related diarrhea
Time frame: Baseline to week 48
Incidence Measures of the Use of antiemetic and/or antimotility therapy
Time frame: Baseline to week 48
Incidence Measures of Adverse events other than nausea and diarrhea
Time frame: Baseline to week 48
Incidence Measures of Laboratory abnormalities, e.g. lipids, liver enzymes
Time frame: Baseline to week 48
Incidence Measures of HIV RNA suppression to <50 copies/ml
Time frame: Baseline to week 48
Preference for Lopinavir/ritonavir liquid, capsules or tablets, and the degree of like or dislike of each
Time frame: Week 8 and week 48
Evaluating the proportion of screened individuals who choose not to be randomized after the liquid Lopinavir/ritonavir taste test
Time frame: Baseline
Evaluating the severity of diarrhea
Time frame: Week 4, week 8 and week 48
Evaluating the severity of nausea
Time frame: Week 4, week 8 and week 48
Evaluating proportion with plasma HIV RNA <50 copies/mL at the end of Step 4
Time frame: Week 4, week 8 and week 48
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jun 2020.
- Results publication1. 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)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eric Daar, MD principal investigator
University of California, Los Angeles
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Different formulations of once-daily lopinavir/ritonavir in people with HIV Infection, run by University of California, San Diego at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: Baseline to week 48). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00281606, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jun 2020.